Evidence of gray matter reduction and dysfunction in chromosome 22q11.2 deletion syndrome

Chromosome 22q11.2 deletion syndrome (22q11DS) is associated with cognitive deficits and morphometric brain abnormalities in childhood and a markedly elevated risk of schizophrenia in adolescence/early adulthood. Determining the relationship between neurocognition and neuroimaging findings would yield crucial information about childhood neurodevelopment and provide a basis for the study of the trajectory that occurs on the pathway to psychosis. We compared morphometric brain findings between non-psychotic children with 22q11DS (n = 22) and healthy controls (n = 16), and examined the association between neurocognitive functioning and morphometric brain findings. Volumetric regional gray matter differences between the 22q11DS and control subjects were measured, and correlations of the regional gray matter volumes and neurocognition were performed. Children with 22q11DS demonstrated reductions in gray matter in several brain regions, chiefly the frontal cortices, the cingulate gyrus and the cerebellum. The volumetric reductions in these salient areas were associated with poor performance in sustained attention, executive function and verbal memory; however, the relation of brain volume with cognitive performance did not differ between the patient and control groups. Thus, children with 22q11DS demonstrate gray matter reductions in multiple brain regions that are thought to be relevant to schizophrenia. The correlation of these volumetric reductions with poor neurocognition indicates that these brain regions may mediate higher neurocognitive functions implicated in schizophrenia.     

Bioavailability Enhancement of Poorly Water Soluble and Weakly Acidic New Chemical Entity with 2-Hydroxy Propyl-β-Cyclodextrin: Selection of Meglumine,a Polyhydroxy Base,as a Novel Ternary Component

The purpose of the present study was to investigate the influence of a polyhydroxy base, N-acetyl glucamine (also know as Meglumine), as a ternary component on the complexation of DRF-4367, a poorly water-soluble and weakly acidic anti-inflammatory molecule, with 2-hydroxypropyl-β-cyclodextrin (HPβCD). The molecular inclusion of DRF-4367 with HPβCD alone and in combination with ternary component was aimed at improvement in solubility and, subsequently, dissolution rate-limited oral bioavailability. The solid complexes of DRF-4367 and HPβCD with or without meglumine (binary and ternary systems, respectively) were prepared as coevaporated product in different stoichiometric ratios and compared against physical mixture. The formation of inclusion complexes was confirmed by using classical instrumental techniques. Phase solubility studies suggested that meglumine was responsible for solubility improvement via multiple factors rather than just providing a favorable pH. Mechanisms and factors governing solubility enhancement were investigated by using phase solubility and thermodynamic parameters. The complexation of DRF-4367 with HPβCD is thermodynamically favored because the Gibbs free energies of transfer of the drug to the cyclodextrin cavity are negative. The solubilization efficiency and stability were further improved while retaining the favorable Gibbs free energies of transfer with the addition of meglumine. Inclusion ternary complex of DRF-4367 with HPβCD and meglumine showed significant improvement in dissolution compared with uncomplexed drug and binary system. Moreover, the phenomena of reprecipitation observed with binary system during dissolution could be avoided with meglumine as an enabling ternary component. This improved physicochemical behavior of ternary complex with the novel inclusion of a polyhydroxy base translated into an enhanced oral bioavailability of DRF-4367 compared with either uncomplexed drug or nanosuspension.     

Development, characterization, and toxicity evaluation of amphotericin B-loaded gelatin nanoparticles

Our aim in the present investigation was to develop a nanoparticulate carrier of amphotericin B (AmB) for controlled delivery as well as reduced toxicity. Nanoparticles of different gelatins (GNPs) (type A or B) were prepared by two-step desolvation method and optimized for temperature, pH, amount of cross-linker, and theoretical drug loading. AmB-loaded GNPs were characterized for size, polydispersity index (PI), shape, morphology, surface charge, drug release, and hemolysis. The developed GNPs (GNP(A300)) were found to be of nanometric size (213 +/- 10 nm), having low PI (0.092 +/- 0.015) and good entrapment efficiency (49.0 +/- 2.9%). All GNPs showed biphasic release characterized by an initial burst followed by controlled release. The in vivo hematological toxicity results suggest nonsignificant reduction (P > .05) in hemoglobin concentration and hematocrit. Nephrotoxicity results showed that there was a nonsignificant (P > .05) increase in blood urea nitrogen and serum creatinine levels. The results confirm that developed GNPs could optimize AmB delivery in terms of cost and safety, and type A gelatin with bloom number 300 was found suitable for such preparation.     

The transversely split gracilis twin free flaps

The gracilis muscle is a Class II muscle that is often used in free tissue transfer. The muscle has multiple secondary pedicles, of which the first one is the most consistent in terms of position and calibre. Each pedicle can support a segment of the muscle thus yielding multiple small flaps from a single, long muscle. Although it has often been split longitudinally along the fascicles of its nerve for functional transfer, it has rarely been split transversely to yield multiple muscle flaps that can be used to cover multiple wounds in one patient without subjecting him/her to the morbidity of multiple donor areas.     

Gall bladder carcinoma presenting as multiple cavitary pulmonary metastases — a rare event

Carcinoma of the gall bladder is the commonest malignancy of the biliary tract. It is either detected incidentally during routine imaging or presents as lump in right hypochondrium or with signs of jaundice. Rarely, it may present with multiple cavitary metastatic lesions in the pulmonary parenchyma. The authors, report such a rare case of gall bladder carcinoma that presented with extensive, bilateral pulmonary cavitary metastases with no evidence of any nodal disease and where the diagnosis was delayed due to this rare presentation.     

Single Miniplate Fixation for Mandibular Symphysis and Parasymphysis Fracture as a Viable Alternative to Conventional Plating Based on Champy’s Principles: A Prospective Comparative Clinical Study

To compare long term and short term outcomes of fixing mandibular symphysis and parasymphysis fractures with single mini plate and conventional fixation using two mini plates. Study design: in this prospective clinical comparative study, 30 patients with fracture in study region were randomly divided into two groups. Group A patients received single 2.5 mm titanium miniplate and Group B patients received two 2 mm titanium miniplates as per Champy's lines of osteosynthesis. Patients were followed up at intervals of 1, 12 and 24 weeks. Parameters assessed were: duration of surgery, fracture stabilization, paresthesia, occlusion and wound dehiscence. Statistically significant difference was observed in mean duration of surgery and wound dehiscence (P < 0.05). No significant difference was observed with respect to other parameters. Single 2.5 mm miniplate for mandibular symphysis and parasymphysis fractures is a time saving and cost effective technique with post-operative outcomes similar to conventional 2 plate fixation.     

Multi-angle ratiometric approach to measure chemical exchange in amide proton transfer imaging

Amide proton transfer imaging, a specific form of chemical exchange saturation transfer imaging, has previously been applied to studies of acute ischemic acidosis, stroke, and cancer. However, interpreting the resulting contrast is complicated by its dependence on the exchange rate between amides and water, the amide concentration, amide and water relaxation, and macromolecular magnetization transfer. Hence, conventional chemical exchange saturation transfer contrast is not specific to changes such as reductions in pH due to tissue acidosis. In this article, a multi-angle ratiometric approach based on several pulsed-chemical exchange saturation transfer scans at different irradiation flip angles is proposed to specifically reflect exchange rates only. This separation of exchange effects in pulsed-chemical exchange saturation transfer experiments is based on isolating rotation vs. saturation contributions, and such methods form a new subclass of chemical exchange rotation transfer (CERT) experiments. Simulations and measurements of creatine/agar phantoms indicate that a newly proposed imaging metric isolates the effects of exchange rate changes, independent of other sample parameters.     

Functional reconstruction of complex tendo Achilles defect by free latissimus dorsi muscle flap

Managing the complex tendo Achilles defect involves reconstructing the Achilles tendon as well as providing soft tissue cover to the heel area. The advent of microsurgery has revolutionised the reconstruction of this difficult defect providing a number of options to the reconstructive surgeon. We present a case of complex tendo Achilles defect reconstructed by the latissimus dorsi free flap.KEY WORDS: Complex defect, reconstruction, tendo-Achille     

Benign Fibrous Histiocytoma: A Rare Case Report and Literature Review

Fibrous histiocytoma is a benign soft tissue tumour that may present as a fibrous mass anywhere in the human body. The involvement of the oral cavity is extremely rare and very few cases have been reported in literature till date. We here report a case of benign fibrous histiocytoma localized in the oral cavity. The clinical and histological features of the lesion are discussed precisely in the light of a literature review of this pathology in oral cavity.