Influence of musical training on sensitivity to temporal fine structure

Objective: The objective of this study was to extend the findings that temporal fine structure encoding is altered in musicians by examining sensitivity to temporal fine structure (TFS) in an alternative (non-Western) musician model that is rarely adopted—Indian classical music. Design: The sensitivity to TFS was measured by the ability to discriminate two complex tones that differed in TFS but not in envelope repetition rate. Study sample: Sixteen South Indian classical (Carnatic) musicians and 28 non-musicians with normal hearing participated in this study. Results: Musicians have significantly lower relative frequency shift at threshold in the TFS task compared to non-musicians. A significant negative correlation was observed between years of musical experience and relative frequency shift at threshold in the TFS task. Test-retest repeatability of thresholds in the TFS tasks was similar for both musicians and non-musicians. Conclusions: The enhanced performance of the Carnatic-trained musicians suggests that the musician advantage for frequency and harmonicity discrimination is not restricted to training in Western classical music, on which much of the previous research on musical training has narrowly focused. The perceptual judgments obtained from non-musicians were as reliable as those of musicians.     

Drug safety evaluation of apremilast for treating psoriatic arthritis

Introduction: Apremilast is an orally available small molecule that targets PDE4. PDE4 modulates intracellular signaling and thereby can impact various proinflammatory and anti-inflammatory mediators. Apremilast has been approved by the USA FDA for the treatment of active psoriatic arthritis (PsA) and moderate-to-severe psoriasis (PsO). Although there are several therapies approved and used for the treatment of PsA, there is still an unmet need for additional effective and well-tolerated therapeutic options. In PsA clinical trials, apremilast has been shown to be efficacious and to have an acceptable safety profile.

Areas covered: This review article covers the mechanism of action of apremilast, its efficacy in clinical trials and a detailed focus on its safety profile, mainly from Phase III clinical trials.

Expert opinion: Based on the available literature, apremilast has proven to be an efficacious therapy for PsA and PsO. It may offer some advantage as compared to other therapeutic options given its favorable safety profile, including a lack of need for routine laboratory monitoring.     

Inhibition of Sphingosine Kinase Prevents Lipopolysaccharide-Induced Preterm Birth and Suppresses Proinflammatory Responses in a Murine Model

Premature delivery occurs in 12% of all births, and accounts for nearly half of long-term neurological morbidity, and 60% to 80% of perinatal mortality. Despite advances in obstetrics and neonatology, the rate of premature delivery has increased approximately 12% since 1990. The single most common cause of spontaneous preterm birth is infection. Several lines of evidence have demonstrated the role of endothelin-1 as both a constrictor of uterine myometrial smooth muscle and a proinflammatory mediator. Endothelin-1 activates the phospholipase C pathway, leading to activation of protein kinase C and, in turn, sphingosine kinase (SphK). The inhibition of SphK has been recently shown to control the proinflammatory response associated with sepsis. We show herein, for the first time, that SphK inhibition prevents inflammation-associated preterm birth in a murine model. Rescue of pups from premature abortion with an SphK inhibitor occurs by suppression of the proinflammatory cytokines tumor necrosis factor α, Il-1β, and Il-6 and attenuation of polymorphonuclear inflammatory cells into the placental labyrinth. Moreover, we postulate that inhibition of SphK leads to suppression of endothelin-converting enzyme-1 expression, indicating the presence of an endothelin-converting enzyme 1/endothelin 1–SphK positive feedback loop. This work introduces a novel approach for the control of infection-triggered preterm labor, a condition for which there is no effective treatment.Preterm birth (PTB), defined as any birth before 37 complete weeks of gestation, accounts for 11.1% of all deliveries worldwide, but next to congenital anomalies, accounts for most perinatal morbidity and mortality. The United States, with a rate of PTB of 11.7%, ranks among the 10 countries that have the highest rates of PTB.¹ The single most common cause of spontaneous PTB is infection.² Intrauterine bacteria interact with cell surface recognition molecules, such as Toll-like receptor-2 (Tlr2) and Tlr4,^3,4 leading to release of T helper cell 1 cytokines, such as Il-1β and tumor necrosis factor α (TNFα).^5–7 This inflammatory response culminates in the final steps of the parturition cascade, consisting of decreased prostaglandin metabolism, functional progesterone withdrawal, increased expression of proteases and contraction-associated proteins, and increased uterine contractile activity.^8–10We have previously shown that endothelin 1 (Edn1) is a key player in lipopolysaccharide (LPS)–induced PTB in a murine model.^11–14 Specifically, we have previously reported that endothelin-converting enzyme 1 (Ece1), the enzyme that synthesizes Edn1, colocalizes with its substrate in the placenta¹⁵ and that the Ece1 inhibitor, phosphoramidon, decreases rates of PTB in a murine model of infection-associated preterm labor.¹¹ Subsequently, we have also shown that Ece1 levels are increased in a mouse model of PTB and that rates of preterm delivery are decreased with endothelin-A receptor antagonists.^12–14 Finally, we have shown that virtually complete control of PTB is achieved in this model by silencing Ece1 mRNA.¹³ LPS, a Gram-negative bacterial wall component that activates Tlr4, stimulates the synthesis of Edn1 by monocytes and endothelial cells in vitro and in vivo.^16–18The activation of the phospholipase C pathway by Edn1 leads to activation of protein kinase C (PKC), which acts upstream of sphingosine kinase (SphK).^19,20 SphK, in turn, can activate Rho kinase, ultimately leading to contraction of myometrial tissue. SphK is the only enzyme that catalyzes the conversion of SphK to sphingosine-1-phosphate, which behaves in an autocrine manner in myometrial tissues and, in orchestration with SphK, PKC, and extracellular signal–regulated kinase, leads to the induction of cyclooxygenase-2 and to labor.²¹Two human SphK isozymes, SphK1 and SphK2, have been identified,²² both of which are inhibited by sphingosine kinase inhibitor II (SKI II), the compound used in the work reported herein. We show herein, for the first time, that inhibition of SphK and consequent suppression of the SphK1-dependent inflammatory pathway prevents infection-triggered PTB.     

Enhanced photoconductivity in CdS/betanin composite nanostructures

Development of novel materials for thin film solar cells are gaining significant attention due to their tunable wide bandgap and extensive application potential in flexible energy harvesters. CdS is a known window material for thin film solar cells. Tuning of the photoconductivity of CdS by doping, substitution and grain size tailoring is widely attempted by researchers. Inorganic core/shell structures like CdS/CdSe, CdS/ZnS etc. are other possible candidates with band gap tailorability. However, such attempts are rare in tailoring the photoconductivity by providing an organic shell over the inorganic core. Here the authors synthesised CdS/betanin core/shell structures using wet chemical routes. Spectroscopic studies show that the composite structure is core/shell like, with CdS as the core and betanin (a natural dye), as the outer shell with an average core particle size of 10 nm. The absorption spectra of the composite system show the signature of an additional band in the lower wavelength region and it is redshifted with increase in betanin percentage. The intermediate band observed in the energy of ∼1.75 eV, helps CdS to enhance the rate of absorption. Simultaneous absorbance of lower and higher energy photons from the solar radiation can increase the efficiency of CdS based solar cells. A huge enhancement in conductivity is observed in CdS/betanin composites on illumination with white light due to the transfer of photogenerated electrons from the conduction band of betanin dye to the conduction band of CdS.

The synthesis is described of inorganic/organic hybrid nanostructured composites based on CdS/betanin with enhanced photoconductivity due to the transfer of photogenerated electrons from the conduction band of betanin to the conduction band of CdS.     

Myocardial Infarction (MI) presenting as acute limb: an extremely rare presentation of MI

Acute embolic occlusion of the bilateral lower limbs from the left ventricular thrombus is an extremely rare medical condition that is not only limb threatening but also potentially life threatening. Several strategies are available but not even a single treatment modality is clearly the best. Here, we present an interesting case that presented with bilateral lower limb ischemia and was later found to have a big thrombus in the left ventricle as the source of the emboli.     

Prevalence of post-traumatic stress disorder in first-episode psychosis

Background: Psychosis can be considered one of the most severe stressors that an individual may face. Previous studies have suggested that the traumatic experience of psychotic symptoms and hospitalization may provoke a post-traumatic type reaction. Aim: The aim of this study was to establish the point prevalence of post-traumatic stress disorder (PTSD) among patients recovering from a first-episode of psychosis in Singapore, and to elucidate the factors associated with it. Methods: Patients from the Early Psychosis Intervention Programme in Singapore, who were recovering from their first psychotic episode, participated in this study. Diagnoses were made using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) – Text Revised Axis I Disorders. The Clinician-Administered PTSD Scale, an interviewer-rated semi-structured interview, was used to diagnose PTSD. Results: Sixty-one patients (30 males, 31 females) were recruited. Twelve (19.7%) patients were diagnosed with PTSD. Hospitalization for treatment, whether compulsory or otherwise, did not increase the rate of PTSD. The Chinese ethnic group had lower risk of developing PTSD (adjusted odds ratio 0.14, P = 0.018). Conclusions: There was a high prevalence of PTSD in patients recovering from their first psychotic episode. This study raises awareness among clinicians and hopes to promote early recognition and treatment of PTSD so as to potentially improve outcome.     

H NMR-based metabonomic investigation of tributyl phosphate exposure in rats

Tributyl phosphate (TBP) is a toxic organophosphorous compound widely used in many industrial applications, including significant usage in nuclear processing. The industrial application of this chemical is responsible for occupational exposure and environmental pollution. In this study, ¹H NMR-based metabonomics has been applied to investigate the metabolic response to TBP exposure. Male Sprague-Dawley rats were given a TBP-dose of 15 mg/kg body weight, followed by 24 h urine collection, as was previously demonstrated for finding most of the intermediates of TBP. High-resolution ¹H NMR spectroscopy of urine samples in conjunction with statistical pattern recognition and compound identification allowed for the metabolic changes associated with TBP treatment to be identified. Discerning NMR spectral regions corresponding to three TBP metabolites, dibutyl phosphate (DBP), N-acetyl-(S-3-hydroxybutyl)-l-cysteine and N-acetyl-(S-3-oxobutyl)-l-cysteine, were identified in TBP-treated rats. In addition, the ¹H NMR spectra revealed TBP-induced variations of endogenous urinary metabolites including benzoate, urea, and trigonelline along with metabolites involved in the Krebs cycle including citrate, cis-aconitate, trans-aconitate, 2-oxoglutarate, succinate, and fumarate. These findings indicate that TBP induces a disturbance to the Krebs cycle energy metabolism and provides a biomarker signature of TBP exposure. We show that three metabolites of TBP, dibutylphosphate, N-acetyl-(S-3-hydroxybutyl)-l-cysteine and N-acetyl-(S-3-oxobutyl)-l-cysteine, which are not present in the control groups, are the most important factors in separating the TBP and control groups (p < 0.0023), while the endogenous compounds 2-oxoglutarate, benzoate, fumarate, trigonelline, and cis-aconetate were also important (p < 0.01).     

Predictors of Complications of Endovascular Chronic Lead Extractions from Pacemakers and Defibrillators: A Single-Operator Experience

Background: National trends in chronic lead extractions from cardiac rhythm management (CRM) devices are on the rise.
Objective: The main objective of the study was to identify the predictors of complications of chronic lead extractions.
Methods: All patients who underwent endovascular chronic CRM lead extraction at our institution between 2002 and 2008 were included in this analysis. Demographic data as well as details of the extraction procedure and its complications within the ensuing 30 days were collected on all patients.
Results: Data of 212 consecutive patients (456 leads, age = 65 ± 17 years, men 75%, left ventricular ejection fraction = 36 ± 16%, coronary artery disease 80%, defibrillators 49%) were analyzed. There were a total of 26 (11.8%) complications in 25 patients including 9 (4.2%) major complications (death 1, hemothorax 4, pneumothorax 2, tamponade 1, stroke 1) and 17 (8.0%) minor complications. Independent predictors of any complications included a higher number of explanted right ventricular leads (HR = 3.51, P = 0.013). Explantation of ICD as opposed to a pacemaker device showed a strong trend toward significance (HR = 2.57, P = 0.053). An elevated white blood cell count also predicted major complications (HR = 1.52, P = 0.005).
Conclusion: Predictors of complications after lead extraction procedures include a higher number of extracted leads and the presence of defibrillator as opposed to pacemaker leads. A new paradigm of the removal of all leads not connected to a device may, therefore, reduce the risk of complications from lead extraction procedures and deserves to be tested prospectively.