Search

AimsHistorically, atherosclerotic cardiovascular disease (ASCVD) risk profile mitigation has had a predominant focus on low density lipoprotein cholesterol (LDL-C). In this narrative review we explore the residual ASCVD risk profile beyond LDL-C with a focus on hypertriglyceridaemia, recent clinical trials of therapeutics targeting hypertriglyceridaemia and novel modalities addressing other residual ASCVD risk factors.FindingsHypertriglyceridaemia remains a significant ASCVD risk despite low LDL-C in statin or proprotein convertase subtilisin/kexin type 9 inhibitor-treated patients. Large population-based observational studies have consistently demonstrated an association between hypertriglyceridaemia with ASCVD. This relationship is complicated by the co-existence of low high-density lipoprotein cholesterol. Despite significantly improving atherogenic dyslipidaemia, the most recent clinical trial outcome has cast doubt on the utility of pharmacologically lowering triglyceride concentrations using fibrates. On the other hand, purified eicosapentaenoic acid (EPA), but not in combination with docosahexaenoic acid (DHA), has produced favourable ASCVD outcomes. The outcome of these trials suggests alternate pathways involved in ASCVD risk modulation. Several other pharmacotherapies have been proposed to address other ASCVD risk factors targeting inflammation, thrombotic and metabolic factors.ImplicationsHypertriglyceridaemia poses a significant residual ASCVD risk in patients already on LDL-C lowering therapy. Results from pharmacologically lowering triglyceride are conflicting. The role of fibrates and combination of EPA and DHA is under question but there is now convincing evidence of ASCVD risk reduction with pure EPA in a subgroup of patients with hypertriglyceridaemia. Clinical guidelines should be updated in line with recent clinical trials evidence. Novel agents targeting non-conventional ASCVD risks need further evaluation.

Abstract Genetic mechanisms of blood pressure (BP) regulation remain poorly defined. Using kidney-specific epigenomic annotations and 3D genome information we generated and validated gene expression prediction models for the purpose of transcriptome-wide association studies in 700 human kidneys. We identified 889 kidney genes associated with BP of which 399 were prioritised as contributors to BP regulation. Imputation of kidney proteome and microRNAome uncovered 97 renal proteins and 11 miRNAs associated with BP. Integration with plasma proteomics and metabolomics illuminated circulating levels of myo-inositol, 4-guanidinobutanoate and angiotensinogen as downstream effectors of several kidney BP genes (SLC5A11, AGMAT, AGT, respectively). We showed that genetically determined reduction in renal expression may mimic the effects of rare loss-of-function variants on kidney mRNA/protein and lead to an increase in BP (e.g., ENPEP). We demonstrated a strong correlation (r = 0.81) in expression of protein-coding genes between cells harvested from urine and the kidney highlighting a diagnostic potential of urinary cell transcriptomics. We uncovered adenylyl cyclase activators as a repurposing opportunity for hypertension and illustrated examples of BP-elevating effects of anticancer drugs (e.g. tubulin polymerisation inhibitors). Collectively, our studies provide new biological insights into genetic regulation of BP with potential to drive clinical translation in hypertension.

Despite growing prevalence of ovarian cancer (OC) in Pakistan, no literature evidence exists regarding its clinic-pathological characteristics, survival and compliance of patients with recurrent ovarian cancer on various chemo-protocols. An observational study was conducted by enrolling 251 recurrent OC patients on 7 different chemo-protocols, from a specialized cancer care hospital, Lahore, Pakistan, using convenient judgmental sampling. The study was conducted for a period of 6 months. Most of the patients were between 18 and 70 years of age, with IIIC FIGO stage and papillary serous histological grade. As per RECIST, improved partial response (PR) (63.3 %) and complete response (CR) (52.1 %) was observed in the CP (carboplatin + paclitaxel) arm, substantiated by improved median progression free survival (PFS) and overall survival (OS) in CP and CD (carboplatin + docetaxel) arms, respectively, yet with no significant differences in survival curves, PFS (p = 0.12) and OS (p = 0.22). Interestingly, the highest and the lowest patient non-compliance were observed in CG (carboplatin + gemcitabine) (81.6 %) and paclitaxel (4.5 %) arms, resp. As per the hazard model for survival, topotecan showed significant association with the therapy related events/deaths compared to other protocols. These data suggest that CP regimen exhibited improved clinical efficacy and decreased toxicity related non-compliance in recurrent ovarian cancer patients of Lahore.

Ageing of the kidney is a multi-dimensional process that occurs simultaneously at the molecular, cellular, histological, anatomical and physiological level. Nephron number and renal cortical volume decline, renal tubules become atrophic and glomeruli become sclerotic with age. These structural changes are accompanied by a decline in glomerular filtration rate, decreased sodium reabsorption and potassium excretion, reduced urinary concentrating capacity and alterations in the endocrine activity of the kidney. However, the pace of progression of these changes is not identical in everyone - individuals of the same age and seemingly similar clinical profile often exhibit stark differences in the age-related decline in renal health. Thus, chronological age poorly reflects the time-dependent changes that occur in the kidney. An ideal measure of renal vitality is biological kidney age – a measure of the age-related changes in physiological function. Replacing chronological age with biological age could provide numerous clinical benefits including improved prognostic accuracy in renal transplantation, better stratification of risk and identification of those who are on a fast trajectory to an age-related drop in kidney health.

A novel mucoadhesive buccal tablet containing flurbiprofen (FLB) and lidocaine HCl (LID) was prepared to relieve dental pain. Tablet formulations (F1-F9) were prepared using variable quantities of mucoadhesive agents, hydroxypropyl methyl cellulose (HPMC) and sodium alginate (SA). The formulations were evaluated for their physicochemical properties, mucoadhesive strength and mucoadhesion time, swellability index and in vitro release of active agents. Release of both drugs depended on the relative ratio of HPMC:SA. However, mucoadhesive strength and mucoadhesion time were better in formulations, containing higher proportions of HPMC compared to SA. An artificial neural network (ANN) approach was applied to optimise formulations based on known effective parameters (i.e., mucoadhesive strength, mucoadhesion time and drug release), which proved valuable. This study indicates that an effective buccal tablet formulation of flurbiprofen and lidocaine can be prepared via an optimized ANN approach.

Harvesting the mechanical energy from environment sources such as wavy motion of plant leaves and branches could power up the low power consumption electrical devices and sensors. Such low power energy harvesting devices will replace the batteries especially at the remote areas where the replacement of batteries is very expensive or sometimes impossible. An environment friendly nano generator using ZnO nanorods can be built easily and useful for energy generation. Although, performance of harvesting ZnO piezoelectric nanorods have gradually improved even then their power is insufficient for real devices. However, the integration of nanogenerator devices for energy harvesting into a single power source is necessary. Therefore, its simulation using MATLAB fuzzy logic and fabrication is presented in this paper with a very low error of 0.24% which shows its excellence in performance by presenting new technique of energy generation with plant leave movement. The fabricated ZnO nano-wires on aluminum substrate connected in series and parallel were also tested and the results are closely in contrast to the stimulated results. The nano-generator shows an enhanced voltage when connected in series and a high current value when connected in parallel. The nano-generator give a voltage of 0.695 mV when connected in series and a current density of 25 nA cm-2when connected in parallel. [ABSTRACT FROM AUTHOR]

Management of molasses-based wastewater generated in yeast and sugar industries is a major environmental concern due to its high chemical oxygen demand and other recalcitrant substances. Several strategies have been used to reduce the inland discharge of wastewater but the results are not satisfactory due to high operating cost. However, reuse of molasses-based wastewater irrigation in agriculture has been a major interest nowadays to reduce the freshwater consumption. Thus, it is crucial to monitor the impacts of molasses-based waste water irrigation on growth, metabolism, yield and nutritional quality of crops for safer consumer's health. In present study, carrot seeds of a local cultivar (T-29) were germinated on filter paper in Petri dishes under controlled conditions. The germinated seeds were then transplanted into pots and irrigated with three different treatments normal water (T0), diluted molasses-based wastewater (T1), and untreated molasses-based wastewater (T2), in six replicates. Results revealed that carrot irrigated with untreated molasses-based waste water had exhibited significant reductions in growth, yield, physiology, metabolism, and nutritional contents. Additionally, accumulation of Cd and Pb contents in carrot roots irrigated with untreated molasses-based waste water exceed the permissible limits suggested by WHO and their consumption may cause health risks. While, diluted molasses-based waste water irrigation positively enhanced the growth, yield of carrot plants without affecting the nutritional quality. This strategy is cost effective, appeared as most appropriate alternative mean to reduce the freshwater consumption in water deficit regions of the world., (© 2024. The Author(s).)

Liquid self-nano emulsifying drug delivery systems (SNEDDS) of furosemide (FSM) have been explored as a potential solution for enhancing solubility and permeability but are associated with rapid emulsification, spontaneous drug release, and poor in vivo correlation. To overcome the shortcoming, this study aimed to develop liquid and solid self-emulsifying drug delivery systems for FSM, compare formulation dynamics, continue in vivo therapeutic efficacy, and investigate the advantages of solidification. For this purpose, liquid SNEDDS (L-SEDDS-FSM) were formed using oleic acid as an oil, chremophore EL, Tween 80, Tween 20 as a surfactant, and PEG 400 as a co-surfactant containing 53 mg/mL FSM. At the same time, solid SNEDDS (S-SEDDS-FSM) was developed by adsorbing liquid SNEDDS onto microcrystalline cellulose in a 1:1 ratio. Both formulations were evaluated for size, zeta potential, lipase degradation, and drug release. Moreover, in vivo diuretic studies regarding urine volume were carried out in mice to investigate the therapeutic responses of liquid and solid SNEDDS formulations. After dilution, L-SEDDS-FSM showed a mean droplet size of 115 ± 4.5 nm, while S-SEDDS-FSM depicted 116 ± 2.6 nm and zeta potentials of -5.4 ± 0.55 and -6.22 ± 1.2, respectively. S-SEDDS-FSM showed 1.8-fold reduced degradation by lipase enzymes in comparison to L-SEDDS-FSM. S-SEDDS-FSM demonstrated a sustained drug release pattern, releasing 63% of the drug over 180 min, in contrast to L-SEDDS-FSM, exhibiting 90% spontaneous drug release within 30 min. L-SEDDS-FSM exhibited a rapid upsurge in urine output (1550 ± 56 μL) compared to S-SEDDS-FSM, showing gradual urine output (969 ± 29 μL) till the 4th h of the study, providing sustained urine output yet a predictable therapeutic response. The solidification of SNEDDS effectively addresses challenges associated with spontaneous drug release and precipitation observed in liquid SNEDDS, highlighting the potential benefits of solid SNEDDS in improving the therapeutic response of furosemide.

This study aimed to prepare tamsulosin hydrochloride (HCl)-loaded in situ gelling formulation by using hydroxypropyl methylcellulose (HPMC), gellan gum, poloxamer 188, and benzalkonium chloride. Physicochemical evaluation of formulations included determination of pH, viscosity, gelation time, gel strength, drug content, and sterility. In silico study was performed to analyze interactions between polymers, drug, and mucin glycoprotein. In vitro degradation time, drug release, ex vivo mucoadhesion time, permeation, in vivo pharmacokinetics, and stability studies were performed to assess the formulation. Formulations were transparent and displayed acceptable physicochemical attributes. Tamsulosin HCl and polymers interacted via non-covalent interactions. HPMC formed hydrogen bonds, hydrophobic and van der Waals interactions with mucin protein while the drug formed hydrogen bonds only. Gel formulation degraded in simulated nasal fluid within 24 h. In situ gelling formulation showed 83.8 ± 1.7% drug release and remained adhered to the mucosa for 24.5 ± 1 h. A higher (~ 1.85 times) drug permeation was recorded through mucosa within 6 h by in situ gelling formulation when compared to control counterparts (aqueous solution of drug and in situ gelling formulation without poloxamer 188). Nasal administration of tamsulosin HCl by using in situ gelling formulation led to a ~ 3.3 and ~ 3.5 times, respectively, higher Cmax (maximum plasma concentration) and AUC total (total area under the curve) than the orally administered aqueous solution. Relative bioavailability of drug delivered by nasal in situ gelling formulation was 3.5 times the oral counterpart. These results indicated that the prepared in situ gelling formulation can act as a promising candidate for systemic administration of tamsulosin HCl., (© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

The adequate elevation of CO 2 concentrations (e [CO 2 ]) could not be assessed by constrained analysis of comparative experimental study for optimum plant growth and yield with improved fruit quality owing to the lack of conjunctive investigation of plant parametric responses. Instead, the principal component analysis (PCA) and technique for order preference by similarity to ideal solution (TOPSIS) assessed and quantified the parametric plant responses to identify the adequate level of e [CO 2 ] for optimum plant growth and yield. In this study, tomato plants were grown under an ambient CO 2 (a [CO 2 ], 500 μmol mol -1 ) and three e [CO 2 ] (700, 850 and 1000 μmol mol -1 ): named EC 700 , EC 850 and EC 1000 , respectively, in autumn-winter (AW) 2020 and spring summer (SS) 2021 growing seasons to investigate and evaluate the plant parametric responses under e [CO 2 ]. The tomato plant's response with maximum transportability of biomass to fruits was observed under 700 μmol mol -1 . The plant height, stem diameter and LAI were enhanced compared to a [CO 2 ] at the optimum level under 1000 μmol mol -1 (by 50.53, 20.98 and 44.44%) and 700 μmol mol -1 (by 22.41, 12.09 and 26.88%) in Aw 2020; Ss 2021, respectively. The optimum yield was increased under 700 μmol mol -1 by 73.95% and 55.58% in Aw 2020; Ss 2021, respectively. EC 700 was ranked as a priority by TOPSIS with 0.632 and 0.694 plant response performance index in Aw 2020; Ss 2021, respectively, to get optimum tomato growth, yield, water use efficiency and fruit quality. The results of this study are beneficial for commercial greenhouse crop production by fumigating the adequate level of e [CO 2 ], to reduce the cost of CO 2 fertigation, enhance the yield and save the water quantity., Competing Interests: Declaration of competing interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my author that the work described was original research. The manuscript has not been published previously and not under consideration for publication elsewhere, in whole or in part., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Objective: This study was conducted to assess the knowledge and attitude of healthcare workers towards basic life support (BLS) in Khyber Teaching Hospital, Peshawar, and to investigate the factors affecting them., Design: Cross-sectional study., Setting: This study was carried out in a tertiary care hospital in Peshawar, Pakistan., Participants: 201 healthcare professionals were recruited for this study through simple convenience sampling which included house officers (HOs), trained medical officers, postgraduate residents, professors, specialty registrars and nurses. Healthcare professionals who were reluctant to give consent were excluded from the study., Results: Among the chosen participants, only 16.4% had good knowledge whereas 63% had a good attitude towards BLS. Knowledge of participants was found to be positively associated with less time elapsed between the training sessions (p=0.041). On the other hand, factors such as age(p=0.004), designation (p=0.05), number of BLS sessions attended (p=0.012) and the time elapsed since the last BLS session attended (p=0.015), were positively associated with the attitude of healthcare professionals., Conclusion: The level of knowledge and attitude towards BLS by healthcare professionals was suboptimal. Those individuals who had attended BLS training sessions frequently had better knowledge and attitude as compared with their counterparts., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Carboxymethyl cellulose (CMC) is a hydrophilic derivative of cellulose whose large volumes have been used in textile processing, protective coatings, detergents, papers, and drilling fluids, while cellulose gum, which is the purified form of CMC, has extensive applications in food, cosmetic, and pharmaceutical industries. Therefore, this work reflects the production of CMC by extracting cellulose with traditional and ionosolv methods from domestic matchstick waste, providing an in-depth view of the overall process where two different kinds of cellulose were obtained from two different pretreatments, and the influence of cellulose on the profile of CMC was checked. All of the procedures have been performed under optimized conditions to reduce the cost and maximize the productiveness. The results depict that cellulose extracted by the ionosolv method using a protic ionic liquid, tetramethylguanidinium hydrogen sulfate (TMG-HSO 4 ), is more degraded than that extracted by the traditional sulfide method using sodium sulfide (Na 2 S) and sodium hydroxide (NaOH). Thus, the produced CMC-2 via ionic liquid-extracted cellulose has more yield, DS (2.3), purity (98.5%), and solubility with less salt and moisture contents than CMC-1 produced by the conventional method due to an effective substitution of the hydroxyl group by the carboxymethyl group. Further, instrumental analyses like FTIR, XRD, 1 H NMR, 13 C NMR, and SEM emphasize the results that CMC-2 has more reduction of the hydroxyl peak in FTIR, a more amorphous structure in XRD, intense peaks in NMR, and the roughness of the surface in SEM., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

In electrochemistry, bio-based materials are preferred over the traditional costly and synthetic polymers due to their abundance, versatility, sustainability and low cost. One of the bio-based polymers is carboxymethyl cellulose (CMC) which has become an overarching material in electrochemical devices pertaining to its amphiphilic nature with multi-carbon functional groups. Owing to its flexible framework with fascinating groups on its surface like hydroxide (-OH) and carboxylate (-COO - ), CMC is able to be modified into conducting materials by blending it with other biopolymers, synthetic polymers, salts, acids and others. This blending has improved the profile of CMC by exploiting the ability of hydrogen bonding, swelling, adhesiveness and dispersion of charges and ions. These properties of CMC have made it possible to utilize this bio-sourced polymer in several applications as a conducting electrolyte, binder in electrodes, detector, sensor and active material in fuel cells, actuators and triboelectric nanogenerators (TENG). Thus, CMC based materials are cheap, environment friendly, hydrophilic, biodegradable, non-toxic and biocompatible which render it a desirable material in energy storage devices., Competing Interests: Authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

The performance of organic solar cells (OSCs) has been improving steadily over the last few years, owing to the optimization of device fabrication, fine-tuning of morphology, and thin-film processing. Thiophene core containing fused ring-type non-fullerene acceptors (NFAs) achieved significant proficiency for highly efficient OSCs. Quantum chemical computations are utilized herein with the motive of suggesting new NIR sensitive, highly efficient low-band gap materials for OSCs. A series of extended conjugated A-π-D-π-A architectured novel fused-ring NFAs (FUIC-1-FUIC-6) containing thieno[2,3- b ]thiophene-based donor core are proposed by substituting the end-capped units of synthesized molecule F10IC. Different properties including frontier molecular orbital analysis, density of states analysis, transition density matrix analysis, excitation energy, reorganizational energies of both holes (λ h ) and electrons (λ e ), and open-circuit voltage ( V oc ) were performed employing the density functional theory approach. Charge transfer analysis of the best-designed molecule with the donor complex was analyzed to comprehend the efficiency of novel constructed molecules (FUIC-1-FUIC-6) and compared with the reference. End-caped acceptor alteration induces the reduction of the energy gap between HOMO-LUMO (1.88 eV), tunes the energy levels, longer absorption in the visible and near-infrared regions, larger V oc , smaller reorganizational energies, and binding energy values in designed structures (FUIC-1-FUIC-6) in comparison to reference (FUIC). The designed molecules show the best agreement with the PTBT-T donor polymer blend and cause the highest charge from the HOMO to the LUMO orbital. Our findings predicted that thieno[2,3- b ] thiophene-based newly designed molecules would be efficient NFAs with outstanding photovoltaic characteristics and can be used in future applications of OSCs., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The coronavirus disease of 2019 (COVID-19) constitutes a serious threat to pregnant women. One of the key strategies for preventing and managing the COVID-19 epidemic is vaccination. Herd immunity is significantly hampered by COVID-19 vaccine reluctance, which poses a potential threat to population health. Therefore, the present work intends to ascertain the incidence and severity of COVID-19 vaccine hesitancy among Pakistani pregnant women, the determinants driving their decision, and a comparative assessment with non-pregnant participants. This cross-sectional survey was carried out from November 2021 to February 2022. The validated vaccination attitude examination (VAX) scale about vaccination reluctance was undertaken by participants, who were also required to indicate whether they would be inclined to acquire the COVID-19 vaccine along with the reasons for reluctance. In comparison to the non-pregnant category with 353 participants, the group of 372 pregnant participants who responded to the questionnaire had a much greater proportion of hesitant respondents. Likewise, contrasted to 31% of non-pregnant participants, about 40% of them attributed their willingness to get vaccinated against coronavirus to social media. They also demonstrated a considerably stronger mean score on all subcategories of the VAX measure. The adjusted odd ratio findings showed that the independent factors for vaccine reluctance appeared to be trusting rumors on social media (adj OR: 2.58), not being afraid of covid-19 (adj OR: 2.01), not believing in COVID-19 existence (adj OR: 2.53), and not believing in vaccines (adj OR: 4.25). Uncertainty about the COVID-19 vaccine is very prevalent among expectant mothers. The investigation accentuates the pressing need to administer COVID-19 vaccination to the general public, including expectant mothers who might be anxious about the vaccine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rehman, Rehman, Akhlaq, Hussain and Holy.)