Assessing melanoma prognosis: the interplay between patient profiles, survival, and BRAF, NRAS, KIT, and TWT mutations in a retrospective multi-study analysis.

The incidence and prevalence of melanoma are increasing globally, presenting a significant public health concern. The main genetic drivers of melanoma include BRAF, NRAS, KIT and triple wild-type (TWT) mutations. Little is known about the effects of these mutations on outcomes in terms of demographics and patient characteristics. We examined differences in melanoma mortality risk and mutation count across mutation type and patient disease profile. We extrapolated primary melanoma patient data from 14 studies via the cBioportal database. Patients were divided into demographic groups and classified according to BRAF, NRAS, KIT and TWT mutation status. Analyses included two-sample Student t-test and two-way analysis of variance tests analysis with Tukey's post hoc test. Survival outcomes were compared via Kaplan-Meier curve and Cox regression. NRAS-mutated patients exhibited decreased overall survival compared to BRAF-mutated patients. Male patients had higher mutation counts across all gene groups than females, with the fewest TWT mutations in comparison to BRAF, NRAS and KIT mutations. Males also exhibited increased mortality risk for NRAS, KIT and TWT mutations compared to BRAF mutations. An unknown primary melanoma was associated with increased mortality risk across all gene groups. NRAS-mutated acral melanoma patients had an increased mortality risk compared to NRAS-mutated cutaneous melanoma patients. Older patients had a higher mortality risk than younger patients. Patients with heavier versus lower weights had lower mortality risk, which was more pronounced for BRAF-mutated patients. These relationships highlight the importance of demographic and pathologic relationships to aid in risk assessment and personalize treatment plans.

Nano-gel formulation of polyphenolic fraction of tobacco stem for wound healing and its inhibitory efficacies against the receptors of chronic wound development.

Current investigation deals with the gel formulation of purified polyphenol loaded nanoparticles for enhanced wound healing. Polyphenols purified using column chromatography an were characterized using HPLC in fractions. Silver nanoparticles were characterization using SEM, AFM, TEM, DLS. Cytotoxic effect was checked on L929 (Mouse fibroblast cells). Bioactive loaded nanoparticles were formulated in gel and subjected for physical characterization. Excision wound wistar rat models were established to measure the wound contraction measurement, histopathological studies, and biochemical assays. Docking and Simulation studies were performed to check the binding and stability with receptors progressing the chronic wound. From the column chromatography, B fraction has shown the presence of maximum polyphenolic content and as well as the polyphenol compounds such as quercetin, rutin and tannic acid as confirmed by the HPLC. Synthesize B fraction-AgNP were found to be below 100 nm in size and spherical in shape as per the characterization. No cytotoxic effect was observed on L929 cells treated with B fraction and its nanoparticles. Formulated B fraction-AgNP gel has revealed the better stability and earlier wound contraction, i.e. before the completion of 14 days of topical treatment. Histopathology studies and collagen content has confirmed the re-epithelization in skin wounds. MD simulation revealed the stability with PI3K and AKT. This can be concluded that tobacco stem polyphenol loaded nanoparticles has potent wound healing activity that can be utilized as nano-drug delivery system for suppression of chronic wound development.Communicated by Ramaswamy H. Sarma.

Unlocking Nature's Toolbox: glutamate-inducible recombinant protein production from the Komagatella phaffii PEPCK promoter.

BACKGROUND: Komagataella phaffii (a.k.a. Pichia pastoris) harbors a glutamate utilization pathway in which synthesis of glutamate dehydrogenase 2 and phosphoenolpyruvate carboxykinase (PEPCK) is induced by glutamate. Glutamate-inducible synthesis of these enzymes is regulated by Rtg1p, a cytosolic, basic helix-loop-helix protein. Here, we report food-grade monosodium glutamate (MSG)-inducible recombinant protein production from K. phaffii PEPCK promoter (PPEPCK) using green fluorescent protein (GFP) and receptor binding domain of SARS-CoV-2 virus (RBD) as model proteins. RESULTS: PPEPCK-RBD/GFP expression cassette was integrated at two different sites in the genome to improve recombinant protein yield from PPEPCK. The traditional, methanol-inducible alcohol oxidase 1 promoter (PAOX1) was used as the benchmark. Initial studies carried out with MSG as the inducer resulted in low recombinant protein yield. A new strategy employing MSG/ethanol mixed feeding improved biomass generation as well as recombinant protein yield. Cell density of 100-120 A600 units/ml was achieved after 72 h of induction in shake flask cultivations, resulting in recombinant protein yield from PPEPCK that is comparable or even higher than that from PAOX1. CONCLUSIONS: We have designed an induction medium for recombinant protein production from K. phaffii PPEPCK in shake flask cultivations. It consists of 1.0% yeast extract, 2.0% peptone, 0.17% yeast nitrogen base with ammonium sulfate, 100 mM potassium phosphate (pH 6.0), 0.4 mg/L biotin, 2.0% MSG, and 2% ethanol. Substitution of ammonium sulphate with 0.5% urea is optional. Carbon source was replenished every 24 h during 72 h induction period. Under these conditions, GFP and RBD yields from PPEPCK equaled and even surpassed those from PAOX1. Compared to the traditional methanol-inducible expression system, the inducers of glutamate-inducible expression system are non-toxic and their metabolism does not generate toxic metabolites such as formaldehyde and hydrogen peroxide. This study sets the stage for MSG-inducible, industrial scale recombinant protein production from K. phaffii PPEPCK in bioreactors.

NOTCH Signaling Pathway: Occurrence, Mechanism, and NOTCH-Directed Therapy for the Management of Cancer.

It is now well understood that many signaling pathways are vital in carrying out and controlling essential pro-survival and pro-growth cellular functions. The NOTCH signaling pathway, a highly conserved evolutionary signaling pathway, has been thoroughly studied since the discovery of NOTCH phenotypes about 100 years ago in Drosophila melanogaster. Abnormal NOTCH signaling has been linked to the pathophysiology of several diseases, notably cancer. In tumorigenesis, NOTCH plays the role of a "double-edged sword," that is, it may act as an oncogene or as a tumor suppressor gene depending on the nature of the context. However, its involvement in several cancers and inhibition of the same provides targeted therapy for the management of cancer. The use of gamma (γ)-secretase inhibitors and monoclonal antibodies for cancer treatment involved NOTCH receptors inhibition, leading to the possibility of a targeted approach for cancer treatment. Likewise, several natural compounds, including curcumin, resveratrol, diallyl sulfide, and genistein, also play a dynamic role in the management of cancer by inhibition of NOTCH receptors. This review outlines the functions and structure of NOTCH receptors and their associated ligands with the mechanism of the signaling pathway. In addition, it also emphasizes the role of NOTCH-targeted nanomedicine in various cancer treatment strategies.

A Novel cause of Massive Hepatosplenomegaly with Fibrosis in two children: Transient Infantile Hypertriglyceridemia.

Background: Transient infantile hypertriglyceridemia (TIH) is a syndrome of hypertriglyceridemia, fatty liver, and deranged liver functions with progression to fibrosis and cirrhosis. It is an autosomal recessive disorder caused by mutations in Glycerol-3-phosphate dehydrogenase 1 gene present on Chromosome 12q12-q13, and has been reported in Israeli Arab families with high consanguinity. TIH is suspected by high serum triglyceride levels and steatosis on liver biopsy; however, diagnosis is confirmed on clinical exome sequencing. Clinical description: We present two cases of TIH belonging to the indigenous Hindu, hilly population of Himachal Pradesh in North India with no history of either consanguinity or family history. Management and outcome: The parents of both the cases were counselled regarding the disease and importance of growth and lipid level monitoring. Conclusion: Though TIH is an extremely rare entity, awareness about it is required as it is a contributor to non-alcoholic fatty liver disease (NAFLD) in children. Any child presenting with hepatomegaly and elevated fasting triglyceride levels should be further investigated for TIH.

Effective seed cake extract of O. sanctum inducing the p53 dependent apoptotic pathway in oral cancer cells.

OBJECTIVE: Present study was to observe the therapeutic aspects of seed cake extracts of Ocimum sanctum against the oral cancer cell line with the activation of p53 apoptotic pathway. METHOD: Seed cake extracts were characterized using GC-MS analysis. Cytotoxic activity was observed on KB cells and L929 cell through MTT assay and scratch assay. Antioxidant activity on KB cells were determined using enzymatic and non enzyme content in the treated cells. Chick chorioallantoic membrane (CAM) was established to check the presence of blood vessel formation and neuvasculature pattern in the treated fertilized eggs. DNA fragmentation and gene expression studies were also determined in the treated cells to check the upregulation of apoptotic pathways. RESULTS: GC-MS analysis confirmed alkaloids, phenols, and many. The cytotoxic activity showed maximum antiproliferative potential with aqueous extract, whereas no cytotoxic effect was observed on L929 cells. The ethanolic and aqueous extract has shown a greater SI value. Scratch assay has signified that aqueous extract has a lower migration rate of KB cells. Aqueous extract showed maximum enzymatic activity and lower malondialdehyde content in cells treated with ethanolic extract. CAM model confirmed that eggs treated with aqueous extract has shown inhibition of vasculature pattern and dissolutions of blood vessels. DNA Fragmentation and Gene expression studies confirmed maximum fold in the KB cell treated with an aqueous extract of seed cake leading to activation of p53 dependent apoptotic pathway. CONCLUSION: The potent therapeutic properties of seed cake extracts have been proven, and they can be used as herbal treatments to prevent oral cancer.

The intersection of video capsule endoscopy and artificial intelligence: addressing unique challenges using machine learning.

Introduction: Technical burdens and time-intensive review processes limit the practical utility of video capsule endoscopy (VCE). Artificial intelligence (AI) is poised to address these limitations, but the intersection of AI and VCE reveals challenges that must first be overcome. We identified five challenges to address. Challenge #1: VCE data are stochastic and contains significant artifact. Challenge #2: VCE interpretation is cost-intensive. Challenge #3: VCE data are inherently imbalanced. Challenge #4: Existing VCE AIMLT are computationally cumbersome. Challenge #5: Clinicians are hesitant to accept AIMLT that cannot explain their process. Methods: An anatomic landmark detection model was used to test the application of convolutional neural networks (CNNs) to the task of classifying VCE data. We also created a tool that assists in expert annotation of VCE data. We then created more elaborate models using different approaches including a multi-frame approach, a CNN based on graph representation, and a few-shot approach based on meta-learning. Results: When used on full-length VCE footage, CNNs accurately identified anatomic landmarks (99.1%), with gradient weighted-class activation mapping showing the parts of each frame that the CNN used to make its decision. The graph CNN with weakly supervised learning (accuracy 89.9%, sensitivity of 91.1%), the few-shot model (accuracy 90.8%, precision 91.4%, sensitivity 90.9%), and the multi-frame model (accuracy 97.5%, precision 91.5%, sensitivity 94.8%) performed well. Discussion: Each of these five challenges is addressed, in part, by one of our AI-based models. Our goal of producing high performance using lightweight models that aim to improve clinician confidence was achieved.

Assessing the potential of rosary pea (Abrus precatorius L.) derived aqueous seed extracts as anticancer agents and their phytoconstituents as COX-2 inhibitor: an in-vitro and in-silico approach.

Abrus precatorius L. is a traditional remedy with a long history of use in medicine around the globe due to its diverse phytochemical composition and bioactivities which are of utmost significance to the scientific community. With the aim to provide new insights into the antioxidant, antiproliferative and antiangiogenic properties of A. precatorius aqueous seed extracts, different extraction methods were employed. Aqueous extract prepared by Soxhlet method APW (Sox) had higher total phenolics, flavonoids and tannin content. In DPPH assay, APW (Sox) had the maximum free radical scavenging activity. The maximum FRAP value was displayed by APW (Mac). The maximum inhibition was shown by APW (Sox) against HPV18 (Hep2C) cells and APW (Mac) against HPV18 (KB) cells. In cervical cancer (Hep2C) cells, catalase (CAT), glutathione-s-transferase (GST) activity, and glutathione (GSH) content were all highest in APW (Sox) extract, whereas APW (Mac) extract demonstrated the highest superoxide dismutase (SOD) activity and the lowest malondialdehyde (MDA) content. Similarly, in oral cancer (KB) cells, APW (Mac) extract showed the highest SOD, CAT, GST activity and GSH content whereas APW (Sox) extract showed the least MDA content. Docking studies showed that tannic acid and rutin had the highest binding affinity, while MD simulations showed that they were stable in complex with COX-2 for at least 90 ns. Promising antiangiogenic activities were observed in both APW (Sox) and APW (Mac) in a dose dependent manner. Therefore, aqueous seed extracts of A. precatorius could be considered promising candidates for anticancer and antiangiogenic drugs.Communicated by Ramaswamy H. Sarma.

Novel biogenic silver nanoconjugates of Abrus precatorius seed extracts and their antiproliferative and antiangiogenic efficacies.

Biogenic silver nanoconjugates (AgNCs), derived from medicinal plants, have been widely explored in the field of biomedicines. AgNCs for the first-time were synthesized using ethyl acetate seed extracts of Abrus precatorius and their antiproliferative and antiangiogenic efficacies were evaluated against cervical and oral carcinoma. Ultraviolet-Visible spectrophotometry, dynamic light Scattering (DLS), and scanning electron microscopy (SEM) were used for characterization of AgNCs. Antiproliferative activity was investigated using MTT, DNA fragmentation and in-vitro antioxidant enzyme activity assays. In-vivo chick chorioallantoic membrane (CAM) model was used to evaluate antiangiogenic activity. A total of 11 compounds were identified in both the extracts in GCMS analysis. The synthesized AgNCs were spherical shaped with an average size of 97.4 nm for AgAPE (Sox) and 64.3 nm for AgAPE (Mac). AgNCs possessed effective inhibition against Hep2C and KB cells. In Hep2C cells, AgAPE (Mac) revealed the highest SOD, catalase, GST activity and lower MDA content, whereas AgAPE (Sox) showed the highest GSH content. On the other hand, in KB cells, AgAPE (Sox) exhibited the higher SOD, GST activity, GSH content, and least MDA content, while AgAPE (Mac) displayed the highest levels of catalase activity. Docking analysis revealed maximum binding affinity of safrole and linoleic acid with selected targets. AgAPE (Sox), AgAPE (Mac) treatment profoundly reduced the thickness, branching, and sprouting of blood vessels in the chick embryos. This study indicates that A. precatorius-derived AgNCs have enhanced efficacies against cervical and oral carcinoma as well as against angiogenesis, potentially limiting tumour growth.

Nutritional Assessment of Lactarius drassinus and L. controversus from the Cold Desert Region of the Northwest Himalayas for Their Potential as Food Supplements.

Kargil is a cold desert with hostile ecological conditions such as low temperature and precipitation, as well as difficult terrains. However, several wild mushrooms thrive well under such an extreme environment. Despite their abundance, the chemical composition of indigenous mushrooms has not been explored. This study aimed to assess the potential of two wild edible mushrooms from Kargil, Lactarius drassinus and Lactarius controversus, as food supplements by evaluating their nutritional and nutraceutical properties. Nutritional attributes such as total protein, available carbohydrates, soluble sugars, and vitamins were found to be high in the mushroom species. Furthermore, high mineral accumulation and relatively lower antinutrient concentrations resulted in higher bioavailabilities of Zn, Fe, Ca, and Mg. Gas-chromatography-mass-spectrometry-based metabolite profiling revealed that although the two mushroom species showed similar metabolite compositions, their relative concentrations differed. Sugars were the predominant compounds identified in both the species, with sugar alcohols being the major contributor. The second most abundant class of compound in L. drassinus was amino acids, with 5-oxoproline as the major contributor. On the other hand, fatty acids were the second most abundant compounds in L. controversus, with high oleic and linoleic acid concentrations. In the ultra-performance-liquid-chromatography-based quantification of phenolic compounds, chlorogenic acid was found to be highest in in terms of its concentration in both the mushrooms studied, followed by quercetin dihydrate and gallic acid in L. drassinus and L. controversus, respectively. Moreover, high antioxidant activities attributable to their high phenol, flavonoid, and carotenoid concentrations were observed. Overall, the two mushrooms offer well-balanced sources of nutritional and nutraceutical compounds, making them healthy foods.

Novel markers of COVID-19 mortality-A comparative study with patients of acute coronary syndrome.

Background: COVID-19 can cause severe pneumonia that can progress to multiple organ failure. It is believed that dysregulation of inflammation and cytokine storm, contributes to severe COVID-19. As inflammatory mediators play an important role in the pathogenesis of the severe disease, inflammatory markers like fever, leucocytosis, and C-reactive protein are known to predict severe disease. Various other biomarkers have been known to have prognostic value in patients with COVID-19 infection. Inflammation, both local and systemic plays an important role in the pathogenesis of acute coronary syndrome (ACS). Thus in this study, we aimed to compare and describe the various biomarkers, and mortality between patients admitted with COVID-19 infection and ACS patients without COVID-19 infection. Methods: In a retrospective observational case-control study, a total of 108 patients admitted to our hospital during the month of May 2021 with COVID-19 were enrolled. Patients of the acute coronary syndrome (tested negative for COVID-19 infection) admitted during the same month were enrolled (including both the intensive care unit and ward) as controls. Results: The median age of patients with COVID was significantly lower than that of patients with acute coronary syndrome [49 years (IQR, 36-62 years) and 60 years (IQR, 52-66 years)]. Left ventricular ejection fraction was significantly higher among patients with COVID infection (58.5 ± 6.3% versus 36.9 ± 9.3%). The total leukocyte count was significantly higher among patients with COVID-19 compared to those with acute coronary syndrome [13200 per microliter (8625-17500) vs 9800 per microliter (8150-12150), P < 0.001]. The blood urea level was significantly higher among patients with COVID infection [52.5 (IQR, 34.7-81.5) versus 20 (IQR, 16-31)]. Levels of C-reactive protein were significantly higher among patients with COVID [39 (IQR, 7.7-100) versus 2 (1.4-3.5)]. The mortality of patients hospitalized with COVID was 4 times higher than those with acute coronary syndrome [25.9% (28) versus 6.1% (6)]. Survivors of COVID-19 had higher hemoglobin levels than those who did not [12.5 g/dLvs 11.5 g/dL, P = 0.03]. Conclusions: Elevated total leukocyte counts reflect underlying secondary bacterial infection among patients with COVID-19 and help initiate appropriate antibiotics. Depletion of intravascular volume reflected by an increased urea/creatinine ratio increases the risk of mortality and warrants aggressive measures of rehydration and albumin infusion.

A Mini-review on Recent Strategies and Applications of Nanomedicines to Combat Antimicrobial Resistance.

One of the key factors contributing to mortality and morbidity globally is infectious ailments. According to recent statistics from WHO, amplified antimicrobial resistance occurrence among bacteria signifies the utmost threat to global public health. Bacteria have developed various strategies to resist antimicrobials, including enzymatic inactivation of antibiotics, drug efflux, modifications of the antibiotic molecule or chemical alteration of the antibiotic, limited drug uptake, etc. Furthermore, the inefficiency of antimicrobial drugs against resistant bacteria due to low solubility, instability, and associated side effects augments challenges to combat these resistant pathogens. This has attracted the attention of researchers to create nano-delivery and targeting techniques. This review presents an overview of antimicrobial resistance (AMR), its various subtypes, as well as mechanisms involved in AMR. This review also describes current strategies and applications of various nanocarriers, including nanoparticles, liposomes, lipid-based nanoparticles, micelles, and polymeric nanoparticles.

Atrial fibrillation and coronary artery disease: An integrative review focusing on therapeutic implications of this relationship.

The incidence of both atrial fibrillation (AF) and coronary artery disease (CAD) increases with advancing age. They share common risk factors and very often coexist. Evidence points to an intricate relationship between atrial tissue excitability and neuronal remodeling with ischemia at the microcirculatory level. In this review, we delineated this complex relationship, identified a common theme between the two, and discussed how the knowledge of this relationship translates into a positive and meaningful impact in patient management. Recent research indicates a high prevalence of CAD among AF patients undergoing coronary angiography. Further, the incidence of AF is much higher in those suffering from CAD compared to age-matched adults without CAD underlying this reciprocal relationship. CAD adversely affects AF by promoting progression via re-entry and increasing excitability of atrial tissue as a result of ischemia and electrical inhomogeneity. AF in turn accelerates atherosclerosis via endothelial dysfunctional and inflammation and together with enhanced thrombogenicity and hypercoagulability contribute to micro and macrothrombi throughout cardiovascular system. In a nutshell, the two form a vicious cycle wherein one disease promotes the other. Most AF recommendations focuses on rate/rhythm control and prevention of thromboembolism. Very few studies have discussed the importance of unmasking coexistent CAD and how the treatment of underlying ischemia will impact the burden of AF in these patients. Inflammation and endothelial dysfunction remain central to both disease processes and form a handsome therapeutic target in the management of the two diseases. The relationship between AF and CAD is complex and much more than mere coincidence. The two diseases share common risk factor and pathophysiology. Hence, it is impractical to treat them in isolation. Accordingly, we share the implications of managing underlying ischemia and inflammation to positively impact and improve quality of life among AF patients.

[Efficacité du tirofiban intracoronaire avant pose d'un stent suivi d'une perfusion dans une charge de thrombus importante prouvée par angiographie : une étude randomisée]. / Efficacy of pre stenting intracoronary tirofiban followed by infusion in angiographically proven large thrombus burden : A randomized controlled study.

BACKGROUND: The presence of angiographic thrombus is associated with poor outcomes in contemporary cardiology practice. Percutaneous coronary intervention (PCI) in such lesions is associated with slow flow and no-reflow phenomenon which translate into poor clinical outcomes. METHODS: This was a single-centre, prospective, open-label, randomized controlled study with 50 patients each in intervention group and control group. Patients with angiographically proven large thrombus burden were recruited. In the intervention group, patients were given loading dose of intracoronary tirofiban (25 mcg/kg infused over 5 minutes) followed by prolonged infusion of tirofiban (0.15 mcg/kg/min for 12-18 hours) followed by PCI after 48-72 hours interval. In control group patients were taken up directly for PCI during the index procedure. Outcomes were assessed angiographically and in terms of clinical endpoints. RESULTS: The primary composite-endpoint of recurrent angina, myocardial infarction, cardiovascular death, target lesion revascularization and unscheduled CABG was significantly lower in the intervention arm compared to control arm (4% vs 16%, p = 0.04). Amongst the secondary endpoints, a statistically significant 30-day increase in ejection fraction from baseline was observed in the intervention group compared to the control group (1.6 ± 1.3 vs 0.2 ± 0.4, p = 0.0001). Overall mortality was similar in the two groups (4% vs 8%, p = 0.39). The primary safety endpoint of major bleeding was also similar in the 2 groups (2% vs 0%, p = 0.31). CONCLUSIONS: Tirofiban use prior to PCI in high thrombus burden was associated with improved clinical and angiographic endpoints with similar adverse events compared to controls.

Biodiversity and Functional Attributes of Rhizospheric Microbiomes: Potential Tools for Sustainable Agriculture.

The quest for increasing agricultural yield due to increasing population pressure and demands for healthy food has inevitably led to the indiscriminate use of chemical fertilizers. On the contrary, the exposure of the crops to abiotic stress and biotic stress interferes with crop growth further hindering the productivity. Sustainable agricultural practices are of major importance to enhance production and feed the rising population. The use of plant growth promoting (PGP) rhizospheric microbes is emerging as an efficient approach to ameliorate global dependence on chemicals, improve stress tolerance of plants, boost up growth and ensure food security. Rhizosphere associated microbiomes promote the growth by enhancing the uptake of the nutrients, producing plant growth regulators, iron chelating complexes, shaping the root system under stress conditions and decreasing the levels of inhibitory ethylene concentrations and protecting plants from oxidative stress. Plant growth-promoting rhizospheric microbes belong to diverse range of genera including Acinetobacter, Achromobacter, Aspergillus, Bacillus, Burkholderia, Flavobacterium, Klebsiella, Micrococcus, Penicillium, Pseudomonas, Serratia and Trichoderma. Plant growth promoting microbes are an interesting aspect of research for scientific community and a number of formulations of beneficial microbes are also commercially available. Thus, recent progress in our understanding on rhizospheric microbiomes along with their major roles and mechanisms of action under natural and stressful conditions should facilitate their application as a reliable component in the management of sustainable agricultural system. This review highlights the diversity of plant growth promoting rhizospheric microbes, their mechanisms of plant growth promotion, their role under biotic and abiotic stress and status of biofertilizers. The article further focuses on the role of omics approaches in plant growth promoting rhizospheric microbes and draft genome of PGP microbes.

Validation of a Novel Supercritical Fluid Extractor/Dryer Combo Instrument.

The current pharmaceutical manufacturing scenario involves different techniques for the processing of materials. For example, the extraction unit is one of the essential aspects of plant-based pharmaceuticals. Recently, various kinds of extraction techniques have been used for analytical and preparative scales; among them, a supercritical fluid extractor (SCFE) is the most widely used technique for extraction. It is used for an extensive range of crude drugs and can be possible with the help of SCFE by varying temperature/pressure. Notably, it uses carbon dioxide (CO2) for extraction instead of other solvents. Simultaneously, lyophilization is an important technique used at different processing steps along with other methods. In lyophilization, CO2 is used as a cooling agent in the shelves of lyophilized equipment. It behaves as a supercritical fluid at critical pressure (Pc) of 72.7 atm and critical temperature (Tc) of 31°C. Considering the criteria mentioned earlier, there is a possibility that liquid CO2 or supercritical carbon dioxide (SC-CO2) can be used as a cooling agent in a lyophilizer and extraction solvent in SCFE. This review presents a brief outline for the possible validation parameters of the proposed novel processor; that is, SCFE/Dryer combo instrument containing Design Qualification, Installation Qualification, Operational Qualification, and Performance Qualification.

Role of fibrinogen, albumin and fibrinogen to albumin ratio in determining angiographic severity and outcomes in acute coronary syndrome.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic unmasked the huge deficit in healthcare resources worldwide. It highlighted the need for efficient risk stratification in management of cardiovascular emergencies. AIM: To study the applicability of the old, available and affordable nonconventional biomarkers: albumin and fibrinogen in their ability to predict angiographic severity and clinical outcomes in patients with acute coronary syndrome (ACS). METHODS: In this prospective, observational study, 166 consecutive patients with ACS were enrolled. Fibrinogen, albumin and their ratio were determined from serum. Patients with underlying chronic liver disease, active malignancy, autoimmune disease, active COVID-19 infection and undergoing thrombolysis were excluded. RESULTS: Mean age of the population was 60.5 ± 1.5 years, 74.1% being males. ST elevation myocardial infarction (STEMI) was most common presentation of ACS seen in 57% patients. Fibrinogen albumin ratio (FAR) ≥ 19.2, had a sensitivity of 76.9% and specificity of 78.9 % [area under the receiver operating characteristic curves (AUROC) = 0.8, P = 0.001] to predict ≤ thrombolysis in myocardial infarction (TIMI) 1 flow in culprit artery in STEMI patients. Even in non-STEMI patients, FAR ≥ 18.85 predicted the same with 80% sensitivity and 63% specificity (AUROC = 0.715, P = 0.006). CONCLUSION: Novel biomarkers, with their high cost, lack of availability and long turn over time are impractical for real-world use. Identifying ≤ TIMI 1 flow in the culprit artery has significant impact of management and outcome. Our study has shown that readily available biomarkers like fibrinogen and albumin can help identify these high-risk patients with good accuracy. This allows risk-stratification and individualization of treatment in ACS.