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ABSTRACT: Fat is an essential component for cookies structure and sensory attributes, but there is a necessity to replace or mimic fat in order to prevent lifestyle diseases. Hence, this study investigated the effect of industrial by-product, i.e., Partially defatted tomato seed flour (PDTSF) as a fat replacer on physicochemical and sensory characteristics of millet-based cookies at 10, 20, 30, and 40% (w/w) fat replacement levels. The physicochemical and functional properties of PDTSF were analyzed. PDTSF exhibited excellent nutritional profile and functional properties. PDTSF supplemented cookies showed a significant increase (p ≤ 0.05) in hardness, protein, ash, and carbohydrate content and the significant decrease in spread ratio, fat, and energy value with an increment of PDTSF. Descriptive sensory evaluation of millet-based cookies at all fat replacement levels showed good acceptability. Storage analysis for 30 days revealed as acceptance of cookies is not affected due to moisture intake and hardness. Hence, the results confirmed the positive effect on PDTSF as a whole food fat replacer to produce Reduced- fat millet cookies at 10 and 20% fat replacement levels.
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INTRODUCTION: Genetic variants contribute to differential responses to non-insulin antidiabetic drugs (NIADs), and consequently to variable plasma glucose control. Optimal control of plasma glucose is paramount to minimizing type 2 diabetes-related long-term complications. India's distinct genetic architecture and its exploding burden of type 2 diabetes warrants a population-specific survey of NIAD-associated pharmacogenetic (PGx) variants. The recent availability of large-scale whole genomes from the Indian population provides a unique opportunity to generate a population-specific map of NIAD-associated PGx variants. RESEARCH DESIGN AND METHODS: We mined 1029 Indian whole genomes for PGx variants, drug-drug interaction (DDI) and drug-drug-gene interactions (DDGI) associated with 44 NIADs. Population-wise allele frequencies were estimated and compared using Fisher's exact test. RESULTS: Overall, we found 76 known and 52 predicted deleterious common PGx variants associated with response to type 2 diabetes therapy among Indians. We report remarkable interethnic differences in the relative cumulative counts of decreased and increased response-associated alleles across NIAD classes. Indians and South Asians showed a significant excess of decreased metformin response-associated alleles compared with other global populations. Network analysis of shared PGx genes predicts high DDI risk during coadministration of NIADs with other metabolic disease drugs. We also predict an increased CYP2C19-mediated DDGI risk for CYP3A4/3A5-metabolized NIADs, saxagliptin, linagliptin and glyburide when coadministered with proton-pump inhibitors (PPIs). CONCLUSIONS: Indians and South Asians have a distinct PGx profile for antidiabetes drugs, marked by an excess of poor treatment response-associated alleles for various NIAD classes. This suggests the possibility of a population-specific reduced drug response in atleast some NIADs. In addition, our findings provide an actionable resource for accelerating future diabetes PGx studies in Indians and South Asians and reconsidering NIAD dosing guidelines to ensure maximum efficacy and safety in the population.
Subject(s)
Diabetes Mellitus, Type 2 , Hypoglycemic Agents , Humans , Hypoglycemic Agents/therapeutic use , Pharmacogenomic Variants , Diabetes Mellitus, Type 2/drug therapy , Insulin/therapeutic use , Gene Frequency , Insulin, Regular, HumanABSTRACT
Recent years have seen an increase in research on biodiesel, an environmentally benign and renewable fuel alternative for traditional fossil fuels. Biodiesel might become more cost-effective and competitive with diesel if a solid heterogeneous catalyst is used in its production. One way to make biodiesel more affordable and competitive with diesel is to employ a solid heterogeneous catalyst in its manufacturing. Based on X-ray diffraction (XRD) and Fourier Transform infrared spectroscopy (FTIR), the researchers in this study proved their hypothesis that iron oxide core-shell nanoparticles were generated during the green synthesis of iron-based nanoparticles (FeNPs) from Camellia Sinensis leaves. The fabrication of spherical iron nanoparticles was successfully confirmed using scanning electron microscopy (SEM). As a heterogeneous catalyst, the synthesised catalyst has shown potential in facilitating the conversion of algae oil into biodiesel. With the optimal parameters (0.5 weight percent catalytic load, 1:6 oil-methanol ratio, 60 °C reaction temperature, and 1 h and 30 min reaction duration), a 93.33% yield was attained. This may be due to its acid-base property, chemical stability, stronger metal support interaction. Furthermore, the catalyst was employed for transesterification reactions five times after regeneration with n-hexane washing followed by calcination at 650 °C for 3 h.
Subject(s)
Biofuels , Camellia sinensis , Plant Leaves , Plant Leaves/chemistry , Catalysis , Camellia sinensis/chemistry , Iron/chemistry , Metal Nanoparticles/chemistry , X-Ray Diffraction , Esterification , Spectroscopy, Fourier Transform InfraredABSTRACT
Aim: The CYP2D6 gene is highly polymorphic, causing large interindividual variability in the metabolism of several clinically important drugs. Materials & methods: The authors investigated the diversity and distribution of CYP2D6 alleles in Indians using whole genome sequences (N = 1518). Functional consequences were assessed using pathogenicity scores and molecular dynamics simulations. Results: The analysis revealed population-specific CYP2D6 alleles (*86, *7, *111, *112, *113, *99) and remarkable differences in variant and phenotype frequencies with global populations. The authors observed that one in three Indians could benefit from a dose alteration for psychiatric drugs with accurate CYP2D6 phenotyping. Molecular dynamics simulations revealed large conformational fluctuations, confirming the predicted reduced function of *86 and *113 alleles. Conclusion: The findings emphasize the utility of comprehensive CYP2D6 profiling for aiding precision public health.
Subject(s)
Cytochrome P-450 CYP2D6 , Genomics , Humans , Cytochrome P-450 CYP2D6/genetics , Cytochrome P-450 CYP2D6/metabolism , Alleles , Phenotype , GenotypeABSTRACT
Differential diagnosis of dementia remains a challenge in neurology due to symptom overlap across etiologies, yet it is crucial for formulating early, personalized management strategies. Here, we present an artificial intelligence (AI) model that harnesses a broad array of data, including demographics, individual and family medical history, medication use, neuropsychological assessments, functional evaluations and multimodal neuroimaging, to identify the etiologies contributing to dementia in individuals. The study, drawing on 51,269 participants across 9 independent, geographically diverse datasets, facilitated the identification of 10 distinct dementia etiologies. It aligns diagnoses with similar management strategies, ensuring robust predictions even with incomplete data. Our model achieved a microaveraged area under the receiver operating characteristic curve (AUROC) of 0.94 in classifying individuals with normal cognition, mild cognitive impairment and dementia. Also, the microaveraged AUROC was 0.96 in differentiating the dementia etiologies. Our model demonstrated proficiency in addressing mixed dementia cases, with a mean AUROC of 0.78 for two co-occurring pathologies. In a randomly selected subset of 100 cases, the AUROC of neurologist assessments augmented by our AI model exceeded neurologist-only evaluations by 26.25%. Furthermore, our model predictions aligned with biomarker evidence and its associations with different proteinopathies were substantiated through postmortem findings. Our framework has the potential to be integrated as a screening tool for dementia in clinical settings and drug trials. Further prospective studies are needed to confirm its ability to improve patient care.
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Differential diagnosis of dementia remains a challenge in neurology due to symptom overlap across etiologies, yet it is crucial for formulating early, personalized management strategies. Here, we present an AI model that harnesses a broad array of data, including demographics, individual and family medical history, medication use, neuropsychological assessments, functional evaluations, and multimodal neuroimaging, to identify the etiologies contributing to dementia in individuals. The study, drawing on 51,269 participants across 9 independent, geographically diverse datasets, facilitated the identification of 10 distinct dementia etiologies. It aligns diagnoses with similar management strategies, ensuring robust predictions even with incomplete data. Our model achieved a micro-averaged area under the receiver operating characteristic curve (AUROC) of 0.94 in classifying individuals with normal cognition, mild cognitive impairment and dementia. Also, the micro-averaged AUROC was 0.96 in differentiating the dementia etiologies. Our model demonstrated proficiency in addressing mixed dementia cases, with a mean AUROC of 0.78 for two co-occurring pathologies. In a randomly selected subset of 100 cases, the AUROC of neurologist assessments augmented by our AI model exceeded neurologist-only evaluations by 26.25%. Furthermore, our model predictions aligned with biomarker evidence and its associations with different proteinopathies were substantiated through postmortem findings. Our framework has the potential to be integrated as a screening tool for dementia in various clinical settings and drug trials, with promising implications for person-level management.
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We present the endoscopic management of two cases of complete ureteric occlusion at vesico-ureteral junction (VUJ) level following iatrogenic injury. Case 1 is a 60-year-old man who developed bilateral ureteric injury at the level of the VUJ following robot-assisted radical prostatectomy (RARP) for Gleason 3 + 4 = 7 T2bN0 prostate cancer. Case 2 is an 81-year-old man with history of recurrent G2pTa transitional cell carcinoma of the bladder originally diagnosed in 2005 and history of radical radiotherapy for prostate cancer. At his most recent transurethral resection of bladder tumour, the left ureteric orifice was not visualized. We describe step-by-step our technique in restoring continuity of the ureter with minimally invasive endoscopic approach, resulting in excellent long-term upper tract drainage for our patients. To our knowledge, combined utilization of a Collins knife to incise the area around the ureteric orifice to unearth them is not reported. We aim to report our technique and its outcomes.
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Early-life adversity (ELA) increases the likelihood of neuropsychiatric diagnoses, which are more prevalent in women than men. Since changes in reproductive hormone levels can also increase the probability of anxiety disorders in women, we examined the effects of ELA on adult female mice across the estrous cycle. We found that during diestrus, when progesterone levels are relatively high, ELA mice exhibit increased avoidance behavior and increased theta oscillation power in the ventral hippocampus (vHIP). We also found that diestrus ELA mice had higher levels of progesterone and lower levels of allopregnanolone, a neurosteroid metabolite of progesterone, in the vHIP compared with control-reared mice. Progesterone receptor antagonism normalized avoidance behavior in ELA mice, while treatment with a negative allosteric modulator of allopregnanolone promoted avoidance behavior in control mice. These results suggest that altered vHIP progesterone and allopregnanolone signaling during diestrus increases avoidance behavior in ELA mice.
Subject(s)
Avoidance Learning , Estrous Cycle , Progesterone , Animals , Female , Mice , Progesterone/metabolism , Pregnanolone/metabolismABSTRACT
Ethnic differences in pharmacogenomic (PGx) variants have been well documented in literature and could significantly impact variability in response and adverse events to therapeutics. India is a large country with diverse ethnic populations of distinct genetic architecture. India's national genome sequencing initiative (IndiGen) provides a unique opportunity to explore the landscape of PGx variants using population-scale whole genome sequences. We have analyzed the IndiGen variation dataset (N = 1029 genomes) along with global population scale databases to map the most prevalent clinically actionable and potentially deleterious PGx variants among Indians. Differential frequencies for the known and novel variants were studied and interaction of the disrupted PGx genes affecting drug responses were analyzed by performing a pathway analysis. We have highlighted significant differences in the allele frequencies of clinically actionable PGx variants in Indians when compared to the global populations. We identified 134 mostly common (allele frequency [AF] > 0.1) potentially deleterious PGx variants that could alter or inhibit the function of 102 pharmacogenes in Indians. We also estimate that on, an average, each Indian individual carried eight PGx variants (single nucleotide variants) that have a direct impact on the choice of treatment or drug dosing. We have also highlighted clinically actionable PGx variants and genes for which preemptive genotyping is most recommended for the Indian population. The study has put forward the most comprehensive PGx landscape of the Indian population from whole genomes that could enable optimized drug selection and genotype-guided prescriptions for improved therapeutic outcomes and minimizing adverse events.
Subject(s)
Genome, Human , Pharmacogenetics , Asian People , Gene Frequency , Genetics, Population , Genotype , HumansABSTRACT
BACKGROUND: Hand eczema (HE), foot eczema (FE), and hand-foot eczema (HFE) manifest on exposure to various agents in day-to-day life or in occupations or both. OBJECTIVES: The objectives of this study were to identify pattern of allergens causing HE, FE, and HFE and to identify multiple and concurrent contact allergies. MATERIALS AND METHODS: A study was conducted from October 2013 to August 2015 which included 190 patients. Patch test was performed for 78.94% of patients (n = 150). The statistical tests used were descriptive, Cramer's V, and Chi-square tests. RESULTS: The most commonly affected group was HFE (55.8%) followed by HE (22.1%) and FE (22.1%). Allergens showed positivity either singly 56.3% (n = 67) or in combination 43.69% (n = 52). Nickel (41.79%) was the most common allergen in all the three groups followed by potassium dichromate. Late reactions (after day 7) were observed in 17.64% of patients (n = 21). Nickel was observed in 42.85% (n = 9) and paraphenylenediamine was observed in 28.57% of patients (n = 6) with P values of <0.001 and 0.050, respectively. Multiple contact allergies were seen in 44% of patients (n = 52). Concurrent reactions (55.8% [n = 29]), polysensitization (34.6% [n = 18]), and mixed reactions (9.6% [n = 5]) (P value of <0.001) were observed. CONCLUSION: Significant multiple contact allergies including concurrent reactions with nickel sulfate, potassium dichromate, cobalt chloride, and polysensitization were observed. No significant differences in allergen pattern were observed in HE, FE, and HFE. RECOMMENDATION: Day 7 reading is recommended in HFE.
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Aim: Numerous drugs are being widely prescribed for COVID-19 treatment without any direct evidence for the drug safety/efficacy in patients across diverse ethnic populations. Materials & methods: We analyzed whole genomes of 1029 Indian individuals (IndiGen) to understand the extent of drug-gene (pharmacogenetic), drug-drug and drug-drug-gene interactions associated with COVID-19 therapy in the Indian population. Results: We identified 30 clinically significant pharmacogenetic variants and 73 predicted deleterious pharmacogenetic variants. COVID-19-associated pharmacogenes were substantially overlapped with those of metabolic disorder therapeutics. CYP3A4, ABCB1 and ALB are the most shared pharmacogenes. Fifteen COVID-19 therapeutics were predicted as likely drug-drug interaction candidates when used with four CYP inhibitor drugs. Conclusion: Our findings provide actionable insights for future validation studies and improved clinical decisions for COVID-19 therapy in Indians.
Subject(s)
COVID-19 Drug Treatment , COVID-19/genetics , Antiviral Agents/therapeutic use , Asian People , Drug Interactions/genetics , Genome/genetics , Genotype , Humans , India , Pharmacogenetics/methods , Pharmacogenomic Testing/methods , Pharmacogenomic Variants/genetics , SARS-CoV-2/drug effectsABSTRACT
BACKGROUND: It has been long recognized that periodontal diseases are infections of the periodontium, comprising the bacterial etiology, an immune response, and tissue destruction. Treatment strategies aiming primarily at suppressing or eliminating specific periodontal pathogens include adjunct use of local and systemic antibiotics as part of nonsurgical periodontal therapy. Unwanted side effects and resistance of microorganisms toward antibiotics due to their widespread use have modified the general perception about their efficacy. Research in phytosciences has revealed various medicinal plants offering a new choice of optional antimicrobial therapy. Cymbopogon citratus, Stapf. (lemongrass) is a popular medicinal plant. At a concentration ≤2%, lemongrass essential oil inhibits the growth of several kinds of microorganisms including periodontal pathogens, especially the reference strains Actinomyces naeslundii and Porphyromonas gingivalis, which were resistant to tetracycline hydrochloride. AIMS: To evaluate the efficacy of locally delivered 2% lemongrass essential oil in gel form as an adjunct to scaling and root planing, as compared to scaling and root planing alone for the treatment of chronic periodontitis. MATERIALS AND METHODS: 2% Lemongrass essential oil gel was prepared and placed in moderate to deep periodontal pockets after scaling and root planing. RESULTS: Statistically significant reduction in probing depth and gingival index and gain in relative attachment level were noted in the experimental group as compared to the control group at 1 and 3 months. CONCLUSION: Locally delivered 2% lemongrass essential oil gel offers a new choice of safe and effective adjunct to scaling and root planing in periodontal therapy.
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The data on the effects of cations such as Cu2+, Cd2+ and Cr6+ on the changes in the biochemical parameters in a freshwater fish, Clarias batrachus L., showed an increase of the protein content in the liver, kidney, stomach, intestine, testis and ovary, and a decrease in the muscle after Cu2+ and Cd2+ treatment as compared with control data; but the Cr6+ did not cause any changes of protein concentration in the kidney and testis. The administration of Cu2+ and Cd2+ increased the concentration of free amino acids in all the fish organs, whereas the Cr6+ did not changes this concentration in the muscle. A decrease in dry weight, and an increase in tissue permeability after these treatments were recorded in all the organs studied. In general, the above biochemical parameters of the organs were affected by treatments of the above cations in the following order: Cd greater than Cu greater than Cr over control values of C. batrachus, and their effects were markedly pronounced in the liver and kidney, followed by the intestine, stomach, muscle, testis and ovary in this species.
Subject(s)
Cadmium/toxicity , Chromium/toxicity , Copper/toxicity , Fishes/metabolism , Animals , Cations , Female , Kidney/drug effects , Kidney/metabolism , Liver/drug effects , Liver/metabolism , Male , Proteins/metabolism , Tissue DistributionABSTRACT
The crystal structure of the title compound, C(32)H(24)O(4), contains three fused dihydropyran rings (A, B and C); ring A is fused with a benzene ring while the other two rings, B and C, are fused with naphthalene rings. Ring A adopts a half-chair conformation with an equatorial methoxy group, whereas ring B assumes a distorted half-chair conformation, the A/B ring junction being trans. Ring C adopts a distorted half-boat conformation and is nearly orthogonal to ring B. Ring C is inclined to the best plane of ring A at an angle of 112.1 (1) degrees.
Subject(s)
HIV Integrase Inhibitors/chemistry , Heterocyclic Compounds, 4 or More Rings/chemistry , Crystallography, X-Ray , Hydrogen Bonding , Molecular StructureABSTRACT
The data on the effect of Hg(II) on changes of biochemical parameters in the freshwater fish, Clarias batrachus L. showed an increased protein content in the liver, kidney, stomach, intestine, testis and ovary, and a decreased content of it in the muscle over control data. A decrease in DNA, RNA and dry weight and an increase in free amino acids, tissue permeability and the activities of protease and RNase were recorded in all the organs by the treatment with Hg(II). In general, the effect of Hg(II) was maximum in the liver and kidney, followed by the intestine, stomach, muscle, testis and ovary of this species.
Subject(s)
Fishes/metabolism , Mercuric Chloride/pharmacology , Amino Acids/metabolism , Animals , DNA/metabolism , Female , Fresh Water , Gastric Mucosa/metabolism , Intestinal Mucosa/metabolism , Kidney/metabolism , Liver/metabolism , Male , Muscles/metabolism , Organ Specificity , Ovary/metabolism , Proteins/metabolism , RNA/metabolism , Testis/metabolismABSTRACT
The data on the effects of Hg(II), As(V) and Pb(II) on the biochemical parameters of the freshwater fish. Clarias batrachus L., showed an increased protein content in the liver, kidney, stomach, intestine, testis and ovary, and a decreased content of it in the muscle as compared to control values. A decrease in dry weight and an increase in free amino acid and tissue permeability were recorded in all the organs after treatment with Hg(II), As(V) and Pb(II). In general, the organs were affected by the treatments in the order: Pb(II) greater than As(V) greater than Hg(II) and their effects were pronounced in the liver and kidney, followed by intestine, stomach, muscle, testis and ovary of the species.