Evaluating the Diagnostic Efficacy of 99mTc-Methionine Single-Photon Emission Computed Tomography-Computed Tomography: A Head-to-Head Comparison with 11C-Methionine Positron Emission Tomography-Magnetic Resonance Imaging in Glioma Patients.

Background: Amino acid positron emission tomography (PET) imaging plays a significant role in the diagnosis of gliomas and in differentiating tumor recurrence from necrosis. In this study, the authors have evaluated the diagnostic efficacy of [99mTc]Tc-methionine single-photon emission computed tomography-computed tomography (SPECT-CT) in comparison with [11C]methionine PET-magnetic resonance imaging (MRI) in delineating tumors. Methods: Thirty-one (primary: 16 and postoperative: 15) patients of confirmed (either MRI or histopathological proven) glioma underwent both [99mTc]Tc-methionine SPECT-CT and [11C]methionine PET-MRI. A comparative analysis was performed between SPECT, PET, and MR images to calculate the concordance between the modalities and to evaluate the diagnostic efficacy of the [99mTc]Tc-methionine SPECT. Results: [99mTc]Tc-methionine SPECT showed comparable uptake in the tumor lesions in comparison to [11C]methionine PET. A significant and strong positive correlation was observed between the volume of tumor (Vt) in PET and Vt MR (p < 0.004). Likewise, a significant and strong positive correlation was found between Vt SPECT and Vt MR. [99mTc]-methionine has a sensitivity and specificity of 91% and 75%, respectively, compared with 82% and 100% for [11C]methionine in postoperative cases to differentiate the tumor recurrence from necrosis. The sensitivity and specificity of [99mTc]Tc-methionine was 92% and 100%, respectively, compared with 92% and 67% for [11C]methionine in primary tumors. Conclusion: [99mTc]Tc-methionine SPECT-CT is as equally good as [11C]methionine for diagnosing and differentiating it from necrosis especially in high-grade glioma.

An Insight into the Effect of Schiff Base and their d and f Block Metal Complexes on Various Cancer Cell Lines as Anticancer Agents: A Review.

Over the last few decades, an alarming rise in the percentage of individuals with cancer and those with multi-resistant illnesses has forced researchers to explore possibilities for novel therapeutic approaches. Numerous medications currently exist to treat various disorders, and the development of small molecules as anticancer agents has considerable potential. However, the widespread prevalence of resistance to multiple drugs in cancer indicates that it is necessary to discover novel and promising compounds with ideal characteristics that could overcome the multidrug resistance issue. The utilisation of metallo-drugs has served as a productive anticancer chemotherapeutic method, and this approach may be implemented for combating multi-resistant tumours more successfully. Schiff bases have been receiving a lot of attention as a group of compounds due to their adaptable metal chelating abilities, innate biologic properties, and versatility to tweak the structure to optimise it for a specific biological purpose. The biological relevance of Schiff base and related complexes, notably their anticancer effects, has increased in their popularity as bio-inorganic chemistry has progressed. As a result of learning about Schiff bases antitumor efficacy against multiple cancer cell lines and their complexes, researchers are motivated to develop novel, side-effect-free anticancer treatments. According to study reports from the past ten years, we are still seeking a powerful anticancer contender. This study highlights the potential of Schiff bases, a broad class of chemical molecules, as potent anticancer agents. In combination with other anticancer strategies, they enhance the efficacy of treatment by elevating the cytotoxicity of chemotherapy, surmounting drug resistance, and promoting targeted therapy. Schiff bases also cause cancer cell DNA repair, improve immunotherapy, prevent angiogenesis, cause apoptosis, and lessen the side effects of chemotherapy. The present review explores the development of potential Schiff base and their d and f block metal complexes as anticancer agents against various cancer cell lines.

Nanoemulsion potentiates the anti-cancer activity of Myricetin by effective inhibition of PI3K/AKT/mTOR pathway in triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) is a heterogeneous tumor with a poor prognosis and high metastatic potential, resulting in poor clinical outcomes, necessitating investigation to devise effective therapeutic strategies. Multiple studies have substantiated the anti-cancer properties of the naturally occurring flavonoid "Myricetin" in various malignancies. However, the therapeutic application of Myricetin is impeded by its poor water solubility and low oral bioavailability. To overcome this limitation, we aimed to develop nanoemulsion of Myricetin (Myr-NE) and evaluate its advantage over Myricetin alone in TNBC cells. The nanoemulsion was formulated using Capryol 90 (oil), Tween 20 (surfactant), and Transcutol HP (co-surfactant). The optimized nano-formulation underwent an evaluation to determine its size, zeta potential, morphology, stability, drug encapsulation efficiency, and in vitro release properties. The anti-cancer activity of Myr-NE was further studied to examine its distinct impact on intracellular drug uptake, cell-viability, anti-tumor signaling, oxidative stress, clonogenicity, and cell death, compared with Myricetin alone in MDA-MB-231 (TNBC) cells. The in vitro drug release and intracellular drug uptake of Myricetin was significantly increased in Myr-NE formulation as compared to Myricetin alone. Moreover, Myr-NE exhibited significant inhibition of cell proliferation, clonogenicity, and increased apoptosis with ~ 2.5-fold lower IC50 as compared to Myricetin. Mechanistic investigation revealed that nanoemulsion augmented the anti-cancer efficacy of Myricetin, most likely by inhibiting the PI3K/AKT/mTOR pathway, eventually leading to enhanced cell death in TNBC cells. The study provides substantial experimental evidence to support the notion that the Myr-NE formulation has the potential to be an effective therapeutic drug for TNBC treatment.

Comparative study of functional outcomes of arthroscopic anterior cruciate ligament reconstruction using anteromedial portal and translateral all-inside technique.

Background: Anterior Cruciate Ligament (ACL) injuries are common in the active population of the Armed Forces. Symptomatic instability prompts individuals to seek a cure or a sheltered appointment. Despite the increasing numbers of ACL reconstructions performed, the outcomes have not been so spectacular with only a meager percentage of our patients returning to preinjury levels of activity. With the premise that an all-inside ACL reconstruction is likely to result in better functional outcomes, the aim of this study was to compare the short-term functional outcomes of a large consecutive series of patients undergoing ACL reconstruction using the translateral all-inside ACL reconstruction technique (AI) and standard anteromedial portal technique (AM) with a minimum follow-up of one year. Methods: A total of 240 patients with isolated ACL tear underwent ACL reconstruction via the AI or AM technique. Their preoperative and postoperative scores were compared to look for any significant differences in functional outcomes. Results: The two groups were matched for age, BMI, mechanism of injury, and interval from injury to surgery. There was no difference in their preoperative scores. Postoperatively, although there were significant improvements across both groups, there was no significant difference between the groups at any point of time. Conclusion: The AI technique has garnered interest in recent literature in addressing ACL injuries. This study found no discernible benefit of the AI technique when compared to the AM technique in terms of functionality following an ACL reconstruction at any point of time up to 1 year following surgery.

Percutaneous Suspensory Stabilization of Chronic Distal Radioulnar Joint (DRUJ) Dislocation Using an Adjustable Loop Endobutton Construct: Case Report.

Chronic distal radioulnar joint (DRUJ) dislocation has been treated historically with complex osteotomies and reconstructive procedures, often resulting in intractable stiffness and loss of function. It is desirable to use a technique of fixation that will not only restore the wrist biomechanics but also be cosmetically appealing to the individual. We present a novel technique of reduction and fixation of a chronically dislocated DRUJ in a 26-year-old male using a minimally invasive approach, with successful restoration of DRUJ function and no postoperative complications.

Radiolabelled folate micellar carriers as proposed diagnostic aid for CNS tumors by nasal route.

Glioma refers to the most atypical variant of the malignant central nervous system tumors posturing massive challenge to the research fraternity owing to the flimsy improvement in the patient survival rate over the past years. The aim of the proposed work was developing a diagnostic aid for brain tumors, which could be administered via the non-invasive intranasal route. Since overexpression of folate receptors in the central nervous system tumors is 500 times more than the normal healthy cells, we aimed at fabricating a radiolabeled folate encapsulated micellar delivery system to be given via the nasal route. Folate conjugated bifunctional chelating agent was synthesized, radiolabeled with 99mTc, and encapsulated in a micellar carrier. The fabricated micelles were further evaluated for in vivo nasal toxicity in rats and the same were found safe for intranasal administration. The fabricated micelles owing to their nano size, mucoadhesive nature, and enhanced permeation were observed to have a higher uptake into the brain (around 16% in 4 h) than as compared to the radiolabeled conjugated folate solution when studied for in vivo biodistribution in mice. Single-photon emission computerized tomography imaging performed in higher animals upon intranasal administration of the micellar formulation revealed enhanced uptake of the micelles into the animal brain. It is believed that the aforementioned formulation can be of a great diagnostic value in the detection of not only brain tumors but also other folate expressing cancers such as cervical, breast, and lungs as the system is fast, non-toxic, accurate, non-invasive, and simple.

Percutaneous Suspensory Stabilization of Chronic Distal Radioulnar Joint (DRUJ) Dislocation Using an Adjustable Loop Endobutton Construct: Case Report / Fixação suspensiva percutânea de luxação crônica da articulação radioulnar distal (ARUD) usando um dispositivo de endobutton de laço ajustável: Relato de caso

Abstract Chronic distal radioulnar joint (DRUJ) dislocation has been treated historically with complex osteotomies and reconstructive procedures, often resulting in intractable stiffness and loss of function. It is desirable to use a technique of fixation that will not only restore the wrist biomechanics but also be cosmetically appealing to the individual. We present a novel technique of reduction and fixation of a chronically dislocated DRUJ in a 26-year-old male using a minimally invasive approach, with successful restoration of DRUJ function and no postoperative complications.

Resumo Luxação crônica da articulação radioulnar distal (ARUD) foi tratada historicamente com osteotomias complexas e procedimentos reconstrutivos, geralmente resultando em rigidez intratável e perda de função. É desejável usar uma técnica de fixação que não apenas restaure a biomecânica do punho, mas também seja esteticamente atraente para o indivíduo. Apresentamos uma nova técnica de redução e fixação de uma ARUD deslocada cronicamente em um homem de 26 anos, usando uma abordagem minimamente invasiva, com restauração bem-sucedida da função da ARUD e sem complicações pós-operatórias.

Targeting of rainwater harvesting structures using geospatial tools and analytical hierarchy process (AHP) in the semi-arid region of Rajasthan (India).

Burgeoning population growth and subsequent demand for freshwater, besides competition among irrigation, domestic, and industrial sectors, coupled with a changing climate, have necessitated prudent and effective management of water resources. Rainwater harvesting (RWH) is considered one of the most effective strategies for water management. However, the location and design of RWH structures are essential for proper implementation, operation, and maintenance. An attempt has been made in this study to locate the most suitable site for RWH structure and design using one of the robust multi-criteria decision analysis techniques, viz. analytic hierarchy process, using geospatial tools in the Gambhir watershed, Rajasthan, India. High-resolution Sentinel-2A data and a digital elevation model of the Advanced Land Observation Satellite were used in this study. Five biophysical parameters, viz. land use and land cover, slope, soil texture, surface runoff, and drainage density, were considered to identify suitable locations for RWH structures. It was observed that runoff is the prime factor in determining the location of RWH structures compared to other parameters. It was revealed that 75.54 km2 (13% of the total area) was very highly suited for the construction of RWH structures, while 114.56 km2 (19%) was highly suitable. A total of 43.77 km2 (7%) of land was determined to be unsuitable for the construction of any type of RWH structure. Farm ponds, check dams, and percolation ponds were suggested for the study area. Furthermore, Boolean logic was used to target a particular type of RWH structure. The study indicated that a total of 25 farm ponds, 14 check dams, and 16 percolation ponds can be constructed at identified locations in the watershed. Water resource development maps of the watershed generated using an analytical approach would be useful for policymakers and hydrologists for targeting and implementing RWH structures in the study watershed.

Assessment of genetic diversity of the fat-tailed Dumba sheep of India by mitochondrial and microsatellite markers.

India has a centuries-old tradition of sheep production and breeding that accomplish economic, agricultural, and religious roles. In addition to the 44 registered sheep breeds, there is a fat-tailed sheep population referred to as Dumba. This study evaluated genetic variation in Dumba sheep and its differentiation from other Indian sheep breeds using mitochondrial DNA and genomic microsatellite loci. Haplotype and nucleotide diversity based on mitochondrial DNA analysis revealed substantially high maternal genetic diversity in Dumba sheep. Major ovine haplogroups A and B observed in sheep populations across the globe registered their presence in the Dumba sheep. The molecular genetic analysis using microsatellite markers also showed high measures of allele (10.125 ± 0.762) and gene diversity (0.749 ± 0.029). Results correspond to the non-bottleneck population that is near mutation-drift equilibrium despite some deficiency in the number of heterozygotes (FIS = 0.043 ± 0.059). Phylogenetic clustering confirmed Dumba to be a distinct population. Results of this study endow authorities with critical information imperative for sustainable utilization and conservation of Indian fat-tailed sheep, which is considered to be an untapped genetic resource contributing to the food security, livelihood, and economic sustainability of rural households in marginal areas of the country.

Nontoxic In Vivo Clearable Nanoparticle Clusters for Theranostic Applications.

Disintegrable inorganic nanoclusters (GIONs) with gold seed (GS) coating of an iron oxide core with a primary nanoparticle size less than 6 nm were prepared for theranostic applications. The GIONs possessed a broad near-infrared (NIR) absorbance at ∼750 nm because of plasmon coupling between closely positioned GSs on the iron oxide nanoclusters (ION) surface, in addition to the ∼513 nm peak corresponding to the isolated GS. The NIR laser-triggered photothermal response of GIONs was found to be concentration-dependent with a temperature rise of ∼8.5 and ∼4.5 °C from physiological temperature for 0.5 and 0.25 mg/mL, respectively. The nanoclusters were nonhemolytic and showed compatibility with human umbilical vein endothelial cells up to a concentration of 0.7 mg/mL under physiological conditions. The nanoclusters completely disintegrated at a lysosomal pH of 5.2 within 1 month. With an acute increase of over 400% intracellular reactive oxygen species soon after γ-irradiation and assistance from Fenton reaction-mediated supplemental oxidative stress, GION treatment in conjunction with radiation killed ∼50% of PLC/PRF/5 hepatoma cells. Confocal microscopy images of these cells showed significant cytoskeletal and nuclear damage from radiosensitization with GIONs. The cell viability further decreased to ∼10% when they were sequentially exposed to the NIR laser followed by γ-irradiation. The magnetic and optical properties of the nanoclusters enabled GIONs to possess a T2 relaxivity of ∼223 mM-1 s-1and a concentration-dependent strong photoacoustic signal toward magnetic resonance and optical imaging. GIONs did not incur any organ damage or evoke an acute inflammatory response in healthy C57BL/6 mice. Elemental analysis of various organs indicated differential clearance of gold and iron via both renal and hepatobiliary routes.

[99mTc]Tc-DTPA-Bis(cholineethylamine) as an Oncologic Tracer for the Detection of Choline Transporter (ChT) and Choline Kinase (ChK) Expression in Cancer.

OBJECTIVE: The elevated choline transporters (ChT), choline kinase (ChK), choline uptake, and phosphorylation in certain tumor cells have influenced the development of radiolabeled choline derivatives as diagnostic probes for imaging cell membrane proliferation. We, therefore, aimed to develop a choline-based moiety for imaging choline kinase-overexpressed tumors by single-photon emission tomography (SPECT). A novel choline-based diagnostic probe was synthesized and evaluated preclinically in various ChT- and ChK-overexpressed tumor models for SPECT imaging applications. METHODS: The synthesis of diethylenetriaminepentaacetic acid-bis-choline ethylamine [DTPA-bis(ChoEA)] featured the conjugation of dimethylaminoethanol to a bifunctional chelator DTPA anhydride. [99mTc]Tc-DTPA-bis(ChoEA) was prepared, and its in vivo characteristics were evaluated in BALB/c mice and tumor-xenografted PC3, A549, and HCT116 athymic mouse models. The in vitro parameters, including cell binding and cytotoxicity, were assessed in PC3, A549, and HCT116 cell lines. To evaluate the specificity of the radioprobe, competitive binding studies were performed. Small-animal SPECT/CT diagnostic imaging was performed for in vivo evaluation. The mouse biodistribution data was further investigated to estimate the radiation dose in humans. RESULTS: In silico studies suggested high binding with enhanced specificity. A standard radiolabeling procedure using stannous chloride as a reducing agent showed a labeling yield of 99.5 ± 0.5%. The in silico studies suggested high binding with enhanced specificity. [99mTc]Tc-DTPA-bis(ChoEA) showed high in vitro stability and specificity. The pharmacokinetic studies of [99mTc]Tc-DTPA-bis(ChoEA) in mice showed an increased tumor-to-background ratio after few minutes of intravenous administration. The first-in-human trial was also conducted. The effective dose was estimated to be 0.00467 mSv/MBq (4.67 mSv/GBq), resulting in a radiation dose of up to 1.73 mSv for the 370 MBq injection of [99mTc]Tc-DTPA-bis(ChoEA). CONCLUSIONS: The synthesized radioprobe [99mTc]Tc-DTPA-bis(ChoEA) accumulates specifically in choline kinase-overexpressed tumors with a high signal-to-noise ratio. The preclinical and first-in-man data suggested that [99mTc]Tc-DTPA-bis(ChoEA) could potentially be used as a diagnostic SPECT tracer in the monitoring and staging of cancer.

Biodegradable Protein-Stabilized Inorganic Nanoassemblies for Photothermal Radiotherapy of Hepatoma Cells.

Inorganic nanomaterials require optimal engineering to retain their functionality yet can also biodegrade within physiological conditions to avoid chronic accumulation in their native form. In this work, we have developed gelatin-stabilized iron oxide nanoclusters having a primary crystallite size of ∼10 nm and surface-functionalized with indocyanine green (ICG)-bound albumin-stabilized gold nanoclusters (Prot-IONs). The Prot-IONs are designed to undergo disintegration in an acidic microenvironment of tumor in the presence of proteolytic enzymes within 72 h. These nanoassemblies demonstrate bio- and hemocompatibility and show significant photothermal efficiency due to strong near infrared absorption contributed by ICG. The surface gold nanoclusters could efficiently sensitize hepatoma cells to γ-irradiation with substantial cytoskeletal and nuclear damage. Sequential irradiation of Prot-ION-treated cancer cells with near infrared (NIR) laser (λ = 750 nm) and γ-irradiation could cause ∼90% cell death compared to single treatment groups at a lower dose of nanoparticles. The superparamagnetic nature of Prot-IONs imparted significant relaxivity (∼225 mM-1 s-1) for T2-weighted magnetic resonance imaging. Additionally, they could also be engaged as photoacoustic and NIR imaging contrast agents. This work demonstrates bioeliminable inorganic nanoassemblies with significant theranostic potential.

Occurrence, molecular characterization and antimicrobial-resistance pattern of Staphylococcus species isolates from buck semen.

Staphylococcus aureus is one of the most prevalent pathogens, and a causative agent of a variety of infections in humans and animals. Most studies concentrated on characterization of staphylococcus isolates and its antimicrobial resistance from various illness of veterinary importance, but there is no specific study that is available on isolates from reproductive tract of small ruminants and especially its semen. Hence, in the current study, a total of 48 semen samples were collected from healthy bucks of different breeds to investigate the occurrence of S. aureus. Antimicrobial resistance and virulence of the Staphylococcus isolates were determined to assess the adverse effects of them on buck fertility. The bacterial isolates were tentatively confirmed as Staphylococcus spp. based on the Gram's staining, growth on Mannitol salt agar and catalase test. Overall, 75% (n = 36) of the samples were positive for Staphylococcus spp. from the total 48 buck semen ejaculates from different breeds and among them 23 (63.89%) were coagulase-negative (CoNS) and 13 (36.11%) were coagulase-positive Staphylococcus (CoPS) strains. The species identified by molecular characterization are S. aureus, S. chromogenes, S. haemolyticus, S. sciuri, S. simulans, and S. epidermidis from buck semen. Further, these isolates exhibited varying degrees of multidrug resistance genotypically as well as phenotypically. The presence of antibiotic resistance and virulence genes may pose a potential threat to reproductive health of animals, the animal handlers and livestock keepers, while simultaneously highlighting the need for vigilant monitoring of these isolates at the time of semen cryopreservation.

Hydraulic performance, consolidation characteristics and shear strength analysis of bentonites in the presence of fly-ash, sewage sludge and paper-mill leachates for landfill application.

A rapid upsurge in urban and industrial developments leads to increased generations of solid wastes. The most accepted technique of waste discarding around the world is landfilling. Leaching chemicals from municipal dumping grounds can pollute the groundwater source and the surrounding environment without appropriate precautionary measures. Bentonite is a low-cost constituent used as a liner material in landfills due to its low permeability, high sealing ability, high specific surface area, and the ability to hold up the impurity migration through adsorption. However, leachate interaction with bentonite may alter its properties and reduce its usefulness as a barrier material in the long term. Also, bentonite having different chemical and mineralogical compositions will behave differently due to the leachate interaction. Therefore, it is necessary to compare the performance of various bentonites in the presence of leachates. In the present investigation, two Indian bentonites of different mineralogical compositions were studied for their change in the index properties, swelling, swelling potential, swelling pressure, hydraulic conductivity, consolidation parameters and shear strength properties in the presence of fly ash, sewage sludge and paper mill leachates. The outcomes showed that in the presence of all the leachates, liquid limit, free swell, compression index, swelling potential, swelling pressure, time to complete 90% of consolidation and shear strength dropped; whereas, hydraulic conductivity and coefficient of consolidation increased. Besides, the quality of bentonite prominently influenced the hydraulic, strength and swelling behaviour. The bentonite having a higher cation exchange capacity, liquid limit, specific surface area, and swelling capability undergoes a higher variability in the free swell (80.0, 73.8 and 76.9% decline), liquid limit (73.5, 61.7 and 69.2% decline), swelling potential (61.3, 55.7 and 51.0% decline), swelling pressure (53.3 and 56.4% decrease), and hydraulic conductivity (57.5, 8.6 and 41.1 times increase at a void ratio of 1.2) values when infused with fly ash, sewage sludge and paper mill leachates, respectively. The study also showed that the fly ash leachate interaction causes a higher variation in bentonite behaviour than sewage sludge and paper mill leachates. The study's findings would prove beneficial to design engineers for selecting bentonite types for landfill liners.

Virtual screening of quinoline derived library for SARS-COV-2 targeting viral entry and replication.

The COVID-19 pandemic infection has claimed many lives and added to the social, economic, and psychological distress. The contagious disease has quickly spread to almost 218 countries and territories following the regional outbreak in China. As the number of infected populations increases exponentially, there is a pressing demand for anti-COVID drugs and vaccines. Virtual screening provides possible leads while extensively cutting down the time and resources required for ab-initio drug design. We report structure-based virtual screening of a hundred plus library of quinoline drugs with established antiviral, antimalarial, antibiotic or kinase inhibitor activity. In this study, targets having a role in viral entry, viral assembly, and viral replication have been selected. The targets include: 1) RBD of receptor-binding domain spike protein S 2) Mpro Chymotrypsin main protease 3) Ppro Papain protease 4) RNA binding domain of Nucleocapsid Protein, and 5) RNA Dependent RNA polymerase from SARS-COV-2. An in-depth analysis of the interactions and G-score compared to the controls like hydroxyquinoline and remdesivir has been presented. The salient results are (1) higher scoring of antivirals as potential drugs (2) potential of afatinib by scoring as better inhibitor, and (3) biological explanation of the potency of afatinib. Further MD simulations and MM-PBSA calculations showed that afatinib works best to interfere with the the activity of RNA dependent RNA polymerase of SARS-COV-2, thereby inhibiting replication process of single stranded RNA virus. Communicated by Ramaswamy H. Sarma.

Does the initial chest radiograph severity in COVID-19 impact the short- and long-term outcome? - a perspective from India.

PURPOSE: The chest radiograph (CXR) is among the most widely used investigations in coronavirus disease 2019 (COVID-19) patients. Little is known about its predictive role on the long-term outcome. The purpose of this study was to explore its association with the short and long-term outcome in COVID-19 patients. METHODS: A total of 1530 patients were assessed for the presence, radiographic pattern and distribution of lung lesions observed on baseline chest radiographs obtained at admission. The Brixia scoring system was applied for semiquantitative assessment of lesion severity. Short-term outcome was determined by clinical severity, duration of hospitalization and mortality. The 1415 survivors in this group were assessed after 5-6 months for the presence of residual symptoms. RESULTS: About 67% patients had an abnormal baseline CXR. Bilateral involvement with a basal preponderance was observed and ground-glass opacification was the most frequent finding. The Brixia score ranged from 0 to 16, median 2, interquartile range (IQR) [0-6]. About 36% patients were symptomatic on 5-6-month follow-up, with fatigability being the commonest symptom. A good correlation was observed between the CXR score and disease severity as well as duration of hospitalization. On multivariate analysis, the CXR score was found to be a significant independent predictor of in-patient mortality as well as presence of long-term residual symptoms in survivors. CONCLUSIONS: Disease severity as seen on the chest radiograph appears to play an important role in driving the short and long-term consequences of COVID-19 and could serve as a prognostic indicator, which influences short-term management and long-term follow-up.

Impact of real and simulated municipal solid waste leachates on the hydraulic and swelling behaviour of bentonites for landfill application.

For the efficient functioning of a landfill, compacted bentonite is an acclaimed liner element due to its excellent adsorption capability, minimal hydraulic conductivity, and superior specific surface area (SSA). However, the leachate generation within the landfill worsens the liner material's quality, causing migration of the leachates, contaminating groundwater, and causing pollution of surrounding environment. With this perspective, a comparative assessment of the influence of real and simulated municipal solid waste (MSW) leachate on two different bentonites has been carried out in the present investigation. The two bentonites, differing precisely by their cation exchange capacity (CEC), liquid limit (LL), and swelling capability, were examined for variation in their LL, free swell (FS), and hydraulic behaviour concerning their interaction with both leachates. Results depicted that in both the leachates, LL and FS, swelling potential (SP) and pressure declined, whereas hydraulic conductivity (HC) rose. Furthermore, the bentonite quality greatly influenced the LL, FS, SP, swelling pressure, and hydraulic behaviour. Bentonite having higher CEC, SSA, and swelling ability experienced a higher variability in the LL (55.5 and 65.2% decrease), free swelling (76.9 and 83.1% decrease), SP, swelling pressure (53.3 and 56.4% decrease), and HC (13.1 and 49.4 times increase) values when permeated with simulated and real MSW leachates, respectively. The study also showed that the real MSW leachate interaction causes a higher variation in bentonite behaviour than its simulated counterpart. The study's findings would prove beneficial to design engineers for selecting bentonite types for landfill liners.

Alpha-ketoglutarate decorated iron oxide-gold core-shell nanoparticles for active mitochondrial targeting and radiosensitization enhancement in hepatocellular carcinoma.

The ability of some tumours to impart radioresistance serves as a barrier in the cancer therapeutics. Mitochondrial metabolism significantly persuades this cancer cell survival, incursion and plays a crucial role in conferring radioresistance. It would be of great importance to target the active mitochondria to overcome this resistance and achieve tumoricidal efficacy. The current report investigates the improved radiosensitization effect (under Gamma irradiation) in hepatocellular carcinoma through active mitochondrial targeting of alpha-ketoglutarate decorated iron oxide-gold core-shell nanoparticles (GNP). The loading of a chemotherapeutic drug N-(4-hydroxyphenyl)retinamide in GNP allows adjuvant chemotherapy, which further sensitizes cancerous cells for radiotherapy. The GNP shows a drug loading efficiency of 8.5 wt% with a sustained drug release kinetics. The X-Ray diffraction (XRD) pattern and High-Resolution Transmission Electron microscopy (HRTEM) indicates the synthesis of core iron oxide nanoparticles with indications of a thin layer of gold shell on the surface with 1:7 ratios of Fe: Au. The GNP application significantly reduced per cent cell viability in Hepatocellular carcinoma cells through improved radiosensitization at 5 Gy gamma radiation dose. The molecular mechanism revealed a sharp increment in reactive oxygen species (ROS) generation and DNA fragmentation. The mitochondrial targeting probes confirm the presence of GNP in the mitochondria, which could be the possible reason for such improved cellular damage. In addition to the active mitochondrial targeting, the currently fabricated nanoparticles work as a potent Magnetic Resonance Imaging (MRI)/Computed Tomography (CT) contrast agent. This multifunctional therapeutic potential makes GNP as one of the most promising theragnostic molecules in cancer therapeutics.

Lamotrigine loaded PLGA nanoparticles intended for direct nose to brain delivery in epilepsy: pharmacokinetic, pharmacodynamic and scintigraphy study.

The present study aimed to investigate the brain targeting efficacy of Lamotrigine (LTG) loaded PLGA nanoparticles (LTG-PNPs) upon intranasal administration. LTG-PNPs were fabricated through the emulsification-solvent evaporation technique and evaluated for % Entrapment efficiency, particle size, in-vitro release, surface morphology, crystallinity, ex-vivo permeation & thermal behaviour. Biodistribution, gamma scintigraphy, and pharmacodynamic studies were performed in BALB/c mice, New Zealand rabbits, and Wistar rats respectively. LTG-PNPs exhibited % EE 71%; particle size 170.0 nm; Polydispersity index 0.191; zeta potential -16.60 mV. LTG-PNPs exhibited a biphasic release pattern. Biodistribution and gamma scintigraphy studies proved a greater amount of LTG in the brain following intranasal delivery of LTG-PNPs in comparison to LTG-SOL. Pharmacodynamic studies demonstrated delayed seizure onset time with LTG-PNPs in comparison to LTG-SOL. Intranasal administration of LTG-PNPs provided prolonged release, higher bioavailability, and better brain targeting bypassing the BBB. The developed formulation could be administered as a once-a-day formulation that would reduce the dosing frequency; dose; dose-related side effects; cost of the therapy and would be beneficial in the management of epilepsy as compared to the LTG-SOL. However, the proof of concept generated through these studies needs to be further validated in higher animals and human volunteers.

Synthesis and evaluation of technetium-99m labelled 1-(2-methoxyphenyl)piperazine derivative for single photon emission computed tomography imaging for targeting 5-HT1A.

Quantitative changes in expression level of 5HT1A are somewhere related to common neurological disorders such as anxiety, major depression and schizophrenia. We have designed EDTA conjugated SPECT imaging probe for localization of 5HT1A receptor in brain. For designing SPECT probe we have employed the concept of bivalent approach and a homodimeric system with desirable pharmacokinetics of 5HT1A imaging. 99mTc-EDHT was also evaluated for its stability through serum stability assay and glutathione challenge experiment. Biodistribution study showed the highest accumulation of radioactivity in kidney which depicted the renal mode of excretion from the body. However in brain the uptake of 1.21% ID per gram was observed in initial 5 min of drug administration. On blocking the receptor this percent get decreased to 0.97% ID per gram. The regional distribution in brain was also performed which showed the accumulation of drug in cerebellum, cortex and hippocampus part, which are already known for 5HT1A expression. Dynamic study in rabbit is also in support of results derived from biodistribution and blood kinetics experiment. These finding suggest that 99mTc-EDHT holds promising place for further optimization before nuclear medicine applications in different animal species.