Temporal Changes in Functional and Structural Neuronal Activities in Auditory System in Non-Severe Blast-Induced Tinnitus.

Background and Objectives: Epidemiological data indicate that blast exposure is the most common morbidity responsible for mild TBI among Service Members (SMs) during recent military operations. Blast-induced tinnitus is a comorbidity frequently reported by veterans, and despite its wide prevalence, it is also one of the least understood. Tinnitus arising from blast exposure is usually associated with direct structural damage that results in a conductive and sensorineural impairment in the auditory system. Tinnitus is also believed to be initiated by abnormal neuronal activities and temporal changes in neuroplasticity. Clinically, it is observed that tinnitus is frequently accompanied by sleep disruption as well as increased anxiety. In this study, we elucidated some of the mechanistic aspects of sensorineural injury caused by exposure to both shock waves and impulsive noise. The isolated conductive auditory damage hypothesis was minimized by employing an animal model wherein both ears were protected. Materials and Methods: After the exposure, the animals' hearing circuitry status was evaluated via acoustic startle response (ASR) to distinguish between hearing loss and tinnitus. We also compared the blast-induced tinnitus against the well-established sodium salicylate-induced tinnitus model as the positive control. The state of the sensorineural auditory system was evaluated by auditory brainstem response (ABR), and this test helped examine the neuronal circuits between the cochlea and inferior colliculus. We then further evaluated the role of the excitatory and inhibitory neurotransmitter receptors and neuronal synapses in the auditory cortex (AC) injury after blast exposure. Results: We observed sustained elevated ABR thresholds in animals exposed to blast shock waves, while only transient ABR threshold shifts were observed in the impulsive noise group solely at the acute time point. These changes were in concert with the increased expression of ribbon synapses, which is suggestive of neuroinflammation and cellular energy metabolic disorder. It was also found that the onset of tinnitus was accompanied by anxiety, depression-like symptoms, and altered sleep patterns. By comparing the effects of shock wave exposure and impulsive noise exposure, we unveiled that the shock wave exerted more significant effects on tinnitus induction and sensorineural impairments when compared to impulsive noise. Conclusions: In this study, we systematically studied the auditory system structural and functional changes after blast injury, providing more significant insights into the pathophysiology of blast-induced tinnitus.

Nanotechnology-based approaches for emerging and re-emerging viruses: Special emphasis on COVID-19.

In recent decades, the major concern of emerging and re-emerging viral diseases has become an increasingly important area of public health concern, and it is of significance to anticipate future pandemic that would inevitably threaten human lives. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged virus that causes mild to severe pneumonia. Coronavirus disease (COVID-19) became a very much concerned issue worldwide after its super-spread across the globe and emerging viral diseases have not got specific and reliable diagnostic and treatments. As the COVID-19 pandemic brings about a massive life-loss across the globe, there is an unmet need to discover a promising and typically effective diagnosis and treatment to prevent super-spreading and mortality from being decreased or even eliminated. This study was carried out to overview nanotechnology-based diagnostic and treatment approaches for emerging and re-emerging viruses with the current treatment of the disease and shed light on nanotechnology's remarkable potential to provide more effective treatment and prevention to a special focus on recently emerged coronavirus.

Sputum culture conversion with moxifloxacin-containing regimens in the treatment of patients with newly diagnosed sputum-positive pulmonary tuberculosis in South India.

BACKGROUND: Rapid sputum culture conversion at 2 months indicates the sterilizing capacity and potential of regimens to shorten duration of tuberculosis treatment. We compared results of sputum culture conversion by moxifloxacin and control regimens and identified factors affecting sputum culture positivity after 2 months of treatment. METHODS: Human immunodeficiency virus-uninfected adults with newly diagnosed smear-positive pulmonary tuberculosis were randomized to receive a 3- or 4-month moxifloxacin regimen (moxifloxacin [M], isoniazid [H], rifampicin [R], pyrazinamide [Z], ethambutol [E]) or the control regimen (RHZE thrice weekly). Bacteriological assessments were done at 15, 30, 45, and 60 days of treatment. Because all patients in the moxifloxacin groups received 2 months of daily RHZEM, they were grouped together for analysis. Statistical methods included χ(2) test and logistic regression analysis. RESULTS: Sputum culture conversion was analyzed in 780 (616 in the moxifloxacin group and 164 in the control group) of 801 enrolled patients. Ninety-five percent of 590 patients in the moxifloxacin group and 81% of 151 patients in the control group had negative sputum cultures at month 2 (P < .001). The control regimen, age (≥35 years), initial sputum culture grade (2+ or 3+), and male sex were significantly associated with higher odds of positive sputum cultures at 2 months. CONCLUSIONS: A 5-drug daily regimen with moxifloxacin results in significantly higher sputum culture conversion in the first 2 months compared with a thrice-weekly, 4-drug regimen in patients with newly diagnosed sputum-positive pulmonary tuberculosis.

Plant-Derived Zein as an Alternative to Animal-Derived Gelatin for Use as a Tissue Engineering Scaffold.

Natural biomaterials are commonly used as tissue engineering scaffolds due to their biocompatibility and biodegradability. Plant-derived materials have also gained significant interest due to their abundance and as a sustainable resource. This study evaluates the corn-derived protein zein as a plant-derived substitute for animal-derived gelatin, which is widely used for its favorable cell adhesion properties. Limited studies exist evaluating pure zein for tissue engineering. Herein, fibrous zein scaffolds are evaluated in vitro for cell adhesion, growth, and infiltration into the scaffold in comparison to gelatin scaffolds and are further studied in a subcutaneous model in vivo. Human mesenchymal stem cells (MSCs) on zein scaffolds express focal adhesion kinase and integrins such as αvß3, α4, and ß1 similar to gelatin scaffolds. MSCs also infiltrate zein scaffolds with a greater penetration depth than cells on gelatin scaffolds. Cells loaded onto zein scaffolds in vivo show higher cell proliferation and CD31 expression, as an indicator of blood vessel formation. Findings also demonstrate the capability of zein scaffolds to maintain the multipotent capability of MSCs. Overall, findings demonstrate plant-derived zein may be a suitable alternative to the animalderived gelatin and demonstrates zein's potential as a scaffold for tissue engineering.

Multicriteria Decision-Making Technique for Choosing the Optimal Ammonia Energy Share in an Ammonia-Biodiesel-Fueled Reactivity-Controlled Compression Ignition Engine.

Low-temperature combustion paired with the use of carbon-free ammonia and carbon-neutral biofuels is a novel approach for improving performance, reducing greenhouse gases, and reducing regulated emissions. Reactivity-controlled compression ignition (RCCI), a low-temperature combustion technology, dramatically reduces NOx and smoke emissions compared to traditional engines. Ammonia can be projected as a good transit fuel in the journey toward achieving net zero emissions and cleaner energy. This study examines the impact of ammonia energy premixing fraction (AEPF) (20, 30, 40, and 50%) as a low-reactive fuel (LRF) and algal biodiesel as a high-reactive fuel on the performance and emission characteristics of a single-cylinder, water-cooled 3.5 kW CI engine at a constant speed of 1500 rpm under various loading conditions. The research results indicate that the 40% ammonia share RCCI mode exhibited a reduction in carbon dioxide (CO2) by 14.16%, nitrogen oxide (NOx) by 22.6%, and smoke by 42.1%, with an 11.5% improvement in thermal efficiency compared to the neat biodiesel-fueled conventional engine. Furthermore, the analytical hierarchy process (AHP) will be used in conjunction with the technique for order of preference by similarity to ideal solution (TOPSIS) of multiple criteria decision-making techniques to determine the optimal energy share in the RCCI combustion with the goal of achieving superior thermal efficiency and lower emissions. According to the AHP-TOPSIS study findings, AEPF40 is the best choice for all engine loads.

Experimental Studies to Reduce Usage of Fossil Fuels and Improve Green Fuels by Adopting Hydrogen-Ammonia-Biodiesel as Trinary Fuel for RCCI Engine.

This study investigates the feasibility of hydrogen addition to achieve lower emissions and higher thermal efficiency in an ammonia-biodiesel-fueled reactivity-controlled compression ignition (RCCI) engine. A single-cylinder light-duty water-cooled compression ignition (CI) engine was adapted to run in RCCI combustion with port-injected ammonia and hydrogen as low reactive fuel (LRF) and direct-injected algal biodiesel as high reactive fuel (HRF). In our earlier study, the ammonia substitution ratio (ASR) was optimized as 40%. To optimize fuel and engine settings, hydrogen is added in quantities ranging from 5 to 20% by energy share. The combustion, performance, and emission characteristics were investigated for the trinary fuel operation. The result shows that the 20% hydrogen premixing with 40% ammonia-biodiesel RCCI operation increased the peak cylinder pressure (CP), peak heat release rate (HRR), and cumulative heat release rate (CHRR) by 15.12, 25.15, and 26.68%, respectively. Ignition delay (ID) and combustion duration (CD) were decreased by 15.53 and 11.24%, respectively. The combustion phasing angle was advanced by 4 °CA. The brake thermal efficiency (BTE) was improved by 15.49%, and brake specific energy consumption (BSEC) was reduced by 21.92%. While the nitrogen oxide (NOx) level was significantly increased by about 31.82%, the hydrocarbon (HC), carbon monoxide (CO), smoke, and exhaust gas temperature (EGT) were reduced by 24.53, 28.16, 25.82, and 17.47% as compared to the optimized ASR40% combustion.

Modulating the Effect of ß-Sitosterol Conjugated with Magnetic Nanocarriers to Inhibit EGFR and Met Receptor Cross Talk.

The cross-talk between the EGFR (Epidermal Growth Factor Receptor) and MET (Hepatocyte Growth Factor Receptor) poses a significant challenge in the field of molecular signaling. Their intricate interplay leads to dysregulation and contributes to cancer progression and therapeutic resistance. ß-Sitosterol (BS), a plant sterol with promising anticancer properties, shows increased research on its potential as a chemopreventive agent. However, significant modifications are required to deliver BS in cancer cells due to its lower efficacy. The present work aims to design a carrier-mediated delivery system specifically targeting cancer cells with EGFR and MET receptor cross-talk. Surface modification of BS was performed with superparamagnetic iron oxide nanoparticles (SPIONs), polyethylene glycol (PEG), and poly(N-isopropylacrylamide) (PNIPAM) to enhance the delivery of BS at the target site. BS was conjugated with SPIONs (BS-S), PNIPAM (BS-SP), PEG, and PNIPAM (BS-SPP) polymers, respectively, and the conjugated complexes were characterized. Results showed an increase in size, stability, and monodispersity in the following order, BS-S, BS-SP, and BS-SPP. The drug encapsulation efficiency was observed to be highest in BS-SPP (82.5%), compared to BS-S (61%) and BS-SP (74.9%). Sustained drug release was achieved in both BS-SP (82.6%) and BS-SPP (83%). The IC 50 value of BS, BS-S, BS-SP, and BS-SPP towards MCF 7 was 242 µg/mL,197 µg/mL, 168 µg/mL, and 149 µg/mL, HEPG2 was 274 µg/mL, 261 µg/mL, 233 µg/mL and 207 µg/mL and NCIH 460 was 191 µg/mL, 185 µg/mL, 175 and 164 µg/mL, indicating highest inhibition towards NCIH 460 cells. Our results conclude that ß-sitosterol conjugated with SPION, PEG, and PNIPAM could be a potential targeted therapy in inhibiting EGFR and MET receptor-expressing cancer cells.

Effect of minocycline and its nano-formulation on central auditory system in blast-induced hearing loss rat model.

Blast injuries are common among the military service members and veterans. One of the devastating effects of blast wave induced TBI is either temporary or permanent hearing loss. Treating hearing loss using minocycline is restricted by optimal drug concentration, route of administration, and its half-life. Therefore, therapeutic approach using novel therapeutic delivery method is in great need. Among the different delivery methods, nanotechnology-based drug delivery is desirable, which can achieve longer systemic circulation, pass through some biological barriers and specifically targets desired sites. The current study aimed to examine therapeutic effect of minocycline and its nanoparticle formulation in moderate blast induced hearing loss rat model through central auditory system. The I.v. administered nanoparticle at reduced dose and frequency than regularly administered toxic dose. After moderate blast exposure, rats had hearing impairment as determined by ABR at 7- and 30-days post exposure. In chronic condition, free minocycline also showed the significant reduction in ABR threshold. In central auditory system, it is found in this study that minocycline nanoparticles ameliorate excitation in inferior colliculus; and astrocytes and microglia activation after the blast exposure is reduced by minocycline nanoparticles administration. The study demonstrated that in moderate blast induced hearing loss, minocycline and its nanoparticle formulation exhibited the optimal therapeutic effect on the recovery of the ABR impairment and a protective effect through central auditory system. In conclusion, targeted and non-targeted nanoparticle formulation have therapeutic effect on blast induced hearing loss.

Enhanced Targeted Delivery of Minocycline via Transferrin Conjugated Albumin Nanoparticle Improves Neuroprotection in a Blast Traumatic Brain Injury Model.

Traumatic brain injury (TBI) is a major source of death and disability worldwide as a result of motor vehicle accidents, falls, attacks and bomb explosions. Currently, there are no FDA-approved drugs to treat TBI patients predominantly because of a lack of appropriate methods to deliver drugs to the brain for therapeutic effect. Existing clinical and pre-clinical studies have shown that minocycline's neuroprotective effects either through high plasma protein binding or an increased dosage requirement have resulted in neurotoxicity. In this study, we focus on the formulation, characterization, in vivo biodistribution, behavioral improvements, neuroprotective effect and toxicity of transferrin receptor-targeted (tf) conjugated minocycline loaded albumin nanoparticles in a blast-induced TBI model. A novel tf conjugated minocycline encapsulated albumin nanoparticle was developed, characterized and quantified using a validated HPLC method as well as other various analytical methods. The results of the nanoformulation showed small, narrow hydrodynamic size distributions, with high entrapment, loading efficiencies and sustained release profiles. Furthermore, the nanoparticle administered at minimal doses in a rat model of blast TBI was able to cross the blood-brain barrier, enhanced nanoparticle accumulation in the brain, improved behavioral outcomes, neuroprotection, and reduced toxicity compared to free minocycline. Hence, tf conjugated minocycline loaded nanoparticle elicits a neuroprotective effect and can thus offer a potential therapeutic effect.

Experimental Investigation on the PCCI Engine Fueled by Algal Biodiesel Blend with CuO Nanocatalyst Additive and Optimization of Fuel Combination for Improved Performance and Reduced Emissions at Various Load Conditions by RSM Technique.

Fossil fuel depletion and environmental pollution are paramount problems the world faces. Despite several measures, the transportation industry is still battling to manage these issues. A combined approach of fuel modification for low-temperature combustion with combustion enhancers could offer a breakthrough. Due to their properties and chemical structure, biodiesels have piqued the interest of scientists. Studies have asserted that microalgal biodiesel might be a viable alternative. Premixed charge compression ignition (PCCI) is an easily adoptable promising low-temperature combustion strategy in compression ignition engines. The objective of this study is to identify the optimal blend and catalyst measure for improved performance and reduced emissions. Microalgae biodiesel at various proportions (B10, B20, B30, and B40) was amalgamated with CuO nanocatalyst and tested to arrive at the right concoction of biodiesel with nanoparticles in a 5.2 kW CI engine for different load conditions. The PCCI function warrants that about 20% of the fuel supplied is vaporized for premixing. Finally, the interplay factors of the independent variables of the PCCI engine were then explored by response surface methodology (RSM) to determine the optimal level of desired dependent and independent variables. The RSM experiment findings suggest that the best biodiesel and nanoparticle concoctions at 20%, 40%, 60%, and 80% loads were B20CuO76, B20Cu60, B18CuO61, and B18CuO65, respectively. These findings were experimentally validated.

Experimental Investigation on the Effect of Graphene Oxide in Higher Alcohol Blends and Optimization of Injection Timing Using an ANN Method.

The use of alternative fuels in diesel engines has become more widespread due to a number of factors, including dwindling petroleum supplies, increasing prices for conventional fossil fuels, and environmental worries about pollutants and greenhouse gas emissions from internal combustion engines. Efficiency and emissions need to be appropriately balanced. Alcohols act as oxygenated fuels similar to octanol, offering a number of benefits over traditional fuels and can boost efficiency, enhance combustion, and reduce air pollution. Therefore, the research aimed to enhance the performance and combustion characteristics of a diesel and octanol blend using graphene oxide (GO) nanoparticles as a fuel additive in a single-cylinder diesel engine while reducing emissions. Research findings will contribute significantly to improving the physical and chemical properties of diesel and octanol blends, thereby mitigating the challenges of limited petroleum reserves and environmental concerns. A range of different blends of diesel and octanol were prepared on a volume/volume basis in proportions of D70OCT30, D60OCT40, and D50OCT50, and then GO was added as a fuel additive to the abovementioned blends in varied proportions (40, 60, and 80 ppm) resulting in nine blends. These blends were analyzed in terms of various performance, combustion, and emission characteristics, and the obtained results helped to shed light on the impact of GO as a fuel additive. The results indicated that the fuel blend D70OCT30GO0.006 yielded the highest values. Furthermore, it is highly imperative that we develop a model that can be used to predict engine behavior and its stability without having to run an engine. For this, a data-driven artificial neural network (ANN) model was developed to predict the optimized injection timing for better combustion and reduced emission. The efficiency and prediction capabilities of the model were compared to the experimental data, which indicated that the ANN model had a better prediction score. The injection timing of the engine was optimized from 21 °CA to 21.5 °CA, which increased the efficiency by 1%. The research findings showed significantly improved physical and chemical properties of the blends, thereby mitigating the challenges of limited petroleum reserves and environmental concerns.

Potential Effect of Lemon Peel Oil with Novel Eco-Friendly and Biodegradable Emulsion in Un-Modified Diesel Engine.

The current research work is based on exploring a novel biological fuel source and renewable fuel offered by waste lemon fruit skin. Furthermore, bio-based multi-wall carbon nanotubes (BMWCNTs), emulsion, fossil diesel, and raw lemon peel oil were procured. The single-cylinder diesel engine was evaluated using these potential ingredients in terms of performance, combustion, and emission. Test engine results reveal that the presence of BMWCNT emulsion in the bio-fuel + blend + emulsion blend produced a lower (4.7%) brake thermal efficiency (BTE) and a higher (13.6%) brake-specific energy consumption (BSEC) at peak engine load conditions with diesel. The same test fuel blend possesses an equivalent heat release rate (HRR) and cylinder pressure trends to the diesel fuel blend due to an optimized air/fuel mixture and oxygen supply. Bio-fuel + blend + emulsion achieved step-down reductions of 7.83% carbon monoxide (CO) and 20.68% hydrocarbon (HC) emissions, as well as reductions of 27.7% nitrogen oxide (NOx) and 37.3% smoke emissions at peak engine load with diesel.

Investigation on Ammonia-Biodiesel Fueled RCCI Combustion Engine Using a Split Injection Strategy.

Advanced combustion concepts in compression ignition are emerging as one of the most promising solutions to reduce nitrogen oxides (NOx) and particle emissions without sacrificing fuel efficiency. Among many advanced combustion concepts, reactive controlled compression ignition (RCCI) can achieve a wider working range. In this study, to implement RCCI operation, ammonia gas is introduced through the manifold as a low-reactive fuel, and biodiesel is injected directly as a high-reactivity fuel with a 40:60 energy ratio. The effect of biodiesel split ratio in a split injection strategy (pre- and main injections) is examined under varied load conditions, and the results are compared with ammonia/biodiesel single injection. Results indicate that the use of the 45% biodiesel split ratio at full load boosts the peak in-cylinder pressure and heat release rate and shifts the peak occurrence toward the top dead center (TDC). An increase in brake thermal efficiency (BTE) to 36.22% and reduced brake specific energy consumption (BSEC) to 8.75 MJ/kWh are 12.33% higher and 19.31% lower than ammonia/biodiesel single injection. Emissions of HC, CO, and smoke opacity were reduced to 50 ppm, 0.098% vol, and 15.6%, which are 34.21, 39.13, and 33.89% lower, while the emission of NOx was increased to 615 ppm, which is 36.06% higher than the single-injection ammonia/biodiesel RCCI combustion.

Effect of Infill Patterns with Machine Learning Techniques on the Tensile Properties of Polylactic Acid-Based Ceramic Materials with Fused Filament Fabrication.

The field of additive manufacturing is quickly evolving from prototyping to manufacturing. Researchers are looking for the best parameters to boost mechanical strength as the demand for three-dimensional (3D) printers grows. The goal of this research is to find the best infill pattern settings for a polylactic acid (PLA)-based ceramic material with a universal testing machine; the impact of significant printing considerations was investigated. An X-ray diffractometer and energy-dispersive X-ray spectroscopy with an attachment of scanning electron microscopy were used to investigate the crystalline structure and microstructure of PLA-based ceramic materials. Tensile testing of PLA-based ceramics using a dog bone specimen was printed with various patterns, as per ASTM D638-10. The cross pattern had a high strength of 16.944 MPa, while the tri-hexagon had a peak intensity of 16.108 MPa. Cross3D and cubic subdivisions have values of 4.802 and 4.803 MPa, respectively. Incorporating the machine learning concepts in this context is to predict the optimal infill pattern for robust strength and other mechanical properties of the PLA-based ceramic model. It helps to rally the precision and efficacy of the procedure by automating the job that would entail substantial physical effort. Implementing the machine learning technique to this work produced the output as cross and tri-hexagon are the efficient ones out of the 13 patterns compared.

Animal model of repeated low-level blast traumatic brain injury displays acute and chronic neurobehavioral and neuropathological changes.

Blast-induced neurotrauma (BINT) is not only a signature injury to soldiers in combat field and training facilities but may also a growing concern in civilian population due to recent increases in the use of improvised explosives by insurgent groups. Unlike moderate or severe BINT, repeated low-level blast (rLLB) is different in its etiology as well as pathology. Due to the constant use of heavy weaponry as part of combat readiness, rLLB usually occurs in service members undergoing training as part of combat readiness. rLLB does not display overt pathological symptoms; however, earlier studies report chronic neurocognitive changes such as altered mood, irritability, and aggressive behavior, all of which may be caused by subtle neuropathological manifestations. Current animal models of rLLB for investigation of neurobehavioral and neuropathological alterations have not been adequate and do not sufficiently represent rLLB conditions. Here, we developed a rat model of rLLB by applying controlled low-level blast pressures (<10 psi) repeated successively five times to mimic the pressures experienced by service members. Using this model, we assessed anxiety-like symptoms, motor coordination, and short-term memory as a function of time. We also examined levels of superoxide-producing enzyme NADPH oxidase, microglial activation, and reactive astrocytosis as factors likely contributing to these neurobehavioral changes. Animals exposed to rLLB displayed acute and chronic anxiety-like symptoms, motor and short-term memory impairments. These changes were paralleled by increased microglial activation and reactive astrocytosis. Conversely, animals exposed to a single low-level blast did not display significant changes. Collectively, this study demonstrates that, unlike a single low-level blast, rLLB exerts a cumulative impact on different brain regions and produces chronic neuropathological changes in so doing, may be responsible for neurobehavioral alterations.

Nanoformulations - Insights Towards Characterization Techniques.

BACKGROUND: Drug-loaded novel nanoformulations are gaining importance due to their versatile properties compared to conventional pharmaceutical formulations. Nanomaterials, apart from their multifactorial benefits, have a wider scope in the prevention, treatment, and diagnosis of cancer. Understanding the chemistry of drug-loaded nano-formulations to elicit its behaviour both at molecular and systemic levels is critical in the present scenario. Drug-loaded nanoformulations are controlled by their size, shape, surface chemistry, and release behavior. The major pharmaceutical drug loaded nanocarriers reported for anticancer drug delivery for the treatment of various forms of cancers such as lung cancer, liver cancer, breast cancer, colon cancer, etc include nanoparticles, nanospheres, nanodispersions, nanocapsules, nanomicelles, cubosomes, nanoemulsions, liposomes and niosomes. The major objectives in designing anticancer drug-loaded nanoformulations are to manage the particle size/morphology correlating with the drug release to fulfil the specific objectives. Hence, nano characterizations are very critical both at in vitro and in vivo levels. OBJECTIVE: The main objective of this review paper is to summarise the major characterization techniques used for the characterization of drug-loaded nanoformulations. Even though information on characterization techniques of various nano-formulations is available in the literature, it is scattered. The proposed review will provide a comprehensive understanding of nanocharacterization techniques. CONCLUSION: To conclude, the proposed review will provide insights towards the different nano characterization techniques along with their recent updates, such as particle size, zeta potential, entrapment efficiency, in vitro release studies (chromatographic HPLC, HPTLC, and LC-MS/MS analysis), EPR analysis, X-ray diffraction analysis, thermal analysis, rheometric, morphological analysis etc. Additionally, the challenges encountered by the nano characterization techniques will also be discussed.

Fisetin, potential flavonoid with multifarious targets for treating neurological disorders: An updated review.

Neurodegenerative disorders pose a significant health burden and imprint a debilitative impact on the quality of life. Importantly, aging is intricately intertwined with the progression of these disorders, and their prevalence increases with a rise in the aging population worldwide. In recent times, fisetin emerged as one of the potential miracle molecules to address neurobehavioral and cognitive abnormalities. These effects were attributed to its actions on several macromolecules and multiple molecular mechanisms. Fisetin belongs to a class of flavonoids, which is found abundantly in several fruits and vegetables. Fisetin has manifested several health benefits in preclinical models of neurodegenerative diseases such as Alzheimer's disease, Vascular dementia, and Schizophrenia. Parkinson's disease, Amyotrophic Lateral Sclerosis, Huntington's disease, Stroke, Traumatic Brain Injury (TBI), and age-associated changes. This review aimed to evaluate the potential mechanisms and pharmacological effects of fisetin in treating several neurological diseases. This review also provides comprehensive data on up-to-date recent literature and highlights the various mechanistic pathways pertaining to fisetin's neuroprotective role.

Phage lysin to supplement phagebiotics to decontaminate processed sputum specimens.

The overgrowth of normal flora escaping the action of sputum processing chemicals is the major problem in broth-based tuberculosis (TB) detection systems. The use of phages to control the overgrowth of normal flora in processed sputum samples has already been established. Phage lysin and its supplementation to phagebiotics for the effective control of normal flora in sputum specimens were evaluated. Crude lysin was prepared from phage host mixture using standard procedures. About 120 sputum samples processed with 4% NaOH were collected and used to evaluate the effect of lysin, phagebiotics and phagebiotics supplemented with lysin on the overgrowth of normal flora. The effect of phagebiotics and lysin on the growth and retrieval of Mycobacterium tuberculosis was studied by conventional methods and the luciferase reporter phage (LRP) assay. Lysin alone and phagebiotics supplemented with lysin arrested the growth of normal flora in a significantly greater number of samples than phagebiotics alone. Lysin and phagebiotics did not show any inhibitory activity on M. tuberculosis. The use of antibiotics can be replaced by lysin or phagebiotics supplemented with lysin to control the overgrowth of normal flora in processed sputum samples without hampering the viability of M. tuberculosis.

Association of common type 1 and type 2 diabetes gene variants with latent autoimmune diabetes in adults: A meta-analysis.

BACKGROUND: The aim of this meta-analysis was to determine the association of common type 1 diabetes (T1D) and type 2 diabetes (T2D) gene variants (protein tyrosine phosphatase non-receptor 22 [PTPN22] rs2476601C/T, insulin [INS] rs689A/T and transcription factor 7-like 2 [TCF7L2] rs7903146C/T) with latent autoimmune diabetes in adults (LADA). METHODS: A systematic search of electronic databases was conducted up to 2017 and data from 16 independent case-control studies for three gene variants were pooled. The pooled allele and genotype frequencies for each T1D and T2D gene variant were used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Heterogeneity tests and evaluation of publication bias were performed for all studies. RESULTS: In all, 8869 cases and 20 829 controls pooled from 16 case-control studies were included in the analysis. For rs2476601, a significant association was found for homozygote TT (OR 2.67; 95% CI 1.92-3.70; P < 0.0001), heterozygote CT (OR 1.61; 95% CI 1.44-1.79; P < 0.0001), and the T allele (OR 1.62; 95% CI 1.48-1.78; P < 0.0001). Overall, a significant inverse association was observed for rs689 in the TT genotype (OR 0.43; 95% CI 0.30-0.64; P < 0.0001), AT genotype (OR 0.53; 95% CI 0.45-0.62; P < 0.0001), and T allele (OR 0.61; 95% CI 0.52-0.71; P < 0.0001). For the rs7903146 polymorphism, the T allele (OR 1.19; 95% CI 1.00-1.40; P = 0.04) may be associated with the risk of LADA. CONCLUSION: The rs2476601C/T, rs689A/T, and rs7903146C/T polymorphisms were found to be associated with the risk of LADA, thereby indicating that, genetically, LADA could be an admixture of both T1D and T2D.

Near infra-red polymeric nanoparticle based optical imaging in Cancer diagnosis.

Cancer disease is a foremost health concern and top basis of death in comparison with many diseases including cardiovascular disorders. During initial diagnosis (usually late diagnosis), a majority of cancer patients suffer from metastatic and advanced cancer stages which resulted in limited therapeutic modalities based interventions and effectiveness. Though considerable advancement has been made in combating the disease, continuous and intense efforts are ongoing for early diagnosis and development of therapies. Generally applied treatment options for cancer are surgery, chemotherapy and radiotherapy, which are restricted by failure to early diagnose, insufficient on-targeted drug delivery, systemic toxicity, and lack of real-time monitoring of therapeutic responses in cancer. Noninvasive imaging or minimally invasive imaging methodology is valuable in clinical diagnostic settings. Specifically, noninvasive optical imaging integrated with polymeric nanomaterial have been extensively investigated in the field of cancer diagnostics and therapy. Currently, optical imaging methods go together with polymer-based fluorescent nanoparticles in accomplishing the molecular level detection of tumor boundaries. NIR probe tagged polymeric nanoparticles have potential to provide an advantage in the early cancer detection, therapeutic monitoring and image guided surgery procedures. This article review the recent progress in state-of-the-art NIRF polymeric nanoparticles used for optical imaging particularly on cancer diagnosis.