The characteristics of craniofacial and cervicovertebral morphology in different genetic syndromes – a literature review and three case reports

Introduction: Patients with genetic syndromes were characterized by variety of skeletal craniofacial and cervicovertebral morphology. Skeletal anomalies are recognized concomitants of the various genetic syndromes. The aim of the study was to review the current literature on this topic and to present the characteristics of craniofacial and cervicovertebral morphology and subsequent anomalies in three patients with Crouzon syndrome, Treacher Collins syndrome and cleidocranial dysplasia. Materials and Methods: A comprehensive electronic search was performed using PubMed via Medline, Web of Science and SCOPUS.A manual search involved references form articles retrieved for possible inclusion. There were no restrictions as to date of publication, study design or language. The search, evaluation of relevant articles, and their critical appraisal were performed by two independent judges. Discrepancies between reviewers were resolved through a consensus with a third party. Case reports: Additionally, this paper presents a radiographic analysis of craniofacial and cervicovertebral morphology in patients with cleidocranial dysplasia, Crouzon, and Treacher Collins syndromes. The most characteristic findings of cervicovertebral morphology were the presence of cervical spine fusions in all three patients. The intervertebral fusions in patients with Crouzon and TreacherCollins syndromes have been characterized with "block vertebrae". Cervicovertebral complex of the patient with cleidocranialdysplasia is characterized by delayed mineralization of vertebral bodies (C1–C7). Results: Although craniofacial and cervicovertebral anomalies in presented syndromes have different phenotype expression, the vast majority of cases are caused by mutations in specific, syndrome-related genes (FGFR2, FGFR3, RUNX2, TCOF1, POLR1C,POLR1D). Craniofacial anomalies, that include changes in development of hard and soft tissues, were considered as traditional concomitant of presented syndromes. Apart from these changes, cervicovertebral region could also be affected. Recent reports show different changes in vertebral structure (delayed mineralization) and unphysiological relations (cervical spine fusions). Conclusion: The limitation of cervical range of motion resulting from these anomalies may have clinical significance on multidisciplinary management approach in these patients. Recent progress in dentistry resulted in better diagnostic and therapeutic options and outcomes for individuals with genetic syndromes

Positive effects of naringenin on near-surface membrane fluidity in human erythrocytes

Purpose: Deformability/rheologic behavior of erythrocytes are related to near-surface membrane fluidity. Specific agents can increase erythrocyte membrane fluidity in order to adjust hemodynamics in cardiovascular diseases. Grapefruit flavanone naringenin has been proposed for potential use in an alternative therapy of cardiovascular conditions. In respect to this, we assessed here effects of two nutritionally relevant concentrations of naringenin (0.1 and 1 μg/ml) on near-surface membrane fluidity in human erythrocytes. Methods: We used electron paramagnetic resonance spectroscopy and fatty acid spin probes (5-DS and 7-DS), the spectra of which are dependent on membrane fluidity. Results: The results showed a significant (p = 0.029) increase of membrane fluidity near the hydrophilic surface in erythrocytes treated with higher concentration of naringenin. In the deeper layer, just below the erythrocyte membrane phospholipid heads, both lower and higher concentration of naringenin significantly increased membrane fluidity (p = 0.036 and p = 0.028, respectively). Conclusions: These data document the positive and dose dependent effect of naringenin on near-surface membrane fluidity in human erythrocytes, recommending its use in the cardiovascular conditions characterized by disturbed hemodynamics

Stipetum novakii ass. nova – a new association of serpentine rocky grassland vegetation (Halacsyetalia sendtneri) in Serbia

Phytosociological characteristics of grassland communities above serpentines (order Halacsyetalia sendtneri H. Ritter-Studni~ka 1970) in Serbia, are analyzed according to Braun-Blanquet methodology. In order to detect the basic floristic differentiation of analyzed communities ordinary correspondence analysiswas applied. Cluster analysis was also performed to see the structure and separation of the communities based on the floristic composition. In order to determine diagnostic species, fidelity indices with presence/ absence data and the size of all groups standardized to equal size were calculated. The new association Stipetum novakii is described in open rocky serpentine grasslands in Brdjani Gorge

Associating Air Pollution with Cytokinesis-Block Micronucleus Assay Parameters in Lymphocytes of the General Population in Zagreb (Croatia).

Air pollution is recognized as one of the most serious public health issues worldwide and was declared to be a leading environmental cause of cancer deaths. At the same time, the cytokinesis-block micronucleus (CBMN) assay serves as a cancer predictive method that is extensively used in human biomonitoring for populations exposed to environmental contamination. The objective of this cross-sectional study is two-fold: to evaluate genomic instability in a sample (N = 130) of healthy, general population residents from Zagreb (Croatia), chronically exposed to different levels of air pollution, and to relate them to air pollution levels in the period from 2011 to 2015. Measured frequencies of CBMN assay parameters were in agreement with the baseline data for the general population of Croatia. Air pollution exposure was based on four factors obtained from a factor analysis of all exposure data obtained for the examined period. Based on the statistical results, we did not observe a significant positive association between any of the CBMN assay parameters tested and measured air pollution parameters for designated time windows, except for benzo(a)pyrene (B[a]P) that showed significant negative association. Our results show that measured air pollution parameters are largely below the regulatory limits, except for B[a]P, and as such, they do not affect CBMN assay parameters' frequency. Nevertheless, as air pollution is identified as a major health threat, it is necessary to conduct prospective studies investigating the effect of air pollution on genome integrity and human health

Air Pollution and Primary DNA Damage among Zagreb (Croatia) Residents: A Cross-Sectional Study.

More than eight million premature deaths annually can be attributed to air pollution, with 99% of the world's population residing in areas below recommended air quality standards. Hence, the present study aimed to examine the association between primary DNA damage and air pollution data among 123 participants enrolled between 2011 and 2015 in Zagreb, Croatia. While most measured air pollutants adhered to regulatory limits, benzo[a]pyrene concentrations bound to PM <sub>10</sub> exceeded them. Factorial analysis narrowed down air pollution data to four exposure factors (particulate matter, two metal factors, and other pollutants). Despite the absence of significant positive associations between modeled air pollution exposure factors and comet assay descriptors (tail length, tail intensity, tail moment, and highly damaged nuclei), the critical health implications of air pollution warrant further investigations, particularly with biomarkers of exposure and different biomarkers of effect in populations facing air pollution exposure

A machine learning-based risk stratification model for ventricular tachycardia and heart failure in hypertrophic cardiomyopathy

Background: Machine learning (ML) and artificial intelligence are emerging as important components of precision medicine that enhance diagnosis and risk stratification. Risk stratification tools for hypertrophic cardiomyopathy (HCM) exist, but they are based on traditional statistical methods. The aim was to develop a novel machine learning risk stratification tool for the prediction of 5-year risk in HCM. The goal was to determine if its predictive accuracy is higher than the accuracy of the state-of-the-art tools. Method: Data from a total of 2302 patients were used. The data were comprised of demographic characteristics, genetic data, clinical investigations, medications, and disease-related events. Four classification models were applied to model the risk level, and their decisions were explained using the SHAP (SHapley Additive exPlanations) method. Unwanted cardiac events were defined as sustained ventricular tachycardia occurrence (VT), heart failure (HF), ICD activation, sudden cardiac death (SCD), cardiac death, and all-cause death. Results: The proposed machine learning approach outperformed the similar existing risk-stratification models for SCD, cardiac death, and all-cause death risk-stratification: it achieved higher AUC by 17%, 9%, and 1%, respectively. The boosted trees achieved the best performing AUC of 0.82. The resulting model most accurately predicts VT, HF, and ICD with AUCs of 0.90, 0.88, and 0.87, respectively. Conclusions: The proposed risk-stratification model demonstrates high accuracy in predicting events in patients with hypertrophic cardiomyopathy. The use of a machine-learning risk stratification model may improve patient management, clinical practice, and outcomes in general

Comparison of two schizophyllum commune strains in production of acetylcholinesterase inhibitors and antioxidants from submerged cultivation

In recent years, fungi have been recognized as producers of acetylcholinesterase (AChE) inhibitors, agents important for the prevention of Alzheimer’s disease (AD). This study aimed to examine the AChE inhibitory, the antioxidative and antibacterial activity of two different Schizophyllum commune strains that originated from Serbia (SRB) and Italy (IT). Submerged cultivation of grown mycelia (M) and fermentation broth (F) of ethanol (EtOH) and polysaccharide (PSH) extracts lasted for 7, 14, 21 and 28 days. For AChE activity Ellman method was performed, while for antioxidative activity, sevendifferent assays were conducted: DPPH, ABTS, FRAP, SOA, OH, NO together with total phenolic content. Antimicrobial screen, LC–MS/MS technique and FTIR measurements were performed. Different isolates exhibited different AChE activity, with PSH being the strongest (SRB, M, 28 days IC90 79.73 ± 26.34 µg/mL), while in EtOH extracts, IT stood out (F, 14 days, IC50 0.8 ± 0.6 µg/mL). PSH extracts (7 days) exhibit significant antioxidative activity (AO), opposite to EtOH extracts where 14 and 21days periods stood out. Only tw extracts showed antibacterial activity. Following LC–MS/MS analysis p-hydroxybenzoic and gallic acids were the most abundant phenolics. PSH extracts demonstrated remarkable results, making this study debut and introducing S. commune as a valuable resource of AChE inhibitors

Antioxidant activity relationship of phenolic compounds in Hypericum perforatum L.

<p>Abstract</p> <p>Background</p> <p>The St John's Wort (<it>Hypericum perforatum</it>; Clusiaceae) has been used in traditional and modern medicine for a long time due to its high content of biologically active phenolics. The purpose of this work was to develop a method for their fractionation and identification, and to determine the most active antioxidant compounds in plant extract.</p> <p>Results</p> <p>An LC-MS method which enables fast qualitative and semiquantitative analysis was developed. The composition determined is in agreement with the previous results, where 6 flavonoids, 4 naphthodianthrones and 4 phloroglucinols have been identified. Significant antioxidant activity was determined for most of the fractions by DPPH assay (the lowest IC₅₀of 0.52 μg/ml), NO scavenging (6.11 μg/ml), superoxide scavenging (1.86 μg/ml), lipid peroxidation (0.0079 μg/ml) and FRAP (the highest reduction capacity of 104 mg Fe equivalents/g) assays.</p> <p>Conclusion</p> <p>LC-MS technique has been successfully applied for a quick separation and identification of the major components of <it>H. perforatum </it>fractions. Majority of the fractions analyzed have expressed a very high antioxidative activity when compared to synthetic antioxidants. The antioxidant activity could be attributed to flavonoids and phenolic acids, while phloroglucinols and naphthodianthrones showed no significant activity. It is demonstrated that it is possible to obtain, by fractionation, <it>H. perforatum </it>preparations with significantly increased phloroglucinols-to-naphthodianthrones ratio (up to 95:5).</p

Education level and physical functional limitations among Japanese community residents-gender difference in prognosis from stroke

<p>Abstract</p> <p>Background</p> <p>Little research has been conducted to examine the relationship between education level and functional limitations among Japanese community residents. We sought to examine the association between education level and physical functional limitations among Japanese men and women, and whether that association was modified by gender and history of stroke.</p> <p>Methods</p> <p>We examined prevalence of physical functional limitation by educational level using the data from a total of 29,134 Japanese men and women aged 50–69 years living in communities in 2000. The information of educational level (junior high school graduates, senior high school graduates, college and/or higher education) and physical functional limitations (no need for assistance, need for assistance when going outdoors, and need for assistance to carry out indoor activities) were obtained by self-administrated questionnaire.</p> <p>Results</p> <p>The proportions of the subjects reported their highest level of schooling were 48% for junior high school, 39% for high school, and 13% for college. Three hundred and twenty eight subjects (1% of total subjects) reported having some physical functional limitations. Multinomial logistic regression analyses showed that the odds ratio of needing assistance to carry out indoor activities were 4.84(95%CI:3.61,6.50) for lowest education level group and 2.21(95%CI:1.00,4.86) for middle education level group compared to highest education level group. The corresponding odds ratios of needing assistance when going outdoors were 2.36(95%CI: 2.03,2.72) and 1.08(95%CI:0.73,1.60), respectively. Further, the significant excess prevalence of having functional limitations associated with the low education level was identified for men regardless of history of stroke and for women without history of stroke.</p> <p>Conclusion</p> <p>Low education level was associated with the higher prevalence of physical functional limitations for both genders. That association among persons with history of stroke was observed for men but not for women probably due to gender differences in stroke subtypes and social support.</p