Study of HLA class II loci reveals DQB1*03:03:02 as a risk factor for asthma in a Pakistani population.

Asthma, a chronic inflammatory disorder of the lungs and airways, typically results from a combination of multiple environmental and genetic factors. Human leucocyte antigen (HLA) region on chromosome 6p21 encodes the most highly polymorphic loci in the human genome, encoding genes with central roles in the immune function where HLA loci are strongly associated with various immune-mediated diseases such as autoimmunity, allergies and infection. The alleles of HLA class II genes such as DRB1 and DQB1 are the key genetic markers in the development of asthma and have been extensively studied in different ethnicities of the world population. However, the genetic screening of HLA class II alleles and haplotypes in Pakistani asthmatics has not been studied so far. The aim of the present study was to screen the HLA class II DRB1 and DQB1 alleles in asthma cases and controls in a Pakistani population. Seven hundred and two healthy controls and asthma patients were genotyped for HLA class II by sequence-specific polymerase chain reaction assays. The HLA-DRB1 and HLA-DQB1 allele and haplotype frequencies were calculated, and their risk or protective association with asthma was determined. Two-locus haplotypes of DRB1 and DQB1 alleles were imputed using Arlequin version 3.1 software. The signals of association with asthma were stronger at the DQB1 locus as compared to DRB1. HLA DQB1*03:03:02 (odds ratio [OR] = 2.42, 95% confidence interval [CI] = 1.34-4.25) was significantly associated with an increased risk of asthma, as was the haplotype comprised allele DRB1*07:01-DQB1*03:03:02 (OR = 2.40, 95% CI = 1.25-4.62). In contrast, DQB1*06 (OR = 0.39, 95% CI = 0.22-0.70) and DQB1*06:02 (OR = 0.27, 95% CI = 0.10-0.71) emerged as protective alleles for asthma. Our data concludes that the HLA DQB1*03:03:02 allele was a risk allele for asthma, whereas two DQB1 alleles, DQB1*06 and DQB1*06:02, were associated with asthma protection. Our findings highlight a prominent role for HLA-DQB1 alleles in asthma pathogenesis in studied Pakistani cases. More studies, especially with a larger study cohort are needed to confirm the utility of HLA DQB1*03:03:02 as a predictive marker.

Recycled algae-based carbon materials as electroconductive 3D printed skeletal muscle tissue engineering scaffolds.

Skeletal muscle is an electrically and mechanically active tissue that contains highly oriented, densely packed myofibrils. The tissue has self-regeneration capacity upon injury, which is limited in the cases of volumetric muscle loss. Several regenerative therapies have been developed in order to enhance this capacity, as well as to structurally and mechanically support the defect site during regeneration. Among them, biomimetic approaches that recapitulate the native microenvironment of the tissue in terms of parallel-aligned structure and biophysical signals were shown to be effective. In this study, we have developed 3D printed aligned and electrically active scaffolds in which the electrical conductivity was provided by carbonaceous material (CM) derived from algae-based biomass. The synthesis of this conductive and functional CM consisted of eco-friendly synthesis procedure such as pre-carbonization and multi-walled carbon nanotube (MWCNT) catalysis. CM obtained from biomass via hydrothermal carbonization (CM-03) and its ash form (CM-03K) were doped within poly(ɛ-caprolactone) (PCL) matrix and 3D printed to form scaffolds with aligned fibers for structural biomimicry. Scaffolds were seeded with C2C12 mouse myoblasts and subjected to electrical stimulation during the in vitro culture. Enhanced myotube formation was observed in electroactive groups compared to their non-conductive counterparts and it was observed that myotube formation and myotube maturity were significantly increased for CM-03 group after electrical stimulation. The results have therefore showed that the CM obtained from macroalgae biomass is a promising novel source for the production of the electrically conductive scaffolds for skeletal muscle tissue engineering.

Design and Development of D‒α‒Tocopheryl Polyethylene Glycol Succinate‒block‒Poly(ε-Caprolactone) (TPGS-b-PCL) Nanocarriers for Solubilization and Controlled Release of Paclitaxel.

The objective of this study was to synthesize and characterize a set of biodegradable block copolymers based on TPGS-block-poly(ε-caprolactone) (TPGS-b-PCL) and to assess their self-assembled structures as a nanodelivery system for paclitaxel (PAX). The conjugation of PCL to TPGS was hypothesized to increase the stability and the drug solubilization characteristics of TPGS micelles. TPGS-b-PCL copolymer with various PCL/TPGS ratios were synthesized via ring opening bulk polymerization of ε-caprolactone using TPGS, with different molecular weights of PEG (1-5 kDa), as initiators and stannous octoate as a catalyst. The synthesized copolymers were characterized using 1H NMR, GPC, FTIR, XRD, and DSC. Assembly of block copolymers was achieved via the cosolvent evaporation method. The self-assembled structures were characterized for their size, polydispersity, and CMC using dynamic light scattering (DLS) technique. The results from the spectroscopic and thermal analyses confirmed the successful synthesis of the copolymers. Only copolymers that consisted of TPGS with PEG molecular weights ≥ 2000 Da were able to self-assemble and form nanocarriers of ≤200 nm in diameter. Moreover, TPGS2000-b-PCL4000, TPGS3500-b-PCL7000, and TPGS5000-b-PCL15000 micelles enhanced the aqueous solubility of PAX from 0.3 µg/mL up to 88.4 ug/mL in TPGS5000-b-PCL15000. Of the abovementioned micellar formulations, TPGS5000-b-PCL15000 showed the slowest in vitro release of PAX. Specifically, the PAX-loaded TPGS5000-b-PCL15000 micellar formulation showed less than 10% drug release within the first 12 h, and around 36% cumulative drug release within 72 h compared to 61% and 100% PAX release, respectively, from the commercially available formulation (Ebetaxel®) at the same time points. Our results point to a great potential for TPGS-b-PCL micelles to efficiently solubilize and control the release of PAX.

Chitosan-Coated Flexible Liposomes Magnify the Anticancer Activity and Bioavailability of Docetaxel: Impact on Composition.

Flexible liposomes (FLs) were developed as promising nano-carriers for anticancer drugs. Coating them with chitosan (CS) could improve their drug delivery properties. The aim of this study was to investigate the physicochemical characteristics, pharmacokinetics behavior, and cytotoxic efficacy of docetaxel (DTX)-loaded CS-coated FLs (C-FLs). DTX-loaded FLs and C-FLs were produced via thin-film evaporation and electrostatic deposition methods, respectively. To explore their physicochemical characterization, the particle size, zeta potential, encapsulation efficiency (EE%), morphology, and DTX release profiles were determined. In addition, pharmacokinetic studies were performed, and cytotoxic effect was assessed using colon cancer cells (HT29). Various FLs, dependent on the type of surfactant, were formed with particle sizes in the nano-range, 137.6 ± 6.3 to 238.2 ± 14.2 nm, and an EE% of 59⁻94%. Moreover, the zeta potential shifted from a negative to a positive value for C-FL with increased particle size and EE%, and the in vitro sustained-release profiles of C-FL compared to those of FL were evident. The optimized C-FL containing sodium deoxycholate (NDC) and dicetyl phosphate (DP) elicited enhanced pharmacokinetic parameters and cytotoxic efficiency compared to those of the uncoated ones and Onkotaxel®. In conclusion, this approach offers a promising solution for DTX delivery.

Flavonostilbenes natural hybrids from Rhamnoneuron balansae as potential antitumors targeting ALDH1A1: molecular docking, ADMET, MM-GBSA calculations and molecular dynamics studies.

Several studies have linked Cancer stem cells (CSCs) to cancer resistance development to chemotherapy and radiotherapy. ALDH1A1 is a key enzyme that regulates the gene expression of CSCs and creates an immunosuppressive tumor microenvironment. It was reported that quercetin and resveratrol were among the inhibitors of ALDH1A1. In early 2022, it was reported that new 11 flavonostilbenes (rhamnoneuronal D-N) were isolated from Rhamnoneuron balansae as potential antiaging natural products. Rhamnoneuronal H (5) could be envisioned as a natural hybrid of quercetin and resveratrol. It was therefore hypothesized that 5 and its analogous isolates rhamnoneuronal D-G (1-4) and rhamnoneuronal I-N (6-11) would have potential ALDH1A1 inhibitory activity. To this end, all isolates were subjected to molecular docking, MM-GBSA, ADMET, and molecular dynamics simulations studies to assess their potential as new leads for cancer treatment targeting ALDH1A1. In silico findings revealed that natural hybrid 5 has a similar binding affinity, judged by MM-GBSA, to the ALDH1A1 active site when compared to the co-crystalized ligand (-64.71 kcal/mole and -64.12 kcal/mole, respectively). Despite having lesser affinity than that of the co-crystalized ligand, the rest of the flavonostilbenes, except 2-4, displayed better binding affinities (-37.55 kcal/mole to -58.6 kcal/mole) in comparison to either resveratrol (-34.44 kcal/mole) or quercetin (-36.48 kcal/mole). Molecular dynamic simulations showed that the natural hybrids 1, 5-11 are of satisfactory stability up to 100 ns. ADMET outcomes indicate that these hybrids displayed acceptable properties and hence could represent an ideal starting point for the development of potent ALDH1A1 inhibitors for cancer treatment.Communicated by Ramaswamy H. Sarma.

Predicting the main pollen season of Broussonetia Papyrifera (paper mulberry) tree.

Paper mulberry pollen, declared a pest in several countries including Pakistan, can trigger severe allergies and cause asthma attacks. We aimed to develop an algorithm that could accurately predict high pollen days to underpin an alert system that would allow patients to take timely precautionary measures. We developed and validated two prediction models that take historical pollen and weather data as their input to predict the start date and peak date of the pollen season in Islamabad, the capital city of Pakistan. The first model is based on linear regression and the second one is based on phenological modelling. We tested our models on an original and comprehensive dataset from Islamabad. The mean absolute errors (MAEs) for the start day are 2.3 and 3.7 days for the linear and phenological models, respectively, while for the peak day, the MAEs are 3.3 and 4.0 days, respectively. These encouraging results could be used in a website or app to notify patients and healthcare providers to start preparing for the paper mulberry pollen season. Timely action could reduce the burden of symptoms, mitigate the risk of acute attacks and potentially prevent deaths due to acute pollen-induced allergy.

Polycaprolactone-Vitamin E TPGS Micellar Formulation for Oral Delivery of Paclitaxel.

This study aimed to investigate the potential of polycaprolactone-vitamin E TPGS (PCL-TPGS) micelles as a delivery system for oral administration of paclitaxel (PTX). The PCL-TPGS copolymer was synthesized using ring opening polymerization, and PTX-loaded PCL-TPGS micelles (PTX micelles) were prepared via a co-solvent evaporation method. Characterization of these micelles included measurements of size, polydispersity, and encapsulation efficiency. The cellular uptake of PTX micelles was evaluated in Caco-2 cells using rhodamine 123 (Rh123) as a fluorescent probe. Moreover, an everted rat sac study was conducted to evaluate the ex vivo permeability of PTX micelles. Additionally, a comparative pharmacokinetic study of PTX micelles versus the marketed formulation, Ebetaxel® (a Taxol generic), was performed after a single oral administration to rats. The results demonstrated that the micellar formulation significantly improved PTX solubility (nearly 1 mg/mL). The in vitro stability and release of PTX micelles in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) demonstrated that PTX micelles remained stable for up to 24 h and significantly slowed the release of PTX in both media compared to Ebetaxel®. The in vitro cellular uptake, ex vivo intestinal permeability, and in vivo pharmacokinetic profile demonstrated that PTX micelles enhanced the permeability and facilitated a rapid absorption of the drug. Conclusively, the PCL7000-TPGS3500 micelles exhibit potential as an effective oral delivery system for PTX.

Polycaprolactone - Vitamin E TPGS micelles for delivery of paclitaxel: In vitro and in vivo evaluation.

This study aimed to present findings on a paclitaxel (PTX)-loaded polymeric micellar formulation based on polycaprolactone-vitamin E TPGS (PCL-TPGS) and evaluate its in vitro anticancer activity as well as its in vivo pharmacokinetic profile in healthy mice in comparison to a marketed formulation. Micelles were prepared by a co-solvent evaporation method. The micelle's average diameter and polydispersity were determined using dynamic light scattering (DLS) technique. Drug encapsulation efficiency was assessed using an HPLC assay. The in vitro cytotoxicity was performed on human breast cancer cells (MCF-7 and MDA-MB-231) using MTT assay. The in vivo pharmacokinetic profile was characterized following a single intravenous dose of 4 mg/kg to healthy mice. The mean diameters of the prepared micelles were ≤ 100 nm. Moreover, these micelles increased the aqueous solubility of PTX from ∼0.3 µg/mL to reach nearly 1 mg/mL. While the PTX-loaded micelles showed an in vitro cytotoxicity comparable to the marketed formulation (Ebetaxel), drug-free PCL-TPGS micelles did not show any cytotoxic effects on both types of breast cancer cells (∼100% viability). Pharmacokinetics of PTX as part of PCL-TPGS showed a significant increase in its volume of distribution compared to PTX conventional formulation, Ebetaxel, which is in line with what was reported for clinical nano formulations of PTX, i.e., Abraxane, Genexol-PM, or Apealea. The findings of our studies indicate a significant potential for PCL-TPGS micelles to act as an effective system for solubilization and delivery of PTX.

100 years of immunotherapy: the Monaco charter. under the high patronage of His Serene Highness Prince Albert II of Monaco.

Aims of the Monaco Charter: (1) to present the current evidence on the efficacy and safety of allergen-specific immunotherapy (SIT) and to address the reasons for its underuse in clinical practice; (2) to develop strategies to increase the awareness about the benefits and the hazards of SIT in allergic patients, lay public and healthcare professionals not trained in allergy, and (3) to make SIT accessible and affordable to eligible patients.

Catalytic evaluation of cellulose pyrolysis by using nanosized metal oxide catalysts.

In this study, effects of TiO2 and ZnO nanometal oxides on cellulose pyrolysis have been investigated. Both catalysts have been synthesized via hydrothermal method and characterized by using different techniques. Catalytic and catalyst-free experiments were carried out so as to identify the catalytic abilities of synthesized nanoparticles. Catalyst-free experiments were carried out at 500, 600, and 700 °C in order to determine the optimal condition for pyrolysis and it was found as 700 °C. Optimum catalyst ratio for cellulose pyrolysis was found as 5% (w/w) for both TiO2 and ZnO catalysts. GC-MS and micro-GC analyses were conducted in order to examine the catalytic properties of synthesized nanoparticles and illuminate the content of pyrolytic oil and gaseous products. Results showed that maximum gas yield was observed at 700 °C in the presence of 5% TiO2. Maximum activity for both catalysts was observed at 700 °C and the char yield was significantly decreased in each catalytic experiment at specified temperatures, compared to catalyst-free experiments. Both nanoparticles catalyzed the dehydration and decarbonylation reactions and significantly increased the amount of furan derivatives, especially furanic aldehydes.

Green catalyst for clean fuel production via hydrodeoxygenation.

The development of new fuel sources to replace nonrenewable fossil fuels has received substantial attention due to the ongoing demand for fossil fuels. Biomass and raw waste materials are crucial sources to produce suitable alternative fuels instead of nonrenewable fuels and offer a greener approach. Therefore, improving the fuel properties of biooils produced from the thermochemical conversion of biomass and raw waste materials is critical as it is used as an alternative to nonrenewable fuel. Developing an economical and eco-friendly method to produce sustainable and renewable oil by improving biooil containing large amounts of phenolic compounds has become imperative. One of the most intriguing and promising technologies for refining biooil to produce renewable fuels of comparable quality to conventional fossil fuels is the hydrodeoxygenation (HDO)-based process for converting biooil to renewable fuels. This method is almost one of the best improving methods described in the literature. At this point, it is of great importance that the HDO process is carried out catalytically. Carbon materials are preferred for both designing catalysts for HDO and supporting metal nanoparticles by providing chemically inert surfaces and tunable functional groups, high surface area and active sites. The HDO of biomass and raw waste materials has significantly advanced thanks to carbon-based catalysts. In this review, the effect of the surface character and catalytic ability of the carbon support, especially prepared by the green synthesis technique, on the HDO reaction during biooil improvement is discussed. Moreover, HDO reaction parameters and recent studies have been investigated in depth. Thus, green carbon catalysts' role in clean fuel production via the HDO process has been clarified.

Association of asthma exacerbations with paper mulberry (Broussenetia papyrifera) pollen in Islamabad: An observational study.

Background: Although the role of airborne plant pollen in causing allergic rhinitis has been established, the association of concentrations of paper mulberry (Broussenetia papyrifera) pollens in the air and incidence of asthma exacerbations has not, despite an observed increase in the number of asthma patients attending physician clinics and hospital Accident and Emergency (A&E) Departments during the paper mulberry pollen season. We aimed to assess the association between paper mulberry pollen concentrations (typically peaking in March each year) and asthma exacerbations in the city of Islamabad. Methods: We used three approaches to investigate the correlation of paper mulberry pollen concentration with asthma exacerbations: A retrospective analysis of historical records (2000-2019) of asthma exacerbations of patients from the Allergy and Asthma Institute, Pakistan (n = 284), an analysis of daily nebulisations in patients attending the A&E Department of the Pakistan Institute of Medical Sciences (March 2020 to July 2021), a prospective peak expiratory flow rate (PEFR) diary from participants (n = 40) with or without asthma and with or without paper mulberry sensitisation. We examined associations between pollen data and asthma exacerbations using Pearson correlation. Results: We found a strong positive correlation between mean paper mulberry pollen counts and clinical records of asthma exacerbations in patients sensitised to paper mulberry (Pearson correlation coefficient (r) = 0.86; P < 0.001), but not in non-sensitised patients (r = 0.32; P = 0.3). There was a moderate positive correlation between monthly nebulisation counts and pollen counts (r = 0.56; P = 0.03), and a strong negative correlation between percent predicted PEFR and pollen counts in sensitised asthma patients (r = -0.72, P < 0.001). However, these correlations were of low magnitude in the non-sensitised asthma (r = -0.16; P < 0.001) and sensitised non-asthma (r = -0.28; P < 0.001) groups. Conclusions: Our three approaches to analysis all showed an association between high paper mulberry pollen concentration in Islamabad and asthma exacerbations. Predicting pollen peaks could enable alerts and mobilise strategies to proactively manage these peaks of asthma exacerbations.

Prioritising the respiratory research needs of primary care: the International Primary Care Respiratory Group (IPCRG) e-Delphi exercise.

BACKGROUND: Community-based care, underpinned by relevant primary care research, is an important component of the global fight against non-communicable diseases. The International Primary Care Research Group's (IPCRG's) Research Needs Statement identified 145 research questions within five domains (asthma, rhinitis, chronic obstructive pulmonary disease (COPD), smoking, respiratory infections). AIMS: To use an e-mail Delphi process to prioritise the research questions. METHODS: An international panel of primary care clinicians scored the clinical importance, feasibility, and international relevance of each question on a scale of 1-5 (5 = most important). In subsequent rounds, informed by the Group's median scores, participants scored overall priority. Consensus was defined as 80% agreement for priority scores 4 or 5. RESULTS: Twenty-three experts from 21 countries completed all three rounds. Sixty-two questions were prioritised across the five domains. A recurring theme was for 'simple tools' (e.g. questionnaires) enabling diagnosis and assessment in community settings, often with limited access to investigations. Seven questions recorded 100% agreement: these involved pragmatic approaches to the diagnosis of COPD and rhinitis, assessment of asthma and respiratory infections, management of rhinitis, and implementing asthma self-management. CONCLUSIONS: Evidence to underpin the primary care approach to diagnosis and assessment and broad management strategies were overarching priorities. If primary care is to contribute to the global challenge of managing respiratory non-communicable diseases, policymakers, funders, and researchers need to prioritise these questions.

Effecting change in primary care management of respiratory conditions: a global scoping exercise and literature review of educational interventions to inform the IPCRG's E-Quality initiative.

This discussion paper describes a scoping exercise and literature review commissioned by the International Primary Care Respiratory Group (IPCRG) to inform their E-Quality programme which seeks to support small-scale educational projects to improve respiratory management in primary care. Our narrative review synthesises information from three sources: publications concerning the global context and health systems development; a literature search of Medline, CINAHL and Cochrane databases; and a series of eight interviews conducted with members of the IPCRG faculty. Educational interventions sit within complex healthcare, economic, and policy contexts. It is essential that any development project considers the local circumstances in terms of economic resources, political circumstances, organisation and administrative capacities, as well as the specific quality issue to be addressed. There is limited evidence (in terms of changed clinician behaviour and/or improved health outcomes) regarding the merits of different educational and quality improvement approaches. Features of educational interventions that were most likely to show some evidence of effectiveness included being carefully designed, multifaceted, engaged health professionals in their learning, provided ongoing support, were sensitive to local circumstances, and delivered in combination with other quality improvement strategies. To be effective, educational interventions must consider the complex healthcare systems within which they operate. The criteria for the IPCRG E-Quality awards thus require applicants not only to describe their proposed educational initiative but also to consider the practical and local barriers to successful implementation, and to propose a robust evaluation in terms of changed clinician behaviour or improved health outcomes.

Development and Evaluation of Interactive Flipped e-Learning (iFEEL) for Pharmacy Students during the COVID-19 Pandemic.

Background: Distance learning has come to the forefront of educational delivery throughout the world due to the COVID-19 pandemic. Presently, there is a paucity of studies that have utilized interactive e-lectures as a model for remote flipped learning. Objectives: To compare educational outcomes for the remote interactive flipped e-learning (iFEEL) activity versus paper-based in-class group learning (PICkLE). Methods: During the spring 2021 semester, tutorials in pharmaceutical quality control and good manufacturing practice were remotely delivered to students by two different approaches: PICkLE and iFEEL. In the latter activity, interactive e-lectures were software-designed and included several audiovisual enhanced illustrations to encourage students to interact with the lecture material prior to attending the virtual class. The class time was reserved for in-class quizzes and discussion. Mean exam scores were compared and voluntary questionnaires were distributed among the participating students as well as healthcare faculty members in 29 Saudi universities. Data from the remotely-delivered course was compared with data from previous course offerings (2018−2020) that used the live PICkLE method. Results: The mean score of post-lecture tests significantly (p < 0.05) increased compared to pre-lecture tests in remote PICkLE and iFEEL, respectively. iFEEL activity showed higher mean post-tests score (95.2%) compared to live PICkLE (90.2%, p = 0.08) and remote PICkLE (93.5%, p = 0.658). Mean comprehensive exam scores increased from 83.8% for remote PICkLE to 89.2% for iFEEL (p = 0.449). On average, 92% of students and 85% of faculty members reported positive feedback on the five quality attributes of the e-lecture. Over 75% of students preferred the iFEEL over PICkLE activity for future course offerings and 84% of faculty members recommend the integration of interactive e-lectures in their future courses. Conclusion: iFEEL represents a novel model of remote flipped learning and shows promising potential to be incorporated into live blended-learning classroom activities.

Catalytic pyrolysis of olive oil residue to produce synthesis gas: the effect of bulk and nano metal oxides.

In this study, olive oil residue (OR) biomass was pyrolyzed in the presence of bulk MgO (B-MgO), nano-MgO (N-MgO), bulk ZnO (B-ZnO)), and nano-ZnO (N- ZnO) metal oxides at different temperatures (400, 600, and 800 ºC). Significant results were obtained in terms of synthesis gas formation and CO2 reduction. The efficiency distribution of the products obtained as a result of the metal oxide-based pyrolysis process and the effects of metal oxides were examined in detail. Nanometal oxides were synthesized by the hydrothermal method. Characterization of metal oxides was carried out by Brunauer-Emmett-Teller (BET), x-ray powder diffraction (XRD) analysis and scanning-electron microscopy-energy dispersive x-ray (SEM-EDX) techniques. The metal concentration of OR biomass was detected via the x-ray fluorescence (XRF) technique. Tar product properties were evaluated by gas chromatography-mass spectrometry (GC-MS) and Fourier transform-infrared spectroscopy (FT-IR) analyzes. Analysis results show that pyrolytic tar is very similar to diesel and gasoline as it contains significant concentrations of aliphatic and aromatic hydrocarbons in composition. In addition, the composition of noncondensable gaseous products was determined by micro gas chromatography (micro-GC) analysis.

Discovery of novel natural products as dual MNK/PIM inhibitors for acute myeloid leukemia treatment: Pharmacophore modeling, molecular docking, and molecular dynamics studies.

MNK-2 and PIM-2 kinases play an indispensable role in cell proliferation signaling pathways linked to tyrosine kinase inhibitors resistance. In this study, pharmacophore modeling studies have been conducted on the co-crystalized ligands of MNK-2 and PIM-2 enzyme crystal structures to determine the essential features required for the identification of potential dual inhibitors. The obtained pharmacophore features were then screened against a library of 270,540 natural products from the ZINC database. The matched natural molecules were docked into the binding sites of MNK-2 and PIM-2 enzymes. The compounds with high docking scores with the two enzymes were further subjected to MM-GBSA calculations and ADME prediction. This led to the identification of compound 1 (ZINC000085569211), compound 2 (ZINC000085569178), and compound 3 (ZINC000085569190), with better docking scores compared to the reference co-crystallized ligands of MNK-2 and PIM-2. Moreover, compounds 1‒3 displayed better MM-GBSA binding free energies compared to the reference ligands. Finally, molecular dynamics (MD) study was used to assess the interaction stability of the compounds with MNK-2. To this end, compounds 1 and 3 bound strongly to the target during the whole period of MD simulation. The findings of the current study may further help the researchers in the discovery of novel molecules against MNK-2 and PIM-2.

Prioritising primary care respiratory research needs: results from the 2020 International Primary Care Respiratory Group (IPCRG) global e-Delphi exercise.

Respiratory diseases remain a significant cause of global morbidity and mortality and primary care plays a central role in their prevention, diagnosis and management. An e-Delphi process was employed to identify and prioritise the current respiratory research needs of primary care health professionals worldwide. One hundred and twelve community-based physicians, nurses and other healthcare professionals from 27 high-, middle- and low-income countries suggested 608 initial research questions, reduced after evidence review by 27 academic experts to 176 questions covering diagnosis, management, monitoring, self-management and prognosis of asthma, COPD and other respiratory conditions (including infections, lung cancer, tobacco control, sleep apnoea). Forty-nine questions reached 80% consensus for importance. Cross-cutting themes identified were: a need for more effective training of primary care clinicians; evidence and guidelines specifically relevant to primary care, adaption for local and low-resource settings; empowerment of patients to improve self-management; and the role of the multidisciplinary healthcare team.

Predictors for detecting chronic respiratory diseases in community surveys: A pilot cross-sectional survey in four South and South East Asian low- and middle-income countries.

BACKGROUND: Our previous scoping review revealed limitations and inconsistencies in population surveys of chronic respiratory disease. Informed by this review, we piloted a cross-sectional survey of adults in four South/South-East Asian low-and middle-income countries (LMICs) to assess survey feasibility and identify variables that predicted asthma or chronic obstructive pulmonary disease (COPD). METHODS: We administered relevant translations of the BOLD-1 questionnaire with additional questions from ECRHS-II, performed spirometry and arranged specialist clinical review for a sub-group to confirm the diagnosis. Using random sampling, we piloted a community-based survey at five sites in four LMICs and noted any practical barriers to conducting the survey. Three clinicians independently used information from questionnaires, spirometry and specialist reviews, and reached consensus on a clinical diagnosis. We used lasso regression to identify variables that predicted the clinical diagnoses and attempted to develop an algorithm for detecting asthma and COPD. RESULTS: Of 508 participants, 55.9% reported one or more chronic respiratory symptoms. The prevalence of asthma was 16.3%; COPD 4.5%; and 'other chronic respiratory disease' 3.0%. Based on consensus categorisation (n = 483 complete records), "Wheezing in last 12 months" and "Waking up with a feeling of tightness" were the strongest predictors for asthma. For COPD, age and spirometry results were the strongest predictors. Practical challenges included logistics (participant recruitment; researcher safety); misinterpretation of questions due to local dialects; and assuring quality spirometry in the field. CONCLUSION: Detecting asthma in population surveys relies on symptoms and history. In contrast, spirometry and age were the best predictors of COPD. Logistical, language and spirometry-related challenges need to be addressed.

The International Primary Care Respiratory Group (IPCRG) Research Needs Statement 2010.

AIM: Respiratory diseases are a public health issue throughout the world, with high prevalence and morbidity. This Research Needs Statement from the International Primary Care Respiratory Group (IPCRG) aims to highlight unanswered questions on the management of respiratory diseases that are of importance to practising primary care clinicians. METHODS: An informal but inclusive consultation process was instigated in 2009. Draft statements in asthma, rhinitis, COPD, tobacco dependence, and respiratory infections were circulated widely to IPCRG members, other recognised experts, and representatives from a range of economic and healthcare backgrounds. An iterative process was used to generate, prioritise and refine research questions in each section. RESULTS: Two overarching themes emerged. Firstly, there is a real need for research to be undertaken within primary care, which recruits patients representative of primary care populations, evaluates interventions realistically delivered within primary care, and draws conclusions that will be meaningful to professionals working within primary care. Secondly, international and national guidelines exist, but there is little evidence on the best strategies for implementing recommendations. Disease-specific research questions focus on effective and cost-effective ways to prevent disease, confirm the diagnosis, assess control, manage treatment, and empower selfmanagement. Practical questions about how to deliver this comprehensive agenda in diverse primary care settings are highlighted. CONCLUSIONS: We hope that this Research Needs Statement will be used by clinicians and patients campaigning for answers to relevant questions, by researchers seeking funding to provide answers to these questions, and by funding bodies to enable them to prioritise research agendas.