Connexin therapeutics:blocking connexin hemichannel pores is distinct from blocking pannexin channels or gap junctions

Compounds that block the function of connexin and pannexin protein channels have been suggested to be valuable therapeutics for a range of diseases.Some of these compounds are now in clinical trials,but for many of them,the literature is inconclusive about the molecular effect on the tissue,despite evidence of functional recovery.Blocking the different channel types has distinct physiological and pathological implications and this review describes current knowledge of connexin and pannexin protein channels,their function as channels and possible mechanisms of the channel block effect for the latest therapeutic compounds.We summarize the evidence implicating pannexins and connexins in disease,considering their homeostatic versus pathological roles,their contribution to excesive ATP release linked to disease onset and progression.     

Dialectical behavior therapy in the Asia‐Pacific Rim region

Background: Borderline personality disorder (BPD) contributes to suicide‐related morbidity and mortality and requires more intensive psychotherapeutic resources due to its high mental health service usage. Accessibility to an evidence‐based treatment program is a cornerstone to support patients with BPD and part of broader suicide prevention efforts as well as improving their quality of life. Aims: In this article, the authors aim to discuss and review available dialectical behavior therapy (DBT) and DBT‐informed services of selected countries in the Asia‐Pacific Rim, namely Singapore, Malaysia, and Mexico. Materials & Methods: We contacted providers of different services and gathered information on the process of setting up the service and adapting the treatment, in addition to reviewing the available literature published in the countries. Results: To date, there have been a pair of DBT‐informed services in Singapore, four in Malaysia, and several in Mexico with a few of them offering standard DBT. Different efforts have been put in place to increase the accessibility to training and also the number of DBT practitioners. Discussion: Important considerations during the process of setting up new services include the use of domestic examples and local language that are contextually appropriate for the local community. Selected challenges faced in common include shortage of workforce, affordability of training programs, and the need for language adaptation with or without translation. Conclusion: Further long‐term evaluation of locally adapted DBT‐informed mental health services will help to elucidate the effectiveness and efficacy of the program which will potentially serve as a guide for other resource‐scarce regions.     

In Silico identification of M. TB proteins with diagnostic potential

TB, caused by Mycobacterium tuberculosis (MTB), is one of the major global infectious diseases. For the pandemic control, early diagnosis with sensitive and specific methods is fundamental. With the advent of bioinformatics’ tools, the identification of several proteins involved in the pathogenesis of TB (TB) has been possible. In the present work, the MTB genome was explored to look for molecules with possible antigenic properties for their evaluation as part of new generation diagnostic kits based on the release of cytokines. Seven proteins from the MTB proteome and some of their combinations suited the computational test and the results suggested their potential use for the diagnosis of infection in the following population groups: Cuba, Mexico, Malaysia and sub-Saharan Africa. Our predictions were performed using public bioinformatics tools plus three computer programs, developed by our group, to facilitate information retrieval and processing.     

Diagnostic accuracy of periapical radiograph,cone beam computed tomography,and intrasurgical linear measurement techniques for assessing furcation defects: a longitudinal randomised controlled trial

Clinical Oral Investigations - The aim of this study was to evaluate the accuracy of cone beam computed tomography (CBCT), periapical radiograph, and intrasurgical linear measurements in the...     

Diet and caries experience among preschool children in Ajman,United Arab Emirates

The study investigated the association between food and drink consumption and the caries experience among young children in Ajman, United Arab Emirates. A one‐stage cluster sample was used to select children who were 5 or 6 yr of age. Clinical examinations for caries were conducted. Parents completed questionnaires seeking information on dietary habits. Principal components analysis was used to derive a summary score for the dietary variables (designated ‘snack consumption level’) and thus overcome the multicollinearity problems associated with using multiple dietary variables. Dental examination and questionnaire data were obtained for 1,036 children (79.9% participation rate). The overall mean number of decayed, missing or filled teeth (dmft) was 4.5. Snacking three or more times per day was associated with a dmft score that was almost one‐third higher than the dmft score for children who snacked only once daily. One‐third of children had a low overall snack consumption level (41% moderate and 25% high). There was a consistent dmft gradient across those categories. The severity of Early Childhood Caries (ECC) in young Ajman children is high, with dietary habits being important determinants. Cariogenic snack consumption can be represented using a summary exposure variable that appears to be valid. Young children in Ajman would benefit from health‐promotion strategies directed towards appropriate dietary practices.     

Paralysis of the phrenic nerve as a risk factor for suboptimal Fontan hemodynamics.

OBJECTIVE: The introduction of the Fontan operation for single ventricle physiology was based on the dual principle of the pulmonary blood flow. It is postulated that normal breathing movements are necessary for passive blood flow into the lungs. We compared patients with and without palsy of the phrenic nerve regarding the sufficiency of Fontan hemodynamics. METHODS: We analyzed 85 consecutive patients, who were available for follow-up after completion of their total cavopulmonary connection (TCPC) between February 1992 and February 2003. The median age at TCPC completion was 4.3 (range 1.3-37) years. Sixty were operated on with an extracardiac conduit and 25 with a lateral tunnel. Fifty patients underwent postoperative heart catheterization with contrast angiography. The diagnosis of diaphragm paralysis was made using echocardiography, fluoroscopy and X-ray examination. Surgical diaphragm plication was performed in 13 patients (Four before and nine after Fontan operation) at a median of 2.2 years after the diagnosis. RESULTS: Twenty-one patients developed fixed palsy of the phrenic nerve during a total of 225 operations before and including completion of TCPC. There were no differences in the incidence of phrenic nerve paralysis between small children (aged <3 years) and older patients or between patients with the extracardiac and intracardiac Fontan procedures. There were no differences in the duration of mechanical ventilation. However, prolonged pleural effusions and a hospital stay of longer than 2 weeks were noted more frequently in patients with palsy (P<0.05). During the median follow-up of 4.6 (range: 0.7-11.4) years significantly more patients with phrenic nerve palsy developed chronic ascites compared to those without palsy (8 of 20 vs. 2 of 65; P<0.001). CONCLUSIONS: Phrenic nerve palsy was recognized as a risk factor for suboptimal Fontan hemodynamics due to the hindrance of passive venous blood flow. Patients with phrenic nerve palsy have a longer hospital stay and a higher incidence of prolonged pleural effusions and of chronic ascites, than those without. Early diaphragm plication may be favorable to optimize the Fontan circuit in these patients. Completion of the TCPC in patients with diaphragm paralysis should be viewed critically.     

Pulmonary and caval blood flow patterns in patients with intracardiac and extracardiac Fontan: a magnetic resonance study

Summary Aims We compared in vivo blood flow and pulsatility after different types of Fontan operation using magnetic resonance imaging. Material and methods A total of 37 consecutive patients (mean age 19±7.9 years, 7.3±3.2 years after Fontan operation), 7 with atriopulmonary anastomosis (APC), 18 with intra-atrial lateral tunnel (LTFO) and 12 with extracardiac Fontan (ECFO) were studied using magnetic resonance phase-contrast velocity mapping. Blood flow (volume flow) in the superior vena cava (SVC), inferior vena cava (IVC) and both pulmonary arteries were measured and a pulsatility index was calculated for each vessel. Results For all modifications, the blood flow distribution between the SVC and IVC was normal (1 : 2). Patients with APC had a normal pulsatility, a dilated right atrium, partial backward flow in the IVC and physiological blood flow distribution between the pulmonary arteries. LTFO and ECFO patients had no retrograde flow in the IVC, equal blood flow distribution between the pulmonary arteries and very low or absent pulsatility. Conclusions MRI allows hemodynamic quantification and characterization of various types of Fontan modifications and may be a valuable tool to predict Fontan failure. Despite showing normal pulsatility, patients with APC have right atrial dilatation and partial backward flow in the IVC, demonstrating suboptimal Fontan circulation. LTFO and ECFO both produce unidirectional antegrade flow in the IVC but pulsatility is very low or absent, which may promote poor pulmonary artery growth and increase of pulmonary vascular resistance contributing to late Fontan failure.