Associations of the glycaemic index and the glycaemic load with risk of type 2 diabetes in 127 594 people from 20 countries (PURE): a prospective cohort study.

BACKGROUND: The association between the glycaemic index and the glycaemic load with type 2 diabetes incidence is controversial. We aimed to evaluate this association in an international cohort with diverse glycaemic index and glycaemic load diets. METHODS: The PURE study is a prospective cohort study of 127 594 adults aged 35-70 years from 20 high-income, middle-income, and low-income countries. Diet was assessed at baseline using country-specific validated food frequency questionnaires. The glycaemic index and the glycaemic load were estimated on the basis of the intake of seven categories of carbohydrate-containing foods. Participants were categorised into quintiles of glycaemic index and glycaemic load. The primary outcome was incident type 2 diabetes. Multivariable Cox Frailty models with random intercepts for study centre were used to calculate hazard ratios (HRs). FINDINGS: During a median follow-up of 11·8 years (IQR 9·0-13·0), 7326 (5·7%) incident cases of type 2 diabetes occurred. In multivariable adjusted analyses, a diet with a higher glycaemic index was significantly associated with a higher risk of diabetes (quintile 5 vs quintile 1; HR 1·15 [95% CI 1·03-1·29]). Participants in the highest quintile of the glycaemic load had a higher risk of incident type 2 diabetes compared with those in the lowest quintile (HR 1·21, 95% CI 1·06-1·37). The glycaemic index was more strongly associated with diabetes among individuals with a higher BMI (quintile 5 vs quintile 1; HR 1·23 [95% CI 1·08-1·41]) than those with a lower BMI (quintile 5 vs quintile 1; 1·10 [0·87-1·39]; p interaction=0·030). INTERPRETATION: Diets with a high glycaemic index and a high glycaemic load were associated with a higher risk of incident type 2 diabetes in a multinational cohort spanning five continents. Our findings suggest that consuming low glycaemic index and low glycaemic load diets might prevent the development of type 2 diabetes. FUNDING: Full funding sources are listed at the end of the Article.

In Vivo Wound-Healing Efficacy of Insulin-Loaded Strontium-Cross-Linked Alginate-Based Hydrogels in Diabetic Rats.

The wound-healing effect of insulin is well studied and reported. However, prolonged topical application of insulin without compromising its biological activity is still a challenge. In this study, the effect of topically delivered insulin on promoting wound healing in diabetic animals was evaluated. Alginate diamine PEG-g-poly(PEGMA) (ADPM2S2) was the material used for the topical delivery of insulin. ADPM2S2 hydrogels release insulin and strontium ions, and they synergistically act to regulate different phases of wound healing. Insulin was released from the ADPM2S2 hydrogel for a period of 48 h, maintaining its structural stability and biological activity. In vitro studies were performed under high-glucose conditions to evaluate the wound-healing potential of insulin. Insulin-loaded ADPM2S2 hydrogels showed significant improvement in cell migration, proliferation, and collagen deposition, compared to control cells under high-glucose conditions. Immunostaining studies in L929 cells showed a reduction in phospho Akt expression under high-glucose conditions, and in the presence of insulin, the expression increased. The gene expression studies revealed that insulin plays an important role in regulating the inflammatory phase and macrophage polarization, which favors accelerated wound closure. In vivo experiments in diabetic rat excision wounds treated with insulin-loaded ADPM2S2 showed 95% wound closure within 14 days compared with 82% in control groups. Thus, both the in vitro and in vivo results signify the therapeutic potential of topically delivered insulin in wound management under high-glucose conditions.

Role of inorganic ions in wound healing: an insight into the various approaches for localized delivery.

Recently, the role of inorganic ions has been explored for its wound-healing applications. Ions do play key role in the normal functioning of the skin, including the epidermal barrier property, maintaining redox balance, enzymatic activities, tissue remodeling, etc. The care of chronic wounds is a concern and new cost-effective therapeutic strategies that modulate the wound microenvironment and cell behaviour are needed. First, this review illustrates the ions that play a role in wound healing and their molecular mechanisms that are accountable for modifying the wound. Further, the emerging strategies using metal ions to modulate the healing will be discussed. In this direction, localized delivery of inorganic ions of importance using advanced wound care biomaterials for wound healing applications is discussed.

The wound repair and regeneration process is regarded as a highly complex biological process that involves multiple phases. Chronic wounds are those that get stalled at the initial phases of wound healing. This review discusses the role of inorganic ions in wound healing and its therapeutic potential that could improve healing outcomes in chronic wounds. Utilizing inorganic ions in innovative ways to modulate the wound-healing processes is an emerging field. In this regard, the review paper also encompasses a comprehensive overview of numerous delivery approaches for the localized release of metal ions to the wound site.

ADVANCEMENTS IN MINIMALLY INVASIVE SURGERY: A COMPREHENSIVE ANALYSIS OF ROBOTIC SURGERY, ENDOSCOPIC TECHNIQUES, AND NATURAL ORIFICE TRANSLUMENAL ENDOSCOPIC SURGERY.

The term "Natural Orifice Transluminal Endoscopic Surgery" (NOTES) defines a surgical approach that leverages the body's natural orifices to access the abdominal cavity, presenting a patient-centric perspective by highlighting its potential to eliminate abdominal wall aggression, mitigate postoperative discomfort, and offer benefits comparable to laparoscopic surgery. This comprehensive paper aims to not only review the existing landscape of NOTES techniques but also to propose advancements in flexible tools augmenting established endoscopic platforms, while also exploring the revolutionary concept of robotic structures grounded in micromechatronics and communication technologies. The thorough analysis encompasses the assessment of advantages and limitations associated with flexible devices and robotic platforms, coupled with an in-depth evaluation of the current array of devices used in NOTES, informed by pertinent literature. The authors' comprehensive approach entails scrutinizing technological breakthroughs and offering viable solutions, fostering a comprehensive understanding. Furthermore, the study encompasses an exhaustive evaluation and juxtaposition of state-of-the-art NOTES devices, supplemented by a nuanced discourse on the merits and demerits of flexible devices and robotic platforms, with a focused emphasis on their inherent strengths and weaknesses. Within this context, the discourse extends to strategic suggestions aimed at refining extant designs and cultivating robust, dependable autonomous robotic platforms purpose-built for NOTES. This narrative encapsulates the multifaceted exploration of benefits, challenges, and potential remedies directed towards enhancing prevailing designs and forging a dependable foundation for the future of NOTES.

Ascorbic acid-loaded gellan-g-poly(ethylene glycol) methacrylate matrix as a wound-healing material.

Ascorbic acid (AA) is one of the important biomolecules involved in all phases of wound healing. The aim of this study was to develop a new hydrogel system that offers topical delivery of ascorbic acid to wounds during wound care management. In this work, we grafted poly (ethylene glycol) methacrylate onto a renewable biopolymer gellan, and the graft copolymer (GPMA) formed was crosslinked covalently and ionically, and used as a matrix for delivering AA to the wounds. By the processes of grafting and crosslinking, the mechanical properties of the gellan increased several fold compared to mechanically weak native gellan. In vitro cytotoxicity evaluation showed that GPMA was non-cytotoxic to fibroblast cells. GPMA hydrogel matrix allowed the sustained release of AA. When AA was incorporated in GPMA, a significant improvement in wound closure was observed in scratch wound assay performed with keratinocytes. Since AA acts as a cofactor in collagen synthesis, the controlled delivery of AA to the wound microenvironment favors the up-regulation of colα1 gene expression. This study revealed that ascorbic acid, at a concentration of 150 µM, has a favorable impact on wound healing when tested in vitro. Overall results indicate that the GPMA matrix could be a promising material for wound healing applications.

Design and evaluation of propranolol hydrochloride loaded thiolated Zein/PEO electrospun fibrous matrix for transmucosal drug delivery.

Thiolated polymers have garnered wide attention from researchers on mucoadhesive drug delivery. This work explores the thiolation of zein protein using cysteine amino acid via the EDC crosslinker. The optimization of thiolation and purification have been done and confirmed using Ellman's assay and Raman spectra. The thiolated Zein/PEO polymer blend has been appraised for electrospinning to fabricate fibrous matrices. The extent of thiol modification augmented the mechanical properties and adhesion in rabbit intestinal mucosa. In vitro cytotoxicity evaluations such as direct contact assay, MTT assay, and live dead assay performed in RPMI 2650 cells corroborated the non-cytotoxicity of the fabricated matrices with and without propranolol hydrochloride (PL). Detailed drug release studies were conducted in PBS. Drug release in PBS followed the Korsmeyer Peppas model of release. On treating RPMI 2650 cells with the matrix, F-actin and adherens junctional proteins retained integrity, and consequently, drug permeation would proceed through the transcellular transport mechanism. Transepithelial electrical resistance (TEER) measurement of the RPMI 2650 cell monolayer also supported the transcellular transport mechanism. Ex vivo permeation study through porcine buccal mucosa showed 41.26 ± 0.56% PL permeation within 24 h of study. It validated the competence of the electrospun thiolated Zein/PEO matrix for transmucosal drug delivery.

Proline conjugated chitosan as wound healing material: In vitro studies on the influence of the scaffold on collagen production and wound healing.

The present study reports the development of L-proline conjugated chitosan scaffold for wound healing application. Proline plays a beneficial role in collagen synthesis, and as a biochemical, it has the potential to modulate wound healing. In this regard, amino acid L-proline was conjugated onto chitosan, and the scaffolds were synthesised. FTIR and NMR analysis confirmed amino acid conjugation. The prepared scaffold was characterized by studies such as swelling, dissolution, tensile strength, porosity, water-vapor transmission rate and in-vitro healing properties. Cell viability assay showed that the scaffold has no cytotoxicity against the L929 and HaCaT cells. The in-vitro wound healing potential of the scaffold by scratch wound assay on the L929 cell line showed 53.35 ± 2.3 %, 72.96 ± 2.2 %, and 50.89 ± 0.3 % wound closure for CS-P 200, CS-P 400 and CS-P 600, respectively when compared to native CS scaffold (38.86 ± 1.6 %). A similar observation was found with HaCaT cells too. The studies showed that the modified scaffold promotes collagen deposition from fibroblast cells. These findings suggest that scaffold cues remodel the wound microenvironment for a better wound-healing state, and the L-proline conjugated scaffold may have considerable potential as a wound dressing to improve wound healing.

Fishing for Developmental Regulatory Regions: Zebrafish Tissue-Specific ATAC-seq.

Interactions between transcription factors and regulatory DNA can be described by gene regulatory networks. These networks provide a systems-level view of embryonic tissue development. Here, we describe a protocol for the isolation, identification, and experimental manipulation of tissue-specific cis-regulatory elements during zebrafish embryonic development using low-input ATAC-seq. With the methods described, genome-wide assessments of regulatory DNA in small populations of developing tissues can be identified, allowing for the construction of gene regulatory networks.

Electrospun Mucoadhesive Zein/PVP Fibroporous Membrane for Transepithelial Delivery of Propranolol Hydrochloride.

Mucoadhesive drug delivery systems have been extensively studied to effectively reduce the limitations of conventional drug delivery systems. Zein and polyvinyl pyrrolidone (PVP) are appraised for mucoadhesive properties. This study focuses on developing a mechanically stable zein/PVP electrospun membrane for propranolol hydrochloride (PL) transport. Fourier transform infrared, Raman spectra, and swelling studies gave evidence for PVP crosslinking, whereas circular dichroism spectroscopy revealed crosslinking of zein owing to the conformational change from α-helix to ß-sheet. A 10 h thermal treatment of zein/PVP imparted 3.92 ± 0.13 MPa tensile strength to the matrix. Thermally crosslinked electrospun zein/PVP matrix showed 22.1 ± 0.1 g mm work of adhesion in porcine buccal mucosa tissue. Qualitative and quantitative evaluation of cytotoxicity in RPMI 2650 has been carried out. The in vitro drug release profile of PL from thermally crosslinked zein/PVP best fitted with the Korsmeyer-Peppas model. Immunostaining of ß-catenin adherens junctional protein confirmed the absence of paracellular transport through the junctional opening. Still, drug permeation was observed through the porcine buccal mucosa, attributed to the transcellular transport of PL owing to its lipophilicity. The ex vivo permeation of PL through porcine buccal mucosa was also evaluated.

Solid Lipid Nanoparticles: A Potential Option for Enhancing Oral Bioavailability of Highly Soluble and Poorly Permeable (BCS Class III) Drugs.

Oral administration of drug is the most preferred one among the other routes for the majority of clinical applications. As compared to the parenteral method of administration, it has potential benefits such as increased patient compliance, fewer problems, and reduced treatment costs. Regardless of these factors, inadequate bioavailability owing to poor solubility or permeability limits the therapeutic effectiveness of orally given drugs. Though most current research focuses on BCS II (drugs with low solubility and high permeability), BCS III (drugs with high solubility and low permeability) also has poor oral bioavailability due to their limited permeability across lipid membranes and is usually administered through the parenteral route. The need for an oral alternative to parenteral administration has prompted a renewed focus on the development of innovative dosage forms that support the absorption of medicines that are poorly permeable through the intestinal epithelium. Because of their unique sizedependent feature in enhancing transmembrane permeability, ability to incorporate both lipophilic and hydrophilic drugs and biocompatible nature of components, the use of nanoparticles for improving drug bioavailability has been a focus of current study in the field of drug delivery in recent years. The lipidbased nanoparticle method presents a potential new avenue for manufacturing BCS Class III medicines with enhanced bioavailability, as poor permeability is the main issue for these agents. This research aims to assess the potential of lipid nanoparticles for improving the oral bioavailability of medicines with permeability-restricted oral absorption, such as pharmaceuticals in Biopharmaceutical Classification System (BCS) class III.

Preparation, Characterization and In Vitro Biological Activities of New Diphenylsulphone Derived Schiff Base Ligands and Their Co(II) Complexes.

The present work describes the chemical preparation of Schiff bases derived from 4,4'-diaminodiphenyl sulfone (L1-L5) and their Co(II) metal complexes. The evaluation of antimicrobial and anticancer activities against MCF-7 cell line and human lung cancer cell line A-549 was performed. The aforementioned synthesized compounds are characterized by spectroscopic techniques and elemental analysis confirms successful synthesis. The results from the above analytical techniques revealed that the complexes are in an octahedral geometry. The antimicrobial activity of the synthesized Schiff base ligands and their metal complexes under study was carried out by using the agar well diffusion method. The ligand and complex interactions for biological targets were predicted using molecular docking and high binding affinities. Further, the anticancer properties of the synthesized compounds are performed against the MCF-7 cell line and human lung cancer cell line A-549 using adriamycin as the standard drug.

Assessment of knowledge and awareness of forensic odontology among dentists in Tamil Nadu - A systematic review.

Aim: The aim of the study is to analyze the knowledge, attitude and practice of forensic odontology among dental practitioners in Tamil Nadu. Materials and Methods: Forensic odontology has immense importance in examining dental evidence and in the identification of victims of mass disaster, abuse or organized crimes. Hence, a cross-sectional survey study was conducted in a sample of 252 dental practitioners practicing in various cities in Tamil Nadu. A questionnaire comprising 22 questions (both open ended and close ended) was prepared, and the survey was conducted to analyze the knowledge and attitude of dentists toward forensic odontology. Results: Many of the practicing dentists had a basic knowledge about forensic odontology, but only 22% knew about the existence of a national association for forensic odontology. Forty-five percent of them knew about cheiloscopy. Seven percent of them only knew about the forensic courses available in India. Ninety-eight percent of them did not have any formal training related to forensic odontology. Seventy-two percent of them were not confident about giving an opinion for a forensic case. Most of them felt that our country has very limited resources for forensic odontology. Conclusion: This study showed that the branch of forensic odontology is still in the infant stage in the state. This condition, however, could be improved if more formal training courses are conducted by the specialist associations imparting knowledge and training in the field.

UV-Crosslinked Electrospun Zein/PEO Fibroporous Membranes for Wound Dressing.

Electrospun zein membranes are suitable for various biomedical applications. A UV-crosslinked electrospun membrane of a zein/PEO blend for wound healing application was explored in this work. The improvement in mechanical properties of the membrane after UV crosslinking was attributed to the change in protein conformation from an α-helix to a ß-sheet. The circular dichroism (CD) spectra and FTIR spectra confirmed this conformational change. XRD analysis was shown to prove the amorphous nature of polymer blends with specific broad peaks at 2θ = 9° and 20°. The water vapor transmission rate (WVTR) of the membrane was found to be in the range of 1500-2000 g m-2 day-1, which was well suited with that of commercially available wound dressing material. Enough number of available functional groups like thiol, amino, and hydroxyl groups supplement a blood clotting index (BCI) to the matrix, causing 99% BCI within 4 min. A 91% cell viability result in the MTT assay with human dermal fibroblast cells confirmed the noncytotoxicity of the membrane. Tripeptides produced after the thermolysin-based hydrolysis of zein caused inhibition of TGF ß1 expression and thus increased fibroblast and collagen production. The membrane stimulated 54% more collagen production compared to control cells at day 2 and caused 84% wound closure in human dermal fibroblast cells, which were desirable index markers of a potential wound care material.

Impact of TAILORx on chemotherapy prescribing and 21-gene recurrence score-guided treatment costs in a population-based cohort of patients with breast cancer.

BACKGROUND: The trial assigning individualized options for treatment (Rx) (TAILORx) confirmed the predictive value of the 21-gene recurrence score (RS) assay in hormone receptor (HR)-positive, HER2-negative, node-negative breast cancer and established thresholds for chemotherapy benefit in younger and older patients. Real-world chemotherapy use and RS-guided treatment costs in British Columbia post-TAILORx were examined. METHODS: The authors assembled 3 cohorts of HR-positive, HER2-negative, node-negative patients with breast cancer defined by diagnosis: before RS funding (cohort 1 [C1]: January 2013-December 2013), after introduction of public RS funding (cohort 2 [C2]: July 2015-June 2016), and after TAILORx results (cohort 3 [C3]: July 2018-June 2019). Chemotherapy use was compared between cohorts by age and RS. Budgetary impacts of RS testing on chemotherapy costs were evaluated pre- and post-TAILORx. RESULTS: Among the 2066 patients included, chemotherapy use declined by 19% after RS funding was introduced and by an additional 23% after TAILORx publication (P = .001). Reduction in chemotherapy use was significant for RS 11-20 tumors (C3 vs C2, P = .004). There was no significant change in chemotherapy use in patients >50 years old (C2:12% vs C3:10%, P = .22). RS testing was associated with higher cost savings post-TAILORx, except in patients 70 to 80 years old, where testing led to excess costs when adjusting for the low rate of RS-concordant chemotherapy prescribed. CONCLUSIONS: TAILORx has had population-based impacts on chemotherapy prescribing in intermediate RS tumors and patients ≤50 years old. The lower clinical use of RS and increased spending in patients 70-80 years old highlights the importance of careful selection of older candidates for high-cost genomic testing. LAY SUMMARY: The 21-gene recurrence score (RS) test helps predict whether patients with hormone-positive, HER2-negative, lymph node-negative breast cancer are likely to benefit from chemotherapy. The recent trial assigning individualized options for treatment (Rx) (TAILORx) found that patients with intermediate RS tumors did not benefit from chemotherapy. The authors assessed whether TAILORx results translated to real-world changes in chemotherapy prescribing patterns. In this study, chemotherapy use decreased by 23% after TAILORx, with the greatest reductions seen among intermediate RS tumors and younger patients. In contrast, RS testing had lower clinical value and increased treatment costs in elderly patients, which requires further study to ensure optimal care for this age group.

Analysis of daily COVID-19 death bulletin data during the first two waves of the COVID-19 pandemic in Thiruvananthapuram district, Kerala, India.

Context: Coronavirus disease 2019 (COVID-19) mortality trends can help discern the pattern of outbreak evolution and systemic responses. Aim: This study aimed to explore patterns of COVID-19 deaths in Thiruvananthapuram district from 31 March 2020 to 31 December 2021. Setting and Design: Secondary data analysis of COVID-19 deaths in Thiruvananthapuram district was performed. Materials and Methods: Mortality data were obtained from the district COVID-19 control room, and deaths in the first and second waves of COVID-19 were compared. Statistical Analysis: We summarised data as proportions and medians with the inter-quartile range (IQR) and performed Chi-square tests to make comparisons wherever applicable. Results: As on 31 December 2021, 4587 COVID-19 deaths were reported in Thiruvananthapuram district, with a case fatality rate of 0.91%. We observed high mortality among older persons (66.7%) and men (56.6%). The leading cause of death was bronchopneumonia (60.6%). The majority (88.5%) had co-morbidities, commonly diabetes mellitus (54.9%). The median interval from diagnosis to hospitalisation was 4 days (IQR 2-7), and that from hospitalisation to death was 2 days (IQR 0-6). The deaths reported during the second wave were four times higher than those of the first wave with a higher proportion of deaths in the absence of co-morbidities (p < 0.001). The majority of the deceased were unvaccinated. Ecological analysis with vaccine coverage data indicated 5.4 times higher mortality among unvaccinated than those who received two vaccine doses. Conclusions: The presence of co-morbidities, an unvaccinated status, and delay in hospitalisation were important reasons for COVID-19 deaths. Primary level health providers can potentially help sustaining vaccination, expeditious referral, and monitoring of COVID-19 patients.

Psychosocial Intervention Model of Kerala, India During Pandemic COVID-19: "Ottakkalla Oppamundu (You're not alone, we're with you)".

Globally, the coronavirus disease 2019 (COVID-19) pandemic has resulted in several psychosocial manifestations across all socioeconomic strata. This study attempted to explore the details of a psychosocial support system implemented in Kerala, India, to address psychosocial issues during this pandemic. It employed a descriptive approach using qualitative and quantitative methods. The results can be summarized into 4 overarching themes: (1) process of implementation, (2) issues addressed, (3) experiences, and (4) success stories. This intervention targeted the whole population, with a specific focus on quarantined/isolated individuals and selected vulnerable groups. COVID pandemic has sowed several negative emotions, such as anxiety; and stigma and fearful thoughts, including suicidal ideations; trepidation regarding family members; and misinfodemics in general. Social and religious corollaries of the pandemic have intensified the psychological agony. The study provides an overview of the psychosocial intervention adopted by the state during the pandemic, which has helped both the beneficiaries and the providers. It has also helped to promote positive thinking and change the attitude toward the disease among the beneficiaries. It is highly commendable that timely intervention could obviate quite a few psychiatric emergencies, including suicides and aggressive behaviors. Considering its efficiency, flexibility, and sustainability, this model can be replicated in any setting.

Synthesis and evaluation of an alginate-methacrylate xerogel for insulin delivery towards wound healing applications.

Background: Alginate is one of the most widely used biopolymer for wound healing. But poor mechanical strength and degradability limits its application especially as a drug-delivery matrix. The aim of this study was to develop stable alginate based scaffold for insulin delivery toward wound care. Materials & methods: The xerogel alginate-g-poly (methacrylic acid; AGM2S) was characterized by various analytical techniques. Results: AGM2S xerogel showed improved physical stability, low degradation, good swelling and water vapour transmission rate (WVTR). About 70% of insulin was released from loaded xerogel over a period of 48 h and favorably modulated the healing response in in vitro scratch wound assay. Conclusion: Grafting improved the strength and stability of alginate xerogel and the results suggest the application of insulin loaded AGM2S xerogels as a potential wound healing material.

Functioning of Arogyakiranam programme in Kerala: A qualitative study.

CONTEXT: Arogyakiranam program, a state-run health entitlement scheme, caters to health care needs of 0 to 18-year-old children, in government hospitals of Kerala. Very few studies have been conducted in this regard. AIM: An interim analysis of the functioning of this program through stakeholder perspective facilitates understanding the mode in which the program is currently progressing, thereby paving way for bettering it further. METHODS AND MATERIAL: A qualitative study in three purposively selected districts of Kerala consisting of in-depth interviews was conducted across different levels of stakeholders including officials from different health care levels and beneficiary caretakers who bring their wards to these centers. RESULTS: The functioning of the scheme with regard to implementation, fund flow, monitoring, documenting, reporting etc., was found to be following a fine structure. The scheme provides financial risk protection to the beneficiaries' families. Perceived challenges were lesser public awareness of the scheme, the requirement of an updated guideline, funds, the need for the availability of specialists and other amenities. Complete electronic hospital proceedings, a separate account for the scheme, staff reorientation/training, more reviews, and appraisals were emphasized. The overall functioning of the scheme is found to be streamlined and highly fruitful in terms of catering to the child population in the state. CONCLUSION: Arogyakiranam program has proven to be a boon to its beneficiaries with nil out-of-pocket expenditure, providing an array of health care amenities, ensuring equity thereby relentlessly working towards universal health coverage.

Synthesis, characterization and anti-inflammatory properties of karanjin (Pongamia pinnata seed) and its derivatives.

Karanja (Pongamia pinnata) is a medicinal tree used in the Indian traditional ayurvedic system for treating several ailments. The seeds contain a unique furano-flavonoid karanjin, which has shown to possess many medicinal properties. Its usage at the clinical level is affected due to poor solubility and absorption. In the present investigation, molecular modifications of karanjin were attempted and evaluated their effect on anti-inflammatory activity. Firstly, Karanja ketone was obtained from karanjin by hydrolysis, and it was converted into karanja ketone oxime. The oxime undergoes Beckmann rearrangement and cyclized to yield furano benzoxazole (karanja oxazole). The new derivatives were purified with >95% purity (HPLC) and spectrally characterized (HR-MS, FTIR, and NMR). Among the test compounds, karanja ketone oxime exhibited higher antioxidant activity with an IC50 value of 360 µg/ml (DPPH). Soy lipoxygenase-1 (LOX-1) inhibitory activity of oxime was higher (IC50 = 65.4 µM) than other compounds. Fluorescence studies showed that oxime had higher quenching capacity with a Qmax of 76.3% and a binding constant of 0.9 × 105 M-1 for soy LOX-1. In-silico interaction studies showed that karanja ketone oxime had the least binding energy of -5.76 kcal/mol with LOX-1 by forming two hydrogen bonds with hydrophobic amino acids Leu 390 and Gly 392. The compounds were evaluated for their acute anti-inflammatory activity by the paw and ear edema in the rat model. Karanjin inhibits paw edema and ear edema by 34.13% and 51.13%, respectively, whereas the derivatives inhibited by 45-57 % and 70-76.8%. This study reports a rational approach to synthesize karanjin derivatives with considerable anti-inflammatory properties, both in-vitro and in-vivo.

Assessment of Quality of Platelet-Rich Plasma Produced With Desktop Centrifuge and Comparison With Standardized Commercially Available Platelet-rich plasma.

AIMS: The aim of this study was to assess the quality of platelet-rich plasma (PRP) produced by in-house desktop centrifuge method and compare it with that of standardized commercial PRP. MATERIALS AND METHODS: REMI desktop centrifuge was used to prepare PRP and to compare with standardized commercial PRP by calculating the quantity of platelets using Beckman Coulter cell counter in 10 PRP samples and assessing the morphological quality of platelets using JEOL JEM transmission electron microscope (TEM). STATISTICAL ANALYSIS USED: The t test for platelet count in desktop PRP with the test value of therapeutic PRP was 12.618. The P value was <0.001, which was significant statistically. The data followed a normal distribution in normal Q-Q plot for platelet count in desktop centrifuge. So the test samples were not much deviated. RESULTS: The platelet count was lesser than that of standardized commercial PRP. When viewed under JEOL JEM transmission electron microscope, the α granules in platelets were intact and the morphological quality of the PRP was good. CONCLUSIONS: With this study, we have determined that the morphological quality of PRP produced by the in-house desktop centrifuge method is comparable to that of standardized commercial PRP. Though the quantity of platelets was less than 1 million cells/µL, the clinical results were good with desired bone formation, thereby providing good avenue for further research.