Validation of Prosthetic Mitral Regurgitation Quantification Using Novel Angiographic Platform by Mock Circulation

ObjectivesThis study aimed to validate a dedicated software for quantitative videodensitometric angiographic assessment of mitral regurgitation (QMR).BackgroundQuantitative videodensitometric aortography of aortic regurgitation using the time-density principle is a well-documented technique, but the angiographic assessment of mitral regurgitation (MR) remains at best semi-quantitative and operator dependent.MethodsFourteen sheep underwent surgical mitral valve replacement using 2 different prostheses. Pre-sacrifice left ventriculograms were used to assess MR fraction (MRF) using QMR and MR volume (MRV). In an independent core lab, the CAAS QMR 0.1 was used for QMR analysis. In vitro MRF and MRV were assessed in a mock circulation at a comparable cardiac output to the in vivo one by thermodilution. The correlations and agreements of in vitro and in vivo MRF, MRV, and interobserver reproducibility for QMR analysis were assessed using the averaged cardiac cycles (CCs).ResultsIn vivo derived MRF by QMR strongly correlated with in vitro derived MRF, regardless of the number of the CCs analyzed (best correlation: 3 CCs y = 0.446 + 0.994x; R = 0.784; p =0.002). The mean absolute difference between in vitro derived MRF and in vivo derived MRF from 3 CCs was 0.01 ± 4.2% on Bland-Altman analysis. In vitro MRV and in vivo MRV from 3 CCs were very strongly correlated (y = 0.196 + 1.255x; R = 0.839; p < 0.001). The mean absolute difference between in vitro MRV and in vivo MRV from 3 CCs was –1.4 ± 1.9 ml. There were very strong correlations of in vivo MRF between 2 independent analysts, regardless of the number of the CCs.ConclusionsIn vivo MRF using the novel software is feasible, accurate, and highly reproducible. These promising results have led us to initiate the first human feasibility study comprising patients undergoing percutaneous mitral valve edge-to-edge repair.     

Clinical assessment and comparison of annotation algorithms in high‐density mapping of regular atrial tachycardias

1 Background

High‐density automated mapping of regular atrial tachycardias (ATs) requires accurate assessment of local activation times (LATs).

2 Objective

To evaluate high‐density mapping of ATs and compare the accuracy of different automated LAT annotation algorithms.

3 Methods

Fifteen patients underwent AT ablation guided by the automated ConfiDENSE? high‐density mapping module (Carto 3 v4) allowing manual reannotation (edited maps). For each AT, unedited automated maps were reconstructed offline by three algorithms: maximum unipolar slope (LAT_Slope), bipolar peak (LAT_Peak), and a new hybrid annotation algorithm (LAT_Hybrid). Five blinded experts were asked to define the (1) tachycardia mechanism, (2) ablation target, and (3) level of difficulty of these unedited maps.

4 Results

Twenty‐one ATs (cycle length 300 ± 46 ms, activation points 955 ± 421) were successfully ablated using LAT_Hybrid guided ablation with manual editing in a small number of points. At 6 months, 14 (93%) of the patients were free of AT recurrences. Unedited LAT_Hybrid maps showed the highest accuracy in defining the tachycardia mechanism (LAT_Hybrid: 49% vs. LAT_Peak: 27% vs. LAT_Slope: 28%, P < 0.001) and ablation target (LAT_Hybrid: 65% vs. LAT_Peak: 39% vs. LAT_Slope: 31%, P < 0.001). Overall, LAT_Hybrid‐annotated maps were graded as “easier to interpret” by the experts (difficulty score 2.3 ± 0.9) versus LAT_Peak (2.8 ± 1) and LAT_Slope (3.2 ± 0.8) (P < 0.001). Only 12% of the LAT_Hybrid maps were annotated as uninterpretable compared to 31% of LAT_Slope and 45% of the LAT_Peak maps (P < 0.001).

5 Conclusion

Automated LAT_Hybrid annotation allows better and easier recognition of the tachycardia mechanism compared to automated LAT_Peak and LAT_Slope algorithms, although fully automated mapping still requires further improvements.     

Older Chinese migrants in coronavirus pandemic: exploring risk and protective factors to increased loneliness

Older migrants may be one of the most vulnerable populations during the coronavirus pandemic, yet the degree of impact remains largely unknown. This study explores (1) the consequences of the coronavirus pandemic for older Chinese migrants in Belgium and the Netherlands in terms of increased loneliness and its risk factors (reduced in-person contact, decreased social participation, feelings of existential threat) and protective factors (increased non-in-person contact, more individual activities), and (2) which risk and protective factors have contributed to the incidence and prevention of higher loneliness levels. Using quantitative data of a survey among 98 Chinese migrants aged 50 years and older in Belgium (n = 84) and the Netherlands (n = 14), the findings first indicate that the coronavirus pandemic has a significant impact on older Chinese migrants’ lives. One in five experienced more loneliness. Second, reduced social participation (measured as less frequent participation in outdoor group activities) and financial insecurity (measured as experiencing financial difficulties) lead to higher than pre-pandemic loneliness levels. Problem-focused coping strategies (measured as increased non-in-person contact, via telephone or social media) and emotion-focused coping (measured as finding distraction through increased participation in individual activities) were not found to protect against increased loneliness in the pandemic. Two practical implications for loneliness interventions for older Chinese migrants are put forward. Organizing COVID-19-safe social participation activities and paying more attention to older Chinese migrants’ financial situation can be beneficial when addressing higher levels of loneliness due to the coronavirus pandemic.     

The role of respiratory tract infections and the microbiome in the development of asthma: A narrative review

Asthma is a common disease in childhood, and might predispose for chronic obstructive respiratory morbidity in adolescence and adulthood. Various early‐life risk factors might influence the risk of wheezing, asthma, and lower lung function in childhood. Cohort studies demonstrated that lower respiratory tract infections in the first years of life are associated with an increased risk of wheezing and asthma, while the association with lung function is less clear. Additionally, the gut and airway microbiome might influence the risk of wheezing and asthma. The interaction between respiratory tract infections and the microbiome complicates studies of their associations with wheezing, asthma, and lung function. Furthermore, the causality behind these observations is still unclear, and several other factors such as genetic susceptibility and the immune system might be of importance. This review is focused on the association of early‐life respiratory tract infections and the microbiome with wheezing, asthma, and lung function, it is possible influencing factors and perspectives for future studies.

     

The hinge region in androgen receptor control

The region between the DNA-binding domain and the ligand-binding domain of nuclear receptors is termed the hinge region. Although this flexible linker is poorly conserved, diverse functions have been ascribed to it. For the androgen receptor (AR), the hinge region and in particular the (629)RKLKKL(634) motif, plays a central role in controlling AR activity, not only because it acts as the main part of the nuclear translocation signal, but also because it regulates the transactivation potential and intranuclear mobility of the receptor. It is also a target site for acetylation, ubiquitylation and methylation. The interplay between these different modifications as well as the phosphorylation at serine 650 will be discussed here. The hinge also has an important function in AR binding to classical versus selective androgen response elements. In addition, the number of coactivators/corepressors that might act via interaction with the hinge region is still growing. The importance of the hinge region is further illustrated by the different somatic mutations described in patients with androgen insensitivity syndrome and prostate cancer. In conclusion, the hinge region serves as an integrator for signals coming from different pathways that provide feedback to the control of AR activity.     

SAMBA, a plant-specific anaphase-promoting complex/cyclosome regulator is involved in early development and A-type cyclin stabilization

The anaphase-promoting complex/cyclosome (APC/C) is a large multiprotein E3 ubiquitin ligase involved in ubiquitin-dependent proteolysis of key cell cycle regulatory proteins, including the destruction of mitotic cyclins at the metaphase-to-anaphase transition. Despite its importance, the role of the APC/C in plant cells and the regulation of its activity during cell division remain poorly understood. Here, we describe the identification of a plant-specific negative regulator of the APC/C complex, designated SAMBA. In Arabidopsis thaliana, SAMBA is expressed during embryogenesis and early plant development and plays a key role in organ size control. Samba mutants produced larger seeds, leaves, and roots, which resulted from enlarged root and shoot apical meristems, and, additionally, they had a reduced fertility attributable to a hampered male gametogenesis. Inactivation of SAMBA stabilized A2-type cyclins during early development. Our data suggest that SAMBA regulates cell proliferation during early development by targeting CYCLIN A2 for APC/C-mediated proteolysis.     

Undersensing by an ICD Due to Alternans of the Ventricular Electrogram

Alternans of the ventricular electrogram (VEGM) during ventricular tachycardia (VT) is a rare cause of ventricular undersensing by an implantable cardioverter‐defibrillator (ICD). This report describes a patient with a St. Jude ICD who exhibited sustained monomorphic VT associated with surface QRS alternans, alternating cycle lengths, alternans of the VEGM causing intermittent undersensing of the smaller component, and intermittent 2:1 counting of ventricular intervals during 1:1 sensing in response to the ICD detection algorithm. VEGM undersensing was corrected noninvasively simply by programming the threshold start from 62.5% to 50% which increased the sensitivity based on the amplitude of the VEGM. This maneuver did not affect the satisfactory and stable defibrillation threshold.     

Interventions for depression symptoms among adolescent survivors of war and displacement in northern Uganda: a randomized controlled trial

Context  Prior qualitative work with internally displaced persons in war-affected northern Uganda showed significant mental health and psychosocial problems. Objective  To assess effect of locally feasible interventions on depression, anxiety, and conduct problem symptoms among adolescent survivors of war and displacement in northern Uganda. Design, Setting, and Participants  A randomized controlled trial from May 2005 through December 2005 of 314 adolescents (aged 14-17 years) in 2 camps for internally displaced persons in northern Uganda. Interventions  Locally developed screening tools assessed the effectiveness of interventions in reducing symptoms of depression and anxiety, ameliorating conduct problems, and improving function among those who met study criteria and were randomly allocated (105, psychotherapy-based intervention [group interpersonal psychotherapy]; 105, activity-based intervention [creative play]; 104, wait-control group [individuals wait listed to receive treatment at study end]). Intervention groups met weekly for 16 weeks. Participants and controls were reassessed at end of study. Main Outcome Measures  Primary measure was a decrease in score (denoting improvement) on a depression symptom scale. Secondary measures were improvements in scores on anxiety, conduct problem symptoms, and function scales. Depression, anxiety, and conduct problems were assessed using the Acholi Psychosocial Assessment Instrument with a minimum score of 32 as the lower limit for clinically significant symptoms (maximum scale score, 105). Results  Difference in change in adjusted mean score for depression symptoms between group interpersonal psychotherapy and control groups was 9.79 points (95% confidence interval [CI], 1.66-17.93). Girls receiving group interpersonal psychotherapy showed substantial and significant improvement in depression symptoms compared with controls (12.61 points; 95% CI, 2.09-23.14). Improvement among boys was not statistically significant (5.72 points; 95% CI, –1.86 to 13.30). Creative play showed no effect on depression severity (–2.51 points; 95% CI, –11.42 to 6.39). There were no statistically different improvements in anxiety in either intervention group. Neither intervention improved conduct problem or function scores. Conclusions  Both interventions were locally feasible. Group interpersonal psychotherapy was effective for depression symptoms among adolescent girls affected by war and displacement. Other interventions should be investigated to assist adolescent boys in this population who have symptoms of depression. Trial Registration  clinicaltrials.gov Identifier: NCT00280319      

Association of thyroid hormone concentrations with levels of organochlorine compounds in cord blood of neonates

BACKGROUND: Thyroid hormones are important regulators of brain development. During critical periods of development, even transient disorders in thyroid hormone availability may lead to profound neurologic impairment. Animal experiments have shown that certain environmental pollutants, including heavy metals and organochlorine compounds such as polychlorinated biphenyls (PCBs) and dioxins, can interfere with thyroid hormone homeostasis. Whether these contaminants can affect circulating levels of thyroid hormones in humans is unclear, however, because the results of available studies are inconsistent. OBJECTIVES: The aim of the present study is to examine the possible relationships between concentrations of environmental pollutants and thyroid hormone levels in human umbilical cord blood. METHODS: We measured concentrations of environmental pollutants [including selected PCBs, dioxin-like compounds, hexachlorobenzene, p,p'-DDE (dichlorodiphenyldichloroethylene), cadmium, lead] and thyroid hormones in the cord blood of 198 neonates. RESULTS: A statistically significant inverse relationship between concentrations of organochlorine compounds and levels of both free triiodothyronine (fT3) and free thyroxine (fT4), but not thyroid-stimulating hormone, was observed. We found no association between concentrations of heavy metals and thyroid hormone levels. CONCLUSIONS: Our results suggest that environmental chemicals may affect the thyroid system of human neonates. Although the differences in fT3 and fT4 levels associated with the organochlorine compounds were within the normal range, the observed interferences may still have detrimental effects on the neurologic development of the individual children, given the importance of thyroid hormones in brain development.