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Cardiovascular genetic counseling has expanded as an established genetic counseling specialty over the last 20 years. Despite guidelines recommending genetic counseling for heritable cardiac diseases, there have been limited descriptions of the practice model types used for different clinical indications seen in this genetic counseling subspecialty. We aimed to describe current clinical practice models used by cardiovascular genetic counselors and to document practice model strengths, challenges, and areas for improvement. Genetic counselor respondents (n = 63) who self-reported seeing cardiovascular indications were recruited through the National Society of Genetic Counselors and Twitter. They completed a survey describing the types of healthcare professionals with whom they collaborate to see common cardiovascular indications, the nature of their collaboration, and their qualitative experiences with their practice models. Clinical indications addressed in this survey were hypertrophic cardiomyopathy, dilated cardiomyopathy, all other cardiomyopathies, arrhythmias, aortopathies, dyslipidemias, pulmonary arterial hypertension, and congenital heart defects. Data were analyzed using descriptive statistics and thematic analysis. We found that the composition of multidisciplinary provider practice models varies by indication, though general cardiologists were the most common collaborative provider reported. Practice models including geneticists were most common for aortopathy indications. Overall, the majority of respondents were satisfied with the practice models they reported. While a wide variety of successes, challenges, and areas for improvement of practice models were reported, collaboration, communication, and access to appropriate providers for patient care were consistent themes across these three questions. To our knowledge, this is the first description of practice models used by cardiovascular genetic counselors. The results of this study add to the knowledge of this specialty of genetic counseling and assist in understanding the needs and challenges for developing cardiovascular genetics programs and clinics.

As wearable technology (WT) has evolved, devices have developed the ability to track a range of physiological variables. These include maximal aerobic capacity (VO2max) and lactate threshold (LT). With WT quickly growing in popularity, independent evaluation of these devices is important to determine the appropriate use-cases for the devices. Therefore, the purpose of this study was to determine the validity of WT in producing estimates of VO2max and LT in athletic populations. METHODS: 21 participants completed laboratory LT and VO2max testing, as well as an outdoor testing session guided by the WT being tested (Garmin fēnix 6® watch and accompanying heart rate monitor). Statistical analysis was completed, using hypothesis testing (ANOVA, t-test), correlation analysis (Pearson’s r, Lin’s Concordance Correlation [CCC]), error analysis (mean absolute percentage error [MAPE]), equivalence testing (TOST test), and bias assessment (Bland–Altman analysis). RESULTS: The Garmin watch was found to have acceptable agreement for VO2max when compared to the 1 min averaged values (MAPE = 6.85%, CCC = 0.7) and for LT and the onset of blood lactate accumulation (OBLA), (MAPE = 7.52%, CCC = 0.79; MAPE = 8.20%, CCC = 0.74, respectively). Therefore, the Garmin fēnix 6® produces accurate measurements of VO2max and LT in athletic populations and can be used to make training decisions among athletes.

FOXJ1 is expressed in ciliated cells of the airways, testis, oviduct, central nervous system and the embryonic left–right organizer. Ablation or targeted mutation of Foxj1 in mice, zebrafish and frogs results in loss of ciliary motility and/or reduced length and number of motile cilia, affecting the establishment of the left–right axis. In humans, heterozygous pathogenic variants in FOXJ1 cause ciliopathy leading to situs inversus, obstructive hydrocephalus and chronic airway disease. Here, we report a novel truncating FOXJ1 variant (c.784_799dup; p.Glu267Glyfs*12) identified by clinical exome sequencing from a patient with isolated congenital heart defects (CHD) which included atrial and ventricular septal defects, double outlet right ventricle (DORV) and transposition of the great arteries. Functional experiments show that FOXJ1 c.784_799dup; p.Glu267Glyfs*12, unlike FOXJ1, fails to induce ectopic cilia in frog epidermis in vivo or to activate the ADGB promoter, a downstream target of FOXJ1 in cilia, in transactivation assays in vitro. Variant analysis of patients with heterotaxy or heterotaxy-related CHD indicates that pathogenic variants in FOXJ1 are an infrequent cause of heterotaxy. Finally, we characterize embryonic-stage CHD in Foxj1 loss-of-function mice, demonstrating randomized heart looping. Abnormal heart looping includes reversed looping (dextrocardia), ventral looping and no looping/single ventricle hearts. Complex CHDs revealed by histological analysis include atrioventricular septal defects, DORV, single ventricle defects as well as abnormal position of the great arteries. These results indicate that pathogenic variants in FOXJ1 can cause isolated CHD.

ZusammenfassungDie akute Nebennierenrindeninsuffizienz (NNRI) ist eine seltene Erkrankung, welche aufgrund ihrer diffusen Symptomatik oft schwer zu diagnostizieren ist. Symptome wie allgemeine Schwäche, Übelkeit/Erbrechen, Müdigkeit, Hyponatriämie, Hyperkaliämie, Hypoglykämie sowie ausgeprägte Hypotonie bis zum Schock können in der Diagnosestellung einer Nebennierenrindenkrise wegweisend sein. Die Grunderkrankung der NNRI ist ebenso von nicht immer eindeutigen Symptomen geprägt und je nach primärer oder sekundärer Form unterschiedlich ausgeprägt.Nach der Diagnosestellung sind die Patientenschulung, die richtige Dosierung der Substitutionsmedikation und die Adhärenz der Patienten entscheidend für den weiteren Verlauf, insbesondere für die Vermeidung einer Nebennierenkrise. Diese stellt eine Ursache der erhöhten Mortalität betroffener Patienten dar, was in der aktuellen Literatur häufig beschrieben ist. Jedoch zeigt sich in der Literaturrecherche, dass der Verlauf solcher Krisen bzw. die Kausalität von letalen Verläufen selten thematisiert wird, obwohl das Wissen um die Erkrankung und ein damit verbundenes, rasches Handeln v. a. für in der Notaufnahme und auf der Intensivstation tätige Ärzte von großer Bedeutung sind.Berichtet wird über eine Patientin, die bei bekannter sekundärer NNRI das Vollbild einer Nebennierenkrise entwickelte. Trotz rascher Diagnosestellung sowie Therapieeinleitung war infolge von prolongierter Hypoxie und Hypoglykämie ein massiver Hirnschaden unabwendbar. Der Fallbericht zeigt die mögliche Symptomatik, v. a. eine massive Hypoglykämie und einen initial katecholaminrefraktären Schock. Außerdem zeigt er die Schwere des Krankheitsbildes und stellt die Bedeutung einer schnellen Therapie trotz erschwerter Diagnosestellung dar.

OBJECTIVEThe authors of this study aimed to evaluate the use of polysomnography (PSG) in children with Down syndrome (DS) between ages 0 and 7 years, to assess the prevalence and severity of obstructive sleep apnea (OSA) and associated comorbidities, and to describe interventions used for OSA.METHODSA retrospective cohort study was performed at Cincinnati Children’s Hospital Medical Center for children with DS born between 2013 and 2019. Data were extracted from the electronic medical record, including demographics, age at PSG, PSG results, and interventions after an abnormal PSG. Statistical analysis included unadjusted bivariate association testing and multivariable logistic regression modeling to investigate associations with OSA severity.RESULTSAmong 397 patients in the cohort, 59% (n = 235) had a documented PSG and 94% (n = 221) had an abnormal study with 60% (n = 141) demonstrating moderate or severe OSA. There was an inverse relationship between age and OSA severity (P < .001). In a multiple regression model, OSA severity was associated with increased rates of failure to thrive (P < .01), aspiration (P = .02), and laryngomalacia (P < .01). After medical or surgical intervention, 73% of patients experienced the resolution of OSA or an improvement in OSA severity.CONCLUSIONIn this study of pediatric patients with DS, OSA was identified most frequently in the first year of life. In addition, to prompt evaluation of symptomatic infants, our data support earlier PSG screening for patients requiring neonatal ICU care and those with feeding difficulties, airway abnormalities, and/or pulmonary hypertension given their increased risk for severe OSA.

Intestinal microbiota, diet, and physical activity are inextricably linked to inflammation occurring in the presence of tumor progression and declining neurocognition. This study aimed to explore how fecal microbiota, inflammatory biomarkers, and neurocognitive behavior are influenced by voluntary exercise and surplus dietary protein and folic acid which are common health choices. Dietary treatments provided over 8 weeks to C57BL/CJ male mice (N = 76) were: Folic Acid (FA) Protein (P) Control (FPC, 17.9% P; 2 mgFA/kg); Folic Acid Deficient (FAD); Folic Acid Supplemented (FAS; 8 mgFA/kg); Low Protein Diet (LPD, 6% P); and High Protein Diet (HPD, 48% P). FAS mice had decreased plasma HCys (p < 0.05), therefore confirming consumption of FA. Objectives included examining influence of exercise using Voluntary Wheel Running (VWR) upon fecal microbiota, inflammatory biomarkers C - reactive protein (CRP), Vascular Endothelial Growth Factor (VEGF), Interleukin-6 (IL-6), nuclear factor kappa ß subunit (NF-κßp65), Caspase-3 (CASP3), Tumor Necrosis Factor-alpha (TNF-α), and neurocognitive behavior. CRP remained stable, while a significant exercise and dietary effect was notable with decreased VEGF (p < 0.05) and increased CASP3 (p < 0.05) for exercised HPD mice. Consumption of FAS did significantly increase (p < 0.05) muscle TNF-α and the ability to build a nest (p < 0.05) was significantly decreased for both FAD and LPD exercised mice. Rearing behavior was significantly increased (p < 0.05) in mice fed HPD. An emerging pattern with increased dietary protein intake revealed more distance explored in Open Field Testing. At week 1, both weighted and unweighted UniFrac principal coordinates analysis yielded significant clustering (permanova, p ≤ 0.05) associated with the specific diets. Consumption of a HPD diet resulted in the most distinct fecal microbiota composition. At the phylum level–comparing week 1 to week 8–we report a general increase in the Firmicutes/Bacteroidetes ratio, characterized by an outgrowth of Firmicutes by week 8 in all groups except the HPD. MaAsLin2 analysis corroborates this finding and emphasizes an apparent inversion of the microbiome composition at week 8 after HPD. Explicit modification of oncogenic inflammatory biomarkers and fecal microbiome post high FA and protein intake along with voluntary exercise contributed to current underlying evidence that this diet and exercise relationship has broader effects on human health and disease–perhaps importantly as a practical modulation of cancer progression and declining neurocognition.

Polygenic scores (PGS) are primed for use in personalized risk assessments for common, complex conditions and population health screening. Although there is growing evidence supporting the clinical validity of these scores in certain diseases, presently, there is no consensus on best practices for constructing PGS or demonstrated clinical utility in practice. Despite these evidence gaps, individuals can access their PGS information through commercial entities, research programs, and clinical programs. This prompts the immediate need for educational resources for clinicians encountering PGS information in clinical practice. This practice resource is intended to increase genetic counselors' and other healthcare providers' understanding and comfort with PGS used in personalized risk assessments. Drawing on best practices in clinical genomics, we discuss the unique considerations for polygenic-based (1) testing, (2) clinical genetic counseling, and (3) translation to population health services. This practice resource outlines the emerging uses of PGS, as well as the critical limitations of this technology that need to be addressed before wide-scale implementation.

The European physical journal / Plus 138(2), 158 (2023). doi:10.1140/epjp/s13360-023-03720-z special issue: "Focus Point on Accelerator-based Photon Science Strategy, Prospects and Roadmap in Europe: a Forward View to 2030 / guest editors: R. Abela, T. Tschentscher, J. Susini, G. García", Published by Springer, Berlin ; Heidelberg

Genetic counselors are one of the many providers involved in caring for patients with congenital heart defects (CHDs); however, little is known about the cardiovascular genetics training they receive by their graduate programs. To explore the recalled education experiences regarding CHDs by practicing genetic counselors, we surveyed graduates of programs primarily accredited by the American Council on Genetic Counseling (ACGC) about their graduate training in this area, the depth of CHD-specific education they received, and whether CHDs are a substantial referral indication in their current practice. Genetic counselors were recruited from the National Society of Genetic Counselors and Twitter (n = 112), and participants reflecting multiple specialties and 35 graduate programs completed an online survey which included questions about fieldwork placements and lectures in cardiovascular genetics, exposure to classification schemes regarding cardiac embryology, and education in counseling strategies for CHDs and CHD-related topics during their graduate training. When asked whether CHDs are a substantial referral indication seen in their current practice, 55% (62/112) responded yes. Most participants (79%, 88/112) recalled receiving some education about CHDs, but 91% (80/88) reported receiving little to no education regarding embryologic classification of CHDs and how to apply classification schemes to their counseling. Both participating prenatal and pediatric GCs reported that CHDs can be a common referral indication, yet they reported receiving limited education on teratogens associated with CHDs, family screening recommendations, and recurrence risk counseling for CHDs. Based on participant responses, the majority of respondents reported receiving sufficient education on syndromes with CHDs which can be beneficial in specialties such as pediatrics. This exploratory study provides insight into opportunities to further support genetic counseling educational opportunities for CHDs. These findings suggest genetic counseling graduate programs could consider implementing education on CHD counseling strategies as a standardized component of the curriculum and that practicing genetic counselors could benefit from educational opportunities and resources with updated information on this topic.

Improvements in technology used for genetic testing have yielded an increased numbers of variants that are identified, each with a potential to return uninformative results. While some genetics providers may expect patients to be responsible for staying abreast of updates to their genetic testing results, it is unknown whether patients are even aware of the possibility of variant reclassification. Little research has assessed the comprehension and attitudes of parents of pediatric patients regarding reclassification of variants of uncertain significance (VUS). Semi-structured telephone interviews were conducted with parents (n = 15) whose children received a VUS from genetic testing in either the pediatric neurogenetics or developmental pediatrics clinics at Riley Hospital for Children in Indianapolis, Indiana. Most participants expressed understanding of the uncertainty surrounding their child’s VUS test result. However, nearly half of participants shared that they had no prior knowledge of its potential reclassification. When asked whose responsibility it is to keep informed about changes to their child’s VUS status, some participants stated that it belonged solely to healthcare providers — a distinctive finding of our study — whereas others felt that it was a joint responsibility between providers and the parents. We additionally found that some patients desire a support group for individuals with VUS. These results provide insight into the importance of pretest genetic counseling and the need for increased social and informational support for parents of children who receive inconclusive genetic testing results. We conclude that relying solely on the patient or guardian to manage uncertain results may be insufficient.

Congenital heart disease (CHD) is an indication which spans multiple specialties across various genetic counseling practices. This practice resource aims to provide guidance on key considerations when approaching counseling for this particular indication while recognizing the rapidly changing landscape of knowledge within this domain. This resource was developed with consensus from a diverse group of certified genetic counselors utilizing literature relevant for CHD genetic counseling practice and is aimed at supporting genetic counselors who encounter this indication in their practice both pre- and postnatally.

Biallelic pathogenic variants in

Cardiometabolic conditions are closely associated with inflammation and oxidative stress. Dietary berries may serve as a beneficial nutrition intervention to address the features of cardiometabolic dysfunction and associated oxidative stress. The high antioxidant status of dietary berries may increase antioxidant capacity and reduce biomarkers of oxidative stress. This systematic review was conducted to investigate these effects of dietary berries. The search was conducted using PubMed, Cochrane Library, Web of Science, and citation searching. Through this search we identified 6309 articles and 54 were included in the review. Each study’s risk of bias was assessed using the 2019 Cochrane Methods’ Risk of Bias 2 tool. Antioxidant and oxidative stress outcomes were evaluated, and the magnitude of effect was calculated using Cohen’s d. A range of effectiveness was reported in the included studies and the quality of the studies differed between the parallel and crossover trials. Considering the inconsistency in reported effectiveness, future investigations are warranted to determine the acute and sustained reductions of oxidative stress biomarkers from dietary berry intake (PROSPERO registration# CRD42022374654).

We performed a cross-sectional, retrospective review of our institution's previous uninformative exome sequencing (ES) results and reanalysis process, and we identified areas of improvement in our genetic testing pipeline. To accomplish this, we performed a detailed chart review of patients who had ES performed from 2013 through 2016 and catalogued data including age, indication for testing, ordering physician specialty, and if a reanalysis was performed. Our final sample included 165 patients with uninformative exome sequencing results, 50 of whom also had reanalysis. Then, descriptive statistics and Fishers exact tests were performed to identify factors associated with whether ES reanalysis had been completed or not. We found that certain factors were more closely associated with a patient having had a reanalysis performed for a normal or uninformative result, like whether the patient had a future appointment within our institution (p = 0.0276). Other factors more closely associated with a patient having reanalysis were if the patient met with a geneticist (p = 0.0018) and/or genetic counselor (p = 0.0027). Other variable such as age, race, and if the patient had a future appointment with their ordering provider were not associated with an increased likelihood of having reanalysis. These results highlight the value of genetics professionals in interpreting complex genetic testing and also identify areas where we may need to improve our current processes. In addition, our results confirm findings from previous studies, implement a basis for other clinics to examine their ES reanalyses pipeline, and allow us to support the call for additional guidelines on ES reanalysis.

The COVID-19 pandemic required genetic counseling services, like most outpatient healthcare, to rapidly adopt a telemedicine model. Understanding the trends in patients' preferences for telemedicine relative to in-person service delivery both before and after the advent of the COVID-19 pandemic may aid in navigating how best to integrate telemedicine in a post-COVID-19 era. Our study explored how respondents' willingness to use, and preference for, telemedicine differed from before to after the onset of the COVID-19 pandemic. Respondents included patients, or their parent/guardian, seen in a general medical genetics clinic in 2018, prior to the COVID-19 pandemic, and in 2021, during the COVID-19 pandemic. Respondents were surveyed regarding their willingness to use telemedicine, preference for telemedicine relative to in-person care, and the influence of various factors. Among 69 pre-COVID-19 and 40 current-COVID-19 respondents, there was no shift in willingness to use, or preference for, telemedicine across these time periods. About half of respondents (50.6%) preferred telemedicine visits for the future. Of the 49.4% who preferred in-person visits, 79.1% were still willing to have visits via telemedicine. Predictors of these preferences included comfort with technology and prioritization of convenience of location. This study suggests that a hybrid care model, utilizing telemedicine and in-person service delivery, may be most appropriate to meet the needs of the diverse patients served. Concern for COVID-19 was not found to predict willingness or preference, suggesting that our findings may be generalizable in post-pandemic contexts.

Radiation sources with a stable carrier-envelope phase (CEP) are highly demanded tools for field-resolved studies of light-matter interaction, providing access both to the amplitude and phase information of dynamical processes. At the same time, many coherent light sources, including those with outstanding power and spectral characteristics lack CEP stability, and so far could not be used for this type of research. In this work, we present a method enabling linear and non-linear phase-resolved terahertz (THz) -pump laser-probe experiments with CEP-unstable THz sources. THz CEP information for each pulse is extracted using a specially designed electro-optical detection scheme. The method correlates the extracted CEP value for each pulse with the THz-induced response in the parallel pump-probe experiment to obtain an absolute phase-resolved response after proper sorting and averaging. As a proof-of-concept, we demonstrate experimentally field-resolved THz time-domain spectroscopy with sub-cycle temporal resolution using the pulsed radiation of a CEP-unstable infrared free-electron laser (IR-FEL) operating at 13 MHz repetition rate. In spite of the long history of IR-FELs and their unique operational characteristics, no successful realization of CEP-stable operation has been demonstrated yet. Being CEP-unstable, IR-FEL radiation has so far only been used in non-coherent measurements without phase resolution. The technique demonstrated here is robust, operates easily at high-repetition rates and for short THz pulses, and enables common sequential field-resolved time-domain experiments. The implementation of such a technique at IR-FEL user end-stations will facilitate a new class of linear and non-linear experiments for studying coherent light-driven phenomena with increased signal-to-noise ratio.

We utilize optical pump – THz probe spectroscopy to estimate electron mobility in strained GaAs/(In,Al)As core/shell nanowires. Our results demonstrate that strain-induced reduction of the effective electron mass leads to a remarkable increase of the mobility. The data analysis indicates an important role of the inhomogeneous plasmon broadening that may affect THz spectra of dense ensembles of nanowires.

A promising route for the development of opto-elelctronic technology is to use terahertz radiation to modulate the optical properties of semiconductors. Here we demonstrate the dynamical control of photoluminescence (PL) emission in few-layer InSe using picosecond terahertz pulses. We observe a strong PL quenching (up to 50%) after the arrival of the terahertz pulse followed by a reversible recovery of the emission on the time scale of 50ps at T =10K. Microscopic calculations reveal that the origin of the photoluminescence quenching is the terahertz absorption by photo-excited carriers: this leads to a heating of the carriers and a broadening of their distribution, which reduces the probability of bimolecular electron-hole recombination and, therefore, the luminescence. By numerically evaluating the Boltzmann equation, we are able to clarify the individual roles of optical and acoustic phonons in the subsequent cooling process. The same PL quenchingmechanismis expected in other van derWaals semiconductors and the effectwill be particularly strong for materials with low carrier masses and long carrier relaxation time, which is the case for InSe. This work gives a solid background for the development of opto-electronic applications based on InSe, such as THz detectors and optical modulators., Comment: The following article has been accepted by Applied Physics Letters. After it is published, it will be found at https://publishing.aip.org/resources/librarians/products/journals/

The pseudomorphic growth of Ge1−x Sn x on Ge causes in-plane compressive strain, which degrades the superior properties of the Ge1−x Sn x alloys. Therefore, efficient strain engineering is required. In this article, we present strain and band-gap engineering in Ge1−x Sn x alloys grown on Ge a virtual substrate using post-growth nanosecond pulsed laser melting (PLM). Micro-Raman and x-ray diffraction (XRD) show that the initial in-plane compressive strain is removed. Moreover, for PLM energy densities higher than 0.5 J cm−2, the Ge0.89Sn0.11 layer becomes tensile strained. Simultaneously, as revealed by Rutherford Backscattering spectrometry, cross-sectional transmission electron microscopy investigations and XRD the crystalline quality and Sn-distribution in PLM-treated Ge0.89Sn0.11 layers are only slightly affected. Additionally, the change of the band structure after PLM is confirmed by low-temperature photoreflectance measurements. The presented results prove that post-growth ns-range PLM is an effective way for band-gap and strain engineering in highly-mismatched alloys.

Genetic diseases that affect the cardiovascular system are relatively common and include cardiac channelopathies, cardiomyopathies, aortopathies, hypercholesterolemias, and structural diseases of the heart and great vessels. The rapidly expanding availability of clinical genetic testing leverages decades of research into the genetic origins of these diseases, helping inform diagnosis, clinical management, and prognosis. Although a number of guidelines and statements detail best practices for cardiovascular genetic testing, there is a paucity of pediatric-focused statements addressing the unique challenges in testing in this vulnerable population. In this scientific statement, we seek to coalesce the existing literature around the use of genetic testing for cardiovascular disease in infants, children, and adolescents.

Cases of diabetes mellitus have seen a global increase in prevalence, but there are inherent differences in the pathology and management of different types of diabetes. Type 2 and gestational diabetes have the most similar pathophysiology. For that reason, many similar management strategies exist between type 2 and gestational diabetes, including nutrition-based interventions. Diabetes self-management education and medical nutrition therapy have been advanced as cost-effective interventions to manage hyperglycemia. Many of these interventions, however, were designed for type 2 diabetes and adapted for diabetes in gestation. Nutrition-education-based interventions in gestational diabetes have not been fully elucidated. We scrutinized this gap by conducting a scoping review of recently published peer-reviewed studies that evaluated clinical endpoints in cases of gestational diabetes with nutrition-education-based interventions. The search yielded 621 articles, and the 12 articles included were published between 2012 and 2022. The nutrition information varied across the heterogeneous diabetes self-management education, whereas the medical nutrition therapy studies were more consistent. Our literature search revealed similar outcomes across self-management education and medical nutrition therapy interventions implemented during the third trimester of pregnancies with diabetes. These results suggest that both generalized and personalized approaches to nutrition education in gestational diabetes can manage hyperglycemia and offset its adverse consequences.

The use of clinical genetics evaluations and testing for infants with congenital heart defects (CHDs) is subject to practice variation. This single-institution cross-sectional study of all inpatient infants with severe CHDs evaluated 440 patients using a cardiovascular genetics service (2014–2019). In total, 376 (85.5%) had chromosome microarray (CMA), of which 55 (14.6%) were diagnostic in syndromic (N = 35) or isolated (N = 20) presentations. Genetic diagnoses were made in all CHD classes. Diagnostic yield was higher in syndromic appearing infants, but geneticists’ dysmorphology exams lacked complete sensitivity and 6.5% of isolated CHD cases had diagnostic CMA. Interestingly, diagnostic results (15.8%) in left ventricular outflow tract obstruction (LVOTO) defects occurred most often in patients with isolated CHD. Geneticists’ evaluations were particularly important for second-tier molecular testing (10.5% test-specific yield), bringing the overall genetic testing yield to 17%. We assess these results in the context of previous studies. Cumulative evidence provides a rationale for comprehensive, standardized genetic evaluation in infants with severe CHDs regardless of lesion or extracardiac anomalies because genetic diagnoses that impact care are easily missed. These findings support routine CMA testing in infants with severe CHDs and underscore the importance of copy-number analysis with newer testing strategies such as exome and genome sequencing.

Acute adrenal cortex insufficiency is a rare disease, which is hard to diagnose because of its diffuse symptoms. Symptoms, such as general weakness, nausea or vomiting, fatigue, hyponatremia, hyperkalemia, hypoglycemia and pronounced hypotension up to shock can be crucial in the diagnosis of an adrenal cortex crisis. The underlying disease of adrenal cortex insufficiency is also characterized by not always obvious symptoms, which are differently expressed depending on whether it is the primary or secondary type.After the diagnosis is made it is important to educate the patients, determine the optimal dosage of the substitution and ensure the compliance of the patients to optimize the further process and avoid an adrenal crisis. An adrenal crisis is one of the reasons for a higher mortality of these patients, which is well-described in the current literature. Descriptions of fatal courses and their reasons are rare; however, knowledge of the disease and the importance of rapid intervention is very important, especially for physicians who work in the emergency room or intensive care unit (ICU).This article reports about a female patient with a known secondary adrenal cortex insufficiency who developed the complete picture of an adrenal crisis. Despite rapid diagnosis and initiation of treatment massive brain damage could not be averted due to hypoxia and hypoglycemia. This case report demonstrates the potential symptoms, in particular a massive hypoglycemia and an initial shock refractory to catecholamine. It also shows the severity of that disease and the importance of rapid treatment even though it is difficult to make the diagnosis.Die akute Nebennierenrindeninsuffizienz (NNRI) ist eine seltene Erkrankung, welche aufgrund ihrer diffusen Symptomatik oft schwer zu diagnostizieren ist. Symptome wie allgemeine Schwäche, Übelkeit/Erbrechen, Müdigkeit, Hyponatriämie, Hyperkaliämie, Hypoglykämie sowie ausgeprägte Hypotonie bis zum Schock können in der Diagnosestellung einer Nebennierenrindenkrise wegweisend sein. Die Grunderkrankung der NNRI ist ebenso von nicht immer eindeutigen Symptomen geprägt und je nach primärer oder sekundärer Form unterschiedlich ausgeprägt.Nach der Diagnosestellung sind die Patientenschulung, die richtige Dosierung der Substitutionsmedikation und die Adhärenz der Patienten entscheidend für den weiteren Verlauf, insbesondere für die Vermeidung einer Nebennierenkrise. Diese stellt eine Ursache der erhöhten Mortalität betroffener Patienten dar, was in der aktuellen Literatur häufig beschrieben ist. Jedoch zeigt sich in der Literaturrecherche, dass der Verlauf solcher Krisen bzw. die Kausalität von letalen Verläufen selten thematisiert wird, obwohl das Wissen um die Erkrankung und ein damit verbundenes, rasches Handeln v. a. für in der Notaufnahme und auf der Intensivstation tätige Ärzte von großer Bedeutung sind.Berichtet wird über eine Patientin, die bei bekannter sekundärer NNRI das Vollbild einer Nebennierenkrise entwickelte. Trotz rascher Diagnosestellung sowie Therapieeinleitung war infolge von prolongierter Hypoxie und Hypoglykämie ein massiver Hirnschaden unabwendbar. Der Fallbericht zeigt die mögliche Symptomatik, v. a. eine massive Hypoglykämie und einen initial katecholaminrefraktären Schock. Außerdem zeigt er die Schwere des Krankheitsbildes und stellt die Bedeutung einer schnellen Therapie trotz erschwerter Diagnosestellung dar.

A large database of shock/turbulent boundary layer interactions is compiled to study the separation length scaling over the range of flow conditions including hypersonic interactions. Experimental and computational data of two-dimensional and axisymmetric geometries are included with Mach number from 2 to 10 and ratio of wall to adiabatic recovery temperature from 0.3 to 1.9. A new scaling shows weak interactions collapse by the upstream boundary layer properties, strong interactions do not, and strong separation cases depend on the structure of the downstream flow.

BACKGROUND Vascular malformations of the genitalia often go undetected in clinical examination. These vascular malformations can cause a variety of clinical symptoms such as swelling, pain and bleeding. AIM To characterize the distribution patterns of genital vascular malformations using magnetic resonance imaging (MRI) and to correlate these patterns with clinical findings in order to guide diagnostic decisions. METHODS A retrospective analysis of MRIs of the pelvis and legs in 370 patients with vascular malformation was performed to determine the involvement of the internal and external genitalia. RESULTS In 71 patients (19%), genital involvement could be identified by MRI. Of these, 11.3% (8 of 71) presented with internal involvement, 36.6% (26 of 71) with external involvement and 52.1% (37 of 71) with both internal and external involvement. Over half (57.1%) of the 49 patients with visible external genital signs detected during a clinical examination had additional internal genital involvement. CONCLUSIONS Genital involvement is a common finding in patients with vascular malformation of the legs and/or pelvis. Based on our data, we recommend MRI of the legs and pelvic region in patients with externally visible signs of a vascular malformation of the external genitalia in order to exclude additional internal involvement.

Despite the steady increase in female participation in sport over the last two decades, comprehensive research on interventions attenuating the influence of female menstrual physiology on performance remains scarce. Studies involving eumenorrheic women often only test in one menstrual phase to limit sex hormone variance, which may restrict the application of these findings to the rest of the menstrual cycle. The impacts of nutrition-based interventions on athletic performance throughout the menstrual cycle have not been fully elucidated. We addressed this gap by conducting a focused critical review of clinical studies that reported athletic outcomes as well as menstrual status for healthy eumenorrheic female participants. In total, 1443 articles were identified, and 23 articles were included. These articles were published between 2011 and 2021, and were retrieved from Google Scholar, Medline, and PubMed. Our literature search revealed that hydration-, micronutrient-, and phytochemical-based interventions can improve athletic performance (measured by aerobic capacity, anaerobic power, and strength performance) or attenuate exercise-induced damage (measured by dehydration biomarkers, muscle soreness, and bone resorption biomarkers). Most performance trials, however, only assessed these interventions in one menstrual phase, limiting the application throughout the entire menstrual cycle. Improvements in athletic performance through nutrition-based interventions may be contingent upon female sex hormone variation in eumenorrheic women.

Stoicism is an ancient philosophical tradition with the goal of teaching individuals how to live virtuously and attain tranquility. Stoicism was built upon the concept of fate and the limits of an individual’s power to change their fate (i.e. external circumstances). Many Stoic practices aim to remind oneself of the limits of their power and to shift one’s attention and concern to phenomena in which they have control. The goal is to cultivate a rational, healthy internal locus of control. There is minimal exploration of philosophical traditions in the genetic counseling literature, and Stoic practices may lend themselves to psychosocial genetic counseling work. Themes and applications of Stoic philosophy are explored here, and these practices may aid patients in developing an internal locus of control. The theme of reorienting one’s perception of control over their diagnosis, health, or situation may have benefit in patient psychosocial adaptation. This work serves to introduce genetic counselors to therapeutic applications of Stoic philosophy which may aid advanced counseling practice. We hope to stimulate future exploration and discussion regarding this and similar approaches in clinical genetic counseling.

Introduction:The SCN5A gene is implicated in many arrhythmogenic and cardiomyopathic processes. We identified a novel SCN5A variant in a family with significant segregation in individuals affected with progressive sinus and atrioventricular nodal disease, atrial arrhythmia, dilated cardiomyopathy, and early sudden cardiac arrest.Methods:A patient pedigree was created following the clinical evaluation of three affected individuals, two monozygotic twins and a paternal half-brother, which lead to the evaluation of a paternal half-sister (four siblings with the same father and three mothers) all of whom experienced varying degrees of atrial arrhythmias, conduction disease, and dilated cardiomyopathy in addition to a paternal history of unexplained death in his 50s with similar autopsy findings. The index male underwent sequencing of 58 genes associated with cardiomyopathies. Sanger sequencing was used to provide data for bases with insufficient coverage and for bases in some known regions of genomic segmental duplications. All clinically significant and novel variants were confirmed by independent Sanger sequencing.Results:All relatives tested were shown to have the same SCN5A variant of unknown significance (p. Asp197His) and the monozygotic twins shared a co-occurring NEXN (p. Glu575*). Segregation analysis demonstrates likely pathogenic trait for the SCN5A variant with an additional possible role for the NEXN variant in combination.Conclusions:There is compelling clinical evidence suggesting that the SCN5A variant p. Asp197His may be re-classified as likely pathogenic based on the segregation analysis of our family of interest. Molecular mechanism studies are pending.

Errors during meiosis are the leading cause of birth defects and miscarriages in humans. Thus, the coordinated control of meiotic events is critical for the faithful inheritance of the genome with each generation..., Crossovers (COs) between homologous chromosomes are critical for meiotic chromosome segregation and form in the context of the synaptonemal complex (SC), a meiosis-specific structure that assembles between aligned homologs. During Caenorhabditis elegans meiosis, central region components of the SC (SYP proteins) are essential to repair double-strand DNA breaks (DSBs) as COs. Here, we investigate the relationships between the SYP proteins and conserved pro-CO factors by examining the immunolocalization of these proteins in meiotic mutants where SYP proteins are absent, reduced, or mislocalized. Although COs do not form in syp null mutants, pro-CO factors COSA-1, MSH-5, and ZHP-3 nevertheless colocalize at DSB-dependent sites during late prophase, reflecting an inherent affinity of these factors for DSB repair sites. In contrast, in mutants where SYP proteins are present but form aggregates or display abnormal synapsis, pro-CO factors consistently track with SYP-1 localization. Further, pro-CO factors usually localize to a single site per SYP-1 structure, even in SYP aggregates or in mutants where the SC forms between sister chromatids, suggesting that CO regulation occurs within these aberrant SC structures. Moreover, we find that the meiotic cohesin REC-8 is required to ensure that SC formation occurs between homologs and not sister chromatids. Taken together, our findings support a model in which SYP proteins promote CO formation by promoting the localization of pro-CO factors to recombination events within an SC compartment, thereby ensuring that pro-CO factors identify a recombination event within an SC structure and that CO maturation occurs only between properly aligned homologous chromosomes.

Individuals diagnosed with thoracic aortic aneurysm/dissection (TAAD) are given activity restrictions in an attempt to mitigate serious health complications and sudden death. The psychological distress resulting from activity restrictions has been established for other diseases or patient populations; however, individuals with non-syndromic TAAD have not been previously evaluated. Seventy-nine participants completed a questionnaire utilizing the Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder (GAD-7) questionnaires, which assess levels of depression and anxiety respectively. Additionally, quantitative and qualitative questions explored self-reported psychological distress in response to activity restrictions. Individuals who reported higher PHQ + GAD scores had been living with a diagnosis longer than two years (p = 0.0004), were between 35 and 65 years old (p = 0.05), reported not coping well (p = 0.0035), and reported physical activity was “very important” (p = 0.04). Results from individual questions showed that individuals who reported their diagnosis affected them financially were 3.5 times more likely to report “feeling nervous, anxious, or on edge” (CI = [0.81, 15.6], p = 0.094). Qualitative analysis revealed themes that identified participant beliefs regarding distress, ability to cope, hindrances to coping ability, and resources. These results show psychological distress can result from physical activity restrictions in non-syndromic TAAD individuals. Additionally, certain subpopulations may be more susceptible to distress. This is the first study to examine the psychological distress individuals with non-syndromic TAAD experience as a result of prescribed activity restrictions. Genetic counselors and other healthcare professionals can utilize this information to provide more tailored cardiovascular genetic counseling and increase its therapeutic potential for patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12687-021-00545-0.