Insulin Use in Type II Diabetic Patients: A Predictive of Mortality in Covid-19 Infection

INTRODUCTION: Starting December 2019, the world has been devastated by the rapid spread of coronavirus disease 2019 (Covid-19). Many risk factors have been associated with worse outcomes and death from Covid-19 pneumonia including having diabetes mellitus. To date, it is not clear if all group of diabetics share the same risk of complications with COVID-19 infection. This study aims to compare disease severity and mortality rate in insulin users versus non-insulin users. METHODS: In this retrospective case–control study conducted at the largest health care network in New York state, we included adult, diabetic patients admitted from March 2020 to October 2020 with Covid-19 pneumonia. We compared the baseline characteristics in addition to outcomes of diabetic patients on home insulin (cases) and non-insulin user diabetics (controls). In addition, to determine if home insulin use is associated with an increased mortality, we conducted a cox regression analysis. RESULTS: We included 696 patients in the study period with a median age of 57 years, interquartile range [IQR] 51–62, and median body mass index 29.9 (IQR: 26–34.7). The majority (476 [68%]) were males. We identified 227 cases (33%) and 469 controls (67%). More cases than controls were hypertensive (74% vs 67%, p = 0.03), on ACE/ARB (50% vs 42%, p = 0.05), and had a hemoglobin A1c > 8.1 (71% vs 44%, p < 0.001). More cases had AKI (52% vs 38%, p < 0.001), however no significant differences were found in intubation rates (26% vs 24%, p = 0.54), detection of pulmonary embolism (4% vs 6%, p = 0.19) or death rate (15% vs 11%, p = 0.22) comparing cases and controls. In a multivariate analysis, we found that home insulin use was independently associated with increased risk of death: Hazard ratio: 1.92, 95% confidence interval (1.13–3.23). CONCLUSION: We showed herein that diabetic patients on home insulin with COVID-19 pneumonia, have worse outcomes and increased mortality compared to diabetics on oral antihyperglycemic agents. Close monitoring of insulin-dependent type II diabetic patients is needed in the current pandemic

Evaluating Permeable Clay Brick Pavement for Pollutant Removal from Varying Strength Stormwaters in Arid Regions

Permeable pavement is a low impact development technology for stormwater (SW) runoff control and pollutant removal. The strength of SW depends on land use of the catchment, e.g., semi-urban vs. industrial. The performance (in terms of pollutants removal) of permeable clay bricks (PCB) has not been adequately assessed for SW of varying strengths. For using the permeable clay bricks as a pavement surface layer, the present research investigates its pollutant removal capacity through SW infiltration using a laboratory setup. SW samples of two different strengths, i.e., high polluted stormwater (HPSW) and less polluted stormwater (LPSW), were tested for a pavement system consisting of the clay brick layer on top of a coarse gravel support layer. The tests were performed at a rainfall intensity of 12.5 mm/h (for a 10-year return period in Buraidah, Qassim) to evaluate the suitability of PCB for the arid and semi-arid regions. The experiments revealed that PCB became fully saturated and achieved a steady-state outflow condition after 10 min of rainfall. Irrespective of contamination level, the pollutant removal efficiency was found to be similar for both HPSW and LPSW. High TSS (&gt;98%) and turbidity (&gt;99%) removals were achieved for both strengths, while BOD5 (78.4%) and COD (76.1%) removals were moderate. Poor to moderate nutrient removal, 30.5% and 39.1% for total nitrogen (TN) and 34.7% and 31.3% for total phosphorus (TP), respectively for HPSW and LPSW, indicates an adsorptive removal of nutrients in the system. Heavy metal removal efficiency ranged from 6.7% to 94%, with higher removals archived for Fe, Mn, Se, and Pb. The study provides insights into the role of PCB as a surface layer in the permeable pavement for pollutant removal. The study also establishes the guidelines for the optimal permeable pavement design to deal with SW of varying contamination levels. Permeable clay bricks showed the potential to be used as a sustainable LID technology for arid regions

Sawdust Recycling in the Development of Permeable Clay Paving Bricks: Optimizing Mixing Ratio and Particle Size

The permeable pavement system (PPS) has effectively contributed to stormwater management as a low-impact development (LID) technology. The suitability of clay bricks, consolidated with waste materials, for sustainable PPS applications in urban infrastructure needs further attention. In this study, several series of permeable clay paving bricks samples were prepared by mixing different ratios and particle sizes of sawdust (SD) with clay soil and firing at 900 °C. The raw soil and SD samples were characterized through sieve analysis, X-ray Fluorescence (XRF), X-ray diffraction (XRD), and Fourier-Transform Infrared Spectroscopy (FTIR). The bricks were tested for their compressive strength, bulk density, apparent porosity, water adsorption, permeability coefficient, and stormwater treatment efficiency. The clay soil comprised 17.5% clay/silt with appropriate amounts of SiO2 (50.47%), Al2O3 (19.14%), and fluxing agents (15.34%) and was suitable for brick manufacturing. XRD and FTIR analysis revealed that the soil predominantly comprises quartz, dolomite calcite, feldspar, kaolinite, illite, and chlorites. The SD samples were enriched with amorphous and crystalline cellulose. The compressive strength of the bricks decreased, while the permeability of the bricks increased with an increasing percentage of SD. An optimal percentage of 10% SD achieved a 21.2 MPa compressive strength and a 0.0556 m/s permeability coefficient, meeting the ASTM specifications for PPS. The optimal size of SD, between 0.5 and 1.0 mm, achieved the desired compressive strength of the bricks. The permeable bricks effectively removed the total suspended solids (TSS), turbidity, and BOD5 from the stormwater, which complies with the guidelines for wastewater reuse applications

Evaluating Permeable Clay Brick Pavement for Pollutant Removal from Varying Strength Stormwaters in Arid Regions

Permeable pavement is a low impact development technology for stormwater (SW) runoff control and pollutant removal. The strength of SW depends on land use of the catchment, e.g., semi-urban vs. industrial. The performance (in terms of pollutants removal) of permeable clay bricks (PCB) has not been adequately assessed for SW of varying strengths. For using the permeable clay bricks as a pavement surface layer, the present research investigates its pollutant removal capacity through SW infiltration using a laboratory setup. SW samples of two different strengths, i.e., high polluted stormwater (HPSW) and less polluted stormwater (LPSW), were tested for a pavement system consisting of the clay brick layer on top of a coarse gravel support layer. The tests were performed at a rainfall intensity of 12.5 mm/h (for a 10-year return period in Buraidah, Qassim) to evaluate the suitability of PCB for the arid and semi-arid regions. The experiments revealed that PCB became fully saturated and achieved a steady-state outflow condition after 10 min of rainfall. Irrespective of contamination level, the pollutant removal efficiency was found to be similar for both HPSW and LPSW. High TSS (>98%) and turbidity (>99%) removals were achieved for both strengths, while BOD5 (78.4%) and COD (76.1%) removals were moderate. Poor to moderate nutrient removal, 30.5% and 39.1% for total nitrogen (TN) and 34.7% and 31.3% for total phosphorus (TP), respectively for HPSW and LPSW, indicates an adsorptive removal of nutrients in the system. Heavy metal removal efficiency ranged from 6.7% to 94%, with higher removals archived for Fe, Mn, Se, and Pb. The study provides insights into the role of PCB as a surface layer in the permeable pavement for pollutant removal. The study also establishes the guidelines for the optimal permeable pavement design to deal with SW of varying contamination levels. Permeable clay bricks showed the potential to be used as a sustainable LID technology for arid regions

Apigenin Loaded Lipoid&ndash;PLGA&ndash;TPGS Nanoparticles for Colon Cancer Therapy: Characterization, Sustained Release, Cytotoxicity, and Apoptosis Pathways

Colon cancer (CC) is one of major causes of mortality and affects the socio-economic status world-wide. Therefore, developing a novel and efficient delivery system is needed for CC management. Thus, in the present study, lipid polymer hybrid nanoparticles of apigenin (LPHyNPs) was prepared and characterized on various parameters such as particle size (234.80 &plusmn; 12.28 nm), PDI (0.11 &plusmn; 0.04), zeta potential (&minus;5.15 &plusmn; 0.70 mV), EE (55.18 &plusmn; 3.61%), etc. Additionally, the DSC, XRD, and FT-IR analysis determined drug entrapment and affinity with the selected excipient, demonstrating a promising drug affinity with the lipid polymer. Morphological analysis via SEM and TEM exhibited spherical NPs with a dark color core, which indicated drug entrapment inside the core. In vitro release study showed significant (p &lt; 0.05) sustained release of AGN from LPHyNPs than AGN suspension. Further, the therapeutic efficacy in terms of apoptosis and cell cycle arrest of developed LPHyNPs against CC was estimated by performing flow cytometry and comparing its effectiveness with blank LPHyNPs and AGN suspension, which exhibited remarkable outcomes in favor of LPHyNPs. Moreover, the mechanism behind the anticancer attribute was further explored by estimating gene expression of various signaling molecules such as Bcl-2, BAX, NF-&kappa;B, and mTOR that were involved in carcinogenic pathways, which indicated significant (p &lt; 0.05) results for LPHyNPs. Moreover, to strengthen the anticancer potential of LPHyNPs against chemoresistance, the expression of JNK and MDR-1 genes was estimated. Outcomes showed that their expression level reduced appreciably when compared to blank LPHyNPs and AGN suspension. Hence, it can be concluded that developed LPHyNPs could be an efficient therapeutic system for managing CC

Development, characterization, and evaluation of α-mangostin-loaded polymeric nanoparticle gel for topical therapy in skin cancer

The aim of this study was to prepare and evaluate α-mangostin-loaded polymeric nanoparticle gel (α-MNG-PLGA) formulation to enhance α-mangostin delivery in an epidermal carcinoma. The poly (D, L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were developed using the emulsion–diffusion–evaporation technique with a 3-level 3-factor Box–Behnken design. The NPs were characterized and evaluated for particle size distribution, zeta potential (mV), drug release, and skin permeation. The formulated PLGA NPs were converted into a preformed carbopol gel base and were further evaluated for texture analysis, the cytotoxic effect of PLGA NPs against B16-F10 melanoma cells, and in vitro radical scavenging activity. The nanoscale particles were spherical, consistent, and average in size (168.06 ± 17.02 nm), with an entrapment efficiency (EE) of 84.26 ± 8.23% and a zeta potential of −25.3 ± 7.1 mV. Their drug release percentages in phosphate-buffered solution (PBS) at pH 7.4 and pH 6.5 were 87.07 ± 6.95% and 89.50 ± 9.50%, respectively. The release of α-MNG from NPs in vitro demonstrated that the biphasic release system, namely, immediate release in the initial phase, was accompanied by sustained drug release. The texture study of the developed α-MNG-PLGA NPs gel revealed its characteristics, including viscosity, hardness, consistency, and cohesiveness. The drug flux from α-MNG-PLGA NPs gel and α-MNG gel was 79.32 ± 7.91 and 16.88 ± 7.18 µg/cm2/h in 24 h, respectively. The confocal study showed that α-MNG-PLGA NPs penetrated up to 230.02 µm deep into the skin layer compared to 15.21 µm by dye solution. MTT assay and radical scavenging potential indicated that α-MNG-PLGA NPs gel had a significant cytotoxic effect and antioxidant effect compared to α-MNG gel (p < 0.05). Thus, using the developed α-MNG-PLGA in treating skin cancer could be a promising approach

Plumbagin-Loaded Glycerosome Gel as Topical Delivery System for Skin Cancer Therapy

Plumbagin (PLM) is a phytochemical which has shown cytotoxicity against of cancer cells both in vitro and in vivo. However, the clinical application of PLM has been hindered due to poor aqueous solubility and low bioavailability. The aim of the present study was to develop, optimize and evaluate PLM-loaded glycerosome (GM) gel and compare with conventional liposome (CL) for therapeutic efficacy against skin cancer. The GM formulations were optimized by employing design expert software by 3-level 3-factor design. The prepared GMs were characterized in vitro for vesicle size, size distribution, zeta potential, vesicle deformability, drug release, skin permeation, retention, texture, antioxidant and cytotoxicity activities. The optimized formulation showed a vesicle size of 119.20 ± 15.67 nm with a polydispersity index (PDI) of 0.145 ± 0.02, the zeta potential of −27 ± 5.12 mV and entrapment efficiency of 76.42 ± 9.98%. The optimized PLM-loaded GM formulation was transformed into a pre-formed gel which was prepared using Carbopol 934 polymer. The drug diffusion fluxes of CL gel and GM-loaded gel were 23.31 ± 6.0 and 79.43 ± 12.43 µg/cm2/h, respectively. The result of texture analysis revealed the adequate hardness, cohesiveness, consistency, and viscosity of the developed GM-loaded gel compared to CL gel. The confocal images showed that glycerosomal gel has deeper skin layer penetration as compared to the control solution. GM-loaded gel treated rat skin showed significantly (p &lt; 0.05) higher drug accumulation in the dermis, higher cytotoxicity and higher antioxidant activity as compared to CL gel and PLM suspension. Thus, findings revealed that novel GM-loaded gel could be potential carriers for therapeutic intervention in skin cancer