Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiomyopathy associated with fibrofatty tissue replacement of the ventricular tissue. The disease can cause ventricular dysfunction and arrhythmias and can increase the risk of sudden cardiac death. This cardiomyopathy can have variable clinical presentations, especially in the pediatric and young adult populations. In this report, we describe the case of an 18-year-old female with myocarditis as the initial presentation of ACM. She presented following a resuscitated cardiac arrest due to ventricular arrhythmia. On arrival, myocardial edema and delayed gadolinium enhancement were present on cardiac magnetic resonance imaging, with no ventricular changes observed, making the diagnosis consistent with myocarditis. Genetic testing revealed a pathogenic mutation in the desmoplakin gene consistent with ACM. Given the unconventional initial presentation of this patient\'s disease, early consideration of genetic testing may be beneficial to aid in the early diagnosis and management of ACM in young patients.

Bacteria are involved in numerous interactions during infection and among host-associated microbial populations. Salmonella enterica serovar Typhimurium is a foodborne pathogen of great importance as well as a model organism to study interactions within a microbial community. In this study, we found that S. Typhimurium becomes tolerant to azithromycin when co-cultured with lactobacilli strains. Similarly, acidified media, from cell-free supernatant of lactobacilli cultures for instance, also induced the tolerance of S. Typhimurium to azithromycin. The addition of membrane disruptors restored the normal sensitivity to azithromycin in acidified media, but not when lactobacilli were present. These results suggested that the acidification of the media led to modification in envelope homeostasis, but that a different mechanism promoted the tolerance to azithromycin in the presence of lactobacilli strains. To further understand how lactobacilli strains modify the sensitivity of S. Typhimurium to azithromycin, a high-throughput assay was performed using the single-gene deletion collection of the S. Typhimurium (1) in co-culture with Lacticaseibacillus rhamnosus and (2) in sterile acidic conditions (pH 5.5 media only). As expected, both screens identified genes involved in envelope homeostasis and membrane permeability. Our results also suggest that changes in the metabolism of S. Typhimurium induce the tolerance observed in the presence of L. rhamnosus. Our results thus highlight two different mechanisms by which lactobacilli induce the tolerance of S. Typhimurium to azithromycin.IMPORTANCEThis study provides valuable insights into the intricate interactions between bacteria during infections and within host-associated microbial communities. Specifically, it sheds light on the significant role of lactobacilli in inducing antibiotic tolerance in Salmonella enterica serovar Typhimurium, a critical foodborne pathogen and model organism for microbial community studies. The findings not only uncover the mechanisms underlying this antibiotic tolerance but also reveal two distinct pathways through which strains of lactobacilli might influence Salmonella\'s response to antibiotics. Understanding these mechanisms has the potential to enhance our knowledge of bacterial infections and may have implications for the development of strategies to combat antibiotic resistance in pathogens, such as Salmonella. Furthermore, our results underscore the necessity to explore beyond the direct antimicrobial effects of antibiotics, emphasizing the broader microbial community context.

OBJECTIVE: To report the long-term outcomes from a longitudinal psychosocial study that forms part of the \'Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted Screening in men at higher genetic risk and controls\' (IMPACT) study. The IMPACT study is a multi-national study of targeted prostate cancer (PrCa) screening in individuals with a known germline pathogenic variant (GPV) in either the BReast CAncer gene 1 (BRCA1) or the BReast CAncer gene 2 (BRCA2).
METHODS: Participants enrolled in the IMPACT study were invited to complete a psychosocial questionnaire prior to each annual screening visit for a minimum of 5 years. The questionnaire included questions on sociodemographics and the following measures: Hospital Anxiety and Depression Scale, Impact of Event Scale, 36-item Short-Form Health Survey, Memorial Anxiety Scale for PrCa, Cancer Worry Scale, risk perception and knowledge.
RESULTS: A total of 760 participants completed questionnaires: 207 participants with GPV in BRCA1, 265 with GPV in BRCA2 and 288 controls (non-carriers from families with a known GPV). We found no evidence of clinically concerning levels of general or cancer-specific distress or poor health-related quality of life in the cohort as a whole. Individuals in the control group had significantly less worry about PrCa compared with the carriers; however, all mean scores were low and within reported general population norms, where available. BRCA2 carriers with previously high prostate-specific antigen (PSA) levels experience a small but significant increase in PrCa anxiety (P = 0.01) and PSA-specific anxiety (P < 0.001). Cancer risk perceptions reflected information provided during genetic counselling and participants had good levels of knowledge, although this declined over time.
CONCLUSIONS: This is the first study to report the longitudinal psychosocial impact of a targeted PrCa screening programme for BRCA1 and BRCA2 carriers. The results reassure that an annual PSA-based screening programme does not have an adverse impact on psychosocial health or health-related quality of life in these higher-risk individuals. These results are important as more PrCa screening is targeted to higher-risk groups.

Newborn screening (NBS) is a public health measure to identify children with treatable disorders within the first days of life allowing presymptomatic treatment. It is the most successful measure of secondary medical prevention and part of public health programs in many countries worldwide. Application of second-tier strategies in NBS allows for increased specificity and consecutively a higher positive predictive value. Second-tier strategies can include analysis of specific biomarkers for a target disorder or may be based on molecular genetic analyses. Improving the quality of NBS, for example by second-tier strategies, is of utmost importance to maintain the high acceptance of NBS by families - especially as an increasing number of target disorders is being consecutively included into NBS programs.

Liver cancer, primarily hepatocellular carcinoma, remains a global health challenge with rising incidence and limited therapeutic options. Genetic factors play a pivotal role in the development and progression of liver cancer. This state-of-the-art paper provides a comprehensive review of the current landscape of genetic screening strategies for liver cancer. We discuss the genetic underpinnings of liver cancer, emphasizing the critical role of risk-associated genetic variants, somatic mutations, and epigenetic alterations. We also explore the intricate interplay between environmental factors and genetics, highlighting how genetic screening can aid in risk stratification and early detection via using liquid biopsy, and advancements in high-throughput sequencing technologies. By synthesizing the latest research findings, we aim to provide a comprehensive overview of the state-of-the-art genetic screening methods for liver cancer, shedding light on their potential to revolutionize early detection, risk assessment, and targeted therapies in the fight against this devastating disease.

In many countries, some form of genetic screening is offered to all or part of the population, either in the form of well-organized screening programs or in a less formalized way. Screening can be offered at different phases of life, such as preconception, prenatal, neonatal and later in life. Screening should only be offered if the advantages outweigh the disadvantages. Technical innovations in testing and treatment are driving changes in the field of prenatal and neonatal screening, where many jurisdictions have organized population-based screening programs. As a result, a greater number and wider range of conditions are being added to the programs, which can benefit couples\' reproductive autonomy (preconception and prenatal screening) and improve early diagnosis to prevent irreversible health damage in children (neonatal screening) and in adults (cancer and cascade screening). While many developments in screening are technology-driven, citizens may also express a demand for innovation in screening, as was the case with non-invasive prenatal testing. Relatively new emerging issues for genetic screening, especially if testing is performed using DNA sequencing, relate to organization, data storage and interpretation, benefit-harm ratio and distributive justice, information provision and follow-up, all connected to acceptability in current healthcare systems.

OBJECTIVE: Noninvasive prenatal testing (NIPT) has increased the number of conditions that can be screened. However, the prevalence of conditions assessed by NIPT has remained stable. The \"prevalence threshold,\" a novel epidemiological concept, uses a test\'s sensitivity and specificity to determine the prevalence below which a test\'s positive predictive value declines most sharply relative to disease prevalence. In this article, we calculated the prevalence threshold for common conditions assessed through NIPT and compared the value with the actual prevalence of each condition to best ascertain the reliability of NIPT results.
METHODS: Six databases and PubMed were searched from January 2010 to March 2023 for sensitivity and specificity parameters of common conditions tested through NIPT. Using an equation previously derived by the authors of the current paper, the prevalence threshold for each condition was calculated. The theoretical number of test iterations required to reach the prevalence threshold was also reported.
RESULTS: None of the conditions tested through the NIPT had a prevalence rate that met or exceeded the calculated prevalence threshold. Trisomy 21 had the greatest concordance between the prevalence rate and the prevalence threshold. In contrast, Angelman, Cri-du-chat, and Prader-Willi syndromes had the most significant discordance. Apart from trisomy 21 and XXY, all remaining conditions required more than one test iteration to reach their respective prevalence threshold.
CONCLUSIONS: We conclude that at the current prevalence levels, the positive predictive value of NIPT remains low, with the prevalence of disease levels significantly lower than the prevalence threshold for each condition tested.

Preimplantation genetic testing (PGT) has become an integral component of assisted reproductive technology (ART), offering couples the opportunity to screen embryos for genetic abnormalities before implantation during in vitro fertilization (IVF). This comprehensive review explores the advancements and applications of PGT in IVF, covering its various types, technological developments, clinical applications, efficacy, challenges, regulatory aspects, and future directions. The evolution of PGT techniques, including next-generation sequencing (NGS) and comparative genomic hybridization (CGH), has significantly enhanced the accuracy and reliability of genetic testing in embryos. PGT holds profound implications for the future of ART by improving IVF success rates, reducing the incidence of genetic disorders, and mitigating the emotional and financial burdens associated with failed pregnancies and genetic diseases. Recommendations for clinicians, researchers, and policymakers include staying updated on the latest PGT techniques and guidelines, exploring innovative technologies, establishing clear regulatory frameworks, and fostering collaboration to maximize the potential benefits of PGT in assisted reproduction. Overall, this review provides valuable insights into the current state of PGT and its implications for the field of reproductive medicine.

Haploid cells are a kind of cells with only one set of chromosomes. Compared with traditional diploid cells, haploid cells have unique advantages in gene screening and drug-targeted therapy, due to their phenotype being equal to the genotype. Embryonic stem cells are a kind of cells with strong differentiation potential that can differentiate into various types of cells under specific conditions in vitro. Therefore, haploid embryonic stem cells have the characteristics of both haploid cells and embryonic stem cells, which makes them have significant advantages in many aspects, such as reproductive developmental mechanism research, genetic screening, and drug-targeted therapy. Consequently, establishing haploid embryonic stem cell lines is of great significance. This paper reviews the progress of haploid embryonic stem cell research and briefly discusses the applications of haploid embryonic stem cells.

Rare disease (RD) is a term used to describe numerous, heterogeneous diseases that are geographically disparate. Approximately 400 million people worldwide live with an RD equating to roughly 1 in 10 people, with 71.9% of RDs having a genetic origin. RDs present a distinctive set of challenges to people living with rare diseases (PLWRDs), their families, healthcare professionals (HCPs), healthcare system, and societies at large. The possibility of inheriting a genetic disease has a substantial social and psychological impact on affected families. In addition to other concerns, PLWRDs and their families may feel stigmatized, experience guilt, feel blamed, and stress about passing the disease to future generations. Stigma can affect all stages of the journey of PLWRDs and their families, from pre-diagnosis to treatment access, care and support, and compliance. It adversely impacts the quality of life of RD patients. To better explore the impact of stigma associated with genetic testing for RDs, we conducted a literature search on PubMed and Embase databases to identify articles published on stigma and RDs from January 2013 to February 2023. There is a dearth of literature investigating the dynamics of stigma and RD genetic testing. The authors observed that the research into the implications of stigma for patient outcomes in low- and middle-income countries (LMICs) and potential interventions is limited. Herein, the authors present a review of published literature on stigma with a focus on RD genetic testing, the associated challenges, and possible ways to address these.