Comparative pharmacokinetics of voriconazole administered orally as either crushed or whole tablets

Voriconazole is a triazole antifungal agent used to treat serious, invasive fungal infections including aspergillosis and candidemia. Limitations with existing formulations of voriconazole including restricted utility in patients with renal dysfunction (intravenous preparation) and the unavailability of an oral suspension in some countries make the administration of crushed tablets desirable in many clinical scenarios. However, concerns that this approach may alter the systemic absorption of voriconazole exist. Therefore, an open-label, randomized, two-way crossover comparative pharmacokinetic (PK) study using healthy volunteers was performed to compare these methods of tablet administration. In a random sequence, subjects received voriconazole tablets either crushed or whole. The voriconazole dose was 400 mg every 12 h for 1 day orally followed by 200 mg every 12 h orally for 5.5 days. Study periods were separated by 7 days. PK parameters were determined by the noncompartmental method. An equivalence approach with no-effect boundaries of 80 to 125% was used to assess bioequivalence. Twenty healthy subjects (10 males; aged 20 to 43 years) were enrolled in and completed the study. The adjusted mean areas under the plasma concentration-time curve from 0 to tau, where tau equals 12 h, for the crushed and whole tablet groups were 9,793 and 11,164 ng . h/ml, respectively (ratio, 87.72; 90% confidence interval [CI], 80.97, 95.04). The ratio of the maximum concentration of drug in serum for the crushed tablet versus whole tablet arms was 94.94 (90% CI, 86.51, 104.22). The only difference noted between groups was a slightly faster time to maximum concentration of drug in serum when subjects received crushed tablets, 0.5 h versus 1.5 h (90% CI, -0.75, -0.25). Treatment-related adverse events occurred in 12 subjects receiving whole tablets and 9 subjects receiving crushed tablets; all were mild. The administration of crushed voriconazole tablets is bioequivalent to whole-tablet administration.     

Oral health status and treatment needs among the Juang tribe‐a particularly vulnerable tribal group residing in Northern Odisha,India: A cross‐sectional study

The study was aimed to assess the oral health status and treatment needs of Juang tribe residing in Bansapal taluk of Northern Odisha. A cross‐sectional survey was carried out among 1,412 Juangs using a cluster random sampling procedure. Bansapal taluk is subdivided into six Gram Panchayat's (GP) with each GP considered as a cluster. From each of the six GP's, equal number of villages was chosen randomly using lottery method in order to get uniform representation. A total of 16 villages were chosen using this method. From each selected village, every alternate household on each side of the street was included and all the people in that household were surveyed through a door‐to‐door survey. Data were collected using the WHO Oral Health Assessment Form, 1997. All the examinations were carried out by a single examiner assisted by a trained recording assistant who was sitting close enough to the examiner so that instructions and codes could be easily heard. The periodontal health status as recorded by Community Periodontal Index indicated that majority of the subjects (75.6%) had calculus. Assessment of loss of attachment showed that majority of the subjects (64.5%) had an attachment loss of 0–3 mm. Caries experience in primary dentition was 34.2% and in permanent dentition was 83.4%. The study population was characterised by high prevalence of periodontal disease, dental caries and high treatment needs. The results from this study could be used as a baseline information for health authorities and dental professionals for planning strategies for oral health promotion, prevention and treatment among the Juang population.     

Prediction of psychosis using neural oscillations and machine learning in neuroleptic-naïve at-risk patients

Objectives: This study investigates whether abnormal neural oscillations, which have been shown to precede the onset of frank psychosis, could be used towards the individualised prediction of psychosis in clinical high-risk patients. Methods: We assessed the individualised prediction of psychosis by detecting specific patterns of beta and gamma oscillations using machine-learning algorithms. Prediction models were trained and tested on 53 neuroleptic-naïve patients with a clinical high-risk for psychosis. Of these, 18 later transitioned to psychosis. All patients were followed up for at least 3 years. For an honest estimation of the generalisation capacity, the predictive performance of the models was assessed in unseen test cases using repeated nested cross-validation. Results: Transition to psychosis could be predicted from current-source density (CSD; area under the curve [AUC]?=?0.77), but not from lagged phase synchronicity data (LPS; AUC?=?0.56). Combining both modalities did not improve the predictive accuracy (AUC?=?0.78). The left superior temporal gyrus, the left inferior parietal lobule and the precuneus most strongly contributed to the prediction of psychosis. Conclusions: Our results suggest that CSD measurements extracted from clinical resting state EEG can help to improve the prediction of psychosis on a single-subject level.     

Pro-brain natriuretic peptide (ProBNP) levels in North Indian children with Kawasaki disease

The diagnosis of Kawasaki disease (KD), a common pediatric vasculitis, is based solely on clinical criteria. There is a need for a robust laboratory marker that can help differentiate KD from other acute, febrile, childhood illnesses and also to predict cardiac involvement. We conducted a cross-sectional study of 25 consecutive patients admitted with diagnosis of KD from January 2013 to April 2014 and compared them with age- and sex-matched febrile controls. We studied the serum pro-brain natriuretic peptide (ProBNP) [ProBNP and N-terminal pro-B-type natriuretic peptide (NT-ProBNP) levels], a marker of myocardial dysfunction, in children with KD in acute and convalescent phases of disease. These levels were also estimated in febrile controls for comparison. The ProBNP (ProBNP and NT-ProBNP) levels were much higher in the acute phase of the KD patients compared to levels in the convalescent phase of KD (p = 0.000014). Similarly, the levels in the acute phase were higher when compared to the age- and sex-matched febrile controls (p = 0.000126). The receiver operating curve (ROC) analysis for the ProBNP levels in the acute phase of KD yielded an area under the curve of 0.954 ± 0.034 (p < 0.000, 95 % CI 0.886–1.0). Based on ROC analysis, a cutoff of 1025 pg/mL for ProBNP levels in the acute phase of KD had 88 % sensitivity and 96 % specificity for the diagnosis of KD. A lower cut-off of 514 pg/mL yielded a 100 % sensitivity and 80 % specificity for the diagnosis of KD. The ProBNP levels were higher in those with coronary artery abnormalities (CAA) compared to those without CAA in both acute (p = 0.013) and convalescent (p = 0.045) phases. ProBNP levels may be used as a surrogate marker for the differentiation of KD from other febrile, infectious illnesses and may also predict the involvement of coronary arteries.     

GnRH-LH secreting cells axis in the pituitary of the teleost Clarias batrachus responds to neuropeptide Y treatment: an immunocytochemical study

An attempt has been made to immunocytochemically visualize the effect of neuropeptide Y (NPY) on the GnRH fibers and luteinizing hormone (LH) secreting cells in the pituitary of the catfish, Clarias batrachus. Two hours following the intracranial administration of NPY at the dose of 20 ng/g body wt, a significant increase in the area occupied by the GnRH-like immunoreactive fibers, and population and size of the LH cells was observed. The treatment also resulted in considerable augmentation of immunoreactivity in the LH cells. Double immunolabeling revealed NPY fibers directly terminating on the LH cells. The results suggest that NPY may (a) stimulate some GnRH containing hypophysiotropic neuronal group in the brain, (b) promote anterograde transport of GnRH to the pituitary gland, and (c) up-regulate the LH cells.     

Enantioselective Diels-Alder reactions catalyzed by hydrogen bonding

Like molecules of life (e.g., proteins and DNA), many pharmaceutical drugs are also asymmetric (chiral); they are not superimposable on their mirror images. One mirror image form (enantiomer) of a drug can have desirable activity, the other not. Consequently, the development of methods for the selective synthesis of one enantiomer is of great scientific and economic importance. We report here that a simple, commercially available chiral alcohol, alpha,alpha,alpha',alpha'-tetraaryl-1,3-dioxolane-4,5-dimethanol (TADDOL), catalyzes the all-carbon Diels-Alder reactions of aminosiloxydienes and substituted acroleins to afford the products in good yields and high enantioselectivities (up to 92% enantiomeric excess). It is remarkable that the reactions are promoted by hydrogen bonding, the ubiquitous "glue" that helps to keep water molecules together and holds up the 3D structures of proteins. Hydrogen bond catalysis is little used in chemical synthesis, wherein most reactions are promoted by complexes of Lewis acidic metal salts coordinated to chiral ligands. As it does for enzymes, hydrogen bonding not only organizes TADDOL into a well defined conformation, but, functioning as a Br?nsted acid catalyst, it also activates the dienophile toward reaction with the diene. The gross structure of the TADDOL has been found to have a profound influence on both the rate and the enantioselectivity of the cycloadditions. These structure-function effects are rationalized by evaluating the conformation adopted by the TADDOLs in the crystal state. It is suggested that pi,pi-stacking plays an central role in the overall catalytic cycle, in particular, the enantioselective step.