Cx43 hemichannel microdomain signaling at the intercalated disc enhances cardiac excitability

Cx43, a major cardiac connexin, forms precursor hemichannels that accrue at the intercalated disc to assemble as gap junctions. While gap junctions are crucial for electrical conduction in the heart, little is known about the potential roles of hemichannels. Recent evidence suggests that inhibiting Cx43 hemichannel opening with Gap19 has antiarrhythmic effects. Here, we used multiple electrophysiology, imaging, and super-resolution techniques to understand and define the conditions underlying Cx43 hemichannel activation in ventricular cardiomyocytes, their contribution to diastolic Ca²⁺ release from the sarcoplasmic reticulum, and their impact on electrical stability. We showed that Cx43 hemichannels were activated during diastolic Ca²⁺ release in single ventricular cardiomyocytes and cardiomyocyte cell pairs from mice and pigs. This activation involved Cx43 hemichannel Ca²⁺ entry and coupling to Ca²⁺ release microdomains at the intercalated disc, resulting in enhanced Ca²⁺ dynamics. Hemichannel opening furthermore contributed to delayed afterdepolarizations and triggered action potentials. In single cardiomyocytes, cardiomyocyte cell pairs, and arterially perfused tissue wedges from failing human hearts, increased hemichannel activity contributed to electrical instability compared with nonfailing rejected donor hearts. We conclude that microdomain coupling between Cx43 hemichannels and Ca²⁺ release is a potentially novel, targetable mechanism of cardiac arrhythmogenesis in heart failure.     

Growth of children living in the outskirts of Ankara: Impact of low socio-economic status

Background:?Most studies of the growth of Turkish schoolchildren are limited to large cities and to subjects from high socio-economic background. Very little is known about growth and development of rural, suburban and low socio-economic children in Turkey.

Aim:?The purpose of this study is to compare height and weight of school-aged children of low socio-economic background with available growth data from high socio-economic strata, and to verify the possible influences of three socio-demographic parameters on their growth.

Subjects and methods:?The sample consisted of 1052 girls and 1223 boys, aged between 7–17 years, living in the outskirts of Ankara, a suburban area of poor socio-economic background. Centile distributions for height and weight were estimated by the LMS-method. ANOVA and Student's t-test were used to compare mean z-scores for height and weight among the various categories of the socio-demographic parameters.

Results:?Children living in the outskirts of Ankara have lower mean values for height and weight when compared with growth data of upper socio-economic strata children. The differences were most pronounced during adolescence. Skinfolds were higher in girls than in boys at all ages (largest p?≤?0.007). There was no clear relationship between growth and the number of siblings, the number of rooms in the house, the mother's and father's education, and the father's professional status (p>0.05), except for the height of girls (p?<?0.05).

Conclusion:?It is suggested that the lower growth status of children living in the outskirts of Ankara is attributable to the poor socio-economic status of this suburban population, which has not changed over the past decades. It is postulated that the growth impairment during adolescence might be due to a reduced tempo of growth in these children.

Résumé. Arrière plan: En Turquie, la plupart des études de croissance ont été limitées à des échantillons de grandes villes et de haut niveau socio-économique. On sait peu de choses sur les modalités de la croissance et du développement des enfants ruraux, périurbains et de niveau socio-économique modeste.

But: Cette étude compare les statures et les poids d’enfants turcs de milieu socioéconomique modeste avec les données des strates socioéconomiques favorisées et analyse les influences éventuelles de trois facteurs sociodémographiques sur leur croissance.

Sujets et méthodes: L’échantillon est formé de 1052 filles et de 1223 garçons âgés de 7 à 17 ans, vivant dans une zone périurbaine défavorisée de la banlieue d’Ankara. Les distributions de centiles pour la stature et pour le poids, ont été estimées par la méthode des moindres carrés et l’analyse de la variance et le test de Student ont été utilisés afin de comparer les z-scores moyens de la stature et du poids en fonction de diverses catégories de paramètres sociodémographiques.

Résultats: Les enfants de la banlieue d’Ankara ont des valeurs moyennes de stature et de poids plus basses que celles des enfants de milieu favorisés, les différences étant plus prononcées lors de l’adolescence. Les plis cutanés sont plus épais chez les filles que chez les garçons quelque soit l’âge (p?≤?0,007). Il n’y a pas d’association nette entre la croissance et le nombre de frères et s?urs, le nombre de pièces du foyer, l’éducation de la mère et du père et le statut professionnel du père (p>0,05), à l’exception de la stature des filles (p<0,05).

Conclusion: Il est vraisemblable que les modalités de croissance moins favorables qu’on observe chez les enfants de la banlieue d’Ankara, soient dues à leur mauvais statut socioéconomique qui n’a pas changé au cours des récentes décennies. On postule que leur déficit de croissance au cours de l’adolescence peut être le fait d’un tempo de croissance réduit.

Zusammenfassung. Hintergrund: Die meisten Wachstumsstudien an Türkischen Schulkindern sind auf große Städte und Probanden mit hohem sozioökonomischen Hintergrund beschränkt. In der Türkei ist sehr wenig über Wachstum und Entwicklung von Kindern aus ländlichen Regionen und Vorstädten und Kindern aus niedrigen sozioökonomischen Schichten bekannt.

Ziel: Sinn dieser Studie ist es, Körperhöhe und Gewicht von Kindern mit niedrigem sozioökonomischen Hintergrund im Schulalter mit verfügbaren Wachstumsdaten aus hohen sozioökonomischen Schichten zu vergleichen und mögliche Einflüsse von drei soziodemographischen Parametern auf ihr Wachstum nachzuweisen.

Probanden und Methoden: Die Stichprobe bestand aus 1052 Mädchen und 1223 Knaben im Alter zwischen 7 und 17 Jahren, die in den Vorstädten von Ankara wohnen, einem suburbanen Bezirk mit sozioökonomisch ärmlichem Hintergrund. Perzentilverteilungen für Körperhöhe und Gewicht wurden nach der LMS-Methode geschätzt. ANOVA und Student's t-Test wurden verwendet, um mittlere Z-Werte für Körperhöhe und Gewicht zwischen den verschiedenen Kategorien der soziodemographischen Parameter zu vergleichen.

Ergebnisse: Kinder, die in den Vorstädten von Ankara leben, haben, im Vergleich mit Wachstumsdaten aus der oberen sozioökonomischen Schicht, niedrigere Mittelwerte für Körperhöhe und Gewicht. Die Unterschiede waren während der Adoleszenz am stärksten ausgeprägt. In allen Altersgruppen waren Hautfettfalten bei Mädchen dicker als bei Knaben (maximal p<0,007). Es gab keine deutliche Korrelation zwischen Wachstum und Geschwisterzahl, Zimmerzahl im Hause, Bildungsgrad von Müttern und Vätern, und dem beruflichen Status des Vaters (p>0,05), mit Ausnahme der Körperhöhe von Mädchen (p<0,05).

Zusammenfassung: Es wird angenommen, dass das geringere Wachstum von Kindern, die in den Vorstädten von Ankara leben, auf den ärmlichen sozioökonomischen Status dieser suburbanen Bevölkerung, der sich in den vergangenen Jahrzehnten nicht geändert hat, zurückzuführen ist. Es wird postuliert, dass der Kleinwuchs in der Adoleszenz die Folge eines verringerten Wachstumstempos dieser Kinder ist.

Resumen. Antecedentes: la mayor parte de los estudios de crecimiento de los escolares turcos se limita a las grandes ciudades y a sujetos de nivel socioeconómico alto. Se sabe muy poco sobre el crecimiento y desarrollo de los niños rurales suburbanos de nivel socioeconómico bajo de Turquía.

Objetivo: el propósito de este estudio es comparar la estatura y el peso de los escolares de nivel socioeconómico bajo con datos disponibles sobre el crecimiento de los estratos de nivel socioeconómico alto, y verificar las posibles influencias de tres parámetros sociodemográficos sobre su crecimiento.

Sujetos y métodos: la muestra la componen 1.052 niñas y 1.223 niños, de 7 a 17 años de edad, residentes en los extrarradios de Ankara, un área suburbana de nivel socioeconómico pobre. Las distribuciones centilares de la estatura y el peso se estimaron mediante el método LMS. Se utilizaron un test ANOVA y la t de Student para comparar las puntuaciones z medias de la estatura y el peso entre las diferentes categorías según los parámetros sociodemográficos.

Resultados: los niños que residen en los extrarradios de Ankara tenían menores valores medios de estatura y peso cuando se les comparó con los niños de los estratos socioeconómicos más altos. Las diferencias fueron más marcadas durante la adolescencia. Los pliegues eran mayores en las chicas que en los chicos a todas las edades (la mayor p<0,007). No había una relación clara entre el crecimiento y el tamaño de la fratría, el número de habitaciones de la casa, el nivel educativo de la madre y del padre y la situación profesional del padre (p>0,05), excepto para la estatura de las chicas (p<0,05).

Conclusión: se sugiere que el menor nivel de crecimiento de los niños que viven en los extrarradios de Ankara es atribuible al bajo nivel socioeconómico de esta población suburbana, que no ha cambiado durante las últimas décadas. Se postula que las diferencias en el crecimiento durante la adolescencia podrían deberse a una reducción del ritmo de crecimiento en estos niños.     

Short-term effects of partial meniscectomy on the clinical results of anterior cruciate ligament reconstruction

Purpose

This study aims to analyse the short-term effects of partial meniscectomy on the clinical results of anterior cruciate ligament reconstruction surgery.

Methods

Clinical outcomes of 19 patients who had partial medial meniscectomy and anterior cruciate ligament reconstruction during the same surgery (Group 1) were compared with the outcomes of 25 patients who had also reconstruction but did not have any meniscal lesion (Group 2). Median follow-up time was 29 months (range 12–67 months) in Group 1 and 27 months (range 12–70 months) in Group 2. Feeling of apprehension in sports activities, International Knee Documentation Committee (IKDC) score, KT-2000 Arthrometer^® measurements and post-operative time to return to sports activity were the criteria for data analysis.

Results

Eight patients (42 %) in Group 1 and 5 patients (20 %) in Group 2 stated feeling of apprehension in sports activities. IKDC score improved to A in 11 patients (58 %) from Group 1, and 18 patients (72 %) from Group 2. Mean anterior translation according to KT-2000 arthrometer measurements was 5.2 ± 1.3 mm in Group 1, and 4.6 ± 1.3 mm in Group 2. Post-operative time to return to sports activity was 8.5 ± 3.0 months in Group 1, and 6.5 ± 2.2 months in Group 2.

Conclusion

Partial meniscectomy for irreparable medial meniscal tears, applied during the same surgery with anterior cruciate ligament reconstruction, negatively affects the clinical outcomes in the short-term follow-up. This study may be a reference for long-term clinical trials and also future investigations of new methods in the treatment of similar cases.

Level of evidence

IV.

     

Cystatin C is better than albuminuria as a predictor of pulse wave velocity in hypertensive patients

Introduction: Arterial stiffness is important in the evaluation of the cardiovascular risk in both general population and hypertensive patients. In this study, we aimed to investigate the associations of both serum cystatin C levels and albuminuria with arterial stiffness in healthy controls and hypertensive patients.

Patients and methods: Seventy-six healthy controls (male/female?=?44/32) and 76 hypertensive patients (male/female?=?43/33) were enrolled. Arterial stiffness parameters such as augmentation index (AIx) and pulse wave velocity (PWV) were non-invasively measured with the Arteriograph (Tensiomed Ltd., Budapest, Hungary).

Results: AIx (31.92?±?14.31 vs. 27.95?±?11.03, p?=?0.03) and PWV (9.84?±?1.62 vs. 8.87?±?2.04, p?p?=?0.002) and higher serum cystatin C levels [0.76 (0.67–0.95) vs. 0.68 (0.62–0.78) mg/L, p?=?0.03]. In the hypertensive group, AIx was significantly correlated with PWV (r?=?0.519, p?r?=?–0.438, p?=?0.003), mean arterial pressure (MAP) (r?=?0.288, p?=?0.015) and urinary albumin–creatinine ratio (ACR) (r?=?0.386, p?=?0.004). PWV was associated with serum cystatin C (r?=?0.442, p?=?0.003) and MAP (r?=?0.377, p?=?0.001). In the linear regression analysis (model r?=?0.577, p?=?0.006) for the prediction of PWV in hypertensive patients, MAP, urinary ACR, age and serum cystatin C levels were included as independent variables. Cystatin C was found to be the significant determinant of PWV in hypertensive patients.

Conclusion: Multivariate analysis revealed that serum cystatin C but not albuminuria was significantly associated with PWV in hypertensive patients. Serum cystatin C may be better than albuminuria as a predictor of arterial stiffness in hypertensive patients.     

Cervical vestibular evoked myogenic potentials in primary headache disorders

ObjectiveTo determine if cervical vestibular evoked myogenic potentials (cVEMPS) differ in patients with migraine without aura (MoA), vestibular migraine (VM) and tension type headache (TTH).MethodsTwenty patients with MoA, 24 patients with VM and 20 patients with TTH were included in the study. Thirty healthy volunteers of comparable age and gender were taken as the control group. The latencies of peaks p13 and n23, peak-to-peak amplitude of p13–n23 divided by a mean prestimulus EMG recorded during cVEMP testing were measured. The amplitude asymmetry between right and left sides was also calculated and taken into consideration. Caloric testing was conducted to check if the results are associated with the results of the cVEMPs.ResultsFive (one on the right, four on the left side) of the 24 patients with VM (20.8%) displayed a unilateral caloric hypofunction. Normal results were recorded from patients with MoA and TTH. p13, n23 latencies and amplitudes of the patient groups were not statistically different from the results of the healthy controls (p > 0.05). An amplitude asymmetry between right and left sides exceeding that of the healthy controls was not also present (p > 0.05).ConclusionsThough a hypofunctioning horizontal semicircular canal was detected in 20.8% of the patients with VM, saccular function seemed to be unaffected. Patients with MoA and TTH did not display any vestibular test abnormality.SignificancePrimary headache disorders seem to be associated with a normal interictal cVEMP profile.     

Trimodality Therapy for Bladder Conservation in Treatment of Invasive Bladder Cancer

During the past 25 years, prospective clinical trials have established that bladder preservation therapy for select patients with muscle-invasive bladder cancer is a safe and effective alternative to an immediate cystectomy. Cisplatin-based chemoradiation is the most well-studied and accepted component of trimodality therapy; however, other systemic agents have recently been shown effective in combination with radiation therapy, increasing the range of options to allow for better personalization of care. In this review, the most recent advances in the field of bladder-preserving trimodality therapy are presented, and future directions for improving the outcomes are outlined.