Broad cellular functions and diseases including muscular dystrophy, arrhythmogenic right ventricular cardiomyopathy (ARVC5) and cancer are associated with transmembrane protein43 (TMEM43/
). The ...study aimed to investigate biological roles of
through genetic regulation, gene pathways and gene networks, candidate interacting genes, and up- or downstream regulators. Cardiac transcriptomes from 40 strains of recombinant inbred BXD mice and two parental strains representing murine genetic reference population (GRP) were applied for genetic correlation, functional enrichment, and coexpression network analysis using systems genetics approach. The results were validated in a newly created knock-in
-S358L mutation mouse model (Tmem43
) that displayed signs of cardiac dysfunction, resembling ARVC5 phenotype seen in humans. We found high
levels among BXDs with broad variability in expression. Expression of
highly negatively correlated with heart mass and heart rate among BXDs, whereas levels of
highly positively correlated with plasma high-density lipoproteins (HDL). Through finding differentially expressed genes (DEGs) between Tmem43
mutant and wild-type (Tmem43
) lines, 18 pathways (out of 42 found in BXDs GRP) that are involved in ARVC, hypertrophic cardiomyopathy, dilated cardiomyopathy, nonalcoholic fatty liver disease, Alzheimer's disease, Parkinson's disease, and Huntington's disease were verified. We further constructed
-mediated gene network, in which
,
,
,
, and
were significantly altered in Tmem43
mice versus Tmem43
controls. Our study defined the importance of
for cardiac- and metabolism-related pathways, suggesting that cardiovascular disease-relevant risk factors may also increase risk of metabolic and neurodegenerative diseases via
-mediated pathways.
While palliative care needs are assumed to improve during ICU care, few empiric data exist on need trajectories or their impact on long-term outcomes. We aimed to describe trajectories of palliative ...care needs during ICU care and to determine if changes in needs over 1 week was associated with similar changes in psychological distress symptoms at 3 months.
Prospective cohort study.
Six adult medical and surgical ICUs.
Patients receiving mechanical ventilation for greater than or equal to 2 days and their family members.
The primary outcome was the 13-item Needs at the End-of-Life Screening Tool (NEST; total score range 0-130) completed by family members at baseline, 3, and 7 days. The Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Post-Traumatic Stress Scale (PTSS) were completed at baseline and 3 months. General linear models were used to estimate differences in distress symptoms by change in need (NEST improvement ≥ 10 points or not). One-hundred fifty-nine family members participated (median age, 54.0 yr interquartile range (IQR), 44.0-63.0 yr, 125 78.6% female, 54 34.0% African American). At 7 days, 53 (33%) a serious level of overall need and 35 (22%) ranked greater than or equal to 1 individual need at the highest severity level. NEST scores improved greater than or equal to 10 points in only 47 (30%). Median NEST scores were 22 (IQR, 12-40) at baseline and 19 (IQR, 9-37) at 7 days (change, -2.0; IQR, -11.0 to 5.0; p = 0.12). There were no differences in PHQ-9, GAD-7, or PTSS change scores by change in NEST score (all p > 0.15).
Serious palliative care needs were common and persistent among families during ICU care. Improvement in needs was not associated with less psychological distress at 3 months. Serious needs may be commonly underrecognized in current practice.
The past 50 years has witnessed the emergence of new viral and bacterial pathogens with global effect on human health. The hyperinvasive group A Streptococcus (GAS) M1T1 clone, first detected in the ...mid‐1980s in the United States, has since disseminated worldwide and remains a major cause of severe invasive human infections. Although much is understood regarding the capacity of this pathogen to cause disease, much less is known of the precise evolutionary events selecting for its emergence. We used high‐throughput technologies to sequence a World Health Organization strain collection of serotype M1 GAS and reconstructed its phylogeny based on the analysis of core genome single‐nucleotide polymorphisms. We demonstrate that acquisition of a 36‐kb genome segment from serotype M12 GAS and the bacteriophage‐encoded DNase Sda1 led to increased virulence of the M1T1 precursor and occurred relatively early in the molecular evolutionary history of this strain. The more recent acquisition of the phage‐encoded superantigen SpeA is likely to have provided selection advantage for the global dissemination of the M1T1 clone. This study provides an exemplar for the evolution and emergence of virulent clones from microbial populations existing commensally or causing only superficial infection.—Maamary, P. G., Ben Zakour, N. L., Cole, J. N., Hollands, A., Aziz, R. K., Barnett, T. C., Cork, A. J., Henningham, A., Sanderson‐Smith, M., McArthur, J. D., Venturini, C., Gillen, C. M., Kirk, J. K., Johnson, D. R., Taylor, W. L., Kaplan, E. L., Kotb, M., Nizet, V., Beatson, S. A., Walker, M. J. Tracing the evolutionary history of the pandemic group A streptococcal M1T1 clone. FASEB J. 26, 4675–4684 (2012). www.fasebj.org
Multi-system inflammatory syndrome in children (MIS-C) in the setting of COVID-19 can be associated with severe cardiopulmonary dysfunction. This clinical deterioration may sometimes necessitate ...veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support. We describe an algorithmic approach including the role of balloon atrial septostomy in this cohort. This is the first reported series of percutaneous VA-ECMO in pediatric patients with MIS-C for better outcomes. The lessons from this approach can be replicated in other pediatric clinical conditions and adds to the armament of multiple pediatric specialties.
The prognosis for patients with macula-off rhegmatogenous retinal detachment (RRD) and concomitant age-related macular degeneration (AMD) is not well known. The purpose of this study is to compare ...visual outcomes in macula-off RRD in eyes with AMD versus a group of comparison eyes without AMD.
This was a retrospective chart review of 1149 patients. A total of 191 eyes met study criteria, 162 non-AMD eyes (controls), and 29 AMD eyes. The main outcome measure was postoperative visual acuity following pars plana vitrectomy (PPV), scleral buckle (SB), or combined PPV/SB in control eyes versus AMD eyes. This was compared using Fisher's exact test.
There was a statistically significant difference in postoperative visual acuity by AMD status, with those without AMD having a worse visual outcome overall (p = 0.0048). A similar percentage of AMD versus non-AMD eyes achieved vision better than 20/40. More patients in the non-AMD group achieved a final visual acuity between 20/40 and 20/200. Of patients with AMD, more had vision worse than 20/200 though 58% maintained functional vision (better than 20/200). Those without AMD had a higher frequency of Count Fingers (CF), Hand Motion (HM), Light Perception (LP), or No Light Perception (NLP) vision (p = 0.023).
Though postoperative visual acuity was worse overall in the non-AMD group with a higher frequency of patients having final vision of CF, HM, LP, or NLP, this is likely a function of the difference in sample size and composition between the two groups. Importantly, this study suggests AMD patients can expect similar outcomes to non-AMD patients after RRD repair. We conclude that AMD patients can achieve functional vision after RRD surgery, similar to those without AMD.
Cardiovascular magnetic resonance (CMR) has become the reference standard for quantitative and qualitative assessment of ventricular function, blood flow, and myocardial tissue characterization. ...There is a preponderance of large CMR studies and registries in adults; However, similarly powered studies are lacking for the pediatric and congenital heart disease (PCHD) population. To date, most CMR studies in children are limited to small single or multicenter studies, thereby limiting the conclusions that can be drawn. Within the PCHD CMR community, a collaborative effort has been successfully employed to recognize knowledge gaps with the aim to embolden the development and initiation of high-quality, large-scale multicenter research. In this publication, we highlight the underlying challenges and provide a practical guide toward the development of larger, multicenter initiatives focusing on PCHD populations, which can serve as a model for future multicenter efforts.
Display omitted
Abstract
Background
Congenital heart defects have been reported with the use of antithyroid medication with ventricular septal defects (VSD) being the most common. As per the current practice ...guidelines maternal Graves’ disease (GD) is not an indication for fetal echocardiogram.
Case presentation
We described three neonates with tetralogy of Fallot (TOF) born to mothers with GD. Only one of the mothers was on antithyroid medication. Two of these neonates were diagnosed postnatally when they failed the pulse oximeter congenital cardiac screening and diagnosis was established by postnatal echocardiogram. Two of the mothers had radioactive iodine ablation and were on levothyroxine during pregnancy. The dose of levothyroxine was increased during pregnancy. There was no other complication during pregnancy. The third mother had hyperthyroidism and developed a thyroid storm during pregnancy requiring inpatient admission and treatment with propylthiouracil (PTU), metoprolol and methimazole. All babies had normal thyroid function test postnatally and eventually had successful repair of TOF defect.
Conclusion
We report the largest known case series of children with TOF born to mothers with GD. Apart from the isolated reports of fetal TOF in mothers with GD, there is no clear association between fetal TOF and maternal GD and antithyroid medication. Based on the review of the literature and our case series, there may be an increased incidence of congenital heart defects in maternal GD irrespective of antithyroid medication use. This case series may add to the current knowledge base and support routine fetal echocardiogram screening for all mothers with GD.
“Cases of SCMR” is a case series on the SCMR website (https://www.scmr.org) for the purpose of education. The cases reflect the clinical presentation, and the use of cardiovascular magnetic resonance ...(CMR) in the diagnosis and management of cardiovascular disease. The 2022 digital collection of cases are presented in this manuscript.
Survival for pediatric patients diagnosed with cancer has improved significantly. This achievement has been made possible due to new treatment modalities and the incorporation of a systematic ...multidisciplinary approach for supportive care. Understanding the distinctive cardiovascular characteristics of children undergoing cancer therapies has set the underpinnings to provide comprehensive care before, during, and after the management of cancer. Nonetheless, we acknowledge the challenge to understand the rapid expansion of oncology disciplines. The limited guidelines in pediatric cardio-oncology have motivated us to develop risk-stratification systems to institute surveillance and therapeutic support for this patient population. Here, we describe a collaborative approach to provide wide-ranging cardiovascular care to children and young adults with oncology diseases. Promoting collaboration in pediatric cardio-oncology medicine will ultimately provide excellent quality of care for future generations of patients.
Switchgrass is C
perennial grass species that is being developed as a cellulosic bioenergy feedstock. It is wind-pollinated and considered to be an obligate outcrosser. Genetic engineering has been ...used to alter cell walls for more facile bioprocessing and biofuel yield. Gene flow from transgenic cultivars would likely be of regulatory concern. In this study we investigated pollen-mediated gene flow from transgenic to nontransgenic switchgrass in a 3-year field experiment performed in Oliver Springs, Tennessee, U.S.A. using a modified Nelder wheel design. The planted area (0.6 ha) contained sexually compatible pollen source and pollen receptor switchgrass plants. One hundred clonal switchgrass 'Alamo' plants transgenic for an orange-fluorescent protein (OFP) and hygromycin resistance were used as the pollen source; whole plants, including pollen, were orange-fluorescent. To assess pollen movement, pollen traps were placed at 10 m intervals from the pollen-source plot in the four cardinal directions extending to 20 m, 30 m, 30 m, and 100 m to the north, south, west, and east, respectively. To assess pollination rates, nontransgenic 'Alamo 2' switchgrass clones were planted in pairs adjacent to pollen traps.
In the eastward direction there was a 98% decrease in OFP pollen grains from 10 to 100 m from the pollen-source plot (Poisson regression, F1,8 = 288.38, P < 0.0001). At the end of the second and third year, 1,820 F
seeds were collected from pollen recipient-plots of which 962 (52.9%) germinated and analyzed for their transgenic status. Transgenic progeny production detected in each pollen-recipient plot decreased with increased distance from the edge of the transgenic plot (Poisson regression, F1,15 = 12.98, P < 0.003). The frequency of transgenic progeny detected in the eastward plots (the direction of the prevailing wind) ranged from 79.2% at 10 m to 9.3% at 100 m.
In these experiments we found transgenic pollen movement and hybridization rates to be inversely associated with distance. However, these data suggest pollen-mediated gene flow is likely to occur up to, at least, 100 m. This study gives baseline data useful to determine isolation distances and other management practices should transgenic switchgrass be grown commercially in relevant environments.
PDF
