Management of comminuted fractures of the shaft of femur by interlocking nailing at a tertiary level hospital in India

Background: Fracture shaft of femur is one of the most common fractures encountered in orthopaedic practice. Fracture shaft of femur is major cause of morbidity and mortality in patients who sustain high energy trauma. This study looks at the epidemiology of patients presenting with femur fracture at a tertiary level hospital in Navi Mumbai.Methods: This prospective study was performed at a tertiary level hospital in Navi Mumbai from January 1, 2014 till July 31, 2015. All patients aged 18 years or above, who presented with comminuted femur fracture and were treated with interlocking nailing was included in the study. Various clinical and radiological parameters were collected during the course of treatment.Results: 50 patients were included in the study; 84% males. 88% aged 50 years or less. Road traffic accident was the most common mode of injury and 54% of patients had fracture in the middle one-third femur. 76% of the patients presented within 24 hours of injury. 52% of the patient’s demonstrated clinical union of the fracture in 12 to 14 weeks and majority showed radiological union in 16 to 18 weeks. Partial weight bearing was started in 36% patients in 10 weeks and full weight bearing in 42% patients in 16 weeks. Majority of the patients stayed in hospital for 10 to 14 days and the functional outcome as measured by Klemm and Borner criteria was excellent in 66% patients. Complications were seen only in 6 patients.Conclusions: In our experience, interlocking nailing had very low complication rate and excellent functional outcome in two thirds patients of comminuted femur fracture

Progressive cavitating leukoencephalopathy: Case report of a rare childhood onset neurodegenerative disease

The leukoencephalopathies with cystic changes form a distinct subtype of childhood onset neurodegenerativedisorders. This group has heterogeneous etiological differentials that primarily include mitochondrial disorders, someleukodystrophies and central nervous system infections. We report this case of a 17-month old girl who presented withseizures, episodic encephalopathy, elevated blood lactate level and lactate peak on magnetic resonance spectroscopy,a typical imaging picture noted on cranial magnetic resonance imaging and absence of deletions or duplications ofmitochondrial deoxyribonucleic acid. Progressive cavitating leukoencephalopathy (PCL) is a recently described entitywith only a few cases reported so far. We report the first case of PCL from India. Accurate diagnosis can be made, notonly, by the presence of typical clinicoradiological findings of PCL, but also by the awareness of, and, ruling out of,the various other differential diagnoses that are discussed in detail below

Resistance/response molecular signature for oral tongue squamous cell carcinoma

Worldwide, the incidence of oral tongue cancer is on the rise, adding to the existing burden due to prevailing low survival and high recurrence rates. This study uses high-throughput expression profiling to identify candidate markers of resistance/response in patients with oral tongue cancer. Analysis of primary and post-treatment samples (12 tumor and 8 normal) by the Affymetrix platform (HG U133 plus 2) identified 119 genes as differentially regulated in recurrent tumors. The study groups had distinct profiles, with induction of immune response and apoptotic pathways in the non-recurrent and metastatic/invasiveness pathways in the recurrent group. Validation was carried out in tissues by Quantitative Real-Time PCR (QPCR) (n = 30) and Immunohistochemistry (IHC) (n = 35) and in saliva by QPCR (n = 37). The markers, COL5A1, HBB, IGLA and CTSC individually and COL5A1 and HBB in combination had the best predictive power for treatment response in the patients. A subset of markers identified (COL5A1, ABCG1, MMP1, IL8, FN1) could be detected in the saliva of patients with oral cancers with their combined sensitivity and specificity being 0.65 and 0.87 respectively. The study thus emphasizes the extreme prognostic value of exploring markers of treatment resistance that are expressed in both tissue and saliva

Solving dielectric and plasmonic waveguide dispersion relations with a pocket calculator

We present a robust iterative technique for solving complex transcendental dispersion equations routinely encountered in integrated optics. Our method especially befits the multilayer dielectric and plasmonic waveguides forming the basis structures for a host of contemporary nanophotonic devices. The solution algorithm ports seamlessly from the real to the complex domain--i.e., no extra complexity results when dealing with leaky structures or those with material/metal loss. Unlike several existing numerical approaches, our algorithm exhibits markedly-reduced sensitivity to the initial guess and allows for straightforward implementation on a pocket calculator.Comment: 18 pages, 11 Figures, 5 Tables, added references, Submitted to Optics Expres

Nonresonant enhancement of spontaneous emission in metal-dielectric-metal plasmon waveguide structures

We theoretically investigate the spontaneous emission process of an optical, dipolar emitter in metal-dielectric-metal slab and slot waveguide structures. We find that both structures exhibit strong emission enhancements at nonresonant conditions, due to the tight confinement of modes between two metallic plates. The large enhancement of surface plasmon-polariton excitation enables dipole emission to be preferentially coupled into plasmon waveguide modes. These structures find applications in creating nanoscale local light sources or in generating guided single plasmons in integrated optical circuitsclose849

Excessive HDAC activation is critical for neurodegeneration in the rd1 mouse

Inherited retinal degenerations, collectively termed retinitis pigmentosa (RP), constitute one of the leading causes of blindness in the developed world. RP is at present untreatable and the underlying neurodegenerative mechanisms are unknown, even though the genetic causes are often established. Acetylation and deacetylation of histones, carried out by histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively, affects cellular division, differentiation, death and survival. We found acetylation of histones and probably other proteins to be dramatically reduced in degenerating photoreceptors in the rd1 human homologous mouse model for RP. Using a custom developed in situ HDAC activity assay, we show that overactivation of HDAC classes I/II temporally precedes photoreceptor degeneration. Moreover, pharmacological inhibition of HDACs I/II activity in rd1 organotypic retinal explants decreased activity of poly-ADP-ribose-polymerase and strongly reduced photoreceptor cell death. These findings highlight the importance of protein acetylation for photoreceptor cell death and survival and propose certain HDAC classes as novel targets for the pharmacological intervention in RP

Synergistic Antitumor Effects of Novel HDAC Inhibitors and Paclitaxel In Vitro and In Vivo

Preclinical studies support the therapeutic potential of histone deacetylases inhibitors (HDACi) in combination with taxanes. The efficacy of combination has been mainly ascribed to a cooperative effect on microtubule stabilization following tubulin acetylation. In the present study we investigated the effect of paclitaxel in combination with two novel HDACi, ST2782 or ST3595, able to induce p53 and tubulin hyperacetylation. A synergistic effect of the paclitaxel/ST2782 (or ST3595) combination was found in wild-type p53 ovarian carcinoma cells, but not in a p53 mutant subline, in spite of a marked tubulin acetylation. Such a synergistic interaction was confirmed in additional human solid tumor cell lines harboring wild-type p53 but not in those expressing mutant or null p53. In addition, a synergistic cytotoxic effect was found when ST2782 was combined with the depolymerising agent vinorelbine. In contrast to SAHA, which was substantially less effective in sensitizing cells to paclitaxel-induced apoptosis, ST2782 prevented up-regulation of p21WAF1/Cip1 by paclitaxel, which has a protective role in response to taxanes, and caused p53 down-regulation, acetylation and mitochondrial localization of acetylated p53. The synergistic antitumor effects of the paclitaxel/ST3595 combination were confirmed in two tumor xenograft models. Our results support the relevance of p53 modulation as a major determinant of the synergistic interaction observed between paclitaxel and novel HDACi and emphasize the therapeutic interest of this combination

Mechanisms of Hsp90 regulation

Heat shock protein 90 (Hsp90) is a molecular chaperone that is involved in the activation of disparate client proteins. This implicates Hsp90 in diverse biological processes that require a variety of co-ordinated regulatory mechanisms to control its activity. Perhaps the most important regulator is heat shock factor 1 (HSF1), which is primarily responsible for upregulating Hsp90 by binding heat shock elements (HSEs) within Hsp90 promoters. HSF1 is itself subject to a variety of regulatory processes and can directly respond to stress. HSF1 also interacts with a variety of transcriptional factors that help integrate biological signals, which in turn regulate Hsp90 appropriately. Because of the diverse clientele of Hsp90 a whole variety of co-chaperones also regulate its activity and some are directly responsible for delivery of client protein. Consequently, co-chaperones themselves, like Hsp90, are also subject to regulatory mechanisms such as post translational modification. This review, looks at the many different levels by which Hsp90 activity is ultimately regulated

Comparative analysis of novel and conventional Hsp90 inhibitors on HIF activity and angiogenic potential in clear cell renal cell carcinoma: implications for clinical evaluation

<p>Abstract</p> <p>Background</p> <p>Perturbing Hsp90 chaperone function targets hypoxia inducible factor (HIF) function in a von Hippel-Lindau (VHL) independent manner, and represents an approach to combat the contribution of HIF to cell renal carcinoma (CCRCC) progression. However, clinical trials with the prototypic Hsp90 inhibitor 17-AAG have been unsuccessful in halting the progression of advanced CCRCC.</p> <p>Methods</p> <p>Here we evaluated a novel next generation small molecule Hsp90 inhibitor, EC154, against HIF isoforms and HIF-driven molecular and functional endpoints. The effects of EC154 were compared to those of the prototypic Hsp90 inhibitor 17-AAG and the histone deacetylase (HDAC) inhibitor LBH589.</p> <p>Results</p> <p>The findings indicate that EC154 is a potent inhibitor of HIF, effective at doses 10-fold lower than 17-AAG. While EC154, 17-AAG and the histone deacetylase (HDAC) inhibitor LBH589 impaired HIF transcriptional activity, CCRCC cell motility, and angiogenesis; these effects did not correlate with their ability to diminish HIF protein expression. Further, our results illustrate the complexity of HIF targeting, in that although these agents suppressed HIF transcripts with differential dynamics, these effects were not predictive of drug efficacy in other relevant assays.</p> <p>Conclusions</p> <p>We provide evidence for EC154 targeting of HIF in CCRCC and for LBH589 acting as a suppressor of both HIF-1 and HIF-2 activity. We also demonstrate that 17-AAG and EC154, but not LBH589, can restore endothelial barrier function, highlighting a potentially new clinical application for Hsp90 inhibitors. Finally, given the discordance between HIF activity and protein expression, we conclude that HIF expression is not a reliable surrogate for HIF activity. Taken together, our findings emphasize the need to incorporate an integrated approach in evaluating Hsp90 inhibitors within the context of HIF suppression.</p