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Providing women who have tested positive for a pathogenic variant in BRCA1 or BRCA 2 relevant information can help them to make informed decisions about managing their cancer risk. However, there is a lack of targeted informational support for BRCA positive women specific to the Irish context. The objective of this study is to identify the information needs of women diagnosed with a pathogenic variant in BRCA1 or BRCA 2 regarding cancer risk management and decision-making. This is a descriptive qualitative study. Participants were recruited using purposive sampling and included women with a pathogenic variant in BRCA1 or BRCA2 without a history of breast or ovarian cancer. Two focus groups were held with women (n = 16) to enable them to generate ideas and understanding of their shared information needs. In addition, ten individual interviews were conducted to capture the additional perspectives of health care and relevant policy stakeholders. Interviews were analysed using inductive coding (Braun and Clarke, 2006), with NVivo software (Qsr international, 1999). Three main themes were identified, Cancer Risk Management, Receiving Information, and Implications to Health and Wellbeing. BRCA-positive women expressed a need for information about managing their cancer risk. They were particularly concerned with managing the impact of cancer risk-reducing interventions on their psychological and physical health, wellbeing, and family life. Many women felt they had to advocate for themselves to get treatment and receive information. Participants expressed a need for a comprehensive informational resource where all relevant information related to BRCA risk management could be accessed at a single location. This study suggests that women diagnosed with a pathogenic variant in BRCA1 or BRCA2 in Ireland need more accessible information about managing their cancer risk, and the impact of a BRCA diagnosis on their family, health and wellbeing. These results will be used to identify relevant content for developing an informational decision aid for Irish women. • There is a lack of targeted informational support for women who have tested positive for a pathogenic variant in BRCA1 or BRCA 2 and women expressed a need for information about managing cancer risk. • Women are particularly concerned with managing the impact of cancer risk-reducing interventions on their psychological and physical health, wellbeing, and family life. • Women who have tested positive for a pathogenic variant in BRCA1 or BRCA 2 need accessible information about managing cancer risk, and the impact of a BRCA diagnosis on health and wellbeing. • Participants expressed a need for a comprehensive informational resource where all relevant information related to BRCA risk management could be accessed at a single location. [ABSTRACT FROM AUTHOR]

This research note explores the intricate nature of tourist traps, going beyond the prevalent negative stigma attached to them. While the term tourist trap is casually used, only a limited number of scholars have investigated the intricacies of this phenomenon, and there is a scarcity of empirical research on this topic. Using a Reflective Collaborative Autoethnography (RCA) approach, this research note presents a reflective analysis of the authors' experience with the phenomenon. Through this exploration, we uncover insights in both psychological and tangible dimensions, contributing to a deeper understanding of the dynamics of tourist traps. Expanding from the findings, this research note conceptualises the concept of a tourist trap from a dual-perspective framework that considers both supply and demand aspects. This framework goes beyond the traditional focus on product or service quality, providing a more nuanced discourse on the multifaceted nature of tourist traps. [ABSTRACT FROM AUTHOR]

Background: The prevalence of falls affects the wellbeing of aging adults and places an economic burden on the healthcare system. Integration of wearable sensors into existing fall risk assessment tools enables objective data collection that describes the functional ability of patients. In this study, supervised machine learning was applied to sensor-derived metrics to predict the fall risk of patients following total hip arthroplasty.Methods: At preoperative, 2-week, and 6-week postoperative appointments, patients (n = 72) were instrumented with sensors while they performed the timed-up-and-go walking test. Preoperative and 2-week postoperative data were used to form the feature sets and 6-week total times were used as labels. Support vector machine and linear discriminant analysis classifier models were developed and tested on various combinations of feature sets and feature reduction schemes. Using a 10-fold leave-some-subjects-out testing scheme, the accuracy, sensitivity, specificity, and area under the receiver-operator curve (AUC) were evaluated for all models.Results: A high performance model (accuracy = 0.87, sensitivity = 0.97, specificity = 0.46, AUC = 0.82) was obtained with a support vector machine classifier using sensor-derived metrics from only the preoperative appointment. An overall improved performance (accuracy = 0.90, sensitivity = 0.93, specificity = 0.59, AUC = 0.88) was achieved with a linear discriminant analysis classifier when 2-week postoperative data were added to the preoperative data.Conclusion: The high accuracy of the fall risk prediction models is valuable for patients, clinicians, and the healthcare system. High-risk patients can implement preventative measures and low-risk patients can be directed to enhanced recovery care programs. [ABSTRACT FROM AUTHOR]

• Endoscopic coronary artery bypass graft (Endo-CABG) avoids median sternotomy by combining thoracoscopy and mini-thoracotomy. • Conventional limitations of minimally invasive CABG do not apply for Endo-CABG. • Patients with multi- and triple-vessel disease can be treated safely with Endo-CABG. • Patients with complex coronary lesions can be treated safely with Endo-CABG. • This technique seems suitable for every patient with an indication for CABG. The aim of this paper is to describe a newly developed endoscopic coronary artery bypass graft (Endo-CABG) technique to treat patients with single- and multi-vessel disease and discuss the short-term clinical results in a large patient cohort. This technique avoids a median sternotomy by combining a thoracoscopic technique via three ∼5 mm thoracic ports and a mini-thoracotomy utility 3–4 cm port through the intercostal space. From January 2016 to January 2018, data from consecutive patients undergoing an elective Endo-CABG were prospectively entered into a customized database and retrospectively reviewed. Patients scheduled for a combined hybrid intervention were excluded. Conversion rate to sternotomy, incidence of surgical revision and postoperative graft failure, one-month survival, morbidity, and length of stay (LOS) were investigated. Subgroup analyses were performed. A total of 342 patients undergoing an Endo-CABG with one (n = 53) or multiple (n = 289) bypasses were included. No conversion to sternotomy occurred and incidence of surgical revision, graft failure, and 30-day mortality was 7.3%, 1.5%, and 1.8%, respectively. Adverse neurological outcomes were rare: cerebrovascular accident, transient ischemic attack, epilepsy, and postoperative delirium were observed in 0.6%, 0.3%, 0.3%, and 5.3% of patients, respectively. Median intensive care unit and hospital LOS were 2.75 (IQR 1.8 to 3.8) and 8.0 days (IQR 7.0 to 10.0), respectively. Thirty-day mortality in obese patients, diabetics, and octogenarians was 0%, 3.6%, and 5.6%, respectively. EuroSCORE II > 5% was associated with a high 30-day mortality (25%). Endo-CABG can be considered a safe and effective procedure to treat single- and multi-vessel coronary artery disease. Individual patient selection seems not necessary to apply this technique. [ABSTRACT FROM AUTHOR]

• The structural behaviour of ATC beams with screwed connections was investigated. • The behaviour of the connections was characterised and used in a FE analysis. • The adopted model adequately captured the response of the ATC joints and beams. • The behaviour of the connection may be modelled using zero-length springs. • The results calculated corresponded to the measured values. The present study investigated the structural behaviour of aluminium-timber composite (ATC) beams. In the proposed ATC system, a timber slab was connected to aluminium girders by hexagon head wood screws. ATC beams are a relatively new civil engineering solution and their behaviour should be investigated to develop relevant methods for calculating their resistance. The authors examined the stiffness and the strength of the screwed connection used to join an aluminium girder with a timber slab. The slip moduli k 0.4 and k 0.6 , and the peak load capacity per one connector were determined experimentally in two push-out tests. These parameters are necessary for designing ATC beams, because the behaviour of an ATC system is depended on the stiffness and the strength of its connections. Moreover, two bending tests were conducted on ATC beams to investigate their short-term behaviour, determine their bending resistance and capture the mode of failure, load-deflection and load-slip response. Based on the guidelines for timber and composite (steel-timber and steel-concrete) elements, the authors of this paper proposed the methods for calculating the bending resistance of the ATC beams, and the stiffness and strength of their screwed connections. The results obtained in the experimental tests were compared with the results from the analytical estimations. In addition, non-linear 3D finite element (FE) models of the tested composite beams and connections were developed and verified against the experimental results. The comparison between the experimental and numerical results demonstrated that the adopted 3D models were able to adequately capture the response of the ATC composite beams and their connections. These models may be used in further numerical analysis of ATC structures, e.g., to evaluate the impact of the number of the shear connectors on the load-bearing capacity of an ATC beam. [ABSTRACT FROM AUTHOR]

This paper presents practical, engineering algorithm which may be used to analyse fire resistance of the Klein's ceiling after its renovation. This type of ceiling consists of bricks and steel beams for which the fire resistance may be obtained using the standard ISO curve and Eurocodes. The authors of this article show also the example in which the problem with fire resistance of Klein's floor is solved. [ABSTRACT FROM AUTHOR]

This paper discusses the problem of existing buildings which lack basic design documentation. This situation might have been caused by the old age of buildings or the loss of documentation. To solve this problem, time-consuming and expensive steps have to be taken, such as assessing the strength of construction materials, identifying loads, evaluating the technical state of structures and their strengthening. The authors present cases in which similar problems were solved. [ABSTRACT FROM AUTHOR]

The paper presents a numerical analysis of the resistance and stiffness of an aluminium-concrete beam with steel connectors. Aluminium-concrete structures are less known than steel and concrete composite structures, they do, however, have a lot of applications. In this paper, the resistance and midspan deflection of a composite beam calculated using the Abaqus program was compared with the results obtained in an experimental study. [ABSTRACT FROM AUTHOR]

The n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may reduce low-grade inflammation associated with obesity. The relationship between therapeutic response to n-3 PUFAs and modification of the transcriptome in obesity or metabolic syndrome remains to be explored. Blood samples were obtained from women with obesity before and after three-months supplementation with a moderate dose of n-3 PUFAs (1.8 g EPA + DHA per day) or from controls. n-3 PUFAs (GC) and plasma concentrations of lipoxins, resolvins, protectin X (GC–MS/MS) and inflammatory markers (ELISA) were measured. Whole blood transcriptome was assayed using microarray. Women supplemented with n-3 PUFAs for 3 months had significantly higher levels of EPA and DHA in plasma phosphatidylcholine. n-3 PUFA supplementation, in contrast to placebo, significantly decreased the concentrations of several inflammatory markers (SELE, MCP-1, sVCAM-1, sPECAM-1, and hsCRP), fasting triglycerides and insulin and increased the concentrations of pro-resolving DHA derivatives in plasma. The microarray data demonstrated effects of n-3 PUFAs on PPAR-α, NRF2 and NF-κB target genes. N-3 PUFAs increased DHA-derived pro-resolving mediators in women with obesity. Elevated resolvins and up-regulation of the resolvin receptor occurred in parallel with activation of PPAR-α target genes related to lipid metabolism and of NRF2 up-regulated antioxidant enzymes. [ABSTRACT FROM AUTHOR]

Mediators such as cytokines, eicosanoids, nitric oxide and growth factors may regulate adipogenesis as well as inflammation. It is well documented that production of some form of eicosanoids activates lipid synthesis during adipogenesis but also contributes to the formation of factors maintaining low-level systemic inflammation. Developing nutrients for reduction of adipogenesis and inflammation can enhance preventive efficacy of daily diet. This study examined the effects of free fatty acid influence on changes in lipid biosynthesis and corresponding gene expression during differentiation of human subcutaneous adipose tissue stromal vascular fraction (SVF) cells. Proadipogenic conditions promoted SVF cell differentiation and lipid droplet (LD) formation up to 15 days. This correlated with gene expression of adipocyte differentiation markers as well as inflammatory cytokines and their receptors. Addition of free fatty acids to differentiation medium increased their incorporation during the first period of differentiation (48 h). Presence of eicosanoid acid (EPA) during the initial period of differentiation by elevation of Perilipin 3 protein (TIP47), may be responsible for smaller LD formation. Presence of arachidonic acid (AA) tends to deposit lipids in large form of LDs. Prolongation of differentiation up to 15 days decreased AA or EPA in cellular lipids. PUFA through up-regulation of both phospholipase 2 and enzymes related to eicosanoid production influenced type and quantity of eicosanoids which regulated the extent of SVF cell differentiation. Formation of small LDs and reduction of pro-inflammatory mediators in adipose tissue are the consequence of eicosanoid production with anti-inflammatory potential from EPA. [ABSTRACT FROM AUTHOR]

The paper presents exemplary applications of aluminium and concrete composite structures. It discusses arguments for using these structures and reasons why in some cases it is advisable to replace a steel beam with an aluminium beam. Additionally, the article aims at analysing aluminium and concrete structures as a part of sustainable development. To this end, an analysis of materials used in aluminium and concrete composite structures was conducted. Moreover, the article presents a new method of joining an aluminium beam and a concrete slab, which may have a practical application. [ABSTRACT FROM AUTHOR]

Highlights: [•] A Dynamic Flexibility Model is offered that can estimate the “system flexibility”. [•] The model offered can evaluate and compare the flexibility of highway networks. [•] The model is able to compare different networks in regard to their perceived congestion. [ABSTRACT FROM AUTHOR]

Abstract: In the paper the influence of boundary conditions on the thermal response of selected steel members subjected to fire loads is investigated. Simply supported and restrained steel beams subjected to uniformly distributed load and fire accidental action are analysed using the standard ISO-fire curve. The iterative procedure to investigate critical temperature is used. At each increment of temperature the ultimate limit state is checked using the EC recommendation. The special attention is focused on axial action occurring due to thermal elongation. The illustrative examples show that, proper modelling of the beam's boundary conditions plays an important role in describing and understanding the real behavior of elements in fire conditions. Moreover, beam's boundary conditions can change structural response and result in reduction of critical temperature and fire resistance time. [Copyright &y& Elsevier]

Abstract: In the paper the analysis of the influence of fire load on class of cross-section of steel structural elements is presented. In the fire situation some cross-sections may have a different class than at room temperature. Special attention is focused on steel structural elements which are Class 3 at room temperature and Class 4 in the fire situation. The examples illustrate a steel element, which obtain different class of cross-section at room temperature and in the fire situation. The reduction of critical temperature and fire resistance time is also taken in to account. The structure under consideration pertains the steel beam, which is a part of the existing building in Poznan. In the paper, the comparison between fire resistance of the beam using simulation of fire in FDS software and procedure according to standard time- temperature ISO curve is presented. [Copyright &y& Elsevier]

Genetic variants of Period 2 {PER2), a circadian clock gene, have been linked to metabolic syndrome (MetS). However, it is still unknown whether these genetic variants interact with the various types of plasma fatty acids. This study investigated whether common single nucleotide polymorphisms (SNPs) in the PER2 locus {rs934945 and rs2304672) interact with various classes of plasma fatty acids to modulate plasma lipid metabolism in 381 participants with MetS in the European LIPGENE study. Interestingly, the rs2304672 SNP interacted with plasma total SFA concentrations to affect fasting plasma TG, TG-rich lipoprotein (TRL-TG), total cholesterol, apoC-ll, apoB, and apoB-48 concentrations (P-interaction < 0.001-0.046). Carriers of the minor allele (GC+GG) with the highest SFA concentration {>median) had a higher plasma TG concentration (P = 0.001) and higher TRL-TG {P< 0.001) than the CC genotype. In addition, participants carrying the minor G allele for rs2304672 SUP and with a higher SFA concentration (>median) had higher plasma concentrations of apo C-l I (P< 0.001 ), apo C-l II (P = 0.009), and apoB-48 (P = 0.028) compared with the homozygotes for the major allele (CC). In summary, the rs2304672 polymorphism in the PER2 gene locus may influence lipid metabolism by interacting with the plasma total SFA concentration in participants with MetS. The understanding of these gene-nutrient interactions could help to provide a better knowledge of the pathogenesis in MetS. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of the study was to compare the prediction power of a simplified non-canonical Poisson crash-prediction model to other model types. The model, fitted to serious and fatal crash data from 86 two-lane low-volume rural highway segments, showed a good fit, which was not significantly different from that of a negative binomial model. The application of the present model uses the linear form of the non-canonical Poisson model. Hence the simplification of the model versus other models results from the finding that the expected number of crashes per 1km is directly proportional to the daily volume, unlike logarithmic functions in other models. In the non-canonical model, it is necessary to estimate only one parameter, whereas estimations of more parameters are needed in the negative binomial model. [Copyright &y& Elsevier]

Abstract: This study concentrated on estimating the percent-time-spent-following (PTSF) on two-lane highways. This measure is a key estimate of level-of-service in traffic engineering applications. Its evaluation to date has been based on simulations that yielded over-estimated values. The present study shows how to estimate this variable from easily obtained field data based on queuing theory. The estimates accord with opinions on yielding significantly lower values of PTSF that are expressed in the relevant traffic literature. An improved relationship between PTSF and two-way flow is provided by fitting the new estimates by means of the least-squares method. [Copyright &y& Elsevier]

Abstract: Objective: The purpose of this study is to describe the musculoskeletal conditions and associated pain and limitation and the effects of massage treatment in a Filipino squatter community. Methods: The study was conducted at the Hands On Philippines Education (HOPE) clinic in Bagong Barrio, Caloocan, Philippines. Baseline data were collected before the first treatment, and follow-up data were collected immediately after the second treatment. Treatment was delivered by massage students who were trained in massage by a chiropractic program faculty member through the Project HOPE charitable community-based initiative. A prospective pretest-posttest observational research design was used. The sample consisted of 290 subjects aged 16 years and older visiting the Project HOPE clinic. One hundred ninety-two subjects completed the follow-up surveys. The outcome measures were sites of pain, self-reported levels of pain, and limitation to activities of daily living at baseline and after the second massage therapy treatment. Results: Three self-reported anatomical locations were identified by each subject. The most frequently reported painful sites over the last 7 days among the 166 respondents were the upper back (36.7%), lower back (18.7%), and shoulders (16.3%). The pre-post treatment analyses of pain and disability was restricted to 66 participants who provided completed outcome measures. After 2 massage therapy treatments, all pain and limitation scores decreased. A comparison of mean self-reported levels of pain and disability at baseline and immediately after the second consultation showed statistically significant decreases of pain (t 65 = 16.97, P < .001) and disability (t 65 = 12.4, P < .001). Conclusion: This study suggests that participants who visited the Filipino squatter community clinic experience a high prevalence of musculoskeletal conditions located primarily within the axial skeleton, and that, in the short term, massage therapy delivered on-site by trained therapists was helpful in reducing self-reported levels of pain and limitation to activities of daily living. [Copyright &y& Elsevier]

Summary: Objective: To describe a massage therapy and training programme in a remote Aboriginal community in Australia and to develop the frameworks, procedures and processes necessary for future research. Method: Self-report health questionnaires (MYMOP and W-BQ12) and an ethnographic enquiry that included participant observation and 15 interviews with clients and key informants. Results: The project was disrupted by typhoons. Baseline questionnaire responses indicate they may be suitable for this context. Qualitative analysis resulted in a conceptual model of the effects of the programme, which is consistent with a system theory approach. People''s accounts were rooted in discussions of the community''s history, emotional and physical distress, and limited health care resources. Community-level effects included increasing participation; strengthening local health and educational projects; and opening up new opportunities. Individual level effects included improvement in physical and emotional symptoms, improved function and the receipt of preventative care. Conclusion: As a result of this early stage research, future studies have a conceptual model to guide them and evidence that a mixed method and a participatory methodology may be the most appropriate design. [Copyright &y& Elsevier]

Objective: The objective of this study was to measure the effects of thoracic spinal manipulation on heart rate variability (HRV) in a cohort of healthy young adults. Methods: A controlled crossover trial that was conducted on 28 healthy young adults (23 men and 5 women; age range, 18-45 years; mean age, 29 ± 7 years) measured HRV before and after a sham procedure and a thoracic spinal manipulation. Results: In healthy young adults, thoracic spinal manipulation was associated with changes in HRV that were not duplicated by the sham procedure. The ratio of the powers of the low-frequency and high-frequency components increased from 0.9562 ± 0.9192 to 1.304 ± 1.118 (P = .0030, Wilcoxon signed rank test). In subjects undergoing sham spinal manipulation, there was no statistically significant change in the low-frequency or the high-frequency component of the power spectrum; neither was there any in the ratio of the two regardless of whether the comparison was made using the paired t test or the Wilcoxon signed rank test. Conclusion: High-velocity and low-amplitude manipulation of the thoracic spine appears to be able to influence autonomic output to the heart in ways that are not duplicated by a sham procedure or by other forms of somatic/physical therapies. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate flow characteristics on two-lane rural highways and to develop criteria for highway widening. The study is conducted on two tracks: theoretical development of delay models and use of a simulation model to estimate the effect of certain parameters on delay and percent-time-spent-following. Models of delay are presented, as are the regions in which the traffic is stable or unstable. It was also possible from the simulation to obtain the percent-time-spent-following, which is a key parameter in determining level-of-service on two-lane highways.The accrued delay over the usable life of a two-lane highway pavement, assumed to be 20 years, was discounted to present monetary value. This was then compared to four typical construction costs for different terrain types. The threshold average daily traffic volumes were determined at the points where the present value of the accumulated delay was equal to the cost of constructing two more lanes. These threshold values can be used as criteria for widening a two-lane highway and converting it into a four-lane facility. Additional criteria, based on percent-time-spent-following, are also presented. [Copyright &y& Elsevier]

The purpose of this paper is to present a microscopic decision model for driver gap-acceptance behavior when waiting at an unsignalized intersection on the secondary road and also to estimate the resulting intersection capacity. The model is based on evaluation of the risk associated with not accepting small gaps against the potential benefit of their acceptance, which is the time saved as a result of shorter waits at the entry line. The model takes into account individual preferences by defining individual critical gap, which is different from the traditional macroscopic critical-gap approach. The latter estimates the critical gap for the entire population of drivers. The paper presents the difference between different driver populations (risk-loving vs. cautious) and shows how this difference actually results in different capacities on the minor road. [Copyright &y& Elsevier]

Background IL-17A is a key driver of human autoimmune diseases, particularly psoriasis. Objective We sought to determine the role of IL-17A in psoriasis pathogenesis and to identify a robust and measurable biomarker of IL-17A–driven pathology. Methods We studied 8 healthy subjects and 8 patients with psoriasis before and after administration of secukinumab, a fully human anti–IL-17A mAb, and used a combination of classical techniques and a novel skin microperfusion assay to evaluate the expression of 170 proteins in blood, nonlesional skin, and lesional skin. For validation, we also tested stored sera from 601 patients with a variety of autoimmune diseases. Results IL-17A was specifically expressed in lesional compared with nonlesional psoriatic skin (9.8 vs 0.8 pg/mL, P < .001). Proteomic and gene transcription analyses revealed dysregulated antimicrobial peptides, proinflammatory cytokines, and neutrophil chemoattractants, levels of which returned to normal after treatment with secukinumab. β-Defensin 2 (BD-2) was identified as a biomarker of IL-17A–driven pathology by comparing protein expression in patients with psoriasis versus that in healthy subjects (5746 vs 82 pg/mL in serum, P < .0001; 2747 vs <218 pg/mL in dermis, P < .001), responsiveness to secukinumab therapy, and synergistic induction by IL-17A and TNF-α in epidermal keratinocytes. In a validation set of sera from 601 patients with autoimmune diseases thought to be IL-17A driven, we found that BD-2 levels are most highly increased in patients with psoriatic skin lesions, and in patients with psoriasis, BD-2 levels correlated well with IL-17A levels ( r = 0.70, n = 199, P < .001) and Psoriasis Area and Severity Index scores ( r = 0.53, n = 281, P < .001). Conclusion IL-17A is a primary driver of skin pathology in patients with psoriasis, and serum BD-2 is an easily measurable biomarker of IL-17A–driven skin pathology. [ABSTRACT FROM AUTHOR]

Drivers’ speed has significant implications on road users’ safety in general, and particularly so if a crash occurs. This paper explores the influence of environmental and road characteristics, situational factors, and individual characteristics on drivers’ observed speed selection in a simulator experiment. The paper presents a theoretical framework for drivers’ speed selection, and applies structural equation modeling for the various factors examined. The simulator experiments collected data of 111 drivers driving in 4 different scenarios composed of 22 segments for each scenario. The dataset was analyzed in several resolutions: Driver level, Trip level, and Segment level. The three models revealed that gender, age, and driving frequency are all significant in determining drivers’ perceptions and attitudes, which in turn influence speed selection. Situational factors such as traffic speed, enforcement, and time-saving-benefits are also related to speed selection, as well as infrastructure characteristics. These findings demonstrate that structural equations provide a flexible modeling tool able to concurrently analyze the variety of factors that relate to speed selection. As a result, Structural Equations Modeling provides more accurate and refined explanations for the combined effects of various factors on drivers’ speed selection than previous research so far. These tools can be useful in developing speed management strategies to improve road safety. [ABSTRACT FROM AUTHOR]

Barth syndrome is a rare disease affecting mitochondria structure and function in males. In our previous study, we have shown a new mutation (c.83T>A, p.Val28Glu) in the TAZ gene in two affected patients with congenital cardiomyopathy. Furthermore, women in this family had no mutations in their blood cells, whereas they only had mutations in the oral epithelial cells. The objective of the project was to evaluate the effect of intertissue mosaicisms on the Barth syndrome phenotypes, searching for another disease-related loci on chromosome X and finally to assess the consequences of the mutation. We conducted the advanced genetic study including cytogenetic research (constitutional karyotyping in blood and fibroblasts), NGS sequencing (with custom chromosome X sequencing together with the evaluation of loss of heterozygosity (LOH) and aberrations (CNV) in the whole genome) in four different tissues and sequencing of tafazzin and deoxyribonuclease 1 like 1 transcripts. The presence of deletions within the 5′untranslated region of the TAZ gene and/or the noncoding regions of the DNASE1L1 gene were detected in several tissues. Whereas, there is no intertissue mosaicism regarding point mutation in TAZ gene in all investigated tissues in female carriers. Only the male patient presented biochemical markers and neurological symptoms of Barth syndrome. All the female carriers are healthy and have normal tafazzin and deoxyribonuclease 1 like 1 transcripts in 2 analyzed tissues. The conclusion of this study is that we cannot rule out or confirm mosaicism in the noncoding regions of TAZ or DNASE1L1 genes, but this is not clinically relevant in female carriers because they are healthy. Finally, it has been proven that mutation (c.83T>A, p.Val28Glu) is responsible for disease in males in this family. • Lack of intertissue inherited mosaicism of mutation c 0.83 T > A in the TAZ gene in a family affected by Barth syndrome. • The possible existence of aberration in the 5′UTR and/or the noncoding region of exon 1 in the TAZ and intronic in DNASE1L1 genes is clinically insignificant in females carriers of disease. • The inactivation of X chromosome with mutation was detected in blood cells and fibroblasts in females. • The pathogenicity of the c 0.83 T > A mutation in the TAZ gene has been confirmed in laboratory and neurologic examinations. [ABSTRACT FROM AUTHOR]