Cardioprotective stimuli mediate phosphoinositide 3-kinase and phosphoinositide dependent kinase 1 nuclear accumulation in cardiomyocytes

The phosphoinositide 3-kinase (PI3K)/phosphoinositide dependent kinase 1 (PDK1) signaling pathway exerts cardioprotective effects in the myocardium through activation of key proteins including Akt. Activated Akt accumulates in nuclei of cardiomyocytes suggesting that biologically relevant targets are located in that subcellular compartment. Nuclear Akt activity could be potentiated in both intensity and duration by the presence of a nuclear-associated PI3K/PDK1 signaling cascade as has been described in other non-myocyte cell types. PI3K/PDK1 distribution was determined in vitro and in vivo by immunostaining and nuclear extraction of cultured rat neonatal cardiomyocytes or transgenic mouse hearts. Results show that PI3K and PDK1 are present at a basal level in cardiomyocytes nuclei and that cardioprotective stimulation with atrial natriuretic peptide (ANP) increases their nuclear localization. In comparison, overexpression of nuclear-targeted Akt does not mediate increased translocation of either PI3K or PDK1 indicating that accumulation of Akt does not drive PI3K or PDK1 into the nuclear compartment. Furthermore, PI3K and phospho-Akt⁴⁷³ show parallel temporal accumulation in the nucleus following (MI) infarction challenge. These findings demonstrate the presence of a dynamically regulated nuclear-associated signaling cascade involving PI3K and PDK that presumably influences nuclear Akt activation.     

Fatigue Intervention by Nurses Evaluation – The FINE Trial. A randomised controlled trial of nurse led self-help treatment for patients in primary care with chronic fatigue syndrome: study protocol. [ISRCTN74156610]

Background

A major change has occurred in the last few years in the therapeutic approach to patients presenting with all forms of acute coronary syndromes. Whether or not these patients present initially to tertiary cardiac care centers, they are now routinely referred for early coronary angiography and increasingly undergo percutaneous revascularization. This practice is driven primarily by the angiographic image and technical feasibility. Concomitantly, there has been a decline in expectant or ischemia-guided medical management based on specific clinical presentation, response to initial treatment, and results of noninvasive stratification. This 'tertiarization' of acute coronary care has been fuelled by the increasing sophistication of the cardiac armamentarium, the peer-reviewed publication of clinical studies purporting to show the superiority of invasive cardiac interventions, and predominantly supporting (non-peer-reviewed) editorials, newsletters, and opinion pieces.

Discussion

This review presents another perspective, based on a critical reexamination of the evidence. The topics addressed are: reperfusion treatment of ST-elevation myocardial infarction; the indications for invasive intervention following thrombolysis; the role of invasive management in non-ST-elevation myocardial infarction and unstable angina; and cost-effectiveness and real world considerations. A few cases encountered in recent practice in community and tertiary hospitals are presented for illustrative purposes The numerous and far-reaching scientific, economic, and philosophical implications that are a consequence of this marked change in clinical practice as well as healthcare, decisional and conflict of interest issues are explored.

Summary

The weight of evidence does not support the contemporary unfocused broad use of invasive interventional procedures across the spectrum of acute coronary clinical presentations. Excessive and unselective recourse to these procedures has deleterious implications for the organization of cardiac health care and undesirable economic, scientific and intellectual consequences. It is suggested that there is need for a new equilibrium based on more refined clinical risk stratification in the treatment of patients who present with acute coronary syndromes.     

Integrated wilderness therapy for avoidant personality disorder

Patients with avoidant personality disorder (APD) are difficult to treat because of their extensive social, emotional and cognitive avoidance. Few studies have addressed outcome in APD and there is no therapy of choice. In this quasi-experimental study, we integrated wilderness therapy in an inpatient group program (integrated wilderness therapy, IWT), in order to enhance outcome for patients with APD. We compared outcome of the IWT group with a similar inpatient group program without wilderness therapy: the comparison condition (CC). The subjects in the IWT-group (n=16) with DSM-IV APD were treated in 11.5 weeks. The subjects in the comparison group (n=37) were selected from our database with the same diagnostic criteria. The participants were examined at pre-care, admission, discharge and 1-year follow-up. Both groups were significantly improved, but there were no significant differences between them. There were some non-significant trends for males to gain most benefit from IWT, whereas females were more improved by the CC. The results indicate that by integrating wilderness therapy we were able to treat more impaired patients at shorter time with almost the same outcome.     

Airway disorders and pulmonary function in snorers. A population-based study

The aim of our study was to determine the relationship between snoring, airway disorders and pulmonary function in the general population. We performed a stratified random sampling from the population (n = 92,364). Four hundred subjects agreed to participate and were invited to the clinic, where a detailed medical history, physical examination, spirometric test and maximal respiratory pressures measurements were carried out. Snoring was reported by 152 subjects (38%). Nasal obstruction and the presence of abnormal pharynx exploration were more frequent in subjects with snoring. Age, body mass index and neck circumference were significantly higher in the snorer group. In addition, we found that the non-snoring group had a significantly higher frequency of tonsillectomy during infancy and adolescence than the snorer group. We did not detect any significant difference in spirometric test values or in maximal respiratory pressure values between snorer group and non-snorer group. In conclusion, in the general population snoring is associated with nasal obstruction and abnormal pharynx exploration. Furthermore, snoring appears not to be associated with modifications in spirometric or in maximal respiratory pressure tests.     

Paclitaxel-loaded glyceryl palmitostearate nanoparticles: in vitro release and cytotoxic activity

Solid lipid nanoparticles (SLNs) of paclitaxel using glyceryl palmitostearate (GPS) as matrix were prepared by modified hot homogenization method. The SLNs were characterized for mean particle size, percent entrapment efficiency, and zeta potential, which were found to be 207 nm, 96.26%, and ?28.26 mV, respectively. Transmission electron microscopic studies revealed that the prepared SLNs were of spherical shape. Drug retarding efficiency of the lipid (GPS) was better in pH 7.4 compared with pH 3.5. The release profile showed tendency to follow Higuchi diffusion pattern in both the media. Chemosensitivity assay carried out using B16F10 cell lines showed that antiproliferative activity of paclitaxel was not hindered because of encapsulation.     

Aetiological agents in chronic suppurative otitis media in Sri Lanka

Background

Chronic suppurative otitis media (CSOM) is assumed to be a complication of acute otitis media (AOM), but the risk factors for CSOM are not clear. Objectives: 1. To study the aetiological organisms for CSOM. 2. To identify the effect of demographic factors on disease manifestation.

Method

This retrospective study included a case series of 234 patients who had been admitted to National Hospital of Sri Lanka (NHSL), with the complaint of ear discharge and from whom the specimens were sent for microscopy and culture at Department Of Microbiology, NHSL. The period of analysis was 1 year extending from 1 January 2009 to 31 December 2009.Consecutive patients who fulfilled the inclusion criteria were recruited to the retrospective analysis.

Results

Among 234 patients studied, 129 (55.1%) were male and 150 (64.1%) were under 40 yrs old. The mean age was 39.5 yrs (range 12 to 60 yrs, SD = 22.6). The mean duration of ear discharge was 1.2 yrs. (range 6 weeks to 20 yrs.) Pseudomonas species (29.5%) was the commonest microbial organism to cause ear discharge, followed by staphylococcus (20.5%) and coliform (16.7%) species. Among the fungal agents identified, candida was the most common. 23.1% of the cultures did not reveal any microbiological agent. Eighteen patients (8%) had a prior history of trauma to the affected ear and 51 patients (21.8%) were diagnosed with diabetes mellitus.

Conclusion

The commonest microbial agents implicated in CSOM was pseudomonas species followed by staphylococci and coliforms. Demographic variables such as gender or age did not seem to affect the disease manifestation significantly, though CSOM was less common among elderly and women.     

Existential dynamic therapy ("VITA") for treatment-resistant depression with Cluster C disorder: Matched comparison to treatment as usual

Abstract Existential suffering may contribute to treatment-resistant depression. The "VITA" treatment model was designed for such patients with long-standing depression accompanied by existential and/or religious concerns. This naturalistic effectiveness study compared the VITA model (n = 50) with a "treatment as usual" comparison group (TAU; n = 50) of patients with treatment-resistant depression and Cluster C comorbidity. The TAU patients were matched on several characteristics with the VITA patients. The VITA model included existential, dynamic, narrative and affect-focused components. The VITA group had significantly greater improvement on symptom distress and relational problems during treatment and from pre-treatment to 1-year follow-up. Patients in the VITA, at follow-up, were more likely to be employed and less likely be using psychotropic medications.