Peanut (Arachis hypogaea L.) flour and oilcake flour: Exploring the influence of roasting and varietal differences on proximal composition, elemental profiling, antimicrobial and antioxidant properties.

Peanuts are highly valued for their abundance of essential nutrients and health-promoting phenolic compounds. Peanut press cake, an inexpensive and underutilized agro-industrial by-product of oil production, is typically discarded or used as animal feed. This study investigated the influence of thermal processing and varietal disparities on the nutritional composition, phenolic content, and biological properties of peanut flour and oilcake flour, aiming to enhance their value as food ingredients. The findings showed that roasting significantly increased the oil (9.98 ± 0.11-44.13 ± 0.10 %), ash (1.28 ± 0.01-5.45 ± 0.05 %), carbohydrate contents (0.90 ± 0.01-28.09 ± 0.28 %), and energy value (406.69 ± 0.09-609.13 ± 1.08 kcal/100 g), along with the total polyphenol content (28.64 ± 0.19-62.79 ± 1.18 mg GAE/g), total flavonoid content (4.20 ± 0.07-18.35 ± 0.06 mg QE/g) and antioxidant activity in both peanut flour and its oilcake. Conversely, it led to a reduction in the moisture (1.48 ± 0.09-6.25 ± 0.15 %) and protein content (49.50 ± 0.05-54.24 ± 0.01 %). Notable variations were found between the two peanut varieties in terms of these nutritional parameters. Elemental analysis unveiled significant discrepancies among peanut varieties and with roasting, with potassium (12,237.56 ± 101.36-14,513.34 ± 168.62 mg/kg) emerging as the predominant macro-element followed by phosphorus (6156.86 ± 36.19-8815.22 ± 130.70 mg/kg) and magnesium (3037.92 ± 13.87-4096.44 ± 8.54 mg/kg), while zinc (53.98 ± 0.61-81.77 ± 0.44 mg/kg) predominated among the microelements. Moreover, peanut and oilcake flours demonstrated antibacterial activity against several bacteria. It can be inferred that roasted peanut and oilcake flours offer substantial nutritional value, making them promising candidates for addressing protein-energy malnutrition and serving as valuable ingredients in developing new food products.

Unveiling the oxidative stability, phytochemical richness, and nutritional integrity of cold-pressed Linum usitatissimum oil under UV exposure.

This study examines the effect of UV irradiation on the oxidation stability of Linum usitatissimum oil, presenting possible changes in the phytochemical profile due to photo-oxidation. GC-MS analysis of the oils identified 11 fatty acid compounds with a high percentage of unsaturated fatty acids, the most important of which is α-linolenic acid (ALA), known as omega-3 (48.88 %), also significant profiles of phytosterol and tcocopherol isomers rich in ß-Sitosterol and γ-tocopherols respectively. As well as physicochemical properties such as free fatty acids (FFA %), peroxide value (PV) and iodine value (IV), and nutritional indexes that determine the significant changes observed during the oxidation process, the most important of which is the progressive increase in acidity, peroxide, conjugated dienes and trienes and degrees of unsaturation over 8 h of UV exposure. High levels of carotenoids and phenolic compounds (TPC) protect and enhance oil quality in the face of irradiation, so a significantly small difference is observed between irradiated and non-irradiated oil during photo-oxidation.

Discontinuation of Tyrosine Kinase Inhibitor Therapy and Treatment Free Remission (TFR) in Chronic Myeloid Leukemia: Successful Achievement of TFR in More Than Two-Third of Patients in a Real-World Practice.

BACKGROUND: Discontinuation of TKI therapy and treatment-free remission (TFR) have become new goals for chronic-phase chronic myeloid leukemia (CP-CML). The aim of this study was to estimate the TFR post discontinuation of TKI therapy at 3 tertiary-care centers. PATIENTS AND METHODS: CP-CML patients aged ≥16 years who had an attempt to discontinue TKI therapy till June 2022, were eligible. The collected data included patients' demographics, prognostic score, type and duration of TKI therapy, response dates, relapse dates, response to re-initiation of TKI therapy, and risk factors for relapse. RESULTS: Fifty-five patients (35, 63.6% females) with a median age of 40 (range 16-74) years at diagnosis discontinued therapy. Forty-eight (87.3%) patients received imatinib as first line therapy. Twenty-nine (52.7%) patients were receiving imatinib at the time of TKI-discontinuation. Median time from diagnosis to TKI discontinuation was 86 months (IQR 60;132) and median duration of TKI therapy after achieving DMR was 66 months (IQR 47;114). After a median follow up of 34 (IQR 12;68) months, 15 (27.3%) patients relapsed. Median time to relapse was 5 months (range 2-38). Most of the relapses occurred during the first 6 months except 3 (20%) patients. All the relapsed patients achieved MMR after a median of 3 (range 2-6) months after restarting TKI therapy. None of the patients progressed to advanced-phase. CONCLUSION: Our experience confirms that discontinuation of TKI therapy in CP-CML patients is feasible and safe in routine clinical practice, and can achieve TFR in more than two-third of carefully selected patients.

Oxidative stability and nutritional quality of stored Linum usitatissmium L. and Argania spinosa L., oil blends: Chemical compositions, properties and nutritional value.

Identification of the chemical compositions of fatty acids and tocopherols shows the high content of linum usitatissimum oil (LO) by linolenic acid 55.3735% and γ-tocopherol 570.927 mg/kg, while argania spinosa oil (AO) is known by the dominance of oleic acid 47.77% followed by linoleic acid 31.08% as well as tocopherols by γ-tocopherols 687.485 mg/kg and δ-tocopherols 51.035 mg/kg. This difference in compositions enables us to enrich the low-stability oil and monitor its behavior during storage at a specific time and under specific conditions. In this study, pure linum usitatissimum and argania spinosa oils extracted by cold pressing as well as their formulations at proportions of (LO: AO) respectively: (80:20; 60:40, 50:50; 40:60; 20: 80) were oxidized at 60 °C for 28 days of storage, during which time the pure oils and blends were assessed for oxidative stability by studying their different fatty acid and tocopherol profiles and physicochemical characteristics such as acidity, peroxide value and chlorophyll and carotenoid pigments, as well as nutritional indexes such as the atherogenic index (AI), the thrombogenic index (TI), and the hypocholesterolemic: hypercholesterolemic ratio (HH), ω3:ω6 ratio, also the oxidative susceptibility (OS), and oxidazability value (Cox), and total phenolic compounds (TPC).

Clinical Validation of the Somatic FANCD2 Mutation (c.2022-5C>T) as a Novel Molecular Biomarker for Early Disease Progression in Chronic Myeloid Leukemia: A Case-Control Study.

Background: Chronic myeloid leukemia (CML) results from chromosomal translocation t(9;22) leading to the formation of the BCR-ABL fusion oncogene. CML has three stages: the chronic phase (CP), the accelerated phase (AP), and the blast crisis (BC). Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of CML. TKIs work well in CP-CML, and these patients have a survival rate similar to the normal population, but TKIs are less effective in advanced-phase CML. Even with current advances in treatment, BC-CML patients have an average overall survival of less than a year. Early recognition of CML patients at risk of disease progression can help in timely interventions with appropriate TKIs or other therapeutic modalities. Although some markers of disease progression like BCR-ABL kinase domain, ASXL1, and GATA2 mutations are available, no universal and exclusively specific molecular biomarkers exist to early diagnose CML patients at risk of CML progression for timely therapeutic interventions to delay or minimize blast crisis transformation in CML. A recent study found that all BC-CML patients harbored the FANCD2 (c.2022-5C>T) mutation. Therefore, the current study was designed to detect this FANCD2 mutant in AP-CML (early progression phase) and to clinically validate its potential as a novel molecular biomarker of early CML progression from CP to AP. Methods: Our study comprised 123 CP-CML (control group) and 60 AP-CML patients (experimental group) from 2 oncology centers, from January 2020 to July 2023. Mean hemoglobin level, WBC count, platelet count, treatment type, hepatomegaly, splenomegaly, and survival status of AP-CML patients were significantly different from those of CP-CML patients. However, as these clinical parameters cannot help in the early detection of patients at risk of CML progression, there was a need for a clinically validated biomarker of AP-CML. DNA was extracted from the patients' blood samples, and the FANCD2 gene was sequenced using an Illumina NextSeq500 next-generation sequencer (NGS). Results: The NGS analysis revealed a unique splice-site mutation in the FANCD2 gene (c.2022-5C>T). This mutation was detected in the majority (98.3%) of AP-CML patients but in none of the CP-CML patients or healthy control sequences from genomic databases. The mutation was confirmed by Sanger sequencing. FANCD2 is a member of the Fanconi anemia pathway genes involved in DNA repair and genomic stability, and aberrations of this gene are associated with many cancers. Conclusions: In conclusion, our study shows that the somatic FANCD2 (c.2022-5C>T) mutation is a new molecular biomarker for early CML progression. We recommend further clinical validation of this biomarker in prospective clinical trials.

Optimization of ultrasound-assisted extraction of phenols from Crocus sativus by-products using sunflower oil as a sustainable solvent alternative.

In the last decade, there's been a rising emphasis on eco-friendly solvents in industry and academia due to environmental concerns. Vegetable oils are now recognized as a practical, non-toxic option for extracting phytochemicals from herbs. This study presents a novel, green, and user-friendly method for extracting phenolic content from Crocus sativus L. waste using ultrasound. It replaces conventional organic solvents with sustainable sunflower oil, making the process eco-friendly and cost-effective. The effects of temperature (18-52 °C), ultrasonic time (5-55 min), and solid-solvent ratio (5-31 g/100 mL) were assessed by applying response surface methodology (RSM) and Central composite design. The combined impact of solid-solvent ratio, temperature, and ultrasonic time led to heightened phenolic content and antioxidant activity in the enriched oil. However, when these variables were at their maximum levels, there was a decline in these attributes. The specific conditions found to be ideal were a solid-to-liquid ratio of 26 g/100 mL, a temperature of 45 °C, and a duration of 45 min. The optimum extraction condition yielded the expected highest phenolic content (317.15 mg/ Kg), and antioxidant activity (89.34%). The enriched oil with flower saffron enabled the utilization of renewable natural ingredients, ensuring the production of a healthy extract or product. Also, enriched oils find diverse applications in areas such as food, aquaculture, and cosmetics.

Screening, awareness and challenges for colorectal cancer treatment in Saudi Arabia: an update.

Colorectal cancer (CRC) is the second most common cancer in the world. In Saudi Arabia, CRC is the most common cancer in males and the third most common in females, and its incidence rate is rising as the country continues to develop. However, the country does not have a national CRC screening program for CRC. This review aims to review recent studies that have attempted to address and rectify this issue and discern the most notable and prevalent barriers. Despite these efforts, guidelines are still lacking. Two prospective studies have been conducted in recent years, one of which was a national pilot screening program conducted by the Ministry of Health (MOH). While both had a similar number of participants, the colonoscopy rate for patients with a positive fecal immunochemical test (FIT) in the MOH program was only 20% compared to 75.8% in the Al-Kharj program. Awareness of the Saudi population regarding CRC and its screening appears to be insufficient. The most common barriers to patients' willingness to undergo screening were embarrassment, fear, and pain. Barriers to physicians are mostly related to factors outside their hands, such as lack of equipment and time. We conclude that efforts should be made to establish a national screening program and improve awareness of the population and physicians.

Eltrombopag for tyrosine kinase inhibitors-associated thrombocytopenia in chronic myeloid leukemia.

Patients with newly diagnosed chronic-phase chronic myeloid leukemia (CP-CML) can develop cytopenias secondary to bone marrow hypoplasia after starting tyrosine kinase inhibitor (TKI) therapy. These adverse effects are usually transient, but cytopenias can persist in some patients. TKI-associated thrombocytopenia can develop in a significant proportion of CML patients and may require TKI dose reduction or dose interruptions. The thrombopoietin receptor agonist eltrombopag may improve thrombocytopenia in these patients, but the supporting literature for this approach is limited. Herein, we describe the case of a 56-year-old woman who developed persistent TKI-associated thrombocytopenia and intracranial hemorrhage. She could not tolerate full doses of imatinib and she failed to achieve a major molecular response (MMR). She responded to eltrombopag and platelet count improved, which allowed commencement and continuation of dasatinib as second-line TKI therapy, resulting in achievement of MMR. TKI-associated thrombocytopenia can cause serious bleeding and may also interfere with the management of CML by necessitating TKI dose interruption or reduction. Use of eltrombopag can help maintain adequate platelet counts and uninterrupted delivery of TKI therapy.

Development and Validation of Reversed-Phase HPLC Method for the Determination of Epirubicin and Its Application to the Pharmacokinetic Study of Epirubicin Loaded Polymeric Nanoparticle Formulations in Rats.

Epirubicin, commonly used as anticancer drug for various types of tumors like breast, liver, lung, stomach, ovaries, and bladder for its improved antitumor efficacy and safety. A rapid, sensitive, and reliable bioanalytical method was developed and validated for epirubicin using conventional reverse phase HPLC with UV detection. The developed method was successfully applied to investigate the pharmacokinetics of epirubicin after intravenous administration of a reference epirubicin and its designed nano-formulations to rats. C18 column was used in an isocratic mode for analyte elution at a flow rate of 1.0 mL/min with UV detection of 234 nm. The mobile phase was composed of acetonitrile 22% (channel A) and 0.025% tri fluoro-acetic acid in water (channel B). Ondansetron was added as an internal standard, and the plasma samples were analyzed after protein precipitation. A concentration range of 0.016-1.024 µg/mL was selected for the construction of calibration curves, with LLOQ of 0.016 µg/mL. Results showed that the value of AUC, half-life, and mean residence time of designed nano-formulation were bounce to 10, 9, and 11 times higher, when compared to the reference epirubicin after intravenous dose of 10 mg/kg of epirubicin to rats, respectively. The designed epirubicin nano-formulations achieved clinically significant pharmacokinetic values in rats. Current method will help epirubicin future research using clinical samples and drug bioequivalence studies on various novel formulations for drug safety purposes.

Spatial distribution, health risk assessment, and public perception of groundwater in Bahawalnagar, Punjab, Pakistan: a multivariate analysis.

The current study investigated the hydrogeochemical behavior of groundwater quality attributes including arsenic (As) and their associated health risks in unexplored groundwater aquifers of Bahawalnagar, Punjab, Pakistan. The groundwater samples were collected from 40 colonies of Bahawalnagar city from electric/hand pumps, tube wells and turbines installed at varying depth (20 to > 100 m). The groundwater possessed the highest concentrations of PO4 (0.5 mg/L), HCO3 (425 mg/L), Cl (623 mg/L), NO3 (136.68 mg/L) and SO4 (749.7 mg/L) concentrations. There was no difference in concentration of As in shallow and deep aquifers. Interestingly, none of the water samples showed As concentration higher than the WHO limit of 10 µg/L for drinking water with groundwater As concentration spanning from 2.5 to 7.9 µg/L. The HQ values for As were less than 1 and there was no apparent non-carcinogenic risk from the long-term consumption of As contaminated water. The questionnaire survey indicated that 82% respondents believe that drinking water quality affects human health and 55% of respondents considered that groundwater in the area is not suitable for drinking. Survey results revealed that 29.11, 22.78, 17.08, 15.19, 7.59, 5.06 and 3.16% respondents/family members suffered from hepatitis, skin problems, diabetes, tuberculosis, kidney disorders, muscular weakness and gastro, respectively. However, the data cannot be correlated with As contamination and disease burden in the local community and it can be anticipated that the groundwater may contain other potentially toxic ions that are deteriorating the water quality and compromising human health. The hydrogeochemical analysis revealed Na-Cl/SO4, K-SO4 type of groundwater suggesting the potential role of sulfate containing minerals in releasing As in the groundwater aquifers.

Insights into metabolic and pharmacological profiling of Aspergillus ficuum through bioinformatics and experimental techniques.

BACKGROUND: Recently, numerous novel bioactive fungal metabolites have been identified that possess broad therapeutic activities including anti-inflammatory, antibiotic, antioxidant, and antitumor. The fungal mycochemicals as well as extracts have increased the interest of the scientific community in drug discovery research through a combination approach such as, molecular metabolic, pharmacological and computational techniques. Therefore, the natural fungus Aspergillus ficuum (A. ficuum) (FCBP-DNA-1266) was selected for metabolic and pharmacological profiling in this study. RESULTS: The metabolic profile of A. ficuum was explored for the first time and revealed the presence of bioactive compounds such as choline sulfate, noruron, hydroxyvittatine, aurasperone D, cetrimonium, kurilensoside, heneicosane, nonadecane and eicosane. Similarly, a pharmacological screen of A. ficuum was performed for the first time in in vivo and in vitro models. Interestingly, both the ethyl acetate and n-hexane fractions of A. ficuum were found to be more active against Bacillus subtilis among five tested bacteria with their zone of inhibition (ZOI) values of 21.00 mm ±1.00 and 23.00 mm ±1.00, at a concentration of 150 µgmL-1 respectively. Similarly, a significant decrease (P<0.001) and (P<0.01) in paw edema was observed in A. ficuum-treated animals at doses of 50 and 150 mgkg-1, respectively, reflecting its potent anti-inflammatory effect. Furthermore, the docking results supported the antibacterial and anti-inflammatory effects of A. ficuum. In addition, the crude extract demonstrated no acute toxicity and the highest percent radical scavenging was recorded for both n-hexane and ethyl acetate extracts. CONCLUSION: The metabolic profile of A. ficuum indicated the presence of biological relevant compounds. A. ficuum extract exhibited potent antibacterial and anti-inflammatory effects supported by docking results. Furthermore, A. ficuum extract demonstrated the highest percentage of radical scavenging activity along with no acute toxicity.

Study of the Role of Titanium and Iron Cathodic Cages on Plasma-Nitrided AISI 430 Ferritic Stainless Steel.

In contrast to austenitic and martensitic stainless steels, ferritic stainless steels have a lower hardness and wear resistance but exhibit excellent corrosion resistance. Due to this fact, their use in the aerospace, automobile, and house construction industries is restricted. Several methods have been utilized to enhance the tribological characteristics of ferritic stainless steels. In this work, titanium nitride coating has been carried out by using a cathodic cage of titanium material, and later on, the titanium cathodic cage is replaced by an AISI-304 cathodic cage in a CCPN chamber to form iron nitride coating on AISI-430 ferritic stainless steel coupons through a plasma nitriding process for 4 h at a fixed temperature of 400 °C. The microstructures and mechanical traits of all processed and control coupons were analyzed using scanning electron microscopy, X-ray diffraction, ball-on-disc wear tester, and microhardness tester techniques. The results showed that hardness increased up to 1489 HV with the titanium cage, which is much higher than the hardness of the base material (270 HV). The titanium cage-treated coupons have high layer thickness, smooth surface morphology, and a minimum crystallite size of 2.2 nm. The wear rate was reduced up to 50% over the base material after the titanium cage plasma treatment. The base coupon exhibited severe abrasive wear, whereas nitrided coupons exhibited dominant adhesive wear. In the iron nitride coatings, this effect is also important, owing to the more influential cleaning process in a glow discharge, and the better adhesion with enhanced interlayer thickness is attributed to the fact that the compliance of the interlayer minimizes shear stresses at the coating-substrate interface. The use of a graded interface improves adhesion compared with the case where no interlayer is used but a titanium interlayer of comparable thickness provides a significant increase in measured adhesion. For both titanium and iron nitride films, there is a reduction in wear volume which is a function of interlayer thickness; this will have a substantial effect on wear lifetime. Thus by careful control of the interlayer thickness and composition, it should be possible to improve coating performance in tribological applications.

Hepatoprotective effects of walnut oil and Caralluma tuberculata against paracetamol in experimentally induced liver toxicity in mice.

Walnut Oil and Caralluma are edible and form part of the traditional medicine system in many countries. These are frequently used in traditional medicine as remedies to relieve a wide range of illnesses and health problems. Walnut Oil and Caralluma species have demonstrated anti-inflammatory, anti-nociceptive, antidiabetics, hepatoprotective, gastric mucosa protecting, antimalarial, antioxidant, anti-trypanosomal, appetite suppressant and cytotoxic activities. The current study was planned to study the impacts of 21 days' oral administration of walnut oil and methanolic extract of Caralluma tuberculata on the levels of some liver-associated parameters and hematological parameters in paracetamol intoxicated mice. It was observed that paracetamol intoxication resulted in a considerable rise in serum ALT, cholesterol, triglycerides, Creatinine, and urea levels while a decrease in HDL level in comparison to mice normal control group (P<0.05). Serum ALT, cholesterol, triglycerides, creatinine, and urea levels of mice that were administered with walnut oil and methanolic extract of C. tuberculata at the doses of (1 ml/kg, 2 ml/kg and 3 ml/kg body weight) were significantly lower when compared to toxic control mice group (P<0.05), While HDL level was significantly increased. The significant reduction had also been observed in the levels of serum parameters of mice group, which received standard hepato-protective drug i.e., vitamin C, at the dose of 8 mg/kg body weight (P<0.05). Based on these results, it was evident that liver toxicity caused by the paracetamol administration has recovered toward the normal range by the walnut oil and C. tuberculata extract. Therefore, the present study revealed that (walnut oil and C. tuberculata) exhibit hepatoprotective activities in paracetamol intoxicated mice.

Effect of pupil dilation on IOLMaster® measurements in Pakistani Eyes.

Objectives: To analyse the effect of pupil dilation on intraocular lens instrument IOLMaster 500 biometric measurements, and to determine the effect of these measurements on intraocular lens power calculations in Asian eyes. METHODS: The prospective study was conducted at the Aga Khan University Hospital, Karachi, between January and April 2017, and comprised all patients scheduled for cataract surgery who underwent scanning with IOLMaster 500. For each patient, pre-dilation and post-dilation measurements were taken. The intraocular lens power was determined through Sanders/Retzlaff/Kraff Theoretical, Holladay, and Hoffer Q formulae. Data was analysed using SPSS 24. RESULTS: There were 276 eyes of 138 participants who had a mean age of 59.7±11.1 years. Anterior chamber depth changed significantly with pupil dilation (p=0.001). No significant changes were observed in the axial length (p=0.410), keratometry measurements (p=0.931), and intraocular lens power calculations (p>0.05). CONCLUSIONS: The change in anterior chamber depth, though significant, was perhaps clinically non-significant.

Formulation Development and Characterization of pH Responsive Polymeric Nano-Pharmaceuticals for Targeted Delivery of Anti-Cancer Drug (Methotrexate).

Oral administration of pH sensitive/stimuli responsive nanoparticles are gaining importance because of the limited side effects, minimum dose and controlled drug release. The objective of this study was to develop and evaluate pH sensitive polymeric nanoparticles for methotrexate with the aim to maximize the drug release at target site. In the presented study, pH sensitive polymeric nanoparticles of methotrexate were developed through modified solvent evaporation technique using polymer Eudragit S100. Different process parameters like drug to polymer ratio, speed of sonication, concentration of surfactant and time of sonication were optimized by evaluating their effects on particle size, PDI, zeta potential, entrapment/encapsulation efficiency. The developed formulations were evaluated for their size, polydispersity (PDI), zeta potential, encapsulation efficiency, XRD, scanning electron microscopy, in-vitro drug release and stability studies. Best results were obtained with poloxamer-407 and PVA and were selected as surfactants. Physicochemical characterization of the developed formulations showed that the particle size lies in the range 165.7 ± 1.85-330.4 ± 4.19, PDI 0.119 ± 0.02-0.235 ± 0.008, zeta potential -0.163 ± 0.11--5.64 ± 0.36 mV, and encapsulation efficiency more than 61%. The results of scanning electron microscopy revealed that nanoparticles have regular geometry with spherical shape. Initially the drug release occur through diffusion followed by erosion. The present studies showed that MTX-ES100 nanoparticles prepared during this study have the desired physicochemical properties, surface morphology and release characteristics used to target the desired organs.

Time for culture conversion and its associated factors in multidrug-resistant tuberculosis patients at a tertiary level hospital in Peshawar, Pakistan.

Objectives: This study aimed to assess the time to sputum culture conversion (SCC) and its determinants among multidrug-resistant tuberculosis (MDR-TB) patients. Methods: This cross-sectional study was conducted from January 2019 to January 2020. A total of 252 MDR-TB patients presenting at a tertiary level teaching hospital in Peshawar, Khyber Pakhtunkhwa (KP), were included. The patient's demographic and clinical data were collected using a structured questionnaire. Time to SCC was calculated from the initiation of treatment till the patient had two consecutive negative cultures. The Cox proportional-hazards analysis was performed to check strength and association between the determinants and time for SCC. Results: Out of 252 MDR-TB patients enrolled, sputum culture conversion was observed in 76.6% of the patients by the end of six months. While, 19.0% of the patients failed to achieve negative culture and remained positive after interim report of their treatment. Age > 45 years (HR = 15.22; 95% CI: 7.27-31.83; p<0.001), female gender (6.22; 2.90-13.36; p<0.001), BMI < 18.5 kg/m2 (10.28; 5.25-20.11; p<0.001), weight loss (0.03; 0.01-0.06; p<0.001), smoking (0.10; 0.05-0.21; p<0.001), diabetes mellitus (0.02; 0.00-0.04 p<0.001) and disease severity on chest X-ray (CXR) (0.03; 0.01-0.09; p<0.001) were the significant determinants of delayed sputum culture conversion. Conclusion: MDR-TB patients with older age, low BMI, weight loss, diabetes, smokers and those with disease severity on CXR are less likely to respond to treatment as they displayed delayed SCC. Therefore, such patients should be meticulously followed up for successful management.

Synthesis, characterization and application of organoclays for adsorptive desulfurization of fuel oil.

The present study encompasses the application of cost effective, organo-modified bentonite material for efficient desulfurization of model oil and real fuel. For the adsorptive desulfurization of oil, dibenzothiophene (DBT) was used as model compound. Various experimental parameters (time, temperature, adsorbent-amount and DBT concentration) were thoroughly investigated. The synthesized material was characterized via X-ray diffraction (XRD), X-ray Fluorescence (XRF), Scanning electron microscopy (SEM), Energy dispersive x-ray (EDX), Thermogravimetric analysis (TGA) and Fourier transform infrared spectroscopy (FT-IR). The modification exhibits the increase in interlayer spacing of clay as confirmed from XRD and modified material shows interesting morphology as compared to unmodified bentonite. The results showed that > 90% of DBT removal was achieved under optimized conditions for B-BTC, B-BTB and B-DSS and > 80% for B-BEHA, for model fuel oil which are greater than unmodified clay (< 45%). Additionally, the findings from desulfurization of real fuel oil declare that 96.76% and 95.83% removal efficiency was achieved for kerosene and diesel oil respectively, at optimized conditions and fuel properties follow ASTM specifications. The obtained findings well fitted with thermodynamic, isothermal (Langmuir) with adsorption capacity (70.8 (B-BTC), 66 (B-BTB), 61.2 (B-DSS) and 55.2 (B-BEHA) in mg/g) and pseudo-second-order kinetics. In thermodynamic studies, negative sign ([Formula: see text] specifies the spontaneity whereas, [Formula: see text] endothermic and positive sign [Formula: see text] show randomness after DBT adsorption onto organoclay.

Design and Characterization of Paclitaxel-Loaded Polymeric Nanoparticles Decorated With Trastuzumab for the Effective Treatment of Breast Cancer.

The aim of the study was to design and formulate an antibody-mediated targeted, biodegradable polymeric drug delivery system releasing drug in a controlled manner to achieve a therapeutic goal for the effective treatment of breast cancer. Antibody-mediated paclitaxel-loaded PLGA polymeric nanoformulations were prepared by the solvent evaporation method using different experimental parameters and compatibility studies. The optimized formulations were selected for in vitro and in vivo evaluation and cytotoxicity studies. The in vitro drug release studies show a biphasic release pattern for the paclitaxel-loaded PLGA nanoparticles showing a burst release for 24 h followed by an extended release for 14 days; however, a more controlled and sustained release was observed for antibody-conjugated polymeric nanoparticles. The cytotoxicity of reference drug and paclitaxel-loaded PLGA nanoparticles with and without antibody was determined by performing MTT assay against MCF-7 cells. Rabbits were used as experimental animals for the assessment of various in vivo pharmacokinetic parameters of selected formulations. The pharmacokinetic parameters such as Cmax (1.18-1.33 folds), AUC0-t (39.38-46.55 folds), MRT (10.04-12.79 folds), t1/2 (3.06-4.6 folds), and Vd (6.96-8.38 folds) have been increased significantly while clearance (4.34-4.61 folds) has been decreased significantly for the selected nanoformulations as compared to commercially available paclitaxel formulation (Paclixil®). The surface conjugation of nanoparticles with trastuzumab resulted in an increase in in vitro cytotoxicity as compared to plain nanoformulations and commercially available conventional brand (Paclixil®). The developed PLGA-paclitaxel nanoformulations conjugated with trastuzumab have the desired physiochemical characteristics, surface morphology, sustained release kinetics, and enhanced targeting.

Combating iron and zinc malnutrition through mineral biofortification in maize through plant growth promoting Bacillus and Paenibacillus species.

Introduction: The burgeoning population of the world is causing food insecurity not only by less food availability but also by the malnutrition of essential nutrients and vitamins. Malnutrition is mostly linked with food having micronutrients lower than the optimal concentration of that specific food commodity and becoming an emerging challenge over the globe. Microbial biofortification in agriculture ensures nutritional security through microbial nitrogen fixation, and improved phosphate and zinc solubilization, which increase the uptake of these nutrients. The present study evaluates the novel plant growth-promoting rhizobacteria (PGPR) to biofortify maize gain. Methods: For this purpose, a pot and two field experiments for maize were conducted. PGPRs were applied alone and in combination for a better understanding of the biofortification potential of these strains. At physiological maturity, the growth parameters, and at harvest, the yield, microbial population, and nutritional status of maize were determined. Results and discussion: Results revealed that the consortium (ZM27+ZM63+S10) has caused the maximum increase in growth under pot studies like plant height (31%), shoot fresh weight (28%), shoot dry weight (27%), root fresh (33%) and dry weights (29%), and microbial count (21%) in the maize rhizosphere. The mineral analysis of the pot trial also revealed that consortium of ZM27+ZM63+S10 has caused 28, 16, 20, 11 and 11% increases in P, N, K, Fe, and Zn contents in maize, respectively, as compared to un-inoculated treatment in pot studies. A similar trend of results was also observed in both field trials as the consortium of ZM27+ZM63+S10 caused the maximum increase in not only growth and biological properties but also caused maximum biofortification of mineral nutrients in maize grains. The grain yield and 1000-grain weight were also found significantly higher 17 and 12%, respectively, under consortium application as compared to control. So, it can be concluded from these significant results obtained from the PGPR consortium application that microbial inoculants play a significant role in enhancing the growth, yield, and quality of the maize. However, the extensive evaluation of the consortium may help in the formulation of a biofertilizer for sustainable production and biofortification of maize to cope with nutritional security.

CLINICAL VALIDATION OF ANKRD36 MUTATIONS AS A NOVEL BIOMARKER FOR MONITORING EARLY PROGRESSION AND TIMELY CLINICAL INTERVENTIONS IN BLAST CRISIS CML.

Background: Chronic Myeloid Leukemia (CML) is initiated in the bone marrow due to the chromosomal translocation t(9;22), resulting in the fusion oncogene BCR-ABL. Tyrosine kinase inhibitors (TKIs) targeting BCR-ABL have transformed fatal CML into an almost curable disease. However, TKIs lose efficacy during disease progression, and the mechanism of CML progression remains to be fully understood. Additionally, common molecular biomarkers for CML progression are lacking. Our studies previously detected ANKRD36 (c.1183_1184 delGC and c.1187_1188 dupTT) associated exclusively with advanced phase CML. However, clinical validation of this finding was pending. Therefore, this study aimed to clinically validate mutated ANKRD36 as a novel biomarker of CML progression. Materials and Methods: The study enrolled 124 patients in all phases of CML, recruited from Mayo Hospital and Hameed Latif Hospital in Lahore, Punjab, between January 2019 and August 2021. All response criteria were adopted from the European LeukemiaNet guideline 2020. Informed consent was obtained from all study subjects. The study was approved by scientific and ethical review committees of all participating centers.Sanger sequencing was employed to detect ANKRD36 mutations in CML patients in accelerated phase (AP) (n=11) and blast crisis (BC) (n=10), with chronic-phase CML (CP-CML) patients as controls (n=103). Samples were processed using Big Dye Terminator Cycle Sequencing Ready Reaction kits and sequenced using ABI Prism 3730 Genetic Analyzer, and sequencing using forward and reverse primers for ANKRD36. Results: During our study, 17% of CML patients progressed to advanced phases AP-CML n=11 (8.9%) and BC-CML n=10 (8.1%). The chronic- and advanced-phase patients showed significant difference with respect to male-to-female ratio, hemoglobin level, WBC count, and platelet count. Sanger sequencing detected ANKRD36 mutations c. 1183 1184 delGC and c. 1187 1185 dupTT exclusively in all AP- and BC-CML patients but in none of the CP-CML patients. Nevertheless, mutations status was not associated with male-to-female ratio, hemoglobin level, WBC count, and platelet count, which makes ANKRD32 as an independent predictor of early and terminal disease progression in CML. Conclusions: The study confirms ANKRD36 as a novel genomic biomarker for early and late CML progression. Further prospective studies should be carried out in this regard. ANKRD36, although fully uncharacterized in humans, shows the highest expression in bone marrow, particularly myeloid cells. Functional integrated genomic studies are recommended to further explore the role of ANKRD36 in the biology and pathogenesis of CML.