Clinico-Pathological Characteristics of Triple Negative and Non Triple Negative High Grade Breast Carcinomas with and Without Basal Marker (CK5/6 and EGFR) Expression at a Rural Tertiary Hospital in India

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Abnormally proximal aortic origin of the brachiocephalic artery: Surgical implications

Abnormal proximal aortic origin of the brachiocephalic artery is a very rare condition. It can occur in isolation or associated with complex congenital heart disease affecting the right ventricular outflow tract. Its recognition carries relevant surgical implications for the safe conduct of cardiopulmonary bypass and for any surgical procedures that directly involve the proximal ascending aorta and its branches

Improvement in the dissolution rate and tableting properties of cefuroxime axetil by melt-granulated dispersion and surface adsorption

AbstractA combination of melt-granulated dispersion and surface adsorption techniques was used to enhance the dissolution and tableting properties of cefuroxime axetil (CA). Gelucire 50/13 was used as the melt-dispersion carrier and Sylysia 350 was used to adsorb the melt dispersion. Solubility studies showed an 8-fold increase in solubility at a ratio of 1:1.5 for CA:Gelucire 50/13. The minimum quantity of Sylysia 350 required to achieve the desired flowability and compressibility was 0.5 parts of Sylysia 350 per unit of Gelucire 50/13. Phase solubility studies showed negative ΔGtr0 values for Gelucire 50/13 at various concentrations (2–10%, w/v), indicating the spontaneous nature of solubilization. FT-IR and DSC spectra exhibited drug-excipient compatibility. Molecular modeling by a computational method employing energy minimization revealed entrapment of CA in Gelucire 50/13. The total potential energy of CA (70.562kcal/mol) was reduced to 33.578kcal/mol after solid dispersion with Gelucire 50/13. P-XRD studies indicated that the presence of Sylysia 350 is less likely to promote the reversion of the amorphous CA to a crystalline state. In vitro dissolution studies demonstrated an improved dissolution rate, and drug release at 15min (Q15min) exhibited a 15-fold improvement. The rapidly dissolving CA tablets showed improved dissolution with improved tableting properties

Myoglobin modulates the Hippo pathway to promote cardiomyocyte differentiation

Summary: The endogenous mechanisms that propagate cardiomyocyte differentiation and prevent de-differentiation remain unclear. While the expression of the heme protein myoglobin increases by over 50% during cardiomyocyte differentiation, a role for myoglobin in regulating cardiomyocyte differentiation has not been tested. Here, we show that deletion of myoglobin in cardiomyocyte models decreases the gene expression of differentiation markers and stimulates cellular proliferation, consistent with cardiomyocyte de-differentiation. Mechanistically, the heme prosthetic group of myoglobin catalyzes the oxidation of the Hippo pathway kinase LATS1, resulting in phosphorylation and inactivation of yes-associated protein (YAP). In vivo, myoglobin-deficient zebrafish hearts show YAP dephosphorylation and accelerated cardiac regeneration after apical injury. Similarly, myoglobin knockdown in neonatal murine hearts shows increased YAP dephosphorylation and cardiomyocyte cycling. These data demonstrate a novel role for myoglobin as an endogenous driver of cardiomyocyte differentiation and highlight myoglobin as a potential target to enhance cardiac development and improve cardiac repair and regeneration

Improvement in Dissolution Rate of Cefuroxime Axetil by using Poloxamer 188 and Neusilin US2

A combination of fusion and surface adsorption techniques was used to enhance the dissolution rate of cefuroxime axetil. Solid dispersions of cefuroxime axetil were prepared by two methods, namely fusion method using poloxamer 188 alone and combination of poloxamer 188 and Neusilin US2 by fusion and surface adsorption method. Solid dispersions were evaluated for solubility, phase solubility, flowability, compressibility, Kawakita analysis, Fourier transform-infrared spectra, differential scanning calorimetry, powder X-ray diffraction study, in vitro drug release, and stability study. Solubility studies showed 12- and 14-fold increase in solubility for solid dispersions by fusion method, and fusion and surface adsorption method, respectively. Phase solubility studies showed negative values for poloxamer 188 at various concentrations (0, 0.25, 0.5, 0.75 and 1%) indicating spontaneous nature of solubilisation. Fourier transform-infrared spectra and differential scanning calorimetry spectra showed that drug and excipients are compatible with each other. Powder X-ray diffraction study studies indicated that presence of Neusilin US2 is less likely to promote the reversion of the amorphous cefuroxime axetil to crystalline state. In vitro dissolution studies, T50% and mean dissolution time have shown better dissolution rate for solid dispersions by fusion and surface adsorption method. Cefuroxime axetil release at 15 min (Q15) and DE15 exhibited 23- and 20-fold improvement in dissolution rate. The optimized solid dispersion formulation was stable for 6 months of stability study as per ICH guidelines. The stability was ascertained from drug content, in vitro dissolution, Fourier transform-infrared spectra and differential scanning calorimetry study. Hence, this combined approach of fusion and surface adsorption can be used successfully to improve the dissolution rate of poorly soluble biopharmaceutical classification system class II drug cefuroxime axetil

Reduced acetylation of TFAM promotes bioenergetic dysfunction in the failing heart

Summary: General control of amino acid synthesis 5-like 1 (GCN5L1) was previously identified as a key regulator of protein lysine acetylation in mitochondria. Subsequent studies demonstrated that GCN5L1 regulates the acetylation status and activity of mitochondrial fuel substrate metabolism enzymes. However, the role of GCN5L1 in response to chronic hemodynamic stress is largely unknown. Here, we show that cardiomyocyte-specific GCN5L1 knockout mice (cGCN5L1 KO) display exacerbated heart failure progression following transaortic constriction (TAC). Mitochondrial DNA and protein levels were decreased in cGCN5L1 KO hearts after TAC, and isolated neonatal cardiomyocytes with reduced GCN5L1 expression had lower bioenergetic output in response to hypertrophic stress. Loss of GCN5L1 expression led to a decrease in the acetylation status of mitochondrial transcription factor A (TFAM) after TAC in vivo, which was linked to a reduction in mtDNA levels in vitro. Together, these data suggest that GCN5L1 may protect from hemodynamic stress by maintaining mitochondrial bioenergetic output