Using multi-label ensemble CNN classifiers to mitigate labelling inconsistencies in patch-level Gleason grading.

This paper presents a novel approach to enhance the accuracy of patch-level Gleason grading in prostate histopathology images, a critical task in the diagnosis and prognosis of prostate cancer. This study shows that the Gleason grading accuracy can be improved by addressing the prevalent issue of label inconsistencies in the SICAPv2 prostate dataset, which employs a majority voting scheme for patch-level labels. We propose a multi-label ensemble deep-learning classifier that effectively mitigates these inconsistencies and yields more accurate results than the state-of-the-art works. Specifically, our approach leverages the strengths of three different one-vs-all deep learning models in an ensemble to learn diverse features from the histopathology images to individually indicate the presence of one or more Gleason grades (G3, G4, and G5) in each patch. These deep learning models have been trained using transfer learning to fine-tune a variant of the ResNet18 CNN classifier chosen after an extensive ablation study. Experimental results demonstrate that our multi-label ensemble classifier significantly outperforms traditional single-label classifiers reported in the literature by at least 14% and 4% on accuracy and f1-score metrics respectively. These results underscore the potential of our proposed machine learning approach to improve the accuracy and consistency of prostate cancer grading.

Non-Diffractive Beams for State-of-the-Art Applications.

Non-diffractive beams, also known as diffraction-free beams, are a class of optical beams that maintain their intensity profile over a long distance without spreading out due to diffraction [...].

3D-printed polyether-ether ketone/carboxymethyl cellulose scaffolds coated with Zn-Mn doped mesoporous bioactive glass nanoparticles.

Patient-specific fabrication of scaffold/implant requires an engineering approach to manufacture the ideal scaffold. Herein, we design and 3D print scaffolds comprised of polyether-ether-ketone (PEEK) and sodium-carboxymethyl cellulose (Na-CMC). The fabricated scaffold was dip coated with Zn and Mn doped bioactive glass nanoparticles (Zn-Mn MBGNs). The synthesized ink exhibit suitable shear-thinning behavior for direct ink write (DIW) 3D printing. The scaffolds were crafted with precision, featuring 85% porosity, 0.3 mm layer height, and 1.5 mm/s printing speed at room temperature. Scanning electron microscopy images reveal a well-defined scaffold with an average pore size of 600 ± 30 µm. The energy dispersive X-ray spectroscopy analysis confirmed a well dispersed/uniform coating of Zn-Mn MBGNs on the PEEK/Na-CMC scaffold. Fourier transform infrared spectroscopy approved the presence of PEEK, CMC, and Zn-Mn MBGNs. The tensile test revealed a Young's modulus of 2.05 GPa. Antibacterial assays demonstrate inhibition zone against Staphylococcus aureus and Escherichia Coli strains. Chick Chorioallantoic Membrane assays also present significant angiogenesis potential, owing to the antigenic nature of Zn-Mn MBGNs. WST-8 cell viability assays depicted cell proliferation, with a 103% viability after 7 days of culture. This study suggests that the PEEK/Na-CMC scaffolds coated with Zn-Mn MBGNs are an excellent candidate for osteoporotic fracture treatment. Thus, the fabricated scaffold can offer multifaceted properties for enhanced patient outcomes in the bone tissue regeneration.

Germline Variants in Sporadic Pituitary Adenomas.

Context: Data on germline genetics of pituitary adenomas (PAs) using whole-exome sequencing (WES) are limited. Objective: This study investigated the germline genetic variants in patients with PAs using WES. Methods: We studied 134 consecutive functioning (80.6%) and nonfunctioning (19.4%) PAs in 61 female (45.5%) and 73 male patients (54.5%). Their median age was 34 years (range, 11-85 years) and 31 patients had microadenomas (23.0%) and 103 macroadenomas (77%). None of these patients had family history of PA or a known PA-associated syndrome. Peripheral blood DNA was isolated and whole-exome sequenced. We used American College of Medical Genetics and Genomics (ACMG) criteria and a number of in silico analysis tools to characterize genetic variant pathogenicity levels and focused on previously reported PA-associated genes. Results: We identified 35 variants of unknown significance (VUS) in 17 PA-associated genes occurring in 40 patients (29.8%). Although designated VUS by the strict ACGM criteria, they are predicted to be pathogenic by in silico analyses and their extremely low frequencies in 1000 genome, gnomAD, and the Saudi Genome Project databases. Further analysis of these variants by the Alpha Missense analysis tool yielded 8 likely pathogenic variants in 9 patients in the following genes: AIP:c.767C>T (p.S256F), CDH23:c.906G>C (p.E302D), CDH23:c.1096G>A (p.A366T), DICER1:c.620C>T (p.A207V), MLH1:c.955G>A (p.E319K), MSH2:c.148G>A (p.A50T), SDHA:c.869T>C (p.L290P) and USP48 (2 patients): c.2233G>A (p.V745M). Conclusion: This study suggests that about 6.7% of patients with apparently sporadic PAs carry likely pathogenic variants in PA-associated genes. These findings need further studies to confirm them.

Evaluation of clinical and laboratory characteristics of dengue viral infection and risk factors of dengue hemorrhagic fever: a multi-center retrospective analysis.

BACKGROUND: Dengue Viral Infection (DVI) has become endemic in Pakistan since the first major outbreak in Karachi in 1996. Despite aggressive measures taken by relevant authorities, Pakistan has been dealing with a worsening dengue crisis for the past two decades. DHF is severe form of dengue infection which is linked with significant morbidity and mortality. Early identification of severe dengue infections can reduce the morbidity and mortality. In this context we planned current study in which we find out the different factors related with DHF as well as clinical laboratory features of DHF and compare them to DF so that patients can be best evaluated for DHF and managed accordingly at admission. METHODS: Retrospective study conducted over a period of 6 years (2013-2018) in two tertiary care hospitals in Pakistan. Data were collected by using a pre-structured data collection form. Data were statistically analyzed to determine the clinical and laboratory characteristics of DVI and risk factors of dengue hemorrhagic fever (DHF). RESULTS: A total 512 dengue cases (34.05 ± 15.08 years; Male 69.53%) were reviewed. Most common clinical manifestations of DVI were fever (99.60%), headache (89.1%), chills (86.5%), rigors (86.5%), myalgia (72.3%). Less common clinical manifestations were vomiting (52.5%), arthralgia (50.2%) and skin rashes (47.5%). Furthermore, nasal bleeding (44.1%), gum bleeding (32.6%), pleural effusion (13.9%) and hematuria (13.1%) were more profound clinical presentations among DHF patients. Mortality rate was 1.5% in this study. Logistic regression analysis indicated that delayed hospitalization (OR: 2.30) and diabetes mellitus (OR:2.71), shortness of breath (OR:2.21), association with risk groups i.e., living near stagnant water, travelling to endemic areas, living in endemic regions (OR:1.95), and presence of warning signs (OR:2.18) were identified as risk factors of DHF. Statistically we found that there is strong association of diabetes mellitus (DM) with DHF while the patient suffering from DM individually had higher odds (2.71) of developing DHF than patients without disease. CONCLUSIONS: The current study demonstrated that the clinical and laboratory profiles of DF and DHF are significantly distinct. Significant predictors of DHF were advanced age, diabetes mellitus, ascites, pleural effusion, thick gallbladder and delayed hospitalization. The identification of these factors at early stage provides opportunities for the clinicians to identify high risk patients and to reduce dengue-related morbidity and mortality.

Formulation and evaluation of miconazole lipogel for enhanced drug permeation.

Hydrophilic drugs could be incorporated into the skin surface by manes of Lipogel. This study aimed to prepare miconazole lipogel with natural ingredients to enhance drug permeability using dimethyl Sulfoxide (DMSO). The miconazole lipogels, A1 (without DMSO) and A2 (with DMSO) were formulated and evaluated for organoleptic evaluation, pH, viscosity, stability studies, freeze-thawing, drug release profile and drug permeation enhancement. Results had stated that prepared lipogel's pH falls within the acceptable range required for topical delivery (4 to 6) while both formulations show good results in organoleptic evaluation. The A2 formulation containing DMSO shows better permeation of miconazole (84.76%) on the artificial skin membrane as compared to A1 lipogel formulation (50.64%). In in-vitro drug release studies, A2 for-mulation showed 87.48% drug release while A1 showed just 60.1% drug release from lipogel. Stability studies were performed on model formulations under environmental conditions and both showed good spreadibility, stable pH, free of grittiness and good consistency in formulation. The results concluded that A2 formulation containing DMSO shows better results as compared to DMSO-free drug lipogel.

Racetrack Ring Resonator-Based on Hybrid Plasmonic Waveguide for Refractive Index Sensing.

In this study, a comprehensive numerical analysis is conducted on a hybrid plasmonic waveguide (HPWG)-based racetrack ring resonator (RTRR) structure, tailored specifically for refractive index sensing applications. The sensor design optimization yields remarkable results, achieving a sensitivity of 275.7 nm/RIU. Subsequently, the boundaries of sensor performance are pushed even further by integrating a subwavelength grating (SWG) structure into the racetrack configuration, thereby augmenting the light-matter interaction. Of particular note is the pivotal role played by the length of the SWG segment in enhancing device sensitivity. It is observed that a significant sensitivity enhancement can be obtained, with values escalating from 377.1 nm/RIU to 477.7 nm/RIU as the SWG segment length increases from 5 µm to 10 µm, respectively. This investigation underscores the immense potential of HPWG in tandem with SWG for notably enhancing the sensitivity of photonic sensors. These findings not only advance the understanding of these structures but also pave the way for the development of highly efficient sensing devices with unprecedented performance capabilities.

A systematic review of the economic burden of diabetes mellitus: contrasting perspectives from high and low middle-income countries.

Introduction: Diabetes increases preventative sickness and costs healthcare and productivity. Type 2 diabetes and macrovascular disease consequences cause most diabetes-related costs. Type 2 diabetes greatly costs healthcare institutions, reducing economic productivity and efficiency. This cost of illness (COI) analysis examines the direct and indirect costs of treating and managing type 1 and type 2 diabetes mellitus. Methodology: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, Cochrane, PubMed, Embase, CINAHL, Scopus, Medline Plus, and CENTRAL were searched for relevant articles on type 1 and type 2 diabetes illness costs. The inquiry returned 873 2011-2023 academic articles. The study included 42 papers after an abstract evaluation of 547 papers. Results: Most articles originated in Asia and Europe, primarily on type 2 diabetes. The annual cost per patient ranged from USD87 to USD9,581. Prevalence-based cost estimates ranged from less than USD470 to more than USD3475, whereas annual pharmaceutical prices ranged from USD40 to more than USD450, with insulin exhibiting the greatest disparity. Care for complications was generally costly, although costs varied significantly by country and problem type. Discussion: This study revealed substantial heterogeneity in diabetes treatment costs; some could be reduced by improving data collection, analysis, and reporting procedures. Diabetes is an expensive disease to treat in low- and middle-income countries, and attaining Universal Health Coverage should be a priority for the global health community.

Kappa-carrageenan and sodium alginate-based pH-responsive hydrogels for controlled release of methotrexate.

Despite remarkable progress in medical sciences, modern man is still fighting the battle against cancer. In 2022, only in the USA, 640 000 deaths and 2 370 000 patients were reported because of cancer. Chemotherapy is the most widely used for cancer treatments. However, chemotherapeutics have severe physicochemical side effects. Therefore, we have prepared poly(amididoamine) dendrimeric carrageenan (CG), sodium alginate (SA) and poly(vinyl alcohol) (PVA) hydrogels by using solution casting methodology. The constituents of hydrogels were cross-linked by mutable quantity of 3-aminopropyl(diethoxy)methyl silane (APDMS). Hydrogels were characterized by Fourier transform infrared spectroscopy, thermal gravimetric analysis, scanning electron microscope and atomic force microscopy. Hydrogels exhibited higher swelling volumes in 5-7 pH range. In vitro biodegradation in ribonuclease-A solution and cytocompatibility analysis against DF-1 fibroblasts established their biodegradable and non-toxic nature, which enables them as a suitable carrier for chemotherapeutic compounds. Hence, methotrexate (MTX) as a model drug was loaded on CAP-8 hydrogel and its release was detected by the UV-visible spectrophotometer in phosphate-buffered saline (PBS) solution. In 13.5 h, 81.25% and 77.23% of MTX were released at pH 7.4 (blood pH) and 5.3 (tumour pH) in PBS, respectively. MTX was released by super case II mechanism and best fitted to zero-order and Korsmeyer-Peppas model. The synthesized APDMS cross-linked CG/SA/PVA dendrimeric hydrogels could be an efficient model platform for the effective delivery of MTX in cancer treatments.

Insight into CMC-PVA-fHNTs Nanocomposite Hydrogel as an Advance Carrier for Cefadroxil Monohydrate: Fabrication and Characterization/Angiogenic Potential Analysis.

Controlled drug delivery is a key strategy aimed at reducing both the frequency of therapeutic dosages and potential systemic side effects, particularly in the case of high drug concentrations. The nanocomposite hydrogel systems presented in this study were synthesized by combining carboxymethyl cellulose, polyvinyl alcohol, and (3-aminopropyl)triethoxysilane-functionalized halloysite nanotubes (fHNTs). This hydrogel system is a potential candidate for the controlled release of cefadroxil monohydrate. These hydrogels are analyzed by Fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis, and rheological measurements. Additionally, swelling properties, porosity, hydrophilicity, drug release, and in vitro and in vivo analyses were also evaluated. The observed trends in swelling and drug release demonstrated that the outcomes are dependent on the presence of fHNTs in the hydrogel matrix. Notably, fHNTs-loaded hydrogels displayed sustained drug release patterns. This innovative approach eliminates the need for traditional encapsulation and presents promising and translatable strategies for achieving more effective drug release.

Exploring Types of Photonic Neural Networks for Imaging and Computing-A Review.

Photonic neural networks (PNNs), utilizing light-based technologies, show immense potential in artificial intelligence (AI) and computing. Compared to traditional electronic neural networks, they offer faster processing speeds, lower energy usage, and improved parallelism. Leveraging light's properties for information processing could revolutionize diverse applications, including complex calculations and advanced machine learning (ML). Furthermore, these networks could address scalability and efficiency challenges in large-scale AI systems, potentially reshaping the future of computing and AI research. In this comprehensive review, we provide current, cutting-edge insights into diverse types of PNNs crafted for both imaging and computing purposes. Additionally, we delve into the intricate challenges they encounter during implementation, while also illuminating the promising perspectives they introduce to the field.

Shaping sustainable pathways: Enhancing mechanical properties of biocomposite through tannic acid treatment of flax fabrics.

Biocomposites developed using natural fibers serve as a sustainable alternative to synthetic composite materials. However, narrowing the performance gap between synthetic composites and biocomposites requires serious efforts. A promising approach is the modification of natural fibers using various chemical treatments. This paper investigates the potential of tannic acid (TA) treatment as a sustainable approach to enhance mechanical performance and reduce moisture absorption of flax fabric-reinforced biocomposites. The methodology involves the treatment of flax woven fabric with tannic acid, a naturally occurring polyphenolic compound, followed by the fabrication of biocomposite using a green epoxy matrix. The variables studied during treatment are TA concentration and processing time. Characterization of untreated and treated flax fabric and its composites was done using various analytical techniques such as FTIR spectroscopy, moisture absorption and mechanical testing (tensile strength, flexural strength, and impact resistance). FTIR spectroscopy of TA-treated flax confirmed attachment of aromatic rings and carbon double bond formation, thus serving for properties enhancement. The mechanical characterization of composites showed that properties are enhanced up to an optimum limit of concentration and processing time i.e., 1 % concentration and 30 min of processing. Moisture absorption of the TA-treated composite also reduced significantly as compared to untreated composites. These findings contribute towards the advancement in sustainable biocomposites and pave the way for their utilization in various applications.

Comparison of Rifaximin Alone and With Quinolones in the Primary Prevention of Spontaneous Bacterial Peritonitis in Patients With Decompensated Chronic Liver Disease.

Background In cirrhotic patients with ascites, primary prevention of spontaneous bacterial peritonitis (SBP) is a key strategy to lower morbidity and death. Rifaximin and fluoroquinolone used alternately as main prophylaxis are as effective as reported. This study aimed to compare the frequency of occurrence of SBP in patients with decompensated chronic liver disease treated with rifaximin alone and in combination with fluoroquinolone. Methodology A total of 76 patients with hepatitis C virus-related decompensated chronic liver disease and ascites were divided into two groups based on matching age, sex, and Child-Pugh class. Group A (38 patients) received rifaximin 1,100 mg/day in two divided doses with daily fluoroquinolone 400 mg/day, whereas group B (38 patients) received rifaximin 1,100 mg/day alone as a two dosage. The patients were monitored for up to three months. The study's endpoints were SBP, hepatocellular carcinoma, compliance failure, death, or liver transplantation. Results In this comparative study involving 76 patients, the demographic and clinical characteristics were assessed across two treatment groups: rifaximin alone (n = 38) and rifaximin with fluoroquinolone (n = 38). The combination therapy demonstrated a statistically significant reduction in SBP compared to rifaximin alone. Additionally, the overall survival rate was higher in the combination group. These findings suggest potential benefits of the combined approach in managing hepatic encephalopathy-related complications. Conclusions When compared to rifaximin alone for primary SBP prophylaxis, the combination of rifaximin with fluoroquinolone exhibited greater effectiveness with the same safety profile.

Comparison of EKFC, Pakistani CKD-EPI and 2021 Race-Free CKD-EPI creatinine equations in South Asian CKD population: A study from Pakistani CKD community cohort.

INTRODUCTION: South Asian individuals possess a high risk of chronic kidney disease. There is a need to study, evaluate, and compare the newly suggested glomerular filtration rate (eGFR) equations for accurate CKD diagnosis, staging, and drug dosing. This study aimed to (1) evaluate the European Kidney Function Consortium (EKFC), Pakistani CKD-EPI, and 2021 Race-Free CKD-EPI creatinine equation in the South Asian population with CKD and (2) to examine the expected implications on both CKD classification as well as End Stage Renal Disease (ESRD) prevalence across these equations in South Asian population. METHODS: We carried out a cross-sectional investigation on 385 participants, a CKD cohort ≥ 18 years, at Allama Iqbal Medical College, Jinnah Hospital, Lahore. Serum creatinine was measured by Jaffe's method and rGFR was measured by inulin clearance. RESULTS: Pakistani CKD-EPI has a lower median difference at -1.33 ml/min/1.73m2 elevated precision (IQR) at 2.33 (-2.36, -0.03) and higher P30 value at 89.35% than 2021 CKD-EPI and EKFC equations. The mean difference (ml/min/1.73m2), 95% agreement limits (ml/min/1.73m2) of CKD-EPI PK: -1.18, -6.14, 2021 CKD-EPI: -5.98, -13.24 and EKFC: -5.62, -13.01 (P <0.001). These equations highly correlated to rGFR (P <0.001). An upward re-classification in GFR categories was shown by 2021 CKD-EPI and EKFC compared to the Pakistani CKD-EPI equation. However, there was an exception regarding the G5 category, where an elevated count of 217 (56.36%) was shown for CKD-EPI PK. The prevalence of ESRD was seen in entire age groups and prevailed among females more than in males overall equations. CONCLUSIONS: Pakistani CKD-EPI exhibited outstanding performance, while 2021 CKD-EPI and EKFC demonstrated poor performances and could not show an adequate advantage for both CKD classification and prevalence of ESRD compared to Pakistani CKD-EPI. Therefore, Pakistani CKD-EPI appears optimal for this region and warrants future validation in other South Asian countries. In contrast, suitable measures must be implemented in Pakistani laboratories.

Prevalence of Long COVID Syndrome and its Association With Blood Group: A Cross-Sectional Study.

BACKGROUND:  The coronavirus disease 2019 (COVID-19) virus pandemic rapidly spread across the globe since 2020. It was characterized by a number of acute signs and symptoms. There were, however, some new-onset signs and symptoms labelled as "Long COVID". This study was conducted to study its prevalence and associations with blood group. METHODS: A retrospective analysis was conducted in Islamabad for patients diagnosed with COVID-19 in 2020-2021. Information was collected through an online and physical questionnaire regarding personal demographics, symptoms during and after COVID-19, and blood group. The data was analyzed using IBM SPSS Statistics for Windows, Version 25.0 (Released 2017; IBM Corp., Armonk, New York, United States). RESULTS: The study identified 196 participants out of which 48.5% were male and 51% were female, with a median age of 30. Most participants (62.2%) belonged to the Punjabi ethnicity. The mean BMI was 25.56 kg/m2. The majority of the study participants reported having blood group B (n=76) followed by A (n=52). Acute symptoms were experienced by 95.4% of participants, with fatigue being the most persistent symptom at four weeks (45.9%). After four weeks, 63.3% of participants reported new symptoms like hair loss. Females were found more likely to experience long COVID symptoms. The perceived severity of acute infection was significantly associated with long COVID symptoms (p=<0.01). There was no association found between long COVID and blood group (p=0.158). CONCLUSION:  There was no association found between long COVID and ABO blood groups. Females were more likely than males to experience long COVID. Long COVID was found to be more likely to develop in those with perceived severe acute infection, highlighting the need for further research regarding aggressive care from the onset of COVID-19 infection.

Control strategies for inverted pendulum: A comparative analysis of linear, nonlinear, and artificial intelligence approaches.

An inverted pendulum is a challenging underactuated system characterized by nonlinear behavior. Defining an effective control strategy for such a system is challenging. This paper presents an overview of the IP control system augmented by a comparative analysis of multiple control strategies. Linear techniques such as linear quadratic regulators (LQR) and progressing to nonlinear methods such as Sliding Mode Control (SMC) and back-stepping (BS), as well as artificial intelligence (AI) methods such as Fuzzy Logic Controllers (FLC) and SMC based Neural Networks (SMCNN). These strategies are studied and analyzed based on multiple parameters. Nonlinear techniques and AI-based approaches play key roles in mitigating IP nonlinearity and stabilizing its unbalanced form. The aforementioned algorithms are simulated and compared by conducting a comprehensive literature study. The results demonstrate that the SMCNN controller outperforms the LQR, SMC, FLC, and BS in terms of settling time, overshoot, and steady-state error. Furthermore, SMCNN exhibit superior performance for IP systems, albeit with a complexity trade-off compared to other techniques. This comparative analysis sheds light on the complexity involved in controlling the IP while also providing insights into the optimal performance achieved by the SMCNN controller and the potential of neural network for inverted pendulum stabilization.

Preparation and Evaluation of a Self-Emulsifying Drug Delivery System for Improving the Solubility and Permeability of Ticagrelor.

Ticagrelor (TCG) is a BCS class IV antiplatelet drug used to prevent platelet aggregation in patients with acute coronary syndrome, having poor solubility and permeability. The goal of this study was to develop a self-nanoemulsifying drug delivery system (SNEDDS) of TCG to improve its solubility and permeability. The excipients were selected based on the maximum solubility of TCG and observed by UV spectrophotometer. Different combinations of oil, surfactant, and co-surfactant (1:1, 2:1, and 3:1) were used to prepare TCG-SNEDDS formulations, and pseudo-ternary phase diagrams were plotted. The nanoemulsion region was observed. Clove oil (10-20%), Tween-80 (45-70%), and PEG-400 (20-45%) were used as an oil, surfactant, and co-surfactant, respectively. The selected formulations (F1, F2, F3, F4, F5, and F6) were analyzed for ζ potential, polydispersity index (PDI), ζ size, self-emulsification test, cloud point determination, thermodynamic studies, entrapment efficiency, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), in vitro dissolution, ex vivo permeation, and pharmacodynamic study. The TCG-SNEDDS formulations exhibited ζ potential from -9.92 to -6.23 mV, a ζ average of 11.85-260.4 nm, and good PDI. The in vitro drug release in phosphate buffer pH 6.8 from selected TCG-SNEDDS F4 was about 98.45%, and F6 was about 97.86%, displaying improved dissolution of TCG in 0.1 N HCl and phosphate buffer pH 6.8, in comparison to 28.05% of pure TCG suspension after 12 h. While the in vitro drug release in 0.1 N HCl from F4 was about 62.03%, F6 was about 73.57%, which is higher than 10.35% of the pure TCG suspension. In ex vivo permeability studies, F4 also exhibited an improved apparent permeability of 2.7 × 10-6versus 0.6708 × 10-6 cm2/s of pure drug suspension. The pharmacodynamic study in rabbits demonstrated enhanced antiplatelet activity from TCG-SNEDDS F4 compared to that from pure TCG suspension. These outcomes imply that the TCG-SNEDDS may serve as an effective means of enhancing TCG's antiplatelet activity by improving the solubility and permeability of TCG.

Approach towards sustainable leather: Characterization and effective industrial application of proteases from Bacillus sps. for ecofriendly dehairing of leather hide.

Tanneries are one of the most polluted industries known for production of massive amount of solid and liquid wastes without proper management and disposal. In this project we demonstrated the ecofriendly single step dehairing of leather hides with minimum pollution load. In this study, Bacillus species (Bacillus paralicheniformis strain BL.HK, Bacillus cereus strain BS.P) capable of producing proteases was successfully isolated by employing the new optimized selective media named M9-PEA as confirmed by 16sRNA genes sequencing. Sequence of 1493 bp long 16S rRNA genes of Bacillus paralicheniformis strain BL.HK and Bacillus cereus strain BS. P was submitted to GenBank under the accession number OP612692.1, OP612721.1 respectively The Bacillus paralicheniformis strain BL.HK, Bacillus cereus strain BS.P produced extracellur proteases of 28 and 37 KDa as resolved by SDS-PAGE respectively. The enzymes showed temperature optima at 50 °C and 55 °C and pH optima at 8.5, 9.5 respectively. The Proteases of Bacillus paralicheniformis strain BL.HK, Bacillus cereus strain BS.P were employed for dehairing of animal hides. The process resulted in significant removal of interfibriller substances without damage to collagen layer after one hour treatment, which was confirmed by histology, scanning electron microscopy. The quantification of various skin constituents (collagen, uronic acid, hexosamines, and GAGs) and pollution load parameters revealed that enzymatic treatment are more reliable. The results of skin application trials at industrial level with complete elimination of chemicals remark the biotechnological potential of these proteases for ecofriendly dehairing of animal hides without affecting the quality of the leathers produced.

Response Surface Methodology (RSM) approach to formulate and optimize the bilayer combination tablet of Tamsulosin and Finasteride.

An orally administered bilayer tablet with Tamsulosin (TAM) as the sustained release (SR) and Finasteride (FIN) as immediate release (IR) was manufactured. A response surface methodology was employed to formulate bilayer tablets with individual release layers, i.e., sustained and immediate release (SR and IR). Independent variables selected in both cases comprise hydroxypropyl methylcellulose (HPMC) as SR polymer, and avicel PH102 in the inner layer while Triacetin and talc in the outer layer, respectively. Tablets were prepared by direct compression, a total of 11 formulations were prepared for inner layer TAM, and 9 formulations for outer layer FIN were designed; these formulations were evaluated for hardness, friability, thickness, %drug content, and %drug release. A central composite design was employed in response surface methodology to design and optimize the formulation. The percentage of drug released was evaluated by in-vitro USP dissolution method of optimized formulation for 0.5, 2, and 6 hrs, and results were 24.63, 52.96, and 97.68 %, respectively. Drug release data was plotted in various kinetic models using a D.D solver, where drug release was first order that is concentration dependent and was best explained by Korsmeyer-Peppa kinetics, as the highest linearity was observed (R2 = 0.9693). However, a very close relationship was also noted with Higuchi kinetics (R2 = 0.9358). The mechanism of drug release was determined through the Korsmeyer model, and exponent "n" was found to be 0.4, indicative of an anomalous diffusion mechanism or diffusion coupled with erosion.