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Oxazoles and Imidazoles are heterocyclic compounds with significant biological activities. The present study explores the pharmacological effects of some new oxazole and imidazole derivatives as potential COX-2 inhibitors. Docking studies of the compounds against targeted proteins COX-2 and TACE manifested good binding affinities for both the targets supporting their anti-inflammatory potential. Compounds (3F-A, 3F-B, N-A, N-B) were evaluated for in vivo anti-inflammatory effects by carrageenan-induced paw edema. Among all, compound N-A was found to be the most effective as it displayed most pronounced reduction in inflammation that was comparable to indomethacin. The in vivo tissue antioxidant activity was performed for estimation of the level of catalase, GSH, GST, and thiobarbituric acid in paw tissue. The results exhibited that targeted compounds improved the oxidative stress and restored the expression of enzymes. H &E staining revealed that aforesaid compounds displayed well-defined restoration of cellular damage. Compound NA exhibited maximum structural and functional preservation. Reduction in the expression of inflammatory markers was also analyzed by ELISA and maximum reduction in protein expression (COX-2 and TNF-a) was observed for compound N-B. Quantification of mRNA was done using PCR and a decrease in the expression of COX-2 mRNA level in treatment groups was depicted by all the new compounds but N-B showed maximum reduction in enzyme expression. All the results obtained from the present study have shown the significant anti-inflammatory potential of new compounds via the COX-2 inhibition pathway.

Background: With the global increase in antibacterial resistance, the challenge faced by developing countries is to utilize the available antibiotics, alone or in combination, against resistant bacterial strains. We aimed to encapsulate the levofloxacin (LVX) into polymeric nanoparticles using biodegradable polymers i.e. Chitosan and PLGA, estimating their physicochemical characteristics followed by functional assessment as nanocarriers of levofloxacin against the different resistant strains of bacteria isolated from biological samples collected from tertiary care hospital in Lahore, Pakistan. Methods: LVX-NPs were synthesized using ion gelation and double emulsion solvent-evaporation method employing chitosan (CS) and poly-lactic-co-glycolic acid (PLGA), characterized via FTIR, XRD, SEM, and invitro drug release studies, while antibacterial activity was assessed using Kirby-Bauer disc-diffusion method. Results: Data revealed that the levofloxacin-loaded chitosan nanoparticles showed entrapment efficiency of 57.14% ± 0.03 (CS-I), 77.30% ± 0.08(CS-II) and 87.47% ± 0.08 (CS-III). The drug content, particle size, and polydispersity index of CS-I were 52.22% ± 0.2, 559 nm ± 31 nm, and 0.030, respectively, whereas it was 66.86% ± 0.17, 595 nm ± 52.3 nm and 0.057, respectively for CS-II and 82.65% ± 0.36, 758 nm ± 24 nm and 0.1, respectively for CS-III. The PLGA-levofloxacin nanoparticles showed an entrapment efficiency of 42.80% ± 0.4 (PLGA I) and 23.80% ± 0.4 (PLGA II). The drug content, particle size and polydispersity index of PLGA-I were 86% ± 0.21, 92 nm ± 10 nm, and 0.058, respectively, whereas it was 52.41% ± 0.45, 313 nm ± 32 nm and 0.076, respectively for PLGA-II. The XRD patterns of both polymeric nanoparticles showed an amorphous nature. SEM analysis reflects the circular-shaped agglomerated nanoparticles with PLGA polymer and dense spherical nanoparticles with chitosan polymer. The in-vitro release profile of PLGA-I nanoparticles showed a sustained release of 82% in 120 h and it was 58.40% for CS-III. Both types of polymeric nanoparticles were found to be stable for up to 6 months without losing any major drug content. Among the selected formulations, CS-III and PLGA-I, CS-III had better antibacterial potency against gram+ve and gram-ve bacteria, except for K. pneumonia, yet, PLGA-I demonstrated efficacy against K. pneumonia as per CSLI guidelines. All formulations did not exhibit any signs of hemotoxicity, nonetheless, the CS-NPs tend to bind on the surface of RBCs. Conclusion: These data suggested that available antibiotics can effectively be utilized as nano-antibiotics against resistant bacterial strains, causing severe infections, for improved antibiotic sensitivity without compromising patient safety.

Digital platforms on the internet are invaluable for collecting user feedback, suggestions, and opinions about various topics, such as company products and services. This data is instrumental in shaping business strategies, enhancing product development, and refining service delivery. Suggestion mining is a key task in natural language processing, which focuses on extracting and analysing suggestions from these digital sources. Initially, suggestion mining utilized manually crafted features, but recent advancements have highlighted the efficacy of deep learning models, which automatically learn features. Models like Convolutional Neural Networks (CNN), Recurrent Neural Networks (RNN), Long Short-Term Memory (LSTM), and Bidirectional Encoder Representations from Transformers (BERT) have been employed in this field. However, considering the relatively small datasets and the faster training time of LSTM compared to BERT, we introduce TransLSTM, a novel LSTM-Transformer hybrid model for suggestion mining. This model aims to automatically pinpoint and extract suggestions by harnessing both local and global text dependencies. It combines the sequential dependency handling of LSTM with the contextual interaction capabilities of the Transformer, thus effectively identifying and extracting suggestions. We evaluated our method against state-of-the-art approaches using the SemEval Task-9 dataset, a benchmark for suggestion mining. Our model shows promising performance, surpassing existing deep learning methods by 6.76% with an F1 score of 0.834 for SubTask A and 0.881 for SubTask B. Additionally, our paper presents an exhaustive literature review on suggestion mining from digital platforms, covering both traditional and state-of-the-art text classification techniques.

Background/Objectives: Fexofenadine hydrochloride is a widely prescribed drug for treating histamine-mediated allergic reactions. This review systematically collates existing research on the clinical pharmacokinetics (PK) of fexofenadine, with a copious emphasis on examining the impact of stereoisomerism, disease states, and drug interactions. Methods: The search engines PubMed, Science Direct, Google Scholar, and Cochrane were scanned systematically for articles concerning the clinical PK of fexofenadine in humans. The extensive literature search yielded 85 articles meeting the inclusion standards. Results: The PK parameters of fexofenadine showed a linear correlation between increasing doses and proportional elevations in PK parameters such as area under the curve from time 0 to infinity (AUC0–∞) and maximum plasma concentration (Cmax). Under fed conditions, its bioavailability was reduced by approximately 50%. Findings from patients with end-stage renal disease (ESRD) displayed a 63% decline in oral clearance (CL/F) of fexofenadine. A drug–food interaction study has displayed that grapefruit juice decreased Cmax (201 ng/mL vs. 128 ng/mL), accompanied by a 30% reduction in the bioavailability of fexofenadine. Furthermore, a drug–herb interaction study with St John’s Wort (SJW) has reported a reduction in CL/F by 10% after a single dose, but long-term administration reversed this effect, resulting in elevated CL/F by 17% of fexofenadine. Conclusions: Since no prior systematic review on the PK of this drug exists, this review amalgamates all pertinent PK parameters in humans by pooling up-to-date data from published studies. This detailed literature review can be advantageous for researchers who want to develop and assess PK models.

Objective: To determine the prognostic significance of bone marrow fibrosis grade in predicting the outcome of myeloproliferative neoplasms. Study Design: Prospective longitudinal study. Duration and Place of Study: Armed Forces Institute of Pathology, Rawalpindi Pakistan, from Jun 2021 to May 2022. Methodology: A total of 114 patients with myeloproliferative neoplasms were included. Under aseptic conditions, a bone marrow aspiration and a Trephine biopsy were obtained. Following processing, the samples underwent staining with Hemotoxylin and Eosin and Reticulin. The WHO bone marrow fibrosis grading system was used to grade the fibrosis. Clinical findings and haematological parameters documented at initial diagnosis were compared with one-year interval follow-up counts. Results: Out of a total 114, 72(63.2%) were male and 42(36.8%) were female. Generalised weakness and pallor were documented in 51(44.7%) and 27(23.7%), respectively. While splenomegaly and/or hepatomegaly were detected in 61(53.5%) and 27(23.7%), respectively, 16(14.9%) transformed into other MPNs and 3(2.6%) into acute leukemia. People who had higher levels of MF-2 and MF-3 reticulin fibrosis had the worst prognosis when it came to peripheral blood cytopenias, disease progression, and transformation. Conclusion: Myeloproliferative neoplasms are very different from one another in terms of how they look and behave. As the grade of fibrosis rises, there is a high chance that the disease will progress to myelofibrosis or change into acute leukaemia, both of which are very bad for overall survival.

Abstract Most of the breast cancers are estrogen receptor-positive recurring with a steady rate of up to 20 years dysregulating the normal cell cycle. Dinaciclib is still in clinical trials and considered as a research drug against such cancers targeting CDK2. The major goal of this study was to identify the potential inhibitors of CDK-2 present in Moringa oleifera for treating hormonal receptor positive breast cancers. For this purpose, in silico techniques; molecular docking, MM-GBSA and molecular dynamics simulations were employed to screen Moringa oleifera compounds and their anticancer potential was determined against CDK-2 protein targets. Among 36 compounds of Moringa oleifera reported in literature, chlorogenic acid (1), quercetin (2), ellagic acid (3), niazirin (4), and kaempferol (5) showed good affinity with the target. The interaction of the compounds was visualized using PYMOL software. The profiles of absorption, distribution, metabolism, excretion (ADME) and toxicity were determined using SWISS and ProTox II webservers. The MTT assay was performed in-vitro using MCF-7 cancer cell lines to validate the anticancer potential of Moringa oleifera leaf extract. MTT assay results revealed no significant change in proliferation of Mcf-7 cells following 24 h treatment with fraction A (petroleum ether). However, significant antiproliferative effect was observed at 200 µg/mL dose of fraction B (ethyl acetate) and cell viability was reduced to 40%. In conclusion, the data suggested that all the compounds with highest negative docking score than the reference could be the potential candidates for cyclin dependent kinase-2 (CDK-2) inhibition while ellagic acid, chlorogenic acid and quercetin being the most stable and potent inhibitors to treat estrogen receptor positive breast cancer targeting CDK-2. Moreover, the data suggested that further investigation is required to determine the optimum dose for significant antiproliferative effects using in-vivo models to validate our findings of in-silico analysis.

Author(s): Aaron G. Lim, Nick Scott, Josephine G. Walker, Saeed Hamid, Margaret Hellard, Peter Vickerman The second sentence of the Acknowledgments is incomplete. The complete sentence reads: AGL, JW, and [...]

Diabetes is a long-term metabolic disease epitomized by postprandial hyperglycemia. The prolonged use of synthetic drugs renders distinct side effects, necessitating the development of safe and cost-effective substitutes. The aim of the current study is to isolate, evaluate the antidiabetic potential and HPLC method development for simultaneous estimation of antidiabetic compounds from the leaves of Tradescantia pallida. The leaves were extracted, fractionated and subjected to column chromatography. The isolated compounds' antidiabetic potential was evaluated using α-amylase and glycosylation of hemoglobin assays. The study employed molecular docking to scrutinize interactions between antidiabetic compounds and human α-amylase and hemoglobin protein. Prime MM-GBSA calculations determined binding energies of ligand–protein complexes. Further analysis of morin and catechin involved exploring dynamic and thermodynamic constraints through molecular dynamics simulations under specific biological conditions. A rapid HPLC method was developed and validated for the simultaneous estimation of isolated compounds. The column chromatography culminated in the isolation of four antidiabetic compounds (syringic acid, catechin, p-coumaric acid and morin). The in vitro analyses revealed that morin and catechin exhibited 72.67 % and 78 % α-amylase inhibition and 67 % and 71.66 % inhibition of hemoglobin glycosylation, respectively. In silico studies substantiated the in vitro assay, confirming the stability of catechin and morin complexes via root mean square deviation analysis. Interactions, encompassing hydrophilic, hydrophobic, water bridges, and ionic interactions, identified key residues involved in these processes. The validated HPLC method exhibited excellent correlation coefficients ranged from 0.9909 to 0.9997. The antidiabetic compounds were quantified from the extract in the range of 0.072 – 0.160 µg/mL. The study concluded that the isolated compounds from Tradescantia pallida have remarkable antidiabetic activity, and the developed method can be successfully used for the identification and quantification of phenolic compounds in Tradescantia pallida and other plant-derived matrix.

Physiologically based pharmacokinetic (PBPK) modeling is of great importance in the field of medicine. This study aims to construct a PBPK model, which can provide reliable drug pharmacokinetic (PK) predictions in both healthy and chronic kidney disease (CKD) subjects. To do so, firstly a review of the literature was thoroughly conducted and the PK information of vildagliptin was collected. PBPK modeling software, PK-Sim®, was then used to build and assess the IV, oral, and drug-specific models. Next, the average fold error, visual predictive checks, and predicted/observed ratios were used for the assessment of the robustness of the model for all the essential PK parameters. This evaluation demonstrated that all PK parameters were within an acceptable limit of error, i.e., 2 fold. Also to display the influence of CKD on the total and unbound AUC (the area under the plasma concentration–time curve) and to make modifications in dose, the analysis results of the model on this aspect were further examined. This PBPK model has successfully depicted the variations of PK of vildagliptin in healthy subjects and patients with CKD, which can be useful for medical practitioners in dosage optimization in renal disease patients.

Introduction: Cancer contributes to a high mortality rate worldwide spanning its diversity from genetics to resistant therapeutic response. To date emerging strategies to combat and manage cancer are particularly focused on the development of targeted therapies as conventional treatments account for the destruction of normal cells as well. In this regard, medicinal plant-based therapies are quite promising in imposing minimal side effects; however, limitations like poor bioavailability and stability of bioactive phytochemicals are associated with them. In parallel, nanotechnology provides nominal solution to deliver particular therapeutic agent without compromising its stability.Methods: In this study, Solanum nigrum, an effective medicinal plant, loaded arabinoxylan cross-linked β-cyclodextrin nanosponges (SN-AXCDNS) were designed to evaluate antitumor activity against breast cancer. Therefore, SN-AXCDNS were prepared by using cross-linker melt method and characterized by physicochemical and pharmacological parameters.Results: Hydrodynamic size, zeta potential and entrapment efficiency (EE%) were estimated as 226 ± 4 nm, −29.15 ± 5.71 mV and 93%, respectively. Surface morphology of nanocomposites showed spherical, smooth, and porous form. Antitumor pharmacological characterization showed that SN loaded nanosponge demonstrated higher cytotoxicity (22.67 ± 6.11 μg/mL), by inducing DNA damage as compared to void SN extract. Flow cytometry analysis reported that encapsulated extract promoted cell cycle arrest at sub-G1 (9.51%). Moreover, in vivo analysis demonstrates the reduction in tumor weight and 85% survival chances in nanosponge treated mice featuring its effectiveness. In addition, in silico analysis revealed that β-cyclodextrin potentially inhibits MELK in breast cancer cell lines (B.E = −10.1 Kcal/mol).Conclusion: Therefore, findings of current study elucidated the therapeutic potential of β-cyclodextrin based nanosponges to be an alternative approach regarding the delivery and solubilization of antitumor drugs.

Abstract Background To estimate the determinants of anxiety and depression among university teachers in Lahore, Pakistan, during COVID-19. Methods A cross-sectional study was conducted by enrolling 668 teachers from the universities of Lahore, Pakistan. Data were collected using a questionnaire. Chi-square for significance and logistic regression for the association were used. Results Majorly, the university teachers, with an average age of 35.29 years, had regular jobs (72.8%), job experience of > 6 years (51.2%) and good self-reported health (55.4%). The majority of the teachers were working as lecturers (59.6%), lecturing in arts (33.5%) or general science (42.5%) departments, having MPhil (37.9%) or master (28.9%) degrees, and teaching via synchronous video (59.3%) mode. Anxiety and depression, severe and extremely severe, were higher among lecturers, MPhil or master degree holders, teachers lecturing arts and general science subjects, and in those on contract employment. Anxiety was significantly associated with academic departments; arts (OR;2.5, p = 0.001) and general science (OR;2.9, p = 0.001), poor health status (OR;4.4, p = 0.018), and contractual employment (OR;1.8, p = 0.003). Depression was associated with academic departments; arts (OR;2.7, p = 0.001) and general science (OR;2.5, p = 0.001), and health status (OR;2.3, p = 0.001). Conclusion Among university teachers, anxiety and depression, severe and extremely severe, were prevalent among lecturers having MPhil or master degrees, belonging to arts and general science departments, and among contract employees. Anxiety and depression were significantly associated with academic disciplines, lower cadre, and poor health status.

Abstract Over the last several decades, angiotensin-converting enzyme inhibitors (ACEIs) have been a staple in the treatment of hypertension and renovascular disorders in children. One of the ACEIs, captopril, is projected to have all the benefits of traditional vasodilators. However, conducting clinical trials for determining the pharmacokinetics (PK) of a drug is challenging, particularly in pediatrics. As a result, modeling and simulation methods have been developed to identify the safe and effective dosages of drugs. The physiologically based pharmacokinetic (PBPK) modeling is a well-established method that permits extrapolation from adult to juvenile populations. By using SIMCYP simulator, as a modeling platform, a previously developed PBPK drug-disease model of captopril was scaled to renally impaired pediatrics population for predicting captopril PK. The visual predictive checks, predicted/observed ratios (ratiopred/obs), and the average fold error of PK parameters were used for model evaluation. The model predictions were comparable with the reported PK data of captopril in mild and severe chronic kidney disease (CKD) patients, as the mean ratiopred/obs Cmax and AUC0−t were 1.44 (95% CI 1.07 − 1.80) and 1.26 (95% CI 0.93 − 1.59), respectively. The successfully developed captopril-CKD pediatric model can be used in suggesting drug dosing in children diagnosed with different stages of CKD.

Objective: To determine the frequency of 17p deletion in patients with Acute Myeloid Leukemia and their clinical-hematologic features using fluorescence in situ hybridization. Study Design: Cross-sectional study. Place & Duration of Study: Department of Hematology, Armed Forces Institute of Pathology, Rawalpindi Pakistan, from Dec 2018 to Dec 2019. Methodology: All diagnosed cases of Acute Myeloid Leukemia of all ages and genders were included. Interphase FISH testing was performed using blood or bone marrow specimens using 10μL of the Meta systems XL p53 probe, and a total of 500 nuclei per assay were analyzed using a fluorescent microscope. Del 17p positivity and negativity were noted. Clinico-haematologic features of the patients with and without del 17p were also noted. Results: In our targeted population of 84 patients, there were 25(29.8%) females and 59(70.2%) males. The mean age of presentation was 36.3±1.6 years. The mean total leucocyte count(TLC)was 31.2±4.2×109/L, and the mean platelet count was 69.3±4.5×109/L. Del 17p was detected in a total of 8(9.5%) patients. The median age of patients with del 17p at diagnosis was 33 years, the mean TLC was 12.32±10.36x109/L, and the mean platelet count was 80±26.73*109/L. Prominent clinical features among patients with del 17p included fever and pallor. Conclusion: Our study suggests a relatively low frequency of del 17p in AML (9.5%), which is consistent with international data.

Nadolol is a long-acting non-selective β–adrenergic antagonist that helps treat angina and hypertension. The current study aimed to develop and validate the physiologically based pharmacokinetic model (PBPK) of nadolol in healthy adults, renal-compromised, and pediatric populations. A comprehensive PBPK model was established by utilizing a PK-Sim simulator. After establishing and validating the model in healthy adults, pathophysiological changes i.e., blood flow, hematocrit, and GFR that occur in renal failure were incorporated in the developed model, and the drug exposure was assessed through Box plots. The pediatric model was also developed and evaluated by considering the renal maturation process. The validation of the models was carried out by visual predictive checks, calculating predicted to observed (Rpre/obs) and the average fold error (AFE) of PK parameters i.e., the area under the concentration–time curve (AUC0-t), the maximum concentration in plasma (Cmax), and CL (clearance). The presented PBPK model successfully simulates the nadolol PK in healthy adults, renal-impaired, and pediatric populations, as the Rpre/obs values of all PK parameters fall within the acceptable range. The established PBPK model can be useful in nadolol dose optimization in patients with renal failure and children with supraventricular tachycardia.

Objective: To determine the frequency and clinico-haematological features of PDGFRA, PDGFRB and FGFR1 gene rearrangements in patients with persistent Eosinophilia using Fluorescence in situ hybridization. Study Design: Cross-sectional study. Place and Duration of Study: Department of Hematology, Armed Forces Institute of Pathology, Rawalpindi Pakistan, from Dec 2018 to Dec 2019. Methodology: All Patients who presented to AFIP having absolute eosinophil count >1.5x109/L persistent for over six months or with Myeloid or Lymphoid neoplasms with persistent Eosinophilia were studied. Patients having reactive Eosinophilia and those on treatment were excluded. Interphase FISH studies were performed. In addition, 2.5ml of sodium heparin blood was taken. After the denaturation of DNA, slides were set up according to standard protocol. FIP1L1/CHIC2/PDGFRA dual colour probe was applied for PDGFRA, 5q32 PDGFRA break apart probe for PDGFRB and XL FGFR1 break apart probe for FGFR1 gene rearrangement. Results: A total of 60 patients were included in the study. Of these, 50(83.3%) were males, and 10(16.7%) were females, with an average absolute Eosinophilia count of 5.92±7.10x109/L. The only rearrangement detected in patients with Eosinophilia was FIPILI-PDGFRA gene fusion, detected in 20% of the patients. No other rearrangement was found. Conclusion: PDGFRA, PDGFRB and FGFR1 mutations are rare yet most prominent in patients with clonal Eosinophilia. About 80% of eosinophilic patients were found to have idiopathic Eosinophilia, which requires further consideration to address the disease prevalence.

Solid lipid nanoparticles (SLNs) have the advantages of a cell-specific delivery and sustained release of hydrophobic drugs that can be exploited against infectious diseases. The topical delivery of hydrophobic drugs needs pharmaceutical strategies to enhance drug permeation, which is a challenge faced by conventional formulations containing a drug suspended in gel, creams or ointments. We report the fabrication and optimization of SLNs with sulconazole (SCZ) as a model hydrophobic drug and then a formulation of an SLN-based topical gel against fungal infections. The SLNs were optimized through excipients of glyceryl monostearate and Phospholipon® 90 H as lipids and tween 20 as a surfactant for its size, drug entrapment and sustained release and resistance against aggregation. The SCZ-SLNs were physically characterized for their particle size (89.81 ± 2.64), polydispersity index (0.311 ± 0.07), zeta potential (−26.98 ± 1.19) and encapsulation efficiency (86.52 ± 0.53). The SCZ-SLNs showed sustained release of 85.29% drug at the 12 h timepoint. The TEM results demonstrated spherical morphology, while DSC, XRD and FTIR showed the compatibility of the drug inside SLNs. SCZ-SLNs were incorporated into a gel using carbopol and were further optimized for their rheological behavior, pH, homogeneity and spreadability on the skin. The antifungal activity against Candida albicans and Trichophyton rubrum was increased in comparison to a SCZ carbopol-based gel. In vivo antifungal activity in rabbits presented faster healing of skin fungal infections. The histopathological examination of the treated skin from rabbits presented restoration of the dermal architecture. In summary, the approach of formulating SLNs into a topical gel presented an advantageous drug delivery system against mycosis.

This study aimed to synthesize and characterize DTX-mPEG-PLA-NPs along with the development and validation of a simple, accurate, and reproducible method for the determination and quantification of DTX in mPEG-PLA-NPs. The prepared NPs were characterized using AFM, DLS, zetasizer, and drug release kinetic profiling. The RP-HPLC assay was developed for DTX detection. The cytotoxicity and anti-clonogenic effects were estimated using MTT and clonogenic assays, respectively, using both MCF-7 and MDA-MB-231 cell lines in a 2D and 3D culture system. The developed method showed a linear response, high precision, accuracy, RSD values of ≤2%, and a tailing factor ≤2, per ICH guidelines. The DTX-mPEG-PLA-NPs exhibited an average particle size of 264.3 nm with an encapsulation efficiency of 62.22%. The in vitro drug kinetic profile, as per the Krosmeyers–Peppas model, demonstrated Fickian diffusion, with initial biphasic release and a multistep sustained release over 190 h. The MTT assay revealed improved in vitro cytotoxicity against MCF-7 and MDA-MB-231 in the 2D cultures and MCF-7 3D mammosphere cultures. Significant inhibitions of the clonogenic potential of MDA-MB-231 were observed for all concentrations of DTX-mPEG-PLA-NPs. Our results highlight the feasibility of detecting DTX via the robust RP-HPLC method and using DTX-mPEG-PLA-NPs as a perceptible and biocompatible delivery vehicle with greater cytotoxic and anti-clonogenic potential, supporting improved outcomes in BC.

A Sorghum flour (SF) is a leading and prominent food source for humans in African countries. Recently extensive studies have been conducted on Sorghum bread (SB) or sorghum composite bread (SCB), covering various aspects. However, there are many technical challenges in the formation of SF and sorghum composite flour (SCF) that impact the quality of the bread and fail to meet the consumer’s desires and expectations. This review primarily focuses on the characteristics of SF, SCF, SB, and SCB, with discussions encompassing the rheological and morphological properties of the dough, improvement strategies, and bread quality. Moreover, a comprehensive analysis has been conducted to investigate the behavior of SF and SCF along with a discussion of the challenges affecting bread quality and the strategies applied for improvement. The significant demand for nutrients-rich and gluten-free bread indicates that sorghum will become one of the most vital crops worldwide. However, further comprehensive research is highly demanded and necessary for an in-depth understanding of the key features of SF and the resulting bread quality. Such understanding is vital to optimize the utilization of sorghum grain in large-scale bread production.

South Africa is a multicultural society characterised by a rich diversity of languages. As a result, many healthcare providers and their patients often do not speak the same language, which makes communication challenging. The language barriers, when present, require an interpreter to ensure accurate and effective communication between the parties. In addition to assisting in a clear exchange of information, a trained medical interpreter also acts as a cultural liaison. This is especially true when the provider and the patient come from different cultural backgrounds. Based on the patient’s needs, preferences, and available resources, clinicians should select and engage with the most appropriate interpreter. The effective use of an interpreter requires knowledge and skill. Patients and healthcare providers can benefit from several specific behaviours during interpreter-mediated consultations. This review article provides practical tips on when and how to use an interpreter effectively during clinical encounters in primary healthcare settings in South Africa.

Asthma is a major non-communicable disease (NCD) affecting adults and children, among whom it is the most common chronic disease reported all around the globe1 Asthma has been a significant cause of hospitalizations and financial burdens for low and lower- middle -income countries like Pakistan. According to the latest WHO data published in 2020, asthma deaths in Pakistan reached a staggering 20,750 or 1.42% of total deaths.2 Many etiologies including social and environmental factors, genetic predispositions, and ambient air pollution, influence asthma morbidity and mortality. In particular, the worsening air quality index in the country needs to be a point of focus as a significant cause of asthma related morbidity. The rapid decline in air quality levels in Pakistan, particularly in major industrial cities such as Lahore and Karachi, is a cause of grave concern. For example, air quality in Lahore has declined over the last two decades: in 1998, its pollution concentration was 33 µg/m³. By 2016, it had doubled to 64 µg/m³—more than six times the WHO guideline.3 Similarly, Karachi, the largest city in Pakistan, has a PM2.5 concentrations, which is 3.4 times the WHO annual air quality guideline value, an alarming scenario for a city where environmental policies and infrastructure is not in place.4 A study in Lahore noted the role of ambient air pollution among various population groups of the city. The research showed a positive Pearson correlation between environmental air pollutants and the number of asthma patients visiting the OPD.5 However, a similar, comprehensive study has not been conducted in Karachi on the same level. As in most cases, the first step toward solving a problem is to recognize it. Hence there’s a need for more research to be conducted to determine the number of hospitalizations of asthmatic patients caused by low air quality as it will give us a better understanding of the true extent of the issue at hand and allow more appropriate prioritization, in the context of public health by the government. Once this is done, resources can be allocated more efficiently towards areas and populations suffering more acutely to relieve the suffering of the majority. In addition, educational campaigns can be designed considering the population’s educational demographics and general knowledge regarding the exact reasons for the worsening air quality in those areas. ---Continue

Abstract To evaluate the antibiotic susceptibility patterns in URTIs reporting to tertiary hospitals of Lahore. A cross-sectional study employing 259 culture sensitivity reports obtained from tertiary care hospitals of Lahore. Using SPSS, descriptive statistics were used to estimate frequencies and percentages. In URTIs, S. aureus (5%) was the frequent gram-positive isolate followed by MRSA (1.5%) and MSSA (1.5%), while P. aeruginosa (15.8%) was the prevalent gram-negative isolate followed by Klebsiella (13.1%) and E. coli (6.9%). Against P. aeruginosa, ceftazidime (7.7%), cefuroxime/ceftriaxone (4.6%), amoxicillin (4.3%) and ciprofloxacin (4.2%), were tested resistant, while imipenem (11.2%), ciprofloxacin (9.2%), amikacin (9.2%), meropenem/ levofloxacin/gentamicin (8.1%) and piptaz (6.9%) were found sensitive. Against Klebsiella, carbepenems (7.3%), amikacin (6.5%), ciprofloxacin (5.4%) and gentamicin (5%) were tested sensitive, whereas, ceftazidime (8.5%), ceftriaxone (5.8%), cefaclor (5.5%), ampicillin (4.6%), co-amoxiclave (4.2%) and ciftazidime/ciprofloxacin (3.8%) were found resistant. Overall, imipenem (35%), meropenem (30.8%) and amikacin (31.9%) were the three most sensitive antibiotics, while ceftazidime (25.4%), ceftriaxone (19.2%) and ampicillin (18.5%) were the three most resistant antibiotics. Data suggested that P.aeruginosa and Klebsiella, were the most frequent bacterial isolates in URTIs of Lahore. These isolates were resistant to ampicillin, cefuroxime and ceftazidime, but were sensitive to carbapenem and aminoglycosides.

Tioconazole (TCZ) is a broad-spectrum fungicidal BCS class II drug with reported activity against Candida albicans, dermatophytes, and certain Staphylococci bacteria. We report the use of TCZ-loaded transethosomes (TEs) to overcome the skin’s barrier function. TCZ-loaded TEs were fabricated by using a cold method with slight modification. Box–Behnken composite design was utilized to investigate the effect of independent variables. The fabricated TEs were assessed with various physicochemical characterizations. The optimized formulation of TCZ-loaded TEs was incorporated into gel and evaluated for pH, conductivity, drug content, spreadability, rheology, in vitro permeation, ex vivo permeation, and in vitro and in vivo antifungal activity. The fabricated TCZ-loaded TEs had a % EE of 60.56 to 86.13, with particle sizes ranging from 219.1 to 757.1 nm. The SEM images showed spherically shaped vesicles. The % drug permeation was between 77.01 and 92.03. The kinetic analysis of all release profiles followed Higuchi’s diffusion model. The FTIR, DSC, and XRD analysis showed no significant chemical interactions between the drug and excipients. A significantly higher antifungal activity was observed for TCZ-loaded transethosomal gel in comparison to the control. The in vivo antifungal study on albino rats indicated that TCZ-loaded transethosomal gel showed a comparable therapeutic effect in comparison to the market brand Canesten®. Molecular docking demonstrated that the TCZ in the TE composition was surrounded by hydrophobic excipients with increased overall hydrophobicity and better permeation. Therefore, TCZ in the form of transethosomal gel can serve as an effective drug delivery system, having the ability to penetrate the skin and overcome the stratum corneum barrier with improved efficacy.

Rationale: Approximately 8,000 new cases of pediatric cancer arise annually in Pakistan. However, there is a dire survival rate of 30–35% due to various factors, especially a lack of competent nurses in pediatric oncology care. Public-private partnerships (PPP) supported by a My Child Matters (MCM) Grant from Sanofi Espoir Foundation was granted to Indus Hospital & Health Network (IH&HN) to improve pediatric nursing standards.Methods: Starting in 2016, nurses from hospitals across Pakistan were enrolled in a continuing education program, which included a comprehensive, hands-on training component. A group chat was created following the training for communication and mentorship regarding challenges faced locally.Results: Seventy-seven pediatric oncology nurses were successfully trained by IH&HN over three years.Discussion: Challenges included lack of government funding, shortage of specialist nurses, frequent shifting of nurses away from pediatric care, and indifferent attitudes. Success of the project could have been maximized if trained nurses were motivated and retained by hospitals.Conclusion: Development and maintenance of PPP in national healthcare systems is essential to improve pediatric oncology nursing care.Key words: Public Private Partnership, pediatric cancer, pediatric oncology nurses, nursing care

Aim: Plants contain many essential constituents and their optimization can result in the discovery of new medicines. One such plant is Brassica rapa that is commonly used as a vegetable to fulfill daily food requirements worldwide. This study intends to screen the phytochemicals, antihypertensive potential, GC-MS, and in silico analysis of the leaves of Brassica rapa.Methods: Powdered leaves were subjected to proximate analysis followed by estimation of primary metabolites. Extracts were obtained by hot and cold extraction and investigated for secondary metabolites. All crude extracts were screened for their antihypertensive potential using an angiotensin-converting enzyme (ACE) inhibition assay. GC-MS analysis was carried out to standardize the extract, and an antihypertensive metabolite was confirmed using an in silico approach.Results: Physicochemical evaluation resulted in moisture content (9.10% ± 0.1), total ash value (18.10% ± 0.6), and extractive values (water 9.46% ± 0.5 and alcohol soluble 4.99% ± 0.1), while phytochemical investigation revealed primary metabolites (total proteins 11.90 mg/g ± 0.9; total fats 3.48 mg/g ± 0.5; and total carbohydrates 57.45 mg/g ± 1.2). Methanol extract showed the highest number of secondary metabolites including polyphenols 93.63 mg/g ± 0.6; flavonoids 259.13 mg/g ± 0.6; and polysaccharides 56.63 mg/g ± 1.4, while water extract (70 mg/g ± 2) was rich in glycosaponins. Methanol extract showed the highest antihypertensive potential by inhibiting ACE (79.39%) amongst all extracts, compared to the standard drug captopril, which inhibited 85.81%. Standardization of methanol extract via GC-MS analysis revealed potent phytoconstituents, and a molecular docking study confirmed that oleic acid is the main antihypertensive metabolite.Conclusion: We conclude that leaves of Brassica rapa can successfully lower hypertension by inhibiting ACE, however; in vivo investigations are required to confirm this antihypertensive activity.

The 1,3,4-oxadiazole derivatives Ox-6a-f have been synthesized by incorporating flurbiprofen moiety with the aim to explore the potential of target molecules to decrease the oxidative stress. The title compounds Ox-6a-f were prepared by simple reactions in which a flurbiprofen –COOH group was esterified with methanol in an acid-catalyzed medium, which was then reacted with hydrazine to afford the corresponding hydrazide. The acid hydrazide was then cyclized into 1,3,4-oxadiazole-2-thiol by reacting with CS2 in the presence of KOH. The title compounds Ox-6a-f were synthesized by the reaction of an –SH group with various alkyl/aryl chlorides, which involves an S-alkylation reaction. The structures of the synthesized Ox-6a-f derivatives were ascertained by spectroscopic data. The in silico molecular docking was performed against target proteins cyclooxygenase-2 COX-2 (PDBID 5KIR) and cyclooxygenase-1 COX-1 (PDBID 6Y3C) to determine the binding affinity of the synthesized compounds with these structures. It has been inferred that most of the synthesized compounds bind well with an active binding site of 5KIR compared to 6Y3C, and especially compound Ox-6f showed excellent binding affinity (7.70 kcal/mol) among all synthesized compounds Ox-6a-f. The molecular dynamic (MD) simulation has also been performed to check the stability of docking complexes of ligands with COX-2 by determining their root mean square deviation and root mean square fluctuation. Little fluctuation was observed in case of Ox-6f, which forms the most stable complex with COX-2. The comprehensive antioxidant potential of the synthesized compounds has been evaluated by determining their free radical scavenging activity, including DPPH, OH, nitric oxide (NO), and iron chelation assay. The derivative Ox-6f showed promising results with 80.23% radical scavenging potential at a dose of 100 µg/mL while ascorbic acid exhibited 87.72% inhibition at the same dose. The anti-inflammatory activity of the final products has also been performed, and inflammatory markers were assayed, such as a thiobarbituric acid-reducing substance, nitric oxide, interleukin-6 (IL-6), and COX-2. The derivatives Ox-6d and Ox-6f displayed higher anti-inflammatory activity, exhibiting 70.56% and 74.16% activity, respectively. The results were compared with standard ibuprofen, which showed 84.31% activity at the same dose, 200 µg/mL. The anti-inflammatory potential has been performed by following the carrageen-induced hind paw edema model, and results showed that derivative Ox-6f exhibited 79.83% reduction in edema volume compared to standard ibuprofen, which reduced 84.31% edema volume. As dry lab and wet lab results confirm each other, it has been deduced that derivative Ox-6f may serve as the lead structure to design potent compounds to address oxidative stress.

Abstract The advancement in the processing speeds of computing machines has facilitated the development of complex physiologically based pharmacokinetic (PBPK) models. These PBPK models can incorporate disease-specific data and could be used to predict pharmacokinetics (PK) of administered drugs in different chronic conditions. The present study aimed to develop and evaluate PBPK drug-disease models for captopril after incorporating relevant pathophysiological changes occurring in adult chronic kidney disease (CKD) and chronic heart failure (CHF) populations. The population-based PBPK simulator Simcyp was used as a modeling and simulation platform. The visual predictive checks and mean observed/predicted ratios (ratio(Obs/pred)) of the PK parameters were used for model evaluation. The developed disease models were successful in predicting captopril PK in all three stages of CKD (mild, moderate, and severe) and CHF, as the observed and predicted PK profiles and the ratio(obs/pred) for the PK parameters were in close agreement. The developed captopril PBPK models can assist in tailoring captopril dosages in patients with different disease severity (CKD and CHF).

Objective: To determine the frequency of trisomy 12 in B-Cell chronic lymphocytic leukaemia (CLL), to correlate its association with clinico-pathologic features and to determine the role of this cytogenetic defect to the prognosis. Study Design: Cross sectional study. Place and Duration of Study: Haematology department, Armed Forces Institute of Pathology, Rawalpindi, from May 2017 to Aug 2018. Methodology: A total of 56 newly diagnosed patients of Chronic Lymphocytic Leukaemia were included in the study. Patients were diagnosed on the basis of National Cancer Institute Working Group guidelines. A detailed history and thorough clinical examination were performed and complete blood counts, biochemical profile, bone marrow examination, immunophenotyping on bone marrow/peripheral blood samples were done for the diagnosis of Chronic lymphocytic leukaemia. Interphase FISH studies were performed on blood/bone marrow aspiration for detection of Trisomy 12 were performed. Results: Out of 56 patients, trisomy was detected in 12 (10.7%) patients. Out of 7 patients with trisomy 12, five patients presented in late stages (Binet stage B and C), however this association of Trisomy 12 with Binet stage was also statistically insignificant (p=0.474). About six with trisomy 12 were positive for CD 38, however this association was also not statistically significant (p=0.124). Results revealed that patients having trisomy 12 underwent chemotherapy at diagnosis and during follow ups as compared to patients having other cytogenic abnormalities. Moreover, patient with trisomy 12 develop progression in disease during course of illness, however association was statistically insignificant (p>0.05)............

Objective: To determine the frequency of Ten-Eleven-Translocation-2 (TET2) gene mutation in Myeloproliferative Neoplasms (MPNs) and to generate a local data for evaluation of disease behavior in ten-eleven-translocation-2 positive and negative Patients. Study Design: Cross-sectional study. Place and Duration of Study: Department of Haematology, Armed Forces Institute of Pathology, Rawalpindi, from Apr 2017 to Apr 2018. Methodology: A total of 50 adult myeloproliferative neoplasms patients (>18 years of age), diagnosed according to WHO 2016 diagnostic criteria for myeloproliferative neoplasms were included in the study. Mutational screening for ten-eleven-translocation-2 gene was performed by flourescent in situ hybridization technique using Meta Systems XL-TET2 Deletion probe REF D-5038- 100-OG, LOT 18181, manufactured by Meta-Systems GmbH, Robert-Bosch - Germany. Bone marrow samples were used for Fluorescence in situ hybridization analysis. A total of 500 interphases were examined in each of the specimen. Data was entered and analyzed using SPSS-22. Distinctive demographic, haematological and molecular results are summarized by descriptive statistics. Results: Total 50 cases of myeloproliferative neoplasms (14 CML, 10 PV, 12 essential thrombocythemia (ET) and 14 primary myelofibrosis (PMF) were analyzed. On fluorescent in situ hybridization studies, ten-eleven-translocation-2 mutation was detected in 8 (16%) patients. The mutational frequency among different myeloproliferative neoplasm entities was 4 (28.5%) in chronic myeloid leukemia (CML), 2 (20%) in Polycythemia Vera (PV), 1 (8.3%) in essential thrombocythemia and 1 (7.1%) in primary myelofibrosis respectively. Among the 15 cases, 36 (72%) patients were positive for JAK2V617F mutation while 14 (28%) were positive for BCR-ABL1 mutation. Ten-eleven-translocation-2 mutation observed...................

Abstract Background Medication Adherence (MA) and Health Related Quality of Life (HRQoL) are two inter-connected concepts, co-influenced by Health Literacy (HL), with significant impact on patient management and care. Thus, we aimed to estimate the association of HL and MA with HRQoL in IHD patients. Methods Cross-sectional study of 251 IHD patients recruited from Lahore over 6 months period. HL, MA and HRQoL was assessed using validated questionnaires; 16-items of HL, Morisky Green Levine Scale (MGLS) and SF-12, respectively. Chi-square for significance, logistic-regression for association and linear regression for predictions were used. Results IHD patients; males (p = 0.0001), having secondary—higher education (p = 0.0001), middle/upper class (p = 0.0001) and employed (p = 0.005) had adequate HL, and were more likely to be adherent (OR; 4.3, p = 0.014). Both physical (PCS-12) and mental (MCS-12) component scores of HRQoL for age, gender, education, area of residence, employment and MA were significantly higher in patients with adequate HL. In multinomial regression, improved PCS-12 scores tend to be higher in subjects having secondary—higher education (OR; 3.5, p = 0.067), employed (OR; 6.1, p = 0.002) and adherent (OR; 2.95, p = 0.218), while MCS-12 scores tend to be higher in patients

Objective: To determine the frequency of Del 13q14 in Chronic lymphocytic leukaemia, to compare its association with clinicpathologic features and to define the contribution of this abnormality to the prognosis. Study Design: Cross-sectional study. Place and Duration of Study: Department of Haematology, Armed Forces Institute of Pathology, Armed Forces Bone Marrow Transplant Centre and Oncology department, Combined Military Hospital Rawalpindi, from Apr 2017 to Jul 2018. Methodology: A total of 56 newly diagnosed cases of CLL were included in the study. Patients were diagnosed on the basis of National Cancer Institute Working Group guidelines for diagnosis of CLL. After detailed history and thorough clinical examination; complete blood counts, biochemical profile, bone marrow examination, immunophenotyping on bone marrow or peripheral blood samples were done and Interphase FISH studies on blood or bone marrow specimens for detection of Del 13q14 were performed. Clinico-pathological features of CLL patients with Del 13q14 were compared with other cytogenetic abnormalities. Results: The frequency of Trisomy 12 was found to be 37.5%. Most of CLL patients with Del 13q14 were aymptomatic and were diagnosed on routine workup. The WBC count and Absolute lymphocyte count was slightly lower in patients with Del13 q14 lower when compared with the CLL patients without 13q14 Deletion. Most of the patients with this aberration presented in early stage (Binet stage A) and this association of Del 13q14 with Binet stage was statistically significant (p

Abstract Background Poor availability and unaffordability of key access antibiotics may increase antimicrobial resistance in the community by promoting inappropriate antibiotic selection and abridged therapy compliance. Objective To check the prices, availability, and affordability of the World Health Organization (WHO) key access antibiotics in private sector pharmacies of Lahore, Pakistan. Methodology A survey of WHO key access antibiotics from WHO essential medicine list 2017 was conducted in private sector pharmacies of 4 different regions of Lahore employing adapted WHO/HAI methodology. The comparison of prices and availability between originator brands (OB) and lowest price generics (LPG) were conducted followed by the effect of medicine price differences on patient’s affordability. The data were analyzed using a preprogrammed WHO Microsoft excel workbook. Results The mean availability of OB products was 45.20% and the availability of LPGs was 40.40%. The OBs of co-amoxiclav, clarithromycin and metronidazole and LPGs of azithromycin and ciprofloxacin were easily available (100%) in all private sector pharmacies. Whereas, antibiotics like chloramphenicol, cloxacillin, nitrofurantoin, spectinomycin, and cefazolin were totally unavailable in all the surveyed pharmacies. The OBs and LPGs with high MPRs were ceftriaxone (OB; 15.31, LPG; 6.38) and ciprofloxacin (OB; 12.42, LPG; 5.77). The median of brand premium obtained was 38.7%, which varied between the lowest brand premium of 3.97% for metronidazole and highest for ceftriaxone i.e. 140%. The cost of standard treatment was 0.5 day’s wage (median) if using OB and 0.4 day’s wage (median) for LPG, for a lowest paid unskilled government worker. Treatment with OB and LPG was unaffordable for ciprofloxacin (OB; 2.4, LPG; 1.1) & cefotaxime (OB; 12.7, LPG; 8.1). Conclusion There is dire need to properly implement price control policies to better regulate fragile antibiotic supply system so that the availability of both OB and LPG of key access antibiotics should be increased. The prices could be reduced by improving purchasing efficiency, excluding taxes and regulating mark-ups. This could increase the affordability of patients to complete their antibiotic therapy with subsequent reduction in antimicrobial resistance.

Objective: To evaluate the efficacy of recombinant factor VIII FC fusion protein in haemophilia A patient receiving on demand treatment only. Study Design: Comparative cross sectional study. Place and Duration of Study: Department of Hematology, Armed Forces Institute of Pathology and Pakistan Hemophilia Welfare Society, Rawalpindi, from Jun to Dec 2017. Methodology: Eighty-nine male patients of Hemophilia A already receiving recombinant factor VIII (20-30 Units/kg) on demand, with no history of inhibitors were included in study. Patients were divided as per age into paediatric and adult group and also on the basis of their basal factor VIII levels into severe, moderate and mild groups. Same patients were switched to recombinant factor VIII FC fusion protein (20-30 Units/kg) and its efficacy was measured and compared with recombinant Factor VIII in terms of dose requirement, injections, bleeds in six month period, presence of inhibitors and side effects. Results: Eighty nine male patients were studied. There was significant reduction in dose from median value of 5750 units for group I to 4000 units for group II. Number of bleed in six month period were reduced from 5.3 in group I to 4.5 in group II. Number of injections were reduced on average to 1-2 injection per bleed in group II. No inhibitors were detected in group II. Conclusion: rFVIII Fc fusion protein has prolong activity and results in reduction of total dose, number of bleed, dose per bleed and has reduced antigenecity.

Abstract Background In Pakistan, drug promotion practices, ethical or unethical, have rarely been in the spotlight. We aimed to assess the perception and barriers of medical representatives (MRs) and doctors (MDs) regarding ethical promotion of pharmaceuticals in Pakistan. Methods A cross sectional survey was conducted in seven major cities of Pakistan for 6-months period. Self-administered questionnaire was used for data collection. Logistic regression and five-point Likert scale scoring was used to estimate the perceptions and barriers. Results Compared to national companies (NCs), the medical representatives (MRs) of multinational companies (MNCs) strongly believed that their companies follow World Health Organization (WHO) (OR; 5.31, p = 0.0005), International Federation of Pharmaceutical Manufacturers & Associations (IFPMA) (OR; 6.45, p = 0.0005) and national codes of ethics (OR; 5.84, p = 0.0005). MNCs trained their MRs (OR; 6.68, p = 0.0005), provide accurate and valid scientific data (OR; 4.01, p = 0.007) with adequate system of accountability and controls on product samples (OR; 1.96, p = 0.047), while, NCs sponsor social or entertainment activities, seminars and conferences, and all sort of facilitation in form of gifts of their choice and clinic renovation for medical doctors (MDs). MDs perceptions were similar to MRs mentioned above, yet strongly agreed that companies offer cash payments or equivalents to MDs. The MRs of NCs/MNCs and MDs agreed/strongly agreed that no external accountability, profiteering, pressure on sale targets, job insecurity, condoning unethical promotion by high-ups’ and business promotion by junior MDs were the predominant barriers. Conclusion In conclusion, MRs of MNCs and MDs believed that MNCs follow certain codes of ethics in the promotion of pharmaceuticals, while NCs tend to be more profit oriented and even condone unethical promotion. All stakeholders, MRs, MDs and companies, might pose certain barriers, intentionally or unintentionally, in ethical promotion.

Abstract Background Gender wise differences exist in anti-hypertensive treatment outcomes, yet still un-explored in Pakistan. Thus, we aimed to estimate the clinical efficacy of four different anti-hypertensive regimens in hypertensive women of Punjab, Pakistan. Methods A longitudinal cohort study of 12 months duration was conducted by enrolling 300 hypertensive women on four anti-hypertensive regimens. Chi-square for significance, logistic regression for association and multilevel regression for changes in outcomes were used. Results Majority of subjects were 65 Kg, having family history, married and hailing from urban areas, with diabetes as the most common comorbidity. Hypertension, adjusted for covariates, was significantly associated with salt intake (OR:2.27, p