Bone Health Status in Indian Overweight/Obese Children

This cross-sectional study, to assess bone health in Indian overweight, obese children in comparison with healthy controls was conducted in 245 (126 girls) children and adolescents aged 6–17 y in Pune, India. It was found that total body bone mineral content, bone area and bone mineral density adjusted for Tanner stage and weight were significantly lower in obese children as compared to overweight children, which in turn, was significantly lower than normal weight children (p?<?0.05). Thus, overweight and obesity is negatively related to bone health in children and adolescents. Interventions need to be planned to increase peak bone mass accrual in overweight and obese children to reduce future risk of fracture and osteoporosis.     

Spectrum of cytopathologic features of epithelioid sarcoma in a series of 7 uncommon cases with immunohistochemical results,including loss of INI1/SMARCB1 in two test cases

Diagnosis of an epithelioid sarcoma (ES) is challenging on fine needle aspiration cytology (FNAC) smears. There are few documented series describing cytopathologic features and immunostaining results of ESs. The present study describes cytopathologic features of seven cases of ES. All seven tumors occurred in males within age‐range of 22–61 years; in sites, such as forearm (n = 3), hand (n = 2), thigh (n = 1), and inguinal region (n = 1). FNAC was performed for metastatic lesions (n = 5), recurrent lesions (n = 4), as well as for a primary diagnosis (n = 1). FNAC smears in most cases were moderate to hypercellular, composed of polygonal cells(seven cases) and spindle cells(three cases), arranged in loosely cohesive groups, non‐overlapping clusters, and scattered singly, containing moderate to abundant cytoplasm, defined cell borders, vesicular nuclei, and discernible nucleoli. Variable cytopathologic features identified in certain cases were “rhabdoid‐like” intracytoplasmic inclusions (n = 5), giant cells (n = 3), and interspersed scanty, metachromatic stroma (n = 4). Histopathologic examination revealed two cases of conventional‐type ES, three of proximal/large cell‐type ES, and two cases of mixed‐type ES, displaying features of conventional and proximal subtypes. By immunohistochemistry (IHC), tumor cells were positive for cytokeratin (CK)(4/5), epithelial membrane antigen (EMA) (6/6), panCK (1/1), vimentin (3/3), and CD34 (7/7). Tumor cells were completely negative for INI1/SMARCB1 (0/2) and CD31 (0/5). In our settings, FNAC was mostly performed in recurrent and/or metastatic cases of ES, and rarely for a primary diagnosis of ES. Important cytopathologic features of ESs include loosely cohesive, non‐overlapping clusters of polygonal cells with variable “rhabdoid‐like” and spindle cells. Optimal diagnostic IHC markers in such cases include CK, EMA, AE1AE3, CD34, and INI1/SMARCB1. Clinical correlation is imperative in all cases. Diagn. Cytopathol. 2016;44:636–642. © 2016 Wiley Periodicals, Inc.     

Micellar formulations of Crizotinib and Dasatinib in the management of glioblastoma multiforme

Glioblastoma multiforme (GBM) defies the currently practiced management of radiotherapy, chemotherapy and surgery and hence, it is associated with a high fatality rate with a median survival of 14.6 months. In our previous work investigating different tyrosine kinase inhibitors (TKIs), we established that a combination of Crizotinib and Dasatinib exerted the most potent effect on different GBM cell lines. In this work, to improve targeted therapy at the site of the tumour and avoid systemic toxicity, we exploited the enhanced permeability and retention effect by designing micellar formulations of these two TKIs. Crizotinib and Dasatinib were successfully encapsulated in poly(styrene-co-maleic acid) (SMA) micelles which were then evaluated for their physicochemical characteristics, anti-proliferative effect, mode of cell death, efficacy in spheroid models, effect on cell signalling, antiangiogenic potential and in vivo anticancer activity. Our results showed that this combination had induced a potent anti-proliferative effect in four GBM cell lines grown as a monolayer and as a spheroid. The combination was also efficacious in in vitro models of angiogenesis and vascular mimicry. In vivo data showed the enhanced activity of the micellar TKIs compared to free drugs. In conclusion, we proved that micellar formulations of Crizotinib and Dasatinib carry promising in vitro and in vivo efficacy that warrant further investigation.     

Gut-disc axis: A cause of intervertebral disc degeneration and low back pain?

Purpose

Low back pain (LBP), a widely prevalent and costly disease around the world, is mainly caused by intervertebral disc (IVD) degeneration (IDD). Although numerous factors may trigger this degenerative process, microbiome dysbiosis has recently been implicated as one of the likely causes. However, the exact relationship between the microbiome and IDD is not well understood. This review summarizes the potential mechanisms and discusses microbiome dysbiosis’s possible influence on IDD and LBP.

Methods

Prospective literature review.

Results

Alterations in microbiome composition and host responses to the microbiota causing pathological bone development and involution, led to the concept of gut-bone marrow axis and gut-bone axis. Moreover, the concept of the gut-disc axis was also proposed to explain the microbiome’s role in IDD and LBP. According to the existing evidence, the microbiome could be an important factor for inducing and aggravating IDD through changing or regulating the outside and inside microenvironment of the IVD. Three potential mechanisms by which the gut microbiota can induce IVD and cause LBP are: (1) translocation of the bacteria across the gut epithelial barrier and into the IVD, (2) regulation of the mucosal and systemic immune system, and (3) regulation of nutrient absorption and metabolites formation at the gut epithelium and its diffusion into the IVD. Furthermore, to investigate whether IVD is initiated by pathogenic bacteria and establish the correlation between the presence of certain microbial groups with the disease in question, microbiome diversity analysis based on16S rRNA data can be used to characterise stool/blood microbiota from IVD patients.

Conclusion

Future studies on microbiome, fungi and viruses in IDD is necessary to revolutionize our thinking about their possible role in the development of IVD diseases. Furthermore, we believe that inflammation inhibition and interruption of amplification of cascade reaction in IVD by targeting the gut and IVD microbiome is worthwhile for the treatment of IDD and LBP.

Level of Evidence I

Diagnostic: individual cross-sectional studies with the consistently applied reference standard and blinding.

     

Synthesis and biological evaluation of pyrrole-2-carboxamide derivatives: oroidin analogues

The reaction of pyrrole or dibromopyrrole-2-trichloroacetone with various amines results in the series of novel pyrrole-2-carboxamide bearing aromatic heterocycle or aryl or alkyl groups. Synthesized molecules were evaluated for their in vitro antibacterial activities. Most of the compounds exhibited potent activity against both Gram-positive and negative pathogens.     

Silymarin ameliorates memory deficits and neuropathological changes in mouse model of high-fat-diet-induced experimental dementia

A huge body evidences suggest that obesity is the single great risk factor for the development of dementia. Recently, silymarin, a flavonoid, clinically in use as a hepatoprotectant, has been reported to prevent amyloid beta-induced memory impairment by reducing oxidative stress and inflammation in mice brain. However, its potential in high-fat-diet (HFD)-induced dementia has not yet been investigated. Therefore, the present study is designed to explore the role of silymarin in HFD-induced experimental dementia in mice. Morris water maze test was employed to assess learning and memory. Various biochemical estimations including brain acetylcholinerstarse activity (AchE), thiobarbituric acid-reactive species (TBARS) level, reduced glutathione level (GSH), nirate/nitrite, and myeloperoxidase (MPO) activity were measured. Serum cholesterol level was also determined. HFD significantly impaired the cognitive abilities, along with increasing brain AchE, TBARS, MPO, nitrate/nitrite, and serum cholesterol levels. Marked reduction of brain GSH levels was observed. On the contrary, silymarin significantly reversed HFD-induced cognitive deficits and the biochemical changes. The present study indicates strong potential of silymarin in HFD-induced experimental dementia.     

Investigation of dual-bend serpentine/spiral waveguides coupled to a microchannel system for competent,evanescent-wave-absorption-based,on-chip,biological-/chemical-sensing applications

U or C-shaped waveguides, coupled to analyte microchannels, have been shown to be very responsive to evanescent-wave-absorption-based sensing. However, due to only having a single C-bend length, for analyte interaction in earlier devices, there was always an opportunity to advance their evanescent-absorbance sensitivity, by including multiple C-bend structures (interfaced with the analyte microchannel system) in the device design. To achieve this objective, two different types of waveguide probes (having a different orientation of two C-bends), i.e. S-bend and spiral-bend, were theoretically analyzed and further, experimentally tested for their comparative sensitivity to evanescent wave absorption, in this pioneering study. A novel single-step fabrication procedure (using an SU-8 photoresist), was executed to fabricate these waveguide structures interfaced (both at their inner and outer bend surfaces) with a microchannel system, along with fiber-to-waveguide coupler structures. Experimentally, the sensitivity of the S-bend waveguides was found to be ∼25% higher compared to that of spiral waveguides of similar dimensions, which corroborated the results from numerical modeling. Compared to our earlier embedded C-bend waveguides, the overall evanescent-wave-absorption-based detection sensitivity of the embedded spiral and S-bend waveguides were found to be improved by ∼7.5 times and ∼9 times respectively. Finally, these devices were found to be ideally suited for more sensitive biological-, as well as, chemical-sensing applications, provided a suitable surface alteration process is performed to these waveguide probes. Further, the proposed device has a possible capability for: facile continuous (real-time) analysis, a fixed sample volume interaction, and control over the evaporation of analyte samples introduced in to the device.

The reported device is a versatile sensing-platform, with high sensitivity, for any chemical/biological-sensing applications, if suitable surface adaptation is first performed to the microchannel-system-embedded duel-bend waveguide-probe.