Nuclear localization of a novel calpain-2 mediated junctophilin-2 C-terminal cleavage peptide promotes cardiomyocyte remodeling.

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. Patients with HF exhibit a loss of junctophilin-2 (JPH2), a structural protein critical in forming junctional membrane complexes in which excitation-contraction takes place. Several mechanisms have been proposed to mediate the loss of JPH2, one being cleavage by the calcium-dependent protease calpain.

Effects of Korsakoff Amnesia on performance and symptom validity testing.

Performance validity tests (PVTs) and Symptom validity tests (SVTs) are developed to identify people that present false or exaggerated symptoms. Although a key factor of both types of tests includes relative insensitivity to cognitive disorders, the direct effects of amnesia have been poorly studied. Therefore, a sample of 20 patients diagnosed with Korsakoff Amnesia (KA) through neuropsychological assessment and 20 healthy comparisons (HC) were administered the Test of Memory Malingering (TOMM), the Structured Inventory of Malingered Symptomatology (SIMS), and the newly developed Visual Association Test - Extended (VAT-E).

The MEF2 transcriptional target DMPK induces loss of sarcomere structure and cardiomyopathy.

Aims: The pathology of heart failure is characterized by poorly contracting and dilated ventricles. At the cellular level, this is associated with lengthening of individual cardiomyocytes and loss of sarcomeres. While it is known that the transcription factor myocyte enhancer factor-2 (MEF2) is involved in this cardiomyocyte remodelling, the underlying mechanism remains to be elucidated.

The RNA-binding protein Rbm38 is dispensable during pressure overload-induced cardiac remodeling in mice.

The importance of tightly controlled alternative pre-mRNA splicing in the heart is emerging. The RNA binding protein Rbm24 has recently been identified as a pivotal cardiac splice factor, which governs sarcomerogenesis in the heart by controlling the expression of alternative protein isoforms. Rbm38, a homolog of Rbm24, has also been implicated in RNA processes such as RNA splicing, RNA stability and RNA translation, but its function in the heart is currently unknown.

A mutation in the glutamate-rich region of RNA-binding motif protein 20 causes dilated cardiomyopathy through missplicing of titin and impaired Frank-Starling mechanism.

Aim: Mutations in the RS-domain of RNA-binding motif protein 20 (RBM20) have recently been identified to segregate with aggressive forms of familial dilated cardiomyopathy (DCM). Loss of RBM20 in rats results in missplicing of the sarcomeric gene titin (TTN). The functional and physiological consequences of RBM20 mutations outside the mutational hotspot of RBM20 have not been explored to date.

Long Non-Coding RNA Malat-1 Is Dispensable during Pressure Overload-Induced Cardiac Remodeling and Failure in Mice.

Background: Long non-coding RNAs (lncRNAs) are a class of RNA molecules with diverse regulatory functions during embryonic development, normal life, and disease in higher organisms. However, research on the role of lncRNAs in cardiovascular diseases and in particular heart failure is still in its infancy. The exceptionally well conserved nuclear lncRNA Metastasis associated in lung adenocarcinoma transcript 1 (Malat-1) is a regulator of mRNA splicing and highly expressed in the heart.

The Reproducibility and Applicability of an EFD(®) Dispenser in the Prosthetic Technology of Maxillofacial Prostheses.

A reproducible method of dosing pigments can be beneficial and more efficient in the current colour matching procedure in maxillofacial prosthetics. In this study the reproducibility and applicability for pigment dosing of a commercial available EFD(®) dispenser were tested. The reproducibility of a Performus™ II type EFD(®) dispenser was tested by repeating dosing experiments with a set of eight syringes filled with pigment pastes (Factor 2; Flagstaff, USA).

MicroRNAs in heart failure: new targets in disease management.

Heart failure is the leading cause of mortality in Western society and represents the fastest growing subclass of cardiovascular diseases. An increasing body of evidence indicates an important role for microRNAs (miRNAs) in the pathogenesis and progression of heart failure. miRNAs are small noncoding RNAs that regulate expression of target genes by sequence-specific binding to the 3' untranslated region of messenger RNA, which results in degradation or translational repression.

Epac2 mediates cardiac β1-adrenergic-dependent sarcoplasmic reticulum Ca2+ leak and arrhythmia.

Background: β-Adrenergic receptor (β-AR) activation can provoke cardiac arrhythmias mediated by cAMP-dependent alterations of Ca(2+) signaling. However, cAMP can activate both protein kinase A and an exchange protein directly activated by cAMP (Epac), but their functional interaction is unclear. In heart, selective Epac activation can induce potentially arrhythmogenic sarcoplasmic reticulum (SR) Ca(2+) release that involves Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) effects on the ryanodine receptor (RyR).

Current state of craniofacial prosthetic rehabilitation.

Purpose: This study aimed to review the current state of the techniques and materials used to rehabilitate maxillofacial defects.

Materials And Methods: The MEDLINE and EMBASE databases were searched for articles pertinent to maxillofacial prostheses published from January 1990 to July 2011. The main clinical stages were the subject of analysis.

Microbial biofilms on facial prostheses.

The composition of microbial biofilms on silicone rubber facial prostheses was investigated and compared with the microbial flora on healthy and prosthesis-covered skin. Scanning electron microscopy showed the presence of mixed bacterial and yeast biofilms on and deterioration of the surface of the prostheses. Microbial culturing confirmed the presence of yeasts and bacteria.

Role of RyR2 phosphorylation at S2814 during heart failure progression.

Rationale: Increased activity of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is thought to promote heart failure (HF) progression. However, the importance of CaMKII phosphorylation of ryanodine receptors (RyR2) in HF development and associated diastolic sarcoplasmic reticulum Ca(2+) leak is unclear.

Objective: Determine the role of CaMKII phosphorylation of RyR2 in patients and mice with nonischemic and ischemic forms of HF.

Disrupted junctional membrane complexes and hyperactive ryanodine receptors after acute junctophilin knockdown in mice.

Background: Excitation-contraction coupling in striated muscle requires proper communication of plasmalemmal voltage-activated Ca2+ channels and Ca2+ release channels on sarcoplasmic reticulum within junctional membrane complexes. Although previous studies revealed a loss of junctional membrane complexes and embryonic lethality in germ-line junctophilin-2 (JPH2) knockout mice, it has remained unclear whether JPH2 plays an essential role in junctional membrane complex formation and the Ca(2+)-induced Ca(2+) release process in the heart. Our recent work demonstrated loss-of-function mutations in JPH2 in patients with hypertrophic cardiomyopathy.

Junctophilin-2 expression silencing causes cardiocyte hypertrophy and abnormal intracellular calcium-handling.

Background: Junctophilin-2 (JPH2), a protein expressed in the junctional membrane complex, is necessary for proper intracellular calcium (Ca(2+)) signaling in cardiac myocytes. Downregulation of JPH2 expression in a model of cardiac hypertrophy was recently associated with defective coupling between plasmalemmal L-type Ca(2+) channels and sarcoplasmic reticular ryanodine receptors. However, it remains unclear whether JPH2 expression is altered in patients with hypertrophic cardiomyopathy (HCM).

Ryanodine receptor phosphorylation by calcium/calmodulin-dependent protein kinase II promotes life-threatening ventricular arrhythmias in mice with heart failure.

Background: approximately half of patients with heart failure die suddenly as a result of ventricular arrhythmias. Although abnormal Ca(2+) release from the sarcoplasmic reticulum through ryanodine receptors (RyR2) has been linked to arrhythmogenesis, the molecular mechanisms triggering release of arrhythmogenic Ca(2+) remain unknown. We tested the hypothesis that increased RyR2 phosphorylation by Ca(2+)/calmodulin-dependent protein kinase II is both necessary and sufficient to promote lethal ventricular arrhythmias.

Orthodontic space closure versus prosthetic replacement of missing upper lateral incisors in patients with bilateral cleft lip and palate.

Objective: To compare dental aesthetics and function of orthodontic space closure versus prosthetic replacement of upper lateral incisors in patients with bilateral cleft lip and palate. The predominant mode of prosthetic replacement was resin-bonded bridges.

Patients And Methods: The retrospective study group consisted of 17 patients treated with orthodontic space closure (13 men, four women; median age, 27.

Malnutrition in patients treated for oral or oropharyngeal cancer--prevalence and relationship with oral symptoms: an explorative study.

Purpose: This study aimed to assess prevalence of malnutrition after treatment for oral/oropharyngeal cancer and to explore how oral symptoms relate to malnutrition after treatment.

Methods: In this cross-sectional study, malnutrition (weight loss ≥ 10% in 6 months or ≥ 5% in 1 month), oral symptoms (EORTC QLQ-H&N35 questionnaire and additional questions to assess chewing problems), dental status, trismus and dietary intake were assessed in 116 adult patients treated for oral/oropharyngeal cancer.

Results: Prevalence of malnutrition was 16% (95%CI: 10% to 23%).

Malnutrition and quality of life in patients treated for oral or oropharyngeal cancer.

Background: This study assessed whether malnourished patients score lower on quality of life after treatment for oral/oropharyngeal cancer.

Methods: Malnutrition (weight loss ≥ 10% in 6 months/ ≥ 5% in 1 month) and quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 questionnaire) were assessed cross-sectionally in patients treated for oral/oropharyngeal cancer. The interval after treatment varied from 1 day to 3 years.

Oral symptoms and functional outcome related to oral and oropharyngeal cancer.

Purpose: This study aimed to assess: (1) oral symptoms of patients treated for oral or oropharyngeal cancer; (2) how patients rank the burden of oral symptoms; (3) the impact of the tumor, the treatment, and oral symptoms on functional outcome.

Methods: Eighty-nine patients treated for oral or oropharyngeal cancer were asked about their oral symptoms related to mouth opening, dental status, oral sensory function, tongue mobility, salivary function, and pain. They were asked to rank these oral symptoms according to the degree of burden experienced.

Genetic inhibition of PKA phosphorylation of RyR2 prevents dystrophic cardiomyopathy.

Aberrant intracellular Ca(2+) regulation is believed to contribute to the development of cardiomyopathy in Duchenne muscular dystrophy. Here, we tested whether inhibition of protein kinase A (PKA) phosphorylation of ryanodine receptor type 2 (RyR2) prevents dystrophic cardiomyopathy by reducing SR Ca(2+) leak in the mdx mouse model of Duchenne muscular dystrophy. mdx mice were crossed with RyR2-S2808A mice, in which PKA phosphorylation site S2808 on RyR2 is inactivated by alanine substitution.

Transverse aortic constriction in mice.

Transverse aortic constriction (TAC) in the mouse is a commonly used experimental model for pressure overload-induced cardiac hypertrophy and heart failure. TAC initially leads to compensated hypertrophy of the heart, which often is associated with a temporary enhancement of cardiac contractility. Over time, however, the response to the chronic hemodynamic overload becomes maladaptive, resulting in cardiac dilatation and heart failure.

Accelerated development of pressure overload-induced cardiac hypertrophy and dysfunction in an RyR2-R176Q knockin mouse model.

In response to chronic hypertension, the heart compensates by hypertrophic growth, which frequently progresses to heart failure. Although intracellular calcium (Ca(2+)) has a central role in hypertrophic signaling pathways, the Ca(2+) source for activating these pathways remains elusive. We hypothesized that pathological sarcoplasmic reticulum Ca(2+) leak through defective cardiac intracellular Ca(2+) release channels/ryanodine receptors (RyR2) accelerates heart failure development by stimulating Ca(2+)-dependent hypertrophic signaling.