Preclinical pharmacology and pharmacokinetics of curcumin tagged cilostazol nanodispersion for the management of diabetic nephropathy in wister rat model.

To evaluate the therapeutic potential of curcumin tagged cilostazol solid nano dispersion in wistar rat streptozotocin-nicotinamide-induced diabetic nephropathy. Cilostazol (CLT), a Phosphodiesterase (PDE) inhibitor has an inhibitory effect on reactive oxygen species (ROS), and Curcumin (Cur), an antioxidant, and anti-inflammatory, are water-soluble. Solid Nano dispersions were developed using the "Box-Behnken Design" and emulsion solvent evaporation procedure to improve the solubility and bioavailability. Streptozotocin (SPZ) and Nicotinamide (NA) caused diabetes in Wistar rats. DN developed 30-45 days after disease induction. All rat groups underwent histological, biochemical and pharmacokinetic evaluation. The optimized batch of Cilostazol Loaded Novel Curcumin Tagged Solid Nanodispersion (CLT-15 SND) estimated renal, lipid, and cytokine profiles better than the conventional batch. CLT-15 SND, given orally to diabetic rats for 45 days, significantly lowered fasting BGL and IL-6 levels and improved lipid and kidney-profile markers and body weight compared to plain Cilostazol Loaded Solid Nanodispersion (CLT-15 WC SND). CLT-15 SND treatment groups showed decreased blood glucose by 3.38 and 9.71 percent, increased body weight by 2.81 and 5.27 percent, improved Interleukin-6 (IL-6) by 21.36 and 18.36 percent, improved urine albumin levels by 5.67 and 14.19 percent and creatinine levels by 3.125 and 37.5 percent, improved serum urea by 30.48 percent, increased serum albumin by 2.59 and 11.18 percent, and decreased creatinine and 5.03 and 8.12 percent, respectively as compared to CLT-15 WC and MP treatment animal groups. CLT and Cur reduced IL-6, kidney, and lipid markers, demonstrating their renoprotective and pancreas-protective effects. CLT and Cur's inhibition may be the mechanism.

Training effectiveness evaluation: Advancing a Kirkpatrick model based composite framework.

The present study aims at ideating a quantitative protocol to evaluate effectiveness of training programmes especially meant for farmers, farm women, and rural youth. The specific objective was to develop a robust framework for measuring the effectiveness of rural training programmes organized by the Farmers Training Centres (FTCs) of India. Kirkpatrick's training evaluation model provides us the foundation to design a four-dimensional composite framework based on range-based indicator normalization, principal component analysis based indicator weight estimation, and rank correlation based framework sensitivity testing. We used cross-sectional primary data generated through household survey and personal interviews with randomly selected one thousand trainees to test and validate our proposed protocol. Applying it on our evaluation target we find that the degree of effectiveness of the training programmes varies; one in every four training programmes may not be effective. Trainees' reactions on various aspects of the training programmes may have positive and significant influence on learning. Training outcomes may be linked with the trainees' post-training changes in behaviour. A sensitivity test confirms that the proposed framework is not susceptible to changes in weighting schemes, implying robustness of indicator selection. The findings offer dissection of individual training programmes guiding policy decisions for a training organization. The proposed framework enriches the Kirkpatrick's training evaluation model by offering standardized indicators for training effectiveness evaluation.

Microbially derived surfactants: an ecofriendly, innovative, and effective approach for managing environmental contaminants.

The natural environment is often contaminated with hydrophobic pollutants such as long-chain hydrocarbons, petrochemicals, oil spills, pesticides, and heavy metals. Hydrophobic pollutants with a toxic nature, slow degradation rates, and low solubility pose serious threats to the environment and human health. Decontamination based on conventional chemical surfactants has been found to be toxic, thereby limiting its application in pharmaceutical and cosmetic industries. In contrast, biosurfactants synthesized by various microbial species have been considered superior to chemical counterparts due to their non-toxic and economical nature. Some biosurfactants can withstand a wide range of fluctuations in temperature and pH. Recently, biosurfactants have emerged as innovative biomolecules not only for solubilization but also for the biodegradation of environmental pollutants such as heavy metals, pesticides, petroleum hydrocarbons, and oil spills. Biosurfactants have been well documented to function as emulsifiers, dispersion stabilizers, and wetting agents. The amphiphilic nature of biosurfactants has the potential to enhance the solubility of hydrophobic pollutants such as petroleum hydrocarbons and oil spills by reducing interfacial surface tension after distribution in two immiscible surfaces. However, the remediation of contaminants using biosurfactants is affected considerably by temperature, pH, media composition, stirring rate, and microorganisms selected for biosurfactant production. The present review has briefly discussed the current advancements in microbially synthesized biosurfactants, factors affecting production, and their application in the remediation of environmental contaminants of a hydrophobic nature. In addition, the latest aspect of the circular bioeconomy is discussed in terms of generating biosurfactants from waste and the global economic aspects of biosurfactant production.

Comparison of the Incidence of Surgical Site Infection in Abdominal Wound Closure: Antibiotic-Coated Polyglactin 910 Suture Versus Polyglactin Suture With Local Infiltration of Antibiotic Along the Incision Line.

Aim and objectives The purpose of this study is to compare the incidence of surgical site infection (SSI) rates in abdominal wound closure utilizing antibacterial-coated (triclosan-coated) suture material versus conventional suture material with subcutaneous antibacterial infiltration along the incision line. Materials and method This prospective and comparative (randomized, non-blinded clinical trial) was conducted at the Postgraduate Department of Surgery, Swaroop Rani Nehru Hospital, associated with Motilal Nehru Medical College, Prayagraj, India. The sample size was calculated to be one hundred. The patients in Group A underwent laparotomy using polyglactin 910 coated with triclosan. The patients in Group B underwent normal suture closure and local infiltration of broad-spectrum antibiotics (1 gram of ceftriaxone in 10 ml distilled water, along with the incision). Results There was no discernible difference between the various groups on postoperative day (POD) 14, 21, and 30. In Group A, 100.0% of individuals had healed wound status (POD 30). Group B had healed wound status among the 96.0% of members (POD 30). Twenty percent of the people in Group A had SSI whereas 38.0% of the participants in Group B had SSI. There was no discernible difference between the two groups regarding the distribution of culture (χ² = 7.741, p = 0.127). Conclusion Triclosan-coated sutures are more effective than subcutaneous antibiotic infiltration along the incision line in lowering the frequency of SSI during primary laparotomy wound closure.

Surface-Engineered Ni2P: An Efficient Oxygen Electrocatalyst for Zinc-Air Battery.

The surface engineering of electrocatalysts is one of the promising strategies to increase the intrinsic activity of electrocatalysts. It generates anion/cation vacancy defects and increases the electrochemically active surface area. We describe the surface engineering of Ni2P to favorably tune the bifunctional oxygen electrocatalytic activity and the development of a rechargeable zinc-air battery (ZAB). Ni2P encapsulated with N and P-dual doped carbon (Ni2P@NPC) is synthesized using a single-source precursor complex tris-(2,2'-bipyridine)nickel(II) bis(hexafluorophosphate). The surface engineering of the as-synthesized Ni2P@NPC is achieved by the controlled acid treatment at room temperature. The surface engineering removes carbon debris and opens the pores, exfoliates the encapsulating carbon layer, increases the P-vacancy in the crystal lattice, and boosts the electrochemically active surface area. The surface-engineered catalyst exhibits enhanced bifunctional activity towards oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). The electrocatalytically active sites of engineered catalysts are highly accessible for facilitated electron transfer kinetics. P-vacancy favors the facile formation of defect-rich OER active metal oxyhydroxide species. The rechargeable ZAB based on the engineered catalyst delivers a specific capacity of 770.25 mA h gZn-1, energy density of 692 Wh kgZn-1, and excellent charge-discharge cycling performance with negligible voltaic efficiency loss (0.6 %) after 100 h.

Radiographic Anatomy of the Common Carotid Artery for Direct Carotid Puncture.

BACKGROUND: Direct common carotid puncture (DCP) is conventionally used as a bailout technique in stroke patients. However, little is known about the relevant anatomy. Our objective was to examine the relationship of the common carotid artery (CCA) to surrounding structures based on different DCP trajectories passing through the artery's center. METHODS: Fifty randomly selected head/neck CTAs were analyzed. The trajectory of DCP and relationship to the internal jugular vein (IJV) and thyroid were analyzed at 1 cm intervals above the clavicle on 7 axial sections. Using the trans-carotid sagittal plane as the 0° trajectory, we plotted 3 additional trajectories at 30° intervals and the relationship with the IJV and thyroid proximity was graded as following: 0=absent, 1=adjacent, and 2=crossing. The CCA tortuosity index was also analyzed for each vessel. RESULTS: Analysis of 2800 trajectories across 100 CCAs showed that the IJV and thyroid were least encountered on the axial sections 2 cm above the clavicle, at 0° on the right (9 thyroids and 6 IJV), and at 90° on the left (0 Thyroids and 14 IJVs). The tortuosity index of the CCA was significantly lower above the clavicle than its entire length (P < 0.001). CONCLUSIONS: DCP performed 2 cm above the clavicle at 0° on the right, and 90° on the left appears to minimize encounters with the IJV and thyroid gland, reducing potential complications. However, despite these findings, ultrasound guidance remains vital for DCP safety. Further focus on endovascular device safety in DCP is needed.

Fabrication Methods, Structural, Surface Morphology and Biomedical Applications of MXene: A Review.

Recently, two-dimensional (2-D) layered materials have revealed outstanding properties and play a crucial role for numerous advanced applications. The emerging transition metal carbides and nitrides, known as MXene with empirical formula Mn+1XnTx, have generated widespread attention and demonstrated impressive potential in various fields. The fabrication of 2-D novel MXene and its composites and their characterizations are applicable to vast applications in different areas such as energy storage, gas sensors, catalysis, and biomedical applications. In this review, the main focus is on the various synthesis methods, their properties, and biomedical applications. This review provides detailed illustrations of MXenes for many biomedical applications, including bioimaging, drug delivery, therapies, biosensors, tissue engineering, and antibacterial reagents. The challenges and future prospects were highlighted in a comprehensive manner, and the existing problems and potential for MXene-based biomaterials were analyzed with the goal of accelerating their use in the biomedical field.

FERONIA regulates salt tolerance in Arabidopsis by controlling photorespiratory flux.

Photorespiration is an energetically costly metabolic pathway in plants that responds to environmental stresses. The molecular basis of the regulation of the photorespiratory cycle under stress conditions remains unclear. Here, we discovered that FERONIA (FER) regulates photorespiratory flow under salt stress in Arabidopsis (Arabidopsis thaliana). FER mutation results in hypersensitivity to salt stress, but disruption of ferredoxin-dependent glutamate synthase 1 (GLU1), an enzyme that participates in the photorespiratory pathway by producing glutamate, greatly suppresses fer-4 hypersensitivity to salt stress primarily due to reduced glycine yield. In contrast, disrupting mitochondrial serine hydroxymethyltransferase1 (SHM1), which is supposed to increase glycine levels by hampering the conversion of glycine to serine in the photorespiratory cycle, aggravates fer-4 hypersensitivity to salt stress. Biochemical data show that FER interacts with and phosphorylates SHM1, and this phosphorylation modulates SHM1 stability. Additionally, the production of proline and its intermediate △1-pyrroline-5-carboxylate (P5C), which are both synthesized from glutamate, also contributes to fer-4 hypersensitivity to salt stress. In conclusion, this study elucidates the functional mechanism of FER in regulating salt tolerance by modulating photorespiratory flux, which greatly broadens our understanding of how plants adapt to high salinity.

Management of Tuberculosis of the Hip With Antitubercular Therapy and Single-Stage Total Hip Replacement: A Case Report.

Hip tuberculosis (TB) is not a common disease, and this devastating illness requires complete treatment. This case study describes the treatment of a 25-year-old female who suffered from hip TB. She came with right hip discomfort, limping, and a restricted range of movement. The clinical examination showed a fixed flexion deformity, adduction, internal rotation, and leg shortening. Radiographic imaging showed arthritis with hip joint space narrowing, bone erosion, and bone disintegration. Laboratory testing revealed increased inflammatory markers, and a synovial fluid investigation showed tuberculous arthritis. The initial treatment consisted of a regular four-drug antitubercular therapy (ATT) regime for six months and then an additional four months of isoniazid and rifampicin. This therapy resulted in improved clinical symptoms and decreased inflammatory markers. However, the level of joint degeneration required surgical intervention. Due to substantial joint damage, the patient received a hybrid total hip replacement (THR) after completing ATT, confirming that the infection had been cured. Intraoperative observations included synovial enlargement, bone erosions, and significant cartilage damage. The patient underwent a rehabilitation program following surgery to regain mobility and hip joint range of motion. The patient reported substantial pain relief and functional improvement at the one-year follow-up with no signs of implant loosening or infection recurrence.

Rodent models in polycystic ovarian syndrome: Dissecting reproductive and metabolic phenotypes for therapeutic advancements.

The most prevalent reason for female infertility is polycystic ovarian syndrome (PCOS) exhibiting two of three phenotypes including biochemical or clinical hyperandrogenism, anovulation and polycystic ovaries. Insulin resistance and obesity are common in PCOS-afflicted women. Androgens are thought to be the primary cause of PCOS causing symptoms including anovulation, follicles that resemble cysts, higher levels of the luteinizing hormone (LH), increased adiposity, and insulin resistance. However, due to the heterogeneity of PCOS, it is challenging to establish a single model that accurately mimics all the reproductive and metabolic phenotypes seen in PCOS patients. In this review, we aimed to investigate rodent models of PCOS and related phenotypes with or without direct hormonal treatments and to determine the underlying mechanisms to comprehend PCOS better. We summarized rodent models of PCOS that includes direct and indirect hormone intervention and discussed the aetiology of PCOS and related phenotypes produced in rodent models. We presented combined insights on multiple rodent models of PCOS and compared their reproductive and/or metabolic phenotypes. Our review indicates that there are various models for studying PCOS and one should select a model most suitable for their purpose. This review will be helpful for consideration of rodent models for PCOS which are not conventionally used to determine mechanisms at the molecular/cellular levels encouraging development of novel treatments and control methods for PCOS.

Defining quality assurance guidance for effective selection of technical grade zero-valent iron production batch for groundwater remediation using permeable reactive barrier.

Zero-valent iron (ZVI) applied to the remediation of contaminated groundwater (GW) in situ, especially using engineered permeable reactive barriers (PRBs), has been proven to be an effective reactive material. However, many of ZVI brands do not represent tailored reagents specifically regarding destroying pollutants in GW. Thus, their reactivity towards certain contaminants in GW may vary significantly in a wide range even with different production batches of the same ZVI brand. This issue has rarely been known and consequently not addressed to a higher extend so far. Therefore, this study implemented extensive, long-term column experiments followed by short-term batch experiments for chlorinated volatile organic compounds (cVOCs) degradation for developing a semi-empirical test methodology to thoroughly resolve this pivotal issue by achieving an improved quality assurance guidance regarding proper field-scale emplacement of different ZVI brands and their production batches. The results showed that during column experiments perchloroethylene (PCE) led to a significant degradation up to a certain period but sulfate-reducing microorganisms enhanced the dehalogenation and led approximately to 100 % PCE removal. However, the efficacy varied for different ZVI brands, i.e., Gotthart Maier (GM) and Sponge Iron (Responge®). Furthermore, it could be shown that it might even vary among different production batches of the same ZVI brand. It was also observed that evolution of sulfate-reducing microorganisms may improve the efficacy of PCE degradation vastly that occur at different intensities with different ZVI brands and their respective production batches over time. Further, comparing comprehensive long-term column (kobs = 0.0488 1/h) and short-term batch experiments (kobs = 0.07794 1/h) as well as refined kinetic analyses (kobs = 0.0424 1/h) clearly prove that an appropriate guidance protocol for successful full-scale in situ remediation is required for properly select the right ZVI brand and production batch before it is loaded to a PRB in the field.

Design and Synthesis of Polyphenolic Imidazo[4,5-c]quinoline Derivatives to Modulate Toll Like Receptor-7 Agonistic Activity and Adjuvanticity.

TLR-7/8 agonists are a well-known class of vaccine adjuvants, with a leading example now included in Covaxin, a licensed human COVID-19 vaccine. This thereby provides the opportunity to develop newer, more potent adjuvants based on structure-function studies of these classes of compounds. Imidazoquinoline-based TLR7/8 agonists are the most potent, but when used as a vaccine adjuvant side effects can arise due to diffusion from the injection site into a systemic circulation. In this work, we sought to address this issue through structural modifications in the agonists to enhance their adsorption capacity to the classic adjuvant alum. We selected a potent TLR7-selective agonist, BBIQ (EC50 = 0.85 µM), and synthesized polyphenolic derivatives to assess their TLR7 agonistic activity and adjuvant potential alone or in combination with alum. Most of the phenolic derivatives were more active than BBIQ and, except for 12b, all were TLR7 specific. Although the synthesized compounds were less active than resiquimod, the immunization data on combination with alum, specifically the IgG1, IgG2b and IgG2c responses, were superior in comparison to BBIQ as well as the reference standard resiquimod. Compound 12b was 5-fold more potent (EC50 = 0.15 µM in TLR7) than BBIQ and induced double the IgG response to SARS-CoV-2 and hepatitis antigens. Similarly, compound 12c (EC50 = 0.31 µM in TLR7) was about 3-fold more potent than BBIQ and doubled the IgG levels. Even though compound 12d exhibited low TLR7 activity (EC50 = 5.13 µM in TLR7), it demonstrated superior adjuvant results, which may be attributed to its enhanced alum adsorption capability as compared with BBIQ and resiquimod. Alum-adsorbed polyphenolic TLR7 agonists thereby represent promising combination adjuvants resulting in a balanced Th1/Th2 immune response.

Neutrophil to lymphocyte ratio and serum procalcitonin level as a predictor of spontaneous ureteral stone passage: A prospective study.

BACKGROUND: Ureteric stone is responsible for around 20% of urinary tract stones and among them 70% of these are located in distal portion of the ureter. Stone causing ureter obstruction produce inflammatory changes in ureteric wall and prevent spontaneous passage of stone. The objective of the study is to compare the predictive role of procalcitonin and Neutrophil-to-lymphocyte ratio (NLR) for spontaneous passage of stone. MATERIALS AND METHODOLOGY: Total 150 participants having ureteric stone of 4-8 mm, were included in prospective observational study. The patients were followed up for 4 weeks. Spontaneous Stone Passage (SSP) was confirmed with either the patient collecting the stone during urination or by Non-Contrast CT performed at 4 weeks. Blood samples of the patients were analysed and White blood cells, sedimentation, Neutrophile to Lymphocyte (NLR), procalcitonin level compared to analyse predictors of future SSP. RESULT: The procalcitonin levels of the Spontaneous stone passing SSP (-ve) group (209.05 ± 78.45 pg/ml) were significantly higher than the not passing the SSP (+ve) group (130.76 ± 24.18) (p < 0.001). NLR is significantly higher in the SSP -ve (3.84 ± 0.41) than the SSP +ve (2.18 ± 0.38) group (p < 0.001). In single and multivariate analysis, significant activity was found for procalcitonin in SP +ve group. CONCLUSION: The findings of the study suggests that high level of procalcitonin, and high NLR have a negative effect on passage of stone. So early intervention can be planned to these patients to prevent complications.

A comprehensive review on nutritional interventions and nutritive elements: Strengthening immunity for effective defense mechanism during pandemic.

The pandemic has brought attention to the importance of a healthy immune system in preventing infectious diseases. In this in-depth review, the process by which nutritional interventions and fundamental nutrients affect immune function has been discussed with the goal of enhancing the body's natural defenses against viral infections. We explored the complex interplay between diet and immunology, highlighting the essential nutrients, vitamins, minerals, and bioactive substances that are crucial for enhancing immune response. We also investigated the effect of dietary patterns and supplementation methods on immune function. We assessed the effectiveness and potential mechanisms of action of various nutritional therapies in modifying immune responses through a thorough examination of scientific literature. Additionally, we go through the significance of individualized nutrition and highlight possible factors to consider for vulnerable groups, such as the elderly and people with chronic conditions. This review attempts to provide a thorough understanding of the role of diet in boosting immunity by synthesizing available research. It also offers insights into practical methods for enhancing the immune function during the current epidemic and in the future.

Stereotactic Body Radiation Therapy for Clinically Localized Prostate Cancer in Men With Hip Prostheses: A Cautionary Note.

PURPOSE: Stereotactic body radiation therapy (SBRT) has been established as a safe and effective treatment for prostate cancer. SBRT requires high accuracy to reduce treatment margins. Metal hip prostheses create artifacts that distort pelvic imaging and potentially decrease the accuracy of target/organ at risk (OAR) identification and radiation dose calculations. Data on the safety and efficacy of SBRT after hip replacement is limited. This single-institution study sought to evaluate the safety and local control following SBRT for prostate cancer in men with hip replacements. METHODS: 23 patients treated with localized prostate cancer and a history of pre-treatment hip replacement, treated with SBRT from 2007 to 2017 at MedStar Georgetown University Hospital were included in this retrospective analysis. Treatment was administered with the CyberKnife® (Accuray Incorporated, Sunnyvale, CA) at doses of 35 Gy or 36.25 Gy in 5 fractions. The targets and OARs were identified and contoured by a single experienced Radiation Oncologist (SPC). The adequacy of the CT and T2W MRI images for treatment planning was assessed with a three-point scale (good, adequate, or suboptimal). During treatment planning, care was taken to avoid treatment beams that directly traversed the hip prosthesis. Toxicities were recorded and scored using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v.4.0). Local recurrence was confirmed by magnetic resonance imaging and/or prostate biopsy. RESULTS: The median follow-up was seven years. The patients were elderly (median age = 71 years) with a high rate of comorbidities (Charlson Comorbidity Index > 2 in 25%). Four patients had bilateral hip replacements. The majority of patients were low to intermediate risk per the D'Amico classification. Around 13% received upfront ADT. In total, 13 patients were treated with 35 Gy, and 10 were treated with 36.25 Gy. The rates of late > Grade 3 GU toxicity and > Grade 2 GI toxicity were 8.6% and 4.3%, respectively. There were no Grade 4 or 5 toxicities. Six patients (26%) developed a local recurrence at a median time of 7.5 years. Of these six patients, four had unilateral hip replacements and two had bilateral. Three underwent salvage cryotherapy and three received salvage ADT. CONCLUSIONS:  In the general population, high-grade toxicities and local recurrences are uncommon following prostate SBRT. However, in this cohort of patients with prior hip replacements, prostate SBRT had higher than expected rates of late toxicity and local recurrence. In the opinion of the authors, such patients should be counseled regarding an elevated risk of late toxicity and local recurrence with prostate SBRT. With its ultrasound guidance, brachytherapy would have the advantage of circumventing the need for MRI/CT-based imaging and thus may represent a preferable radiation alternative in this patient population. If these patients are treated with SBRT, they should be monitored closely for local recurrence so early salvage can be performed. We hope that recent advances in metal artifact reduction techniques and dose-calculation algorithms will improve future outcomes.

Human immunodeficiency virus infection challenges: Current therapeutic limitations and strategies for improved management through long-acting injectable formulation.

HIV infection has been a severe global health burden, with millions living with the virus and continuing new infections each year. Antiretroviral therapy can effectively suppress HIV replication but requires strict lifelong adherence to daily oral medication regimens, which presents a significant challenge. Long-acting formulations of antiretroviral drugs administered infrequently have emerged as a promising strategy to improve treatment outcomes and adherence to HIV therapy and prevention. Long-acting injectable (LAI) formulations are designed to gradually release drugs over extended periods of weeks or months following a single injection. Critical advantages of LAIs over conventional oral dosage forms include less frequent dosing requirements, enhanced patient privacy, reduced stigma associated with daily pill regimens, and optimised pharmacokinetic/pharmacodynamic profiles. Several LAI antiretroviral products have recently gained regulatory approval, such as the integrase strand transfer inhibitor cabotegravir for HIV preexposure prophylaxis and the Cabotegravir/Rilpivirine combination for HIV treatment. A leading approach for developing long-acting antiretroviral depots involves encapsulating drug compounds in polymeric microspheres composed of biocompatible, biodegradable materials like poly (lactic-co-glycolic acid). These injectable depot formulations enable high drug loading with customisable extended-release kinetics controlled by the polymeric matrix. Compared to daily oral therapies, LAI antiretroviral formulations leveraging biodegradable polymeric microspheres offer notable benefits, including prolonged therapeutic effects, reduced dosing frequency for improved adherence, and the potential to kerb the initial HIV transmission event. The present manuscript aims to review the pathogenesis of the virus and its progression and propose therapeutic targets and long-acting drug delivery strategies that hold substantial promise for enhancing outcomes in HIV treatment and prevention.

Synthesis of thiazolidine-2,4-dione tethered 1,2,3-triazoles as α-amylase inhibitors: In vitro approach coupled with QSAR, molecular docking, molecular dynamics and ADMET studies.

A new series of thiazolidine-2,4-dione tethered 1,2,3-triazole derivatives were designed, synthesized and screened for their α-amylase inhibitory potential employing in vitro and in silico approaches. The target compounds were synthesized with the help of Cu (I) catalyzed [3 + 2] cycloaddition of terminal alkyne with numerous azides, followed by unambiguously characterizing the structure by employing various spectroscopic approaches. The synthesized derivatives were assessed for their in vitro α-amylase inhibition and it was found that thiazolidine-2,4-dione derivatives 6e, 6j, 6o, 6u and 6x exhibited comparable inhibition with the standard drug acarbose. The compound 6e with a 7-chloroquinolinyl substituent on the triazole ring exhibited significant inhibition potential with IC50 value of 0.040 µmol mL-1 whereas compound 6c (IC50 = 0.099 µmol mL-1) and 6h (IC50 = 0.098 µmol mL-1) were poor inhibitors. QSAR studies revealed the positively correlating descriptors that aid in the design of novel compounds. Molecular docking was performed to investigate the binding interactions with the active site of the biological receptor and the stability of the complex over a period of 100 ns was examined using molecular dynamics studies. The physiochemical properties and drug-likeliness behavior of the potent derivatives were investigated by carrying out the ADMET studies.

Revolutionizing Relief: Cervical Radiculopathy With Neurological Deficits Rescued by Cervical Disc Replacement.

Cervical radiculopathy is a common condition characterized by neck pain radiating to the upper and lower limbs, often accompanied by tingling sensations, numbness, and weakness. We present the case of a 32-year-old male who presented with left-sided cervical radiculopathy and neurological deficits. Clinical examination revealed left C5/C6/C7 hypoesthesia, diminished grip strength, reduced power in the left upper and lower extremities, and a positive Spurling test. Magnetic resonance imaging (MRI) of the cervical spine revealed multilevel cervical disc herniations at C4-C5 and C5-C6 levels, resulting in stenosis. The patient underwent anterior cervical discectomies with artificial disc replacement (cervical disc arthroplasty (CDA)) at the C5-C6 level. The surgical procedure was uneventful, and the patient experienced prompt relief from neurological symptoms within two weeks postoperatively. Follow-up radiographs at one week post-surgery demonstrated a preserved range of motion at each operated level with the artificial disc in situ. This case highlights the successful management of cervical radiculopathy with neurological deficits using anterior cervical discectomy and artificial disc replacement. The timely intervention led to the resolution of symptoms and restoration of function, demonstrating the efficacy of this surgical approach in alleviating radicular symptoms and preserving cervical spine mobility. Further studies and long-term follow-up are warranted to validate the long-term outcomes and durability of artificial disc replacement in such cases.