Evaluation of Early Left Ventricular Dysfunction in Patients with Duchenne Muscular Dystrophy Using Two-Dimensional Speckle Tracking Echocardiography and Tissue Doppler Imaging.

Although progressive cardiac dysfunction is the leading cause of death in patients with Duchenne muscular dystrophy (DMD), their cardiac function measured by conventional echocardiography has been generally interpreted as normal at a young age. We aimed to determine whether two-dimensional speckle tracking echocardiography (STE) or tissue Doppler imaging (TDI) could be used for early identification and detection of cardiac dysfunction in young patients with DMD. Thirteen pediatric patients (mean age, 9.69 ± 2.2 years) with DMD and 26 age-matched healthy children (mean age, 9.65 ± 2.2 years) were included in the study. All patients were examined via conventional echocardiography, TDI, and STE. Standard echocardiographic measurements of left ventricular (LV) systolic and diastolic function were obtained. Myocardial velocities including peak-systolic and early- and late-diastolic myocardial velocities were calculated in longitudinal direction in the interventricular septum, using TDI. Speckle tracking analyses were performed by acquiring apical four-, three-, and two-chamber views with the highest possible frame rates. Conventional parameters were similar between the two groups, but heart rates were higher in patients with DMD than in controls. The results of LV diastolic function evaluated using TDI showed that annular peak velocity during early diastole (e'; 10.9 ± 1.7 vs. 14.6 ± 1.7 cm/s), e'/a' ratio (2.0 ± 0.5 vs. 3.0 ± 0.5), E/e' ratio (9.4 ± 1.4 vs. 7.3 ± 0.8), and myocardial performance index (0.46 ± 0.05 vs. 0.36 ± 0.06) of the mitral septal annulus among patients with DMD differed significantly from those of healthy children. A significant decrease in global longitudinal systolic strain was found in patients with DMD (- 16.6 ± 3.7 vs. - 21.2 ± 2.1), with a marked decrease in the LV basal inferolateral and basal inferior walls. In young patients with DMD who have global normal systolic function, reductions in systolic deformation parameters as well as reduced early diastolic myocardial velocities can be detected particularly in the basal inferolateral LV walls. The prognostic significance of these findings warrants further longitudinal follow-up.

Relationship Between Fragmented QRS Complexes and Cardiac Status in Duchenne Muscular Dystrophy: Multimodal Validation Using Echocardiography, Magnetic Resonance Imaging, and Holter Monitoring.

The presence of fragmented QRS is a known marker of heterogeneous ventricular activation around the myocardial scar area. We validated whether fragmented QRS shows any association with ventricular dysfunction, fibrosis, or ventricular arrhythmias in patients with Duchenne muscular dystrophy (DMD). Thirty-seven patients with DMD were evaluated using electrocardiography (ECG), echocardiography, cardiac magnetic resonance, and 24-h Holter monitoring. Associations between fragmented QRS and ventricular dysfunction, fibrosis, or ventricular arrhythmia were investigated. Fragmented QRS complexes were present in 31 of 37 (83.7%) patients, and they were associated with a significantly lower left ventricular ejection fraction along with an increased left ventricular Tei index as evaluated by echocardiography, and more frequent ventricular arrhythmia as indicated using 24-hour Holter monitoring compared with patients without fragmented QRS. The number of leads with fragmented QRS correlated negatively with left ventricular ejection fraction both using echocardiography (r = -0.616) and CMR (r = -0.516). Further, the number of leads with fragmented QRS showed a significant correlation with several other echocardiographic measurements (mitral Em and Sm, and left ventricular Tei index), and 2-dimensional speckle-tracking echocardiography derived global left ventricular longitudinal strain. The frequency of ventricular arrhythmia observed using Holter monitoring showed a significant positive correlation with the frequency of fragmented QRS on ECG (r = 0.674). There was a positive trend of correlation between fragmented QRS and the amount of myocardial fibrosis as assessed by late gadolinium enhancement using CMR, but the statistical significance of the relationship was low (r = 0.433, p = 0.056). Fragmentation of QRS complexes is associated with degrees of left ventricular dysfunction, fibrosis, and ventricular arrhythmias in patients with DMD.

Effect of the Push-up Plus (PUP) Exercise at Different Shoulder Rotation Angles on Shoulder Muscle Activities.

[Purpose] Although the Push-Up Plus is a useful exercise method for shoulder stabilization, few studies have examined its effects at different angles of shoulder rotation. Therefore, the present study investigated the most effective exercise method for shoulder stabilization by analyzing muscle activities of the rotator cuff muscles at different angles of shoulder rotation. [Subjects] Fifteen healthy university students in their 20s were the subjects of this study. [Methods] Changes in muscle EMG related to shoulder stabilization were analyzed by performing the Push-Up Plus in shoulder positions of neutral, internal and external rotation. [Results] The highest muscle activity was found in external rotation, and in internal rotation the pectoralis major and levator scapula showed significantly lower activities than the other positions. [Conclusion] Selectively changing the rotation angle of the shoulder for different purposes of the shoulder exercise would be an effective exercise method.

Congestive heart failure: an unusual presentation of pseudohypoparathyroidism.

We report on an infant presenting with acute cardiogenic shock. She was eventually diagnosed with pseudohypoparathyroidism, which is a heterogeneous group of disorders characterized by severe hypocalcemia, hyperphosphatemia, and increased parathyroid hormone. The patient responded dramatically to calcium and vitamin D supplementation; left ventricular systolic function was normalized within days of treatment. Although the diagnosis of pseudohypoparathyroidism is rare, this case is a reminder of the importance of obtaining calcium levels in patients presenting in acute cardiogenic shock.

Gender Differences in the Relationships between Perceived Stress, Eating Behaviors, Sleep, Dietary Risk, and Body Mass Index.

BACKGROUND: Obesity is a growing epidemic among university students, and the high levels of stress reported by this population could contribute to this issue. Singular relationships between perceived stress; engagement in restrained, uncontrolled, and emotional eating; sleep; dietary risk; and body mass index (BMI) have been reported in the current body of literature; however, these constructs interact with each other, and the complex relationships among them are infrequently examined. Therefore, the aim of the present study was to explore the complex relationships between these constructs using mediation and moderation analyses stratified by gender. METHODS: A cross-sectional study, enrolling university students from the United States (U.S.), the Netherlands, South Korea, Malaysia, Ireland, Ghana, and China, was conducted between October 2020 and January 2021 during the COVID-19 pandemic. Perceived stress; maladaptive eating behaviors including restrained, uncontrolled, and emotional eating; sleep duration and quality; dietary risk; and BMI were assessed using validated questionnaires, which were distributed through an online platform. RESULTS: A total of 1392 students completed the online survey (379 male, 973 female, and 40 who self-identified as "other"). Uncontrolled and emotional eating mediated the relationship between perceived stress and dietary risk for both males and females; higher sleep quality weakened this relationship among female students but not males. Emotional eating mediated the relationship between perceived stress and BMI for both males and females, but higher sleep quality weakened this relationship only among females. CONCLUSIONS: Our findings suggest that students in higher education are likely to benefit from interventions to reduce uncontrolled and emotional eating. Programs that improve sleep quality, especially during highly stressful periods, may be helpful.

Reply to Kuo et al. Comment on "Du et al. Gender Differences in the Relationships between Perceived Stress, Eating Behaviors, Sleep, Dietary Risk, and Body Mass Index. Nutrients 2022, 14, 1045".

We thank Kuo et al. for their comments [...].

Congestive heart failure as an initial manifestation of reninoma.

Reninoma or juxtaglomerular cell tumor (JCT) of the kidney is a rare but curable cause of severe hypertension. We report a case of reninoma in an 18-year-old woman. Interestingly, she initially presented with dilated cardiomyopathy, without any relevant history or signs of hypertension. Malignant hypertension, one of the cardinal signs of JCT, did not become apparent in the patient until several months later. Following a thorough evaluation, we detected a small mass in the left renal cortex as well as elevated plasma renin activity, which suggested the presence of a renin-producing tumor in the kidney. The patient's blood pressure and plasma renin activity rapidly declined after a successful laparoscopic partial nephrectomy. We postulate that hyperreninemic-hyperaldosteronism followed by fluid retention caused a sudden severe increase in ventricular afterload and subsequent congestive heart failure in this patient.

The Association between Assisted Reproduction Technology (ART) and Social Perception of Childbearing Deadline Ages: A Cross-Country Examination of Selected EU Countries.

The advancement of assisted reproductive technologies (ART) has gained much attention in relation to childbearing postponement. Our study's purpose was to empirically examine how perceptions of childbearing deadline age vary in association with availability and prevalence of ART across different countries. The present study used data from the 2006 European Social Survey and the 2006 European Society of Human Reproduction and Embryology to examine selected EU countries. A total sample of 17,487 respondents was examined. Multilevel regression modeling was used. Results showed that first, younger generations were more generous with maternal childbearing ages but stricter with paternal deadline ages. Second, respondents residing in countries with higher percentage of reproductive clinics per population were more generous with maternal ages, however no significant association was observed with regard to paternal childbearing ages. Third, on the contrary, respondents residing in countries with higher utilization of ART treatments were stricter with maternal ages, which may be because they are more likely to be aware of the physiological and financial difficulties associated with ART treatments. The present study is meaningful in that it is the first study to empirically examine social perceptions of childbearing ages in relation with ART.

Mothers' Parenting Stress and Neighborhood Characteristics in Early Childhood (Ages 0-4).

Neighborhood characteristics are important when raising children. Traditional approaches to parental stress research have focused on the impacts of daily hassles and how individual factors, such as children's temperament, family resources, and social support from friends and family reduce or exacerbate parental stress. There have been few studies on neighborhood characteristics and parental stress, and even fewer studies have examined the association longitudinally. The goal of the present study was to explore the association between mothers' parental stress and neighborhood characteristics longitudinally across early childhood (ages 0-4). Using the 2008-2012 Panel Study on Korean Children, we followed 1536 mothers. The results showed that mothers' parenting stress was highest when children were aged two to three, and neighborhood characteristics had significant associations with parenting stress. The study indicated that mothers who reported that their neighborhoods had sufficient childcare facilities, were convenient to access public recreational and cultural facilities, and those who reported that their neighborhoods were good places to raise children, exhibited significantly lower levels of parenting stress. Further, the effects of neighborhoods on mothers' parenting stress were greatest when children were aged one and four. Hence, such findings should be incorporated when designing and developing communities.

Dropping out of voluntary community-based health insurance in rural Uganda: Evidence from a cross-sectional study in rural south-western Uganda.

AIM: Community Based Health Insurance (CBHI) schemes have become central to health systems financing as avenues of achieving universal health coverage in developing countries. Yet, while emphasis in research and policy has mainly concentrated on enrolment, very little has been apportioned to high rates of dropping out after initial enrolment. The main aim of this study is to understand the factors behind CBHI dropping out through a cross-sectional quantitative research design to gain insights into curtailing the drop out of CBHI in Uganda. METHODS: The survey for the quantitative research component took place between August 2015 and March 2016 covering 464 households with under-5 children in south-western Uganda. To understand the factors associated with dropping out of CBHI, we employ a multivariate logistic regression on a subsample of 251 households who were either currently enrolled or had enrolled at one time and later dropped out. RESULTS: Overall, we find that 25.1 percent of the households that had ever enrolled in insurance reported dropping out. Household socioeconomic status (wealth) was one of the key factors that associated with dropping out. Larger household sizes and distance from the hospital were significantly associated with dropping out. More socially connected households were less likely to drop out revealing the influence of community social capital in keeping households insured. CONCLUSION: The findings have implications for addressing equity and inclusion concerns in community-based health insurance programmes such as one in south-western Uganda. Even when community based informal system aim for inclusion of the poorest, they are not enough and often the poorest of the poor slip into the cracks and remain uninsured or drop out. Moreover, policy interventions toward curtailing high dropout rates should be considered to ensure financial sustainability of CBHI schemes.

Health Behaviors of Higher Education Students from 7 Countries: Poorer Sleep Quality during the COVID-19 Pandemic Predicts Higher Dietary Risk.

Health behaviors of higher education students can be negatively influenced by stressful events. The global COVID-19 pandemic presents a unique opportunity to characterize and compare health behaviors across multiple countries and to examine how these behaviors are shaped by the pandemic experience. Undergraduate and graduate students enrolled in universities in China, Ireland, Malaysia, South Korea, Taiwan, the Netherlands and the United States (USA) were recruited into this cross-sectional study. Eligible students filled out an online survey comprised of validated tools for assessing sleep quality and duration, dietary risk, alcohol misuse and physical activity between late April and the end of May 2020. Health behaviors were fairly consistent across countries, and all countries reported poor sleep quality. However, during the survey period, the COVID-19 pandemic influenced the health behaviors of students in European countries and the USA more negatively than Asian countries, which could be attributed to the differences in pandemic time course and caseloads. Students who experienced a decline in sleep quality during the COVID-19 pandemic had higher dietary risk scores than students who did not experience a change in sleep quality (p = 0.001). Improved sleep quality was associated with less sitting time (p = 0.010). Addressing sleep issues among higher education students is a pressing concern, especially during stressful events. These results support the importance of making education and behavior-based sleep programming available for higher education students in order to benefit students' overall health.

The Effects of Sleep Quality and Resilience on Perceived Stress, Dietary Behaviors, and Alcohol Misuse: A Mediation-Moderation Analysis of Higher Education Students from Asia, Europe, and North America during the COVID-19 Pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has increased the already high levels of stress that higher education students experience. Stress influences health behaviors, including those related to dietary behaviors, alcohol, and sleep; yet the effects of stress can be mitigated by resilience. To date, past research studying the connections between dietary behaviors, alcohol misuse, sleep, and resilience commonly investigated singular relationships between two of the constructs. The aim of the current study was to explore the relationships between these constructs in a more holistic manner using mediation and moderation analyses. METHODS: Higher education students from China, Ireland, Malaysia, South Korea, Taiwan, the Netherlands, and the United States were enrolled in a cross-sectional study from April to May 2020, which was during the beginning of the COVID-19 pandemic for most participants. An online survey, using validated tools, was distributed to assess perceived stress, dietary behaviors, alcohol misuse, sleep quality and duration, and resilience. RESULTS: 2254 students completed the study. Results indicated that sleep quality mediated the relationship between perceived stress and dietary behaviors as well as the relationship between perceived stress and alcohol misuse. Further, increased resilience reduced the strength of the relationship between perceived stress and dietary behaviors but not alcohol misuse. CONCLUSION: Based on these results, higher education students are likely to benefit from sleep education and resilience training, especially during stressful events.

Congenital left atrial appendage aneurysm diagnosed by fetal echocardiography.

A newborn infant was evaluated because of a large cystic mass adjacent to the left atrium on prenatal ultrasound. The diagnosis was an aneurysm of the left atrial appendage. Most cases of this rare lesion are recognized between the 2nd and 4th decades of life. The present case, however, was detected on fetal echocardiography. The patient showed significant mitral regurgitation caused by the compression of the left atrioventricular groove. Simple aneurysmectomy without mitral valvuloplasty was sufficient to relieve significant mitral regurgitation in this case.

Acute Myocarditis in Children: a 10-year Nationwide Study (2007-2016) based on the Health Insurance Review and Assessment Service Database in Korea.

BACKGROUND AND OBJECTIVES: We performed a nationwide study to assess the incidence, treatment patterns, and outcomes of acute myocarditis in Korean children. METHODS: The nationwide incidence, treatment patterns, and outcomes of acute myocarditis in Korean children were assessed using data between 2007 and 2016 from the Health Insurance Review and Assessment database. RESULTS: We investigated 1,627 children during the study period. The overall incidence of acute myocarditis was 1.4 per 100,000 children in 2007 and 2.1 per 100,000 children in 2016, which indicates a significant increase in the trend over time. A bimodal age distribution was observed with a larger peak in infancy and a smaller peak in the mid-teenage years. No sex difference was observed in the incidence rate of acute myocarditis in children aged ≤5 years (373 boys vs. 366 girls); however, the incidence rate of acute myocarditis in adolescents aged ≥13 years showed significant male preponderance (482 boys vs. 152 girls). Acute fulminant myocarditis occurred in 371 children (22.8%) who needed extracorporeal membrane oxygenation and/or mechanical ventilator support. Of the 371 children with acute fulminant myocarditis, 258 (69.5%) survived. The survival rate of children with acute fulminant myocarditis remained nearly identical over the 10-year study period. CONCLUSIONS: This was the first nationwide epidemiological study to investigate acute myocarditis in Korean children. In our view, this study would help clinicians in decision-making and planning for optimal management of acute myocarditis in children.

Increased Resilience Weakens the Relationship between Perceived Stress and Anxiety on Sleep Quality: A Moderated Mediation Analysis of Higher Education Students from 7 Countries.

High levels of perceived stress and anxiety among university students are a global concern and are known to negatively influence sleep. However, few studies have explored how stress response styles, like psychological resilience and rumination, might alter these relationships. Using validated tools, perceived stress, anxiety, stress response styles, and sleep behaviors of undergraduate and graduate students from seven countries during the height of the COVID-19 pandemic were characterized in order to examine the relationships between these factors using mediation and moderation analyses. Students enrolled in universities in China, Ireland, Malaysia, Taiwan, South Korea, the Netherlands, and the United States were recruited in May 2020. A total of 2254 students completed this cross-sectional study. Perceived stress and anxiety were negatively associated with sleep quality through the mediation of rumination. Increased psychological resilience weakened the relationships between perceived stress and anxiety on sleep quality. The majority of students reported that COVID-19 negatively influenced their mental health and sleep quality but not sleep duration. Based on these results, university students would likely benefit from sleep education and mental health promotion programs that include trainings to increase psychological resilience and reduce rumination, particularly during times of increased stress.

Bortezomib reverses a post-translational mechanism of tumorigenesis for patched1 haploinsufficiency in medulloblastoma.

BACKGROUND: Tumor initiation has been attributed to haploinsufficiency at a single locus for a large number of cancers. Patched1 (Ptc1) was one of the first such loci, and Ptc1 haploinsufficiency has been asserted to lead to medulloblastoma and rhabdomyosarcoma in mice. PROCEDURE: To study the role of Ptc1 in cerebellar tumor development and to create a preclinical therapeutic platform, we have generated a conditional Ptc1 haploinsufficiency model of medulloblastoma by inactivating Ptc1 in Pax7-expressing cells of the cerebellum. RESULTS: These mice developed exclusively medulloblastoma. We show that despite the presence of transcription of Ptc1, Ptc1 protein is nearly undetectable or absent in tumors. Our results suggest that Ptc1 loss of function is complete, but achieved at the protein level rather than by the classic genetic two-hit mechanism or a strict half-dosage genetic haploinsufficiency mechanism. Furthermore, we found that bortezomib, a 26S proteasome inhibitor, had a significant anti-tumor activity in vitro and in vivo, which was accompanied by restoration of Ptc1 protein and downregulation of the hedgehog signaling pathway. The same effect was seen for both human and mouse medulloblastoma tumor cell growth. CONCLUSIONS: These results suggest that proteasome inhibition is a potential new therapeutic approach in medulloblastoma.

Effects of gamma ray, electron beam, and X-ray on the reduction of Aspergillus flavus on red pepper powder (Capsicum annuum L.) and gochujang (red pepper paste).

Aspergillus flavus is the potential pathogenic mold in red pepper powder (Capsicum annuum L.) and gochujang (red pepper paste), which can produce mycotoxins. This study investigated the effects of gamma ray, e-beam, and X-ray irradiation on the reduction of A. flavus on red pepper powder and gochujang and physicochemical and sensory quality changes. Gamma ray and e-beam at 3.5 kGy reduced A. flavus effectively (>4 log), without deteriorating the physicochemical quality. Same dose of X-ray did not cause any deterioration of the physicochemical quality. However, reduction effect of A. flavus in red pepper powder and gochujang by 3.5 kGy X-ray was under 2 log. Further, sensory quality analysis showed no significant difference in color, appearance, texture, and overall acceptability after three irradiations. However, flavor changes of red pepper powder and gochujang after three irradiations were mentioned by panelists. In this study, gamma ray and e-beam irradiation were effective in eliminating A. flavus present in red pepper powder and gochujang, but X-ray irradiation was not effective. The results indicate gamma ray and e-beam are effective in controlling microorganisms present in powdery or paste foods, but the X-ray was not effective.

Health Risk in Urbanizing Regions: Examining the Nexus of Infrastructure, Hygiene and Health in Tashkent Province, Uzbekistan.

Worldwide, development agencies have increased their investments in water supply and sanitation as a "powerful preventive medicine" to address infectious diseases. These interventions have focused on on-site technical interventions or social engineering approaches, emulating the result-based targets of the development goals. Against this backdrop, the study examines the following research question: What is the role of socio-cultural backgrounds, housing characteristics, and environmental hygiene practices in addressing water-transmitted diseases in the Tashkent province of Uzbekistan. In a country where public statistics and official maps are rarely accessible, and research is restrictive, the study carried out a household survey using open data kit (ODK) between July and October 2015 in Olmalik, an industrial district, and the Kibray urbanizing district in the province. The findings reveal that demographic factors, poor sanitation practices, housing characteristics, and social behaviors are key predictors of water-transmitted diseases in the two districts. In the industrial township, poor housing, larger household size, and poor excreta disposal habits increased the occurrence of diseases, while in urbanizing districts, higher household size, frequently eating out, and access to public taps significantly increased the occurrence of water-transmitted diseases. The study, which was carried out in a challenging institutional environment, highlights the need for Uzbekistan to focus their policies on environmental hygiene, demographic factors and social behavior as key interventions rather than merely on on-site drinking water and sanitation interventions.

Efficacy of Stiripentol in Dravet Syndrome with or without SCN1A Mutations.

BACKGROUND AND PURPOSE: The aim of this study was to determine the effectiveness of stiripentol (STP) add-on therapy to valproate and clobazam in patients with Dravet syndrome (DS) according to the presence of mutations in the sodium channel alpha-1 subunit gene (SCN1A). METHODS: We performed direct sequencing to analyze SCN1A mutations in 32 patients with clinically confirmed with DS, and classified them into mutation (pathogenic or likely pathogenic) and nonmutation groups based on American College of Medical Genetics and Genomics guidelines. We compared the efficacy of STP in reducing the seizure frequency between the two groups. RESULTS: The 32 patients comprised 15 patients in the mutation group (with definite SCN1A mutations) and 17 patients in the nonmutation group with variants of unknown significance or benign variants. The clinical profile did not differ significantly between the mutation and nonmutation groups. The seizure frequency relative to baseline reduced by 72.53±23.00% (mean±SD) in the mutation group versus 50.58±40.14% in the nonmutation group (p=0.004). The efficacy of STP was better in DS patients with missense mutations that in those with truncation mutations, and was not favorable in patients with mutations at linkers between domains (DII-DIII), linkers between segments of domain I (DI S1-S2), or splice sites, although the small number of patients prevented statistical analyses. CONCLUSIONS: The efficacy of STP was significantly better in DS patients with definite SCN1A mutations than in those without mutations.

Efficient strategy for the molecular diagnosis of intractable early-onset epilepsy using targeted gene sequencing.

BACKGROUND: We intended to evaluate diagnostic utility of a targeted gene sequencing by using next generation sequencing (NGS) panel in patients with intractable early-onset epilepsy (EOE) and find the efficient analytical step for increasing the diagnosis rate. METHODS: We assessed 74 patients with EOE whose seizures started before 3 years of age using a customized NGS panel that included 172 genes. Single nucleotide variants (SNVs) and exonic and chromosomal copy number variations (CNVs) were intensively examined with our customized pipeline and crosschecked with commercial or pre-built software. Variants were filtered and prioritized by in-depth clinical review, and finally classified according to the American College of Medical Genetics and Genomics guidelines. Each case was further discussed in a monthly consensus meeting that included the participation of all laboratory personnel, bioinformaticians, geneticists, and clinicians. RESULTS: The NGS panel identified 28 patients (37.8%) with genetic abnormalities; 25 patients had pathogenic or likely pathogenic SNVs in 17 genes including SXTBP1 (n = 3), CDKL5 (n = 2), KCNQ2 (n = 2), SCN1A (n = 2), SYNGAP1 (n = 2), GNAO1 (n = 2), KCNT1 (n = 2), BRAT1, WWOX, ZEB2, CHD2, PRICKLE2, COL4A1, DNM1, SCN8A, MECP2, SLC9A6 (n = 1). The other 3 patients had pathogenic CNVs (2 duplications and 1 deletion) with varying sizes (from 2.5 Mb to 12 Mb). The overall diagnostic yield was 37.8% after following our step-by-step approach for clinical consensus. CONCLUSIONS: NGS is a useful diagnostic tool with great utility for patients with EOE. Diagnostic yields can be maximized with a standardized and team-based approach.