Spatiotemporal variation of physicochemical parameters in Aripal and Watalara streams of Kashmir Himalaya using multivariate statistical techniques.

The sustainability and management of ecological services provided by the stream ecosystem requires regular assessment of its physicochemical parameters. The anthropogenic pressure in terms of deforestation, urbanization, use of fertilizers and pesticides, land use, and climate change are the major factors responsible for the deterioration of water quality. In the present study, we monitored 14 physicochemical parameters at three different sites from June 2018 to May 2020 in both the Aripal and Watalara streams of Kashmir Himalaya. The data was analyzed through one-way ANOVA, Duncan's multiple range test, two-tailed Pearson's correlation, and multivariate statistical techniques like principal component analysis (PCA) and cluster analysis (CA). A significant variation (p < 0.05) was observed in all the physicochemical parameters on both spatial (except AT, WT, and DO) and seasonal (except TP and NO3-N) scales. Pearson's correlation revealed a significantly strong positive correlation for AT, WT, EC, Alk, TDS, TP, NO3-N, and NO2-N. PCA's first four principal components were considered significant as they represented the highest cumulative percent variances of 76.49% and 74.72% in Aripal and Watalara streams, respectively. The loading and scatter plots revealed that AT, WT, TP, NO3-N, and NO2-N influence water quality. The strong loading of these parameters indicates the anthropogenic activities in the streams. CA depicted two well-defined clusters, wherein cluster-I is comprised of sites A3 and W3 which indicate poor water quality. In contrast, cluster-II is comprised of sites A1, W1, A2, and W2 which indicate good water quality. The present study could be helpful to ecologists, limnologists, policymakers, and other stakeholders in developing long-term management programs and conservation strategies for water resources.

Assessment of physicochemical parameters of Vishav stream: an important tributary of river Jhelum, Kashmir Himalaya, India.

The deteriorating conditions in stream ecosystems are detrimental for society as far as its health, and development is concerned if the underlying factors continue to operate without regular monitoring. In order to maintain the health of a stream ecosystem, assessment of spatiotemporal changes in its physicochemical attributes and identification of all factors that could alter its hydrological regime is an essential component for managing it. The current 2-year study (October-2017 to September-2019) assessed the physicochemical regime of lower stretches of the Vishav stream, a major left-bank tributary of river Jhelum on a spatiotemporal basis. The physicochemical data was analyzed through linear regression, ANOVA (followed by Duncan's test), multivariate statistical analysis, viz., principal component analysis (PCA) and cluster analysis (CA). Linear regression pointed out the nature and magnitude of the relationship between different physicochemical variables (p < 0.05). PCA showed that WT, pH, EC, NO3-N, TDS, TH, and DO are the major factors reflecting the water quality of the Vishav stream. The range in water quality parameters of the Vishav stream was found conducive for the inhabitant fishes. Two well-defined clusters were obtained, wherein Cluster-I comprising of Site-III (a downstream pollution prone site) and Cluster-II comprising of Site-II and Site-I (mid- and upstream site respectively) are less prone to human interferences. The present study could serve as baseline information to manage and conserve this precious element of the aquatic ecosphere in terms of better water quality for humans and its inhabitant faunal elements especially fish which play a significant role in the economy of that region.

Three-Dimensional Printing of Curcumin-Loaded Biodegradable and Flexible Scaffold for Intracranial Therapy of Glioblastoma Multiforme.

A novel drug delivery system preventing Glioblastoma multiforme (GBM) recurrence after resection surgery is imperatively required to overcome the mechanical limitation of the current local drug delivery system and to offer personalised treatment options for GBM patients. In this study, 3D printed biodegradable flexible porous scaffolds were developed via Fused Deposition Modelling (FDM) three-dimensional (3D) printing technology for the local delivery of curcumin. The flexible porous scaffolds were 3D printed with various geometries containing 1, 3, 5, and 7% (w/w) of curcumin, respectively, using curcumin-loaded polycaprolactone (PCL) filaments. The scaffolds were characterised by a series of characterisation studies and in vitro studies were also performed including drug release study, scaffold degradation study, and cytotoxicity study. The curcumin-loaded PCL scaffolds displayed versatile spatiotemporal characteristics. The polymeric scaffolds obtained great mechanical flexibility with a low tensile modulus of less than 2 MPa, and 4 to 7-fold ultimate tensile strain, which can avoid the mechanical mismatch problem of commercially available GLIADEL wafer with a further improvement in surgical margin coverage. In vitro release profiles have demonstrated the sustained release patterns of curcumin with adjustable release amounts and durations up to 77 h. MTT study has demonstrated the great cytotoxic effect of curcumin-loaded scaffolds against the U87 human GBM cell line. Therefore, 3D printed curcumin-loaded scaffold has great promise to provide better GBM treatment options with its mechanical flexibility and customisability to match individual needs, preventing post-surgery GBM recurrence and eventually prolonging the life expectancy of GBM patients.

Pharmaceutical Development of 5-Fluorouracil-Eluting Stents for the Potential Treatment of Gastrointestinal Cancers and Related Obstructions.

BACKGROUND: Drug-eluting gastrointestinal (GI) stents are emerging as promising platforms for the treatment of GI cancers and provide the combined advantages of mechanical support to prevent lumen occlusion and as a reservoir for localized drug delivery to tumors. Therefore, in this work we present a detailed quality assurance study of 5-fluorouracil (5FU) drug-eluting stents (DESs) as potential candidates for the treatment of obstructive GI cancers. METHODS: The 5FU DESs were fabricated via a simple two-step sequential dip-coating process of commercial GI self-expanding nitinol stents with a 5FU-loaded polyurethane basecoat and a drug-free protective poly(ethylene-co-vinyl acetate) topcoat. The drug loading, content uniformity and drug stability were determined using a validated high-performance liquid chromatography (HPLC) method, which is also recommended in the United States Pharmacopeia. In vitro drug release studies were performed in phosphate buffered saline to determine the drug releasing properties of the two 5FU-loaded stents. Gas chromatography (GC) and HPLC were employed to determine total residual tetrahydrofuran and N,N-dimethylformamide in the stents remaining from the manufacturing process. Sterilization of the stents was performed using gamma radiation and stability testing was carried out for 3 months. RESULTS: The drug loading analysis revealed excellent uniformity in the distribution of 5FU between and within individual stents. Determination of drug stability in the biorelevant release media confirmed that 5FU remains stable over 100 d. In vitro drug release studies from the stents revealed sustained release of 5FU across two different time scales (161 and 30 d), and mathematical modeling of drug release profiles revealed a diffusion-controlled mechanism for the sustained 5FU release. GC and HPLC analysis revealed that the daily residual solvent leached from the stents was below the United States (US) Food and Drug Administration (FDA) guidelines, and therefore, unlikely to cause localized/systemic toxicities. Sterilization of the stents with gamma radiation and accelerated stability tests over a period of 3 months revealed no significant effect on the stability or in vitro release of 5FU. CONCLUSION: Our results demonstrate that the 5FU DESs meet relevant quality standards and display favourable drug release characteristics for the potential treatment of GI cancers and related obstructions.

Drug-Loaded, Polyurethane Coated Nitinol Stents for the Controlled Release of Docetaxel for the Treatment of Oesophageal Cancer.

For several decades, self-expanding metal stents (SEMSs) have shown significant clinical success in the palliation of obstructive metastatic oesophageal cancer. However, these conventional oesophageal stents can suffer from stent blockage caused by malignant tumour cell growth. To overcome this challenge, there is growing interest in drug-releasing stents that, in addition to palliation, provide a sustained and localized release of anticancer drugs to minimise tumour growth. Therefore, in this study we prepared and evaluated an oesophageal stent-based drug delivery platform to provide the sustained release of docetaxel (DTX) for the treatment of oesophageal cancer-related obstructions. The DTX-loaded oesophageal stents were fabricated via dip-coating of bare nitinol stents with DTX-polyurethane (PU) solutions to provide PU coated stents with DTX loadings of 1.92 and 2.79% w/w. Mechanical testing of the DTX-PU coated stents revealed that an increase in the drug loading resulted in a reduction in the ultimate tensile strength, toughness and Young's modulus. In vitro release studies showed a sustained release of DTX, with ~80-90% released over a period of 33 days. While the DTX-loaded stents exhibited good stability to gamma radiation sterilisation, UV sterilisation or accelerated storage at elevated temperatures (40 °C) resulted in significant DTX degradation. Cell proliferation, apoptosis and Western blotting assays revealed that the DTX released from the stents had comparable anticancer activity to pure DTX against oesophageal cancer cells (KYSE-30). This research demonstrates that the dip-coating technique can be considered as a promising approach for the fabrication of drug-eluting stents (DESs) for oesophageal cancer treatment.

Development and In Vitro Evaluation of 5-Fluorouracil-Eluting Stents for the Treatment of Colorectal Cancer and Cancer-Related Obstruction.

Self-expanding metal stents (SEMSs) are currently the gold standard for the localised management of malignant gastrointestinal (GI) stenosis and/or obstructions. Despite encouraging clinical success, in-stent restenosis caused by tumour growth is a significant challenge. Incorporating chemotherapeutic drugs into GI stents is an emerging strategy to provide localised and sustained release of drugs to intestinal malignant tissues to prevent tumour growth. Therefore, the aim of this work was to develop and evaluate a local GI stent-based delivery system that provides a controlled release of 5-fluorouracil (5FU) over a course of several weeks to months, for the treatment of colorectal cancer and cancer-related stenosis/obstructions. The 5FU-loaded GI stents were fabricated via sequential dip-coating of commercial GI stents with a drug-loaded polyurethane (PU) basecoat and a drug-free poly(ethylene-co-vinyl acetate) (PEVA) topcoat. For comparison, two types of commercial stents were investigated, including bare and silicone (Si) membrane-covered stents. The physicochemical properties of the 5FU-loaded stents were evaluated using photoacoustic Fourier-transform infrared (PA-FTIR) spectroscopy, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and thermal analysis. In vitro release studies in biological medium revealed that the 5FU-loaded stents provided a sustained release of drug over the period studied (18 d), and cell viability, cell cycle distribution and apoptosis assays showed that the released 5FU had comparable anticancer activity against human colon cancer cells (HCT-116) to pure 5FU. This study demonstrates that dip-coating is a facile and reliable approach for fabricating drug-eluting stents (DESs) that are promising candidates for the treatment of GI obstructions and/or restenosis.

Three-dimensional printed 5-fluorouracil eluting polyurethane stents for the treatment of oesophageal cancers.

Oesophageal stents have been widely used to prevent occlusion or stenosis in the treatment of oesophageal cancers. However, stent restenosis caused by tumour ingrowth occurs frequently after stent placement. Incorporating anti-cancer drugs into endoluminal stents is a promising strategy to provide a sustained release of drugs to oesophageal malignant tissues while prolonging the retention of the stent and relieving dysphagia. Recognizing the potential of 3D printing to produce personalised stents with patient specific geometries, we herein report the development of a drug-loaded 3D printed stent for the sustained local delivery of 5-fluorouracil (5-FU) to treat oesophageal cancer. The 3D printed drug-eluting stents (DESs) were fabricated via fused deposition modelling using 5-FU-loaded polyurethane filament. Determination of the 5-FU in the filament and stent (>97%) confirmed that minimal degradation of the drug occurred during the thermal extrusion and 3D printing processes. The physicochemical properties of the stents were investigated using photoacoustic Fourier-transform infrared (PA-FTIR) spectrophotometry, X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA) and mechanical testing. In vitro release studies revealed that the drug-loaded stents provided a sustained release of 5-FU over a period of 110 days and allowed the constant diffusion of 5-FU when in contact with oesophageal mucosa. Furthermore, the 3D printed stents exhibited good stability following sterilization with gamma or UV irradiation, and during accelerated storage. This study demonstrates that 3D printing is a powerful tool for manufacturing DESs which could easily be customized to provide personalized, patient specific geometries and drug doses.

Influence of Polymer Composition on the Controlled Release of Docetaxel: A Comparison of Non-Degradable Polymer Films for Oesophageal Drug-Eluting Stents.

Following the huge clinical success of drug-eluting vascular stents, there is a significant interest in the development of drug-eluting stents for other applications, such as the treatment of gastrointestinal (GI) cancers. Central to this process is understanding how particular drugs are released from stent coatings, which to a large extent is controlled by drug-polymer interactions. Therefore, in this study we investigated the release of docetaxel (DTX) from a selection of non-degradable polymer films. DTX-polymer films were prepared at various loadings (1, 5 and 10% w/w) using three commercially available polymers including poly(dimethylsiloxane) (PSi), poly (ethylene-co-vinyl acetate) (PEVA) and Chronosil polyurethane (PU). The formulations were characterised using different techniques such as photoacoustic Fourier-transform infrared (PA-FTIR) spectrophotometry, X-ray diffraction (XRD) and differential scanning calorimetry (DSC). The effect of DTX on the mechanical properties of the films, in-vitro release, and degradation tests were also assessed. For all polymers and DTX loadings, the drug was found to disperse homogenously without crystallisation within the polymer matrix. While no specific interactions were observed between DTX and PSi or PEVA, hydrogen-bonding appeared to be present between DTX and PU, which resulted in a concentration-dependent decrease in the Young's moduli of the films due to disruption of inter-polymeric molecular interactions. In addition, the DTX-PU interactions were found to modulate drug release, providing near-linear release over 30 days, which was accompanied by a significant reduction in degradation products. The results indicate that DTX-loaded PU films are excellent candidates for drug-eluting stents for the treatment of oesophageal cancer.

Study of Angiopoietin-2 and vascular endothelial growth factor as markers of diabetic nephropathy onset in Egyptians diabetic patients with non-albuminuric state.

BACKGROUND: Vascular endothelial growth factor (VEGF) and angiopoietin (Ang-2) systems have a central role in vasculogenesis and neoangiogenesis during glomerular development. disruption, their levels are associated with alterations in the glomerular filtration barrier and proteinuria as in diabetic nephropathy. Aim of this study to assess the validity of blood Ang-2 and VEGF as biomarkers for early detection of diabetic nephropathy as well as to study the relation between them and inflammation in diabetic nephropathy patients. SUBJECTS AND METHODS: Cross-sectional study included 180 diabetic nephropathy patients. Patients were classified to non-albuminuric, microalbuminuria and macroalbuminuria patients. Patients with macroalbuminuria complicated to renal impairment and ESRD on top of diabetic nephropathy. Ang-2 and VEGF were measured beside urinary albumin creatinine ratio (UACR). RESULTS: Significant increase of Ang-2 and VEGF levels among patients with normoalbuminuric state compared to control but there is no significant difference of UACR between both groups. Ang-2 and VEGF concentrations were significantly higher in patients with microalbuminuria and macroalbuminuria compared to healthy. Ang-2 and VEGF levels increase with the progression of albuminuria. There were significant positive correlation between CRP and Ang-2 in addition to VEGF. Significant negative correlation between eGFR, Ang-2 and VEGF. CONCLUSION: VEGF and Ang-2 were significantly elevated in diabetic nephropathy patients without albuminuria, their levels steadily increase with the progress of albuminuria, So can use them as markers for diagnosis of diabetic nephropathy onset and progression specially in patients without an increase in albumin excretion.

Drug-eluting non-vascular stents for localised drug targeting in obstructive gastrointestinal cancers.

Stents are currently the primary choice for the treatment of both vascular and non-vascular occlusions and/or stenosis. Despite the proven history of clinical safety and efficacy, the benefit of traditional vascular or non-vascular stenting is often limited by in-stent restenosis, resulting in failure of existing stent or reintervention by use of another stent. Coronary drug-eluting stents (DESs) significantly reduce restenosis of vascular stents and have revolutionised the percutaneous coronary intervention (PCI) treatment in coronary stenting patients. Following the similar concept of coronary DESs, non-vascular DESs are being investigated to reduce non-vascular restenosis caused by tumour growth, enhance stenting functions, and increase their effectiveness in the treatment of obstructive gastrointestinal (GI) cancers. This article summarises and updates the outcomes of preclinical and clinical studies on non-vascular DESs for localised management of malignant GI obstructions with emphasis on fabrication techniques and regulatory requirements relevant to development and marketing approval.

Trending Weight Loss Patterns in Obese and Super Obese Adolescents: Does Laparoscopic Sleeve Gastrectomy Provide Equivalent Outcomes in both Groups?

BACKGROUND: Many factors, including preoperative weight, may determine final weight loss after bariatric surgery; however, their proportional contribution is unclear. To such end, we evaluated weight loss patterns among obese adolescents. METHODS: We evaluated 57 adolescents who underwent laparoscopic sleeve gastrectomy from 2011 to 2017. Data collection included demographics, anthropometrics, and comorbidities and was done over a 3-year follow-up period. Statistical analysis was performed using Student's t test and repeated measures ANOVA. RESULTS: In the morbidly obese (MO) group, 82% were female, while 52% were male in the super obese (SMO) group (P < 0.0059). While 13/34 patients in the obese group achieved > 60% percent excess body weight loss (%EBWL), only 3/23 super obese patients achieved > 60% EBWL (P = 0.0695). %EBWL at 1-year follow-up significantly differed between the obese and super obese groups, 61.7 ± 14.6% and 47.7 ± 14.9% respectively (P = 0.035). The average BMI in the obese group was 29.8 at 1 year and 41.3 in the super obese group. There was a significant difference in the rate of excess weight loss (%EBWL/month) between the two groups (P < 0.01). There was good comorbidity resolution (about 70%) in both groups after surgery. CONCLUSION: Comorbidity resolution after sleeve gastrectomy is excellent in the adolescent population irrespective of initial BMI. Consideration should be given to earlier bariatric intervention in SMO adolescents to facilitate return to near normal BMI. Focus on education of referral sources, such as community pediatricians and family practitioners to facilitate early bariatric evaluation should be considered. Weight loss in postsurgical SMO patients should be carefully monitored and adjunctive interventions should be considered.