Genistein mitigates nitroglycerine-induced migraine: modulation of nitric oxide-mediated vasodilation and oxidative stress.

Migraine is a widespread brain condition described by frequent, recurrent episodes of incapacitating, moderate-to-severe headaches with throbbing pain that are usually one-sided. It is the 2nd most debilitating state lived with disability in terms of years, with a prevalence rate of 15-20%. Significant drops in estrogen levels have been associated with triggering acute migraine attacks in certain cases. Phytoestrogens are plant-derived compounds that resemble estrogen in structure, enabling them to imitate estrogen's functions in the body by attaching to estrogen receptors. Thus, the study was aimed to explore the protective effect of genistein against migraine. Moreover, the role of nitric oxide was also studied in the observed effect of genistein. Nitric oxide (NO) is implicated in migraine pathophysiology due to its role in promoting cerebral vasodilation and modulation of pain perception. Exploring L-NAME, a nitric oxide synthase inhibitor in migraine research helps scientists better understand the role of NO in migraine. Nitroglycerine treatment significantly increased the facial-unilateral head pain and spontaneous pain, as evidenced by the increased number of head scratching and groomings. Nitroglycerine treatment also induced anxiogenic behavior in mice. A significant reduction in the number of entries in the light phase and open arm, respectively. Biochemical analysis indicated a significant increase in inflammatory and oxidative stress in the nitroglycerin group. A significant increase and decrease in brain TBARS and GSH were observed with nitroglycerine treatment, respectively. Moreover, nitroglycerine treatment has uplifted the serum TNF-α level. Genistein (20 mg/kg) significantly mitigated the facial-unilateral head pain, spontaneous pain, photophobia, and anxiety-like behavior induced by nitroglycerine. Biochemical analysis showed that genistein (20 mg/kg) significantly abrogated the nitroglycerine-induced lipid peroxidation and increased serum TNF-α level. Genistein treatment also upregulated the brain GSH level and downregulated the serum TNF-α level. The L-NAME-mediated alleviation of the protective effect of genistein might be attributed to the vasodilatory effect of L-NAME. Conclusively, it can be suggested that genistein might provide relief from migraine pain by inhibiting nitric oxide-mediated vasodilation and oxidative stress.

Pre-clinical and cellular safety assessment of oral administered DHA rich microalgae oil from Schizochytrium sp. (Strain ATCC-20889): acute, sub-chronic and genotoxicity.

The lack of toxicity data for DHA-rich oil from Schizochytrium sp. (Strain ATCC-20889) leads to its exclusion from the Qualified Presumption of Safety list. Therefore, present study addresses toxicity evaluation of DHA-rich microalgae oil using ex-vivo (cytotoxicity assay) and in-vivo methods (acute (OECD 423 guidelines), sub-chronic (OECD 452 guidelines), and genotoxicity assay). The ex-vivo results showed >90% cell viability of Caco-2 cells after 48 h of treatment (200 µg/mL of DHA). Additionally, the in-vivo acute toxicity study found that microalgae oil was nontoxic and classified under category 5 molecule according to OECD 423 guidelines with a highest degree of safety at 2000 mg/kg b.w. The in-vivo sub-chronic study revealed no significant mortality and changes in feed intake, body weight, haematological, biochemical, neurological, and urine parameters after repeated 180-days administration of DHA-rich microalgae oil at 250 mg/kg, 500 mg/kg, and 1000 mg/kg. Moreover, histopathology evaluation, comet assay, chromosomal aberration, and micronuclei assay also confirmed the nontoxic behavior of DHA-rich oil. Thus, the results from the ex-vivo and in-vivo studies indicate that DHA-rich oil from Schizochytrium sp. (Strain ATCC-20889) is safe for use as a novel food, and can be included in infants, adults, pregnant women, and children formula.

Propellant Free Pressurized Spray System of Etodolac to Manage Acute Pain Conditions: In Vitro and In Vivo Evaluation.

This study aimed to develop a propellant-free topical spray formulation of Etodolac (BCS-II), a potent NSAID, which could be beneficial in the medical field for the effective treatment of pain and inflammation conditions. The developed novel propellant-free spray formulation is user-friendly, cost-effective, propellant-free, eco-friendly, enhances the penetration of Etodolac through the skin, and has a quick onset of action. Various formulations were developed by adjusting the concentrations of different components, including lecithin, buffering agents, film-forming agents, plasticizers, and permeation enhancers. The prepared propellant-free spray formulations were then extensively characterized and evaluated through various in vitro, ex vivo, and in vivo parameters. The optimized formulation exhibits an average shot weight of 0.24 ± 0.30 ml and an average drug content or content uniformity of 87.3 ± 1.01% per spray. Additionally, the optimized formulation exhibits an evaporation time of 3 ± 0.24 min. The skin permeation study demonstrated that the permeability coefficients of the optimized spray formulation were 21.42 cm/h for rat skin, 13.64 cm/h for mice skin, and 18.97 cm/h for the Strat-M membrane. When assessing its potential for drug deposition using rat skin, mice skin, and the Strat-M membrane, the enhancement ratios for the optimized formulation were 1.88, 2.46, and 1.92, respectively against pure drug solution. The findings from our study suggest that the propellant-free Etodolac spray is a reliable and safe topical formulation. It demonstrates enhanced skin deposition, and improved effectiveness, and is free from any skin irritation concerns.

Novel Hyaluronic Acid ethosomes based gel formulation for topical use with reduced toxicity, better skin permeation, deposition, and improved pharmacodynamics.

Hyaluronic Acid (HA) has been applied as an anti-ageing molecule in the form of topical products. Current topical commercial formulations of HA face the limitations of very small and stagnant skin permeation, thereby demanding enduring administration of the formulation to sustain its action. In this study, Lipid-based nanocarriers in the form of ethosomes were formulated in a 1% w/w HA strength and were extensively evaluated in vitro, ex-vivo, and in vivo parameters along with a comparison to it's commercial counterpart. The optimised ethosomes-based HA gel formulation revealed required pH (6.9 ± 0.2), small globule size (1024 ± 9 nm), zeta potential of -6.39 ± 0.2 mV, and 98 ± 1.1% HA content. The ex vivo skin permeation and deposition potenwere conferred on synthetic membrane Strat-M, Human cadaver skin, mice skin, rat skin, and pig skin, and both parameters were found to be much higher in comparison to the commercial topical formulation. Skin deposition capacity of the optimised HA formulation was further confirmed by Scan Electron Microscopy (SEM) and Confocal Laser Scanning Microscopy (CLSM) and it was observed that the developed ethosomal gel formulation got deposited more on the treated skin. The in vivo anti-ageing effect of optimised ethosomal gel on rats was found to be greater when compared to commercial formulation of HA and the developed carrier-based system proved to deliver the HA molecule in very small amounts into the systemic circulation. The results endorse the ethosomal carrier-based formulation of HA as a attractive technique for better local bioavailability of HA.

Removal of cadmium and arsenic from water through biomineralization.

Due to anthropogenic activities, heavy metals such as cadmium (Cd) and arsenic (As) are one of the most toxic xenobiotics contaminating water, thus affecting human health and the environment. The objective of the present investigation was to study the effect of ureolytic bacteria Bacillus paramycoides-MSR1 for the bioremediation of Cd and As from contaminated water. The B. paramycoides showed high resistance to heavy metals, Cd and As, with minimum inhibitory concentration (MIC) of 12.84 µM and 48.54 µM, respectively. The urease activity and calcium carbonate (CaCO3) precipitation were evaluated in artificial wastewater with different concentrations of Cd (0, 10, 20, 30, 40, 50, and 60 µM) and As (0, 20, 40, 60, 80, and 100 µM). The maximum urease activity in Cd-contaminated artificial wastewater was observed after 96 hours, which showed a 76.1% decline in urease activity as the metal concentration increased from 0 to 60 µM. Similarly, 14.1% decline in urease activity was observed as the concentration of As was increased from 0 to 100 µM. The calcium carbonate precipitation at the minimum inhibitory concentration of Cd and As-contaminated artificial wastewater was 189 and 183 mg/100 ml, respectively. The percentage removal of metal from artificially contaminated wastewater with varied concentrations was analyzed using atomic absorption spectroscopy (AAS). After 168 hours of incubation, 93.13% removal of Cd and 94.25% removal of As were observed. Microstructural analysis proved the presence of calcium carbonate in the form of calcite, confirming removal of cadmium and arsenic by microbially induced calcium carbonate precipitation (MICCP) to be promising technique for water decontamination.

rGO-WO3 Heterostructure: Synthesis, Characterization and Utilization as an Efficient Adsorbent for the Removal of Fluoroquinolone Antibiotic Levofloxacin in an Aqueous Phase.

Herein, the heterostructure rGO-WO3 was hydrothermally synthesized and characterized by HRTEM (high-resolution transmission electron microscopy), FESEM (field emission scanning electron microscopy), XRD (X-ray diffraction), FT-IR (Fourier transform infrared spectroscopy), XPS (X-ray photoelectron microscopy), nitrogen physisorption isotherm, Raman, TGA (thermogravimetric analysis) and zeta potential techniques. The HRTEM and FESEM images of the synthesized nanostructure revealed the successful loading of WO3 nanorods on the surface of rGO nanosheets. The prepared heterostructure was utilized as an efficient adsorbent for the removal of a third-generation fluoroquinolone antibiotic, i.e., levofloxacin (LVX), from water. The adsorption equilibrium data were appropriately described by a Langmuir isotherm model. The prepared rGO-WO3 heterostructure exhibited a Langmuir adsorption capacity of 73.05 mg/g. The kinetics of LVX adsorption followed a pseudo-second-order kinetic model. The adsorption of LVX onto the rGO-WO3 heterostructure was spontaneous and exothermic in nature. Electrostatic interactions were found to have played a significant role in the adsorption of LVX onto the rGO-WO3 heterostructure. Thus, the prepared rGO-WO3 heterostructure is a highly promising material for the removal of emerging contaminants from aqueous solution.

Olive oil and oleic acid-based self nano-emulsifying formulation of omega-3-fatty acids with improved strength, stability, and therapeutics.

AIM: To develop, characterise, and optimise SNEDDS formulation to enhance organoleptics, bioavailability, physical & oxidative-stability, and extend shelf-life of pure Ω-3-fatty acids oil for use in the food fortification industry as nutraceuticals. METHODS: SNEDDS formulations were prepared using a simple stirring technique and optimised based on in-vitro characterisation. RESULTS: The optimised SNEDDS formulation (F3) had a mean diameter of 52.9 ± 0.4 nm, PDI of 0.229 ± 0.02, zeta potential of -17.3 ± 0.1 mV, cloud temperature of 92 ± 0.2 °C, self-emulsification time of 50 ± 0.2 sec, and stable under accelerated stability conditions. Intestinal permeability study on rat ileum depicted absorption of 88.5 ± 0.2% DHA at 5 h for F3 formulation in comparison to 61.5 ± 0.2% for commercial counterpart. F3 formulation exhibited better therapeutics for melamine-induced cognitive dysfunction. CONCLUSIONS: The developed Ω-3-loaded SNEDDS heralds the future for an efficacious, safer, and higher strength formulation intended as a better substitute for currently available formulations.

Luliconazole vesicular based gel formulations for its enhanced topical delivery.

Luliconazole is a new drug candidate for treatment of topical fungal infections. Its present therapy is associated with limitations of very poor and slow skin permeation, leading to required long term repeated administration for complete cure of disease. Lipid nanocarriers based elastic lipogel and ethogel formulations were developed in strength of 1% w/w and extensively characterized in vitro, ex-vivo, and in vivo and compared for their results to the marketed formulation. The prepared formulations were found to have ideal pH, nanometric vesicle size, encapsulation efficiency (92.7% and 91.2%), zeta potential (-17.0 and -32.8 mV), and viscosity (6.6 and 7.8 Pa.s) with no signs of instability on storage. In vitro activity against Candida albicans and dermatophytes demonstrated the prepared formulations to be 3 and 2.5 times more potent than marketed formulation, respectively. Ex vivo skin permeation and deposition studies, performed on various biological membranes and a synthetic membrane, manifest that Strat-M membrane resembles closest to the human skin followed by porcine ear skin, rat, and mice skin. Enhanced skin deposition of elastic lipogel and ethogel as compared to conventional marketed cream is also confirmed by SEM and CLSM analysis of the treated skin. In vivo antifungal activity on albino rats demonstrated vesicle based gel formulations to be safe, non irritant and more effective in topical treatment of fungal infections, with no drug reaching to systemic circulation. Thus, findings of the study demonstrate elastic liposomes and ethosomes, as a carrier are an attractive approach for enhanced topical delivery of Luliconazole.

Development, Characterization and Evaluation of Parenteral Formulation of Diclofenac Sodium.

Diclofenac sodium is a potent NSAID, classified under BCS class II category having a poor aqueous solubility. Recently, its injectable formulation got banned and withdrawn from the market due to its severe nephrotoxicity caused by the use of synthetic surfactant, i.e. Transcutol-P as solubilizer. Therefore, the present study was aimed to prepare Transcutol-P free injectable using Vitamin E TPGS as a biosurfactant which is in list of inactive ingredients by US-FDA. Various cost effective aqueous injectable formulations were prepared by mixed solvency method that were characterized and optimized for different in vitro quality control parameters. Further, ex vivo hemolytic study showed the increased safety (23.4 ± 1.6%) of optimized formulation as compared with its commercial counterpart (100 ± 4.2%) at 75 mg/ml. Furthermore, in vivo acute and sub-acute toxicity study demonstrated an increase in LD50 to 123.75 ± 6.2 mg/kg to that of a commercial counterpart (109.96 ± 5.5 mg/kg). In addition, optimized formulation demonstrated better mean residence time and area under curve when compared with commercial test group, respectively. Moreover, optimized formulation was also evaluated for its therapeutic efficacy. The results obtained from acetic acid-induced writhing test in albino mice showed 78 ± 2.1% protection from writhes after 120 min, whereas the commercial formulation had only 48.3 ± 1.9% protection. Additionally, carrageenan-induced rat paw edema model also confirmed the better anti-inflammatory activity of optimized aqueous injectable formulation than its commercial counterpart. Thus, the developed aqueous injectable formulation of diclofenac is free from toxic Transcutol-P with enhanced safety and therapeutic efficacy.

May-Thurner syndrome: an uncommon and incidental finding in a postpartum female.

May-Thurner syndrome or Cockett syndrome is a pathological condition that arises due to extrinsic compression on iliocaval venous territory, leading to venous outflow obstruction. Here, author presents an incidental finding of left common iliac vein extrinsic compression by right common iliac artery with collateral vessels in the pelvis in a postpartum female.

Propofol sparing effect of dexmedetomidine and magnesium sulfate during BIS targeted anesthesia: A prospective, randomized, placebo controlled trial.

BACKGROUND AND AIMS: Maintenance of adequate depth of anesthetic is crucial to prevent awareness and to reduce stress response associated with surgery. Goals of balanced general anesthetic are met by use of adjuvants to facilitate use of lower anesthetic dose, while ensuring adequate anesthetic depth. This study employed BIS monitoring to compare the anesthetic sparing effects of intravenous dexmedetomidine and magnesium sulphate on induction dose of propofol by maintaining a BIS value of 40-50. MATERIAL AND METHODS: One hundred and twenty ASA I and II patients undergoing elective surgery under general anesthetic were included in three groups of forty each. Group D received 1 µg/kg of dexmedetomidine, Group M was given 30 mg/kg of magnesium sulphate in 100 ml saline and Group N received 100 ml saline over 15-20 minutes 15 minutes before induction. Data compared were dose of propofol and vecuronium, Ramsay sedation score, BIS values and hemodynamic parameters intraoperatively. RESULTS: Propofol required in group D was significantly lower 101.3 ± 16.5 than group M and N with dose of 114 ± 15.5 and 160.50 ± 25.08 respectively (p <0.001). Dose requirement of vecuronium was significantly reduced in group M 5.4 ± 0.8 and group D 6.6 ± 1.2 as compared to N 7.9 ± 1.4 (p <0.001). No significant differences were seen regarding baseline hemodynamics, RSS and BIS values in all groups. After study drug infusion, RSS was 4.59 ± 0.75 in dexmedetomidine group compared to 1.9 ± 0.7 and 1.4 ± 0.5 in group M and N (p <0.001). During maintenance, significantly lower HR, MAP and BIS values were seen in group D and M than N (p <0.001). CONCLUSION: Our study showed that pretreatment with dexmedetomidine and magnesium sulphate significantly reduced the induction dose of propofol by maintaining a constant BIS in value at 40-50. However, both the drugs reduced the time to reach BIS 40-50 but sedation and sparing of propofol was more in dexmedetomidine group.

Clinical reappraisal of vasculobiliary anatomy relevant to laparoscopic cholecystectomy.

BACKGROUND: Laparoscopic cholecystectomy (LC) has many advantages as compared to open cholecystectomy. However, vasculobiliary injuries still continue to be a matter of concern despite advances in laparoscopic techniques. Misidentification and misperception of vasculobiliary structures is considered to be a pivotal factor leading to injuries. Although many studies since time immemorial have stressed on the importance of anatomy, an insight into laparoscopic anatomy is what essentially constitutes the need of the hour. OBJECTIVE: To assess the frequency and the relevance of anatomical variations of extrahepatic biliary system in patients undergoing LC. MATERIALS AND METHODS: The present study is an observational study performed for a period of 2 years from August 2014 to August 2016. It included all diagnosed patients of cholelithiasis undergoing routine LC performed by a single surgeon by achieving a critical view of safety. During dissection, vascular and ductal anomalies were noted and assessed for their relevance in LC. RESULTS: Seven hundred forty cases of cholelithiasis, irrespective of pathology, comprising 280 (37.83%) men and 460 (62.16%) females with a mean age of 39.85 ± 18.82 years were included in the study. Photodocumentation and operative recordings were available in 93% of cases. Operative findings revealed 197 (26.62%) vascular anomalies and 90 (12.16%) ductal anomalies. A single cystic artery was seen in 340 cases, and a normal cystic duct was seen in 650 cases. Variations in ductal anatomy were fewer than variations in vascular anatomy. CONCLUSION: Extra-biliary anatomy relevant to LC is unpredictable and varies from patient to patient. Vascular anomalies are more frequent than the ductal anomalies, and surgeon should be alert regarding their presence.

Physical characteristics and nutritional composition of some new soybean (Glycine max (L.) Merrill) genotypes.

Soybean is a major source of high quality protein and oil and soybean seed quality is often determined by seed nutritional and antinutritional parameters. The objective of this study was to investigate the physical characteristics and nutritional composition of some new soybean genotypes. Hundred seed weight and volume of soybean genotypes ranged from 8.7 to 11.1 g and 8.1 to 12.0 ml respectively, whereas, percent water absorption and percent volume expansion values ranged from 94.3 to 119.5% and 70.8 to 159.5% respectively. The genotypes contained % crude protein (39.4-44.4), oil (14.0-18.7), starch (4.3-6.7), total soluble sugars (5.6-7.9), reducing sugars (0.21-0.33) and sucrose (5.6-11.8). The free fatty acid and triglyceride content ranged from 31-71 mg 100 g(-1) oil and 90.1-93.9 g 100 g(-1) oil respectively. The antinutritional components determined include: mg g(-1) TIA (41.5-85.0), phytate (2.3-5.6), total phenols (1.0-1.5), flavonols (0.20-0.34) and ortho-dihydroxy phenols (0.10-0.21). A significant variation for the 11S/7S ratio was observed among the 8 soybean genotypes and the values ranged from 0.70 ('SL 768' and 'SL 869') to 2.4 ('SL 794').

Oral beta-hydroxybutyrate alleviates COVID-19 related acute respiratory distress syndrome: A randomized, single-blind, placebo-controlled trial.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a lung complication of COVID-19 that requires intensive care and ventilation. Beta-hydroxybutyrate (BHB) is a ketone body that can modulate metabolism and inflammation in immune cells and lung tissues. We hypothesized that oral BHB could alleviate COVID-19 related ARDS by reducing pro-inflammatory cytokines and increasing anti-inflammatory cytokines. METHODS: We randomized 75 patients with mild (as per Berlin criteria) ARDS symptoms to receive oral 25 g twice daily or placebo for five days. The primary outcome was the change in pro-inflammatory cytokines (Interleukin-1ß, Interleukin-6, interleukin-18, tumour necrosis factor-alpha) and anti-inflammatory cytokine (interleukin-10) from baseline to day 5. The secondary outcomes were the change in BHB levels from baseline to day 5, the number of hospitalization days, and the occurrence of adverse events. RESULTS: Treatment with formulated BHB resulted in a significant decrease in pro-inflammatory cytokines; Interleukin-1ß (p = 0.0204), Interleukin-6 (p = 0.0309), interleukin-18 (p = 0.0116), tumour necrosis factor-alpha (p = 0.0489) and increase in interleukin-10 (p = 0.0246) compared treatment with placebo. Importantly, higher BHB levels (p = 0.0001) were observed after supplementation; additionally, patients who underwent this approach were hospitalized for fewer days. No serious adverse events were reported. CONCLUSION: Beta-hydroxybutyrate, an oral adjunct therapy, has shown promising results in ameliorating symptoms of ARDS. This includes reduced inflammation, oxidative stress, and decreased patient fatigue levels. Further study with a large sample size is warranted to assess the potential of BHB therapy's effectiveness in reducing the development of severe illness. CLINICAL TRIAL REGISTRATION: (http://ctri.nic.in/CTRI/2021/03/031790).

A Comprehensive Analysis of Deep Learning-Based Approaches for Prediction and Prognosis of Infectious Diseases.

Artificial intelligence is the most powerful and promising tool for the present analytic technologies. It can provide real-time insights into disease spread and predict new pandemic epicenters by processing massive amount of data. The main aim of the paper is to detect and classify multiple infectious diseases using deep learning models. The work is conducted by using 29,252 images of COVID-19, Middle East Respiratory Syndrome Coronavirus, Pneumonia, normal, Severe Acute Respiratory Syndrome, tuberculosis, viral pneumonia, and lung opacity which has been collected from various disease datasets. These datasets are used to train the deep learning models such as EfficientNetB0, EfficientNetB1, EfficientNetB2, EfficientNetB3, NASNetLarge, DenseNet169, ResNet152V2, and InceptionResNetV2. The images have been initially graphically represented using exploratory data analysis to study the pixel intensity and find anomalies by extracting the color channels in an RGB histogram. Later, the dataset has been pre-processed to remove noisy signals using image augmentation and contrast enhancement techniques. Further, feature extraction techniques such as morphological values of contour features and Otsu thresholding have been applied to extract the feature. The models have been evaluated on the basis of various parameters, and it has been discovered that during the testing phase, the InceptionResNetV2 model generated the highest accuracy of 88%, best loss value of 0.399, and root mean square error of 0.63.

Highly fluorescent nickel based metal organic framework for enhanced sensing of Fe3+ and Cr2O72- ions.

Heavy metal contamination has sparked widespread concern among the populace. The significant issues necessitate the creation of high-performance fluorescent pigments that can identify harmful elements in water. The present study deals with metal organic framework [MOF] based on nickel [Ni-BDC MOF]. The Ni-BDC MOF was prepared by facile solvothermal method using nickel nitrate hexahydrate and terephthalic acid ligand as precursors. The MOF was characterized by various techniques in order to examine the crystal, morphological, structural, composition, thermal and optical properties. The detailed characterizations revealed that the synthesized Ni-BDC MOF are well-crystalline with high purity and possessing 3D rhombohedral microcrystals with rough surface. The MOF demonstrate good luminescence performance and excellent water stability. According to the Stern Volmer plot, the tests set up under optimized conditions demonstrate a linear correlation between the fluorescence intensity and concentration of both ions, i.e. Fe3+, and Cr2O72- ions. The linear range and detection limit for Fe3+ and Cr2O72- were found to be 0-1.4 nM and 0.159 nM, and 0-1 nM and 0.120 nM, respectively. The mechanisms for the selective detection of cations and anions were also explored. The recyclability for the prepared MOF was checked up to five cycles which showed excellent stability with just a slight reduction in efficiency. The constructed sensor was also used to assess the presence of Fe3+ and Cr2O72- ions in actual water samples. The results of the different experiments revealed that the prepared MOF is a good material for detecting Fe3+ and Cr2O72- ions.

Nascent Nanoformulations as an Insight into the Limitations of the Conventional Systemic Antifungal Therapies.

More than 150 million people have significant fungal diseases that greatly impact health care and economic expenditures. The expansion of systemic fungal infections and invasive mycoses is being driven by an increase in the number of immunocompromised patients and the recent COVID-19 patients, especially severely ill. There have been numerous cases of fungal infections linked to COVID-19, with pulmonary aspergillosis dominating at first but with the subsequent appearance of mucormycosis, candidiasis, and endemic mycoses. Candida spp. is the most frequent pathogen, with approximately 1 billion infections yearly, among other species causing the most prevalent invasive fungal infections. The importance of recognizing the epidemiological shifts of invasive fungal infections in patient care cannot be overstated. Despite the enormous antifungal therapies available, these infections are difficult to diagnose and cause high morbidity and mortality rates. Treatment choices for systemic fungal infections are severely limited due to the limitations of conventional therapy effectiveness and drug toxicities. So the researchers are still looking for novel therapeutic options, such as carrier-based approaches that are convenient and cost-effective with high and long-lasting fungal infection cure rates with reduced toxicities. The focus of this study is on summarizing the nanotechnology, immunotherapy methods and the drugs under clinical trials that have been employed in treatment as carrier-based antifungal formulations. Most of these have been reported to be promising strategies with broad-spectrum antifungal action and the potential to overcome antibiotic resistance mechanisms. We speculate that this review summarized the current knowledge to its best that will help the future developments of new antifungal therapies.

Carrier transport and photoconductivity properties of BN50/NiO50 nanocomposite films.

BN50/NiO50 and Au-loaded BN50/NiO50 nanocomposite films were separately fabricated on the glass substrates for carrier transport and photoconductivity properties. X-ray diffraction pattern of the films show the hexagonal structure of BN and presence of defect states by Nelson Riley factor analysis. Morphological images show spherical shaped particles with highly porous structure. The incorporation of NiO may hindered growth of BN layers and resulted in spherical particles. Temperature-dependent conductivity describes semiconductor transport behaviour for deposited nanocomposite films. Thermal activation conduction with low activation energy (∼0.308 eV) may be responsible for the resulting conductivity. Further, the light intensity dependent photoelectrical properties of BN50/NiO50 and Au-loaded BN50/NiO50 nanocomposites have been explored. The effect of Au nanoparticles loading on enhanced photo-conductivities (∼22% increase) than bare nanocomposite film has been elaborated by proposed mechanism. This study provided the insightful information for carrier transport and photoconductivity of BN-based nanocomposites.

Accuracy Differences in Cannabis Retailer Information Ascertained from Webservices and Government-Maintained State Registries Across US States Legalizing the Sale of Cannabis in 2019.

Cannabis retailer locations used to investigate geographic cannabis access are frequently ascertained from two sources: 1) webservices which provide locations of cannabis retailers (e.g., Yelp) or 2) government-maintained registries. Characterizing the operating status and location information accuracy of cannabis retailer data sources on a state-by-state level can inform research examining the health implications of cannabis legalization policies. This study ascertained cannabis retailer name and location from webservices and government-maintained registries for 26 states and the District of Columbia legalizing cannabis sales in 2019. Validation subsamples were created using state-level sequential sampling. Phone surveys were conducted by trained researchers for webservice samples (n=790, November 2019 - May 2020) and government-maintained registry (n=859, February - June 2020) to ascertain information about operating status and location. Accuracy was calculated as the percent agreement among subsample and phone survey data. For operating status and location, webservice derived data was 78% (614/790) and 79% (484/611) accurate, whereas government-maintained registry derived data was 76% (657/859) and 95% (622/655) accurate, respectively. Fifty-nine percent (15/27) of states and the District of Columbia had over 80% accuracy for operating status and 48% (13/27) states had over 80% accuracy for location information with both data sources. However, government-maintained registry derived information was more accurate in 33% (9/27) states for operating status and 41% (11/27) states for location information. Both data sources had similar operating status accuracy. Research using spatial analysis may prefer government-maintained registry derived data due to high location information accuracy, whereas studies looking at broad trends across states may prefer webservice derived. State level COVID-19 restrictions had minimal impact on ascertainment of cannabis retailer operating status and location information via phone survey derived from webservices and government-maintained registries.

Revolutionizing Pharmaceutical Industry: The Radical Impact of Artificial Intelligence and Machine Learning.

This article explores the significant impact of artificial intelligence (AI) and machine learning (ML) on the pharmaceutical industry, which has transformed the drug development process. AI and ML technologies provide powerful tools for analysis, decision-making, and prediction by simplifying complex procedures from drug design to formulation design. These techniques could potentially speed up the development of better medications and drug development processes, improving the lives of millions of people. However, the use of these techniques requires trained personnel and human surveillance for AI to function effectively, if not there is a possibility of errors like security breaches of personal data and bias can also occur. Thus, the present review article discusses the transformative power of AI and ML in the pharmaceutical industry and provides insights into the future of drug development and patient care.