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Abstract Background Dyspnea is considered a silent threat to people diagnosed with Parkinson’s disease and may be a common concern in patients, however, little is known about how it affects quality of life. This study explored the experiences of independently mobile people who are affected by dyspnea in daily life. Methodology This was a cross-sectional mixed methods study that included an online questionnaire and semi-structured interviews. The participants were included if they were diagnosed with Parkinson’s disease; had a self-reported Hoehn and Yahr Score I, II or III; were mobilizing independently; and were Arabic speakers. Participants were excluded if they had any other musculoskeletal, cardiac, respiratory, or neurological diseases; or were previous or current smokers; or had been previously hospitalized due to respiratory complications. Results A total of 117 participants completed the Arabic version of the Dyspnea-12 Questionnaire. Dyspnea was reported in all participants and that it had an adverse effect on their quality of life, especially during activities of daily living. Additionally, participants reported a lack of knowledge about pulmonary rehabilitation and were unaware of the availability and potential benefits of participation in programs. Conclusion Dyspnea was reported in people in the early stages (Hoehn and Yahr Stages I, II, and III) of Parkinson’s disease, and may benefit from routine assessment of lung function, dyspnea management and participation in pulmonary rehabilitation.

Health Information Seeking Behavior (HISB) refers to the behavior and strategies used to attain, clarify, or confirm health information. The uptake of health information depends on system-level and individual-level factors. The purpose of the present study is to understand the sources from which Punjabi elders obtain COVID-19 vaccine-related information and their information seeking behavior. A cross-sectional survey was conducted among 391 Punjabi elders aged 50+ years in the Greater Toronto Area (GTA), Ontario. The survey questions included the need for COVID-19 vaccine information, the type of information sought, sources of information, and barriers to seeking information. Descriptive analysis was conducted using frequencies and percentages, and logistic regression was performed to understand the associations between participants’ sociodemographic characteristics and HISB. The results suggested that Punjabi elders are more likely to use informal sources and less likely to seek information from health professionals and government health and wellness websites. The results also suggested that most participants do not cross-check their information with other sources and are more likely to cross-check the information with family/friends, compared to credible care providers, across all demographics. Ultimately, there may be a need for stakeholders to collaborate to regulate the accuracy and type of health-information that is disseminated through media, and to tailor health communication to the health information seeking behavior of this population.

Abstract Biochar is increasingly recognized for its ability to enhance hydro-physical properties of soil, offering promising solutions for improving soil structure, water retention, and overall agricultural productivity. In this study, sandy loam soil was amended at different rates (0, 15, 30, and 60 t ha−1) of biochar produced from olive pomace (Jift) at different pyrolysis temperatures (300, 400, 500, and 600 °C), and incubated for 30, 60, and 90 days. The biochar-amended soils were collected for analysis after each incubation period for infiltration rate, aggregate stability, soil water retention, water repellency, and penetration resistance. At 300 °C, aggregate stability increased with biochar amendments; the highest value (65%) was after 60 days of incubation. At other pyrolysis temperatures, aggregate stability decreased, or no effect of temperature was observed. Also, at 300 °C, the infiltration rate was decreased with biochar application and the lowest value of (0.14 ml/min) was at 90 days of incubation. At other pyrolysis temperatures, the infiltration rate was increased with increased biochar application rate. Water retention was increased with biochar application at 300 °C; however, biochar application did not affect water retention at other pyrolysis temperatures. These results strongly suggest the improvement of soil physical and hydraulic properties following the addition of biochar amendment. Overall, biochar had positive effects on hydro-physical properties. The biochar produced at 300 °C pyrolysis temperature was the most beneficial to agriculturally relevant hydraulic conditions. However, field assessments are necessary to evaluate the long-term effects of biochar on hydro-physical properties.

Abstract Background While a connection has been established between serum interleukin-6 (IL-6) levels and the IL-6 gene (− 174G/C) polymorphism in allergic diseases such as asthma, its specific association with severe asthma remains unexplored. This study examined the relationship between the IL-6 (− 174G/C) gene polymorphism and mild and severe asthma, focusing on its influence on type 2 inflammation. Methods Our study comprised 98 patients with mild asthma and 116 with severe asthma. Additionally, we recruited 121 healthy participants to serve as controls for comparative analyses. The IL-6 gene (− 174G/C) polymorphism was assessed utilizing the polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) method. Results In our study, the risk of mild asthma exhibited a significant fourfold increase in individuals with the GG genotype pattern compared to healthy controls, yielding an odds ratio (OR) of 4.4 (p

Retinoblastoma is a kind of cancer that mostly affects children's eyes, and this study intends to find drugs that can suppress the protein kinase cyclin-dependent kinase 4 (CDK4). CDK4 overexpression leads to the hyper-phosphorylation of RB tumor suppressor protein, which ultimately results in uncontrolled cell division. Aberration of cell cycle regulation, specifically the excessive expression of transcription factors responsible for uncontrolled cell division causes retinoblastoma progression. Hence, we screened 25,000 kinase-targeted small molecules against CDK-4 by Glide in Maestro, the top 11 were chosen based on docking scores, binding modes, chemical variety, and other parameters. We ran molecular dynamics (MD) simulations of top hits found in the docking studies and determined their free binding energy. This helped us to understand their thermodynamic and dynamic properties, as well as confirm the docking results, finally the two most promising ligands (3396 and 960) were obtained. As a result of our research, we have identified promising new compounds for treating retinoblastoma. To validate the possible therapeutic and preventative effects of this ligand, rigorous experimental validation, animal studies as well as clinical trials would be required.

Antimicrobial resistance (AMR) is currently a global health concern, mostly caused by microorganisms like bacteria, viruses, parasites, and fungi that acquire resistance to antimicrobial drugs. Salmonella is responsible for a variety of diseases but mainly cause typhoid. The primary concern is the rise in resistance in both non-typhoid and typhoid strains of this species. To address this issue, it is necessary to identify novel targets and strategies for the development of new antibacterial drugs. Lipid A, a strong bacterial endotoxin that modulates the immune system in human, is a key component of the virulence factor generated during the salmonella infection. Lipid A is synthesized in case of Gram-negative bacteria by cascade of nine enzyme pathway. The second step in case of Lipid A biosynthesis, catalysed by LpxC, a Zn+ dependent metallo-amidase considered as rate limiting step. In this manuscript we have used protein-ligand interaction fingerprint (PLIF)–derived pharmacophore models to screen small molecules (natural products library from Zinc database, Asinex database, Thiophene analogues) against Salmonella typhi LpxC (StLpxC). Further top hit molecules were subjected to MD-simulation and ADMET studies. We identified three optimal compounds, s1_dl_mseq2, s1_ll_mseq2, and s2_ll_mseq8, that exhibit strong binding affinity towards the LpxC active site.

Mucopolysaccharidosis type I (MPS I) is an autosomal recessive lysosomal storage disorder characterized by deficient or absent α-L-iduronidase (IDUA) enzyme activity due to pathogenic variants in the IDUA gene. Early treatment with hematopoietic stem cell transplantation and/or enzyme replacement therapy is associated with improved outcomes in this progressive multisystem disease. The diagnosis is usually delayed due to late presentation and non-specific symptoms, which result in high morbidity and mortality. The incidence of MPS I is unknown in Kuwait. This pilot study was undertaken to screen MPS I in all Kuwaiti neonates born at Farwaniya Hospital (FH), a major center in Kuwait, over 12 months. This study examined the incidence of MPS I for inclusion in the national newborn screening (NBS) to enable its early detection and adequate treatment. All Kuwaiti neonates born at FH between December 2021 and December 2022 were screened for MPS I. The screening consisted of determining IDUA enzyme activity in dried blood spot-derived samples using tandem mass spectrometry. A follow-up genetic analysis of the IDUA gene has been planned to screen the cases with diminished IDUA enzyme activity as second-tier testing. A total of 618 newborns, including 331 (54%) boys and 287 (46%) girls, were screened. Of them, 20 had deficient IDUA enzyme activity but showed negative genetic testing. However, we have diagnosed one additional female infant with MPS I who belonged to FH, but the parents chose to deliver in a private hospital. The molecular genetic study revealed the presence of a previously reported pathogenic nonsense variant in the IDUA c.1882C>T, which is associated with severe phenotype. That being included, MPS I is estimated to be approximately 0.2% of all screened cases in Kuwait. Our study is the first to evaluate the incidence of MPS I in Kuwait. Given the single center, small number of screened infants, and the short study duration thus far, it is premature to calculate the incidence. It is anticipated that as the study continues, we would be able to estimate the incidence in our population correctly. Screening newborns in all maternity hospitals in Kuwait is necessary to calculate the actual incidence of this severe disorder. Still, our preliminary data support the inclusion of MPS I in national NBS program to allow early initiation of treatment and thus improve disease outcome.

We report a patient from Panama who had lobomycosis caused by Paracoccidioides (Lacazia) loboi. We used combined clinical-epidemiologic and phylogenetic data, including a new gene sequence dataset on this fungus in Panama, for analysis. Findings contribute useful insights to limited knowledge of this fungal infection in the Mesoamerican Biologic Corridor.

Instruction To help determine the health protectiveness of government regulations and policies for air pollutant control for Americans, our study aimed to investigate the health and economic impacts of work loss due to sickness associated with daily all-source and wildfire-specific PM2.5 (particulate matter with an aerodynamic diameter smaller than 2.5 μm) exposures in California.Methods We linked the 2015–2018 California Health Interview Survey respondents’ geocoded home addresses to daily PM2.5 estimated by satellites and atmospheric modelling simulations and wildfire-related PM2.5 from Community Multiscale Air Quality models. We calculated and applied the coefficient for the association between daily PM2.5 exposure and work loss from regression analyses to the Environmental Benefits Mapping and Analysis Program—Community Edition (BenMAP-CE) platform to assess the health and economic impacts of PM2.5 exposure on work loss due to sickness.Results We observed that each 1 µg/m3 increase in daily total PM2.5 exposure will lead to about 1 million days of work loss per year ranging from 1.1 to 1.6 million person-days, and the related economic loss was $310–390 million. Wildfire smoke alone could contribute to 0.7–2.6 million work-loss days with a related economic loss of $129–521 million per year in 2015–2018. Using the function coefficient in the current BenMAP, the excess work-loss days due to sickness was about 250 000 days and the estimated economic loss was about $45–50 million for each 1 µg/m3 increase in daily total PM2.5 exposure, and wildfire smoke alone would lead to 0.17–0.67 million work-loss days with related economic loss of $31–128 million per year during the same period.Conclusions Both conventional and wildfire-specific sources of PM2.5 produced substantial work loss and cost in California. Updating the current BenMAP-CE calculations for work-loss days will be essential in quantifying the current health impacts of PM2.5 to help inform the policies and regulations to protect public health.

The use of medicinal plants exists before the existence of humans. Healing with herbal treatments is of utmost significance because medicinal plants contain bioactive compounds. The objective of the current investigation was to evaluate the biological potential of methanolic (PAM) and chloroform (PAC) extracts of Portulacaria afra root, leaf, seed and flower. FT-IR (Fourier Transform Infrared Spectroscopy) spectroscopy was completed to detect the different functional groups. Total antioxidant capacity (TAC), total reducing power (TRP) and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) assays, were done for the determination of antioxidant potential of medicinal plant P. afra. Five different bacterial strains were used to evaluate the antibacterial potential using disc diffusion method. Cytotoxicity assay was used to test the cytotoxic potential against brine shrimps and shown the maximum cytotoxic potential with lowest IC50 value (41.41 ± 0.80 µg/mL) in PAM. Radish seed germination phytotoxicity assay was performed and revealed the highest phytotoxic potential in PAM extract. ANOVA was applied via statistics version-8.1, and experimentations were done in triplicates. Maximum DPPH scavenging potential was observed in methanol extract of P. afra (PAM). The PAM extract has the highest flavonoid concentration (30.70 mg/g). PAM demonstrated maximum total reducing power (73.46 gallic acid equivalents per gram (GAE/g). Antibacterial activity was performed against different bacterial strains and PAM shown the best antibacterial activity with largest zone of inhibition (17 mm) contrary to Pseudomonas aeruginosa. The bioactive compounds found in P. afra extracts have antibacterial, antioxidant, and cytotoxic properties, revealing their ability to induce cell death in cancerous cell lines, indicating potential anticancer agents and making them intriguing candidates for future research and the possible creation of new therapeutics. we advise the use of these extracts against biofilms as these extracts have shown significant antibacterial activity against gram negative bacteria“.

Objective(s): The present study evaluated the protein-based analysis to unravel the role and mechanism behind the Dendropthae falcata plant extract treatment in breast cancer cells. Materials and Methods: The protein sample was extracted from the cancer cells after treatment with the plant extract and subjected to two-dimensional electrophoresis for protein separation. Further, the proteins that were differentially regulated among the samples which were treated and non-treated were selected and processed further for protein identification using a tandem mass spectrometry approach.Results: Using these strategies, we identified 16 potential candidates which were showing remarkable changes in treated samples. All the candidates were analyzed further for gene ontology analysis, and it was observed that all proteins were involved in multiple pathways pertaining to the carcinogenesis process. Specifically, apoptotic pathway proteins including BAD, BIK, BID, CASP8, MCL1, BCL2, and BAK1 were highly impacted by treatment with D. falcata plant extract. All these protein hits were further taken for validation experiments using RT PCR analysis. Conclusion: Initiation of these apoptotic proteins by D. falcata plant extract treatment in breast cancer cells shows a positive direction toward nature-based alternative medicine.

This paper presents the parallelization of two widely used implicit numerical solvers for the solution of partial differential equations on structured meshes, namely, the ADI (Alternating-Direction Implicit) solver for tridiagonal linear systems and the SIP (Strongly Implicit Procedure) solver for the penta-diagonal systems. Both solvers were parallelized using CUDA (Computer Unified Device Architecture) Fortran on GPGPUs (General-Purpose Graphics Processing Units). The parallel ADI solver (P-ADI) is based on the Parallel Cyclic Reduction (PCR) algorithm, while the parallel SIP solver (P-SIP) uses the wave front method (WF) following a diagonal line calculation strategy. To map the solution schemes onto the hierarchical block-threads framework of the CUDA on the GPU, the P-ADI solver adopted two mapping methods, one block thread with iterations (OBM-it) and multi-block threads (MBMs), while the P-SIP solver also used two mappings, one conventional mapping using effective WF lines (WF-e) with matrix coefficients and solution variables defined on original computational mesh, and a newly proposed mapping using all WF mesh (WF-all), on which matrix coefficients and solution variables are defined. Both the P-ADI and the P-SIP have been integrated into a two-dimensional (2D) hydrodynamic model, the CCHE2D (Center of Computational Hydroscience and Engineering) model, developed by the National Center for Computational Hydroscience and Engineering at the University of Mississippi. This study for the first time compared these two parallel solvers and their efficiency using examples and applications in complex geometries, which can provide valuable guidance for future uses of these two parallel implicit solvers in computational fluids dynamics (CFD). Both parallel solvers demonstrated higher efficiency than their serial counterparts on the CPU (Central Processing Unit): 3.73~4.98 speedup ratio for flow simulations, and 2.166~3.648 speedup ratio for sediment transport simulations. In general, the P-ADI solver is faster than but not as stable as the P-SIP solver; and for the P-SIP solver, the newly developed mapping method WF-all significantly improved the conventional mapping method WF-e.

Background and Objectives: Robotics is commonly used in the rehabilitation of neuro-musculoskeletal injuries and diseases. While in these conditions, robotics has clear benefits, it is unknown whether robotics will also enhance the outcome of cardiac rehabilitation. This systematic review evaluates the use of robotics in cardiac rehabilitation. Methods: A systematic literature search was conducted using PubMed (MEDLINE), CINAHL, AMED, SPORTDiscus, and the Physiotherapy Evidence Database. Longitudinal interventional studies were included if they met specified criteria. Two reviewers independently conducted title, abstract, and full-text screening and data extraction. The quality assessment and risk of bias were conducted according to the PEDRO scale and Cochrane Risk of Bias tool 2, respectively. Results: Four trials were included in this review out of 60 screened studies. The quality of the included studies was good with a low risk of bias. The trials used different robotic systems: Lokomat® system, Motomed Letto/Thera Trainer tigo, BEAR, and Myosuit. It was found that interventions that included the use of robotic assistance technologies improved the exercise capacity, VO2 max/peak, left ventricular ejection fraction, QOL, and physical functioning in people with cardiac diseases. Conclusions: Robotic assistance technologies can be used in cardiac rehabilitation programs. Further studies are needed to confirm the results and determine whether the use of robotics enhances intervention outcomes above standard interventions.

Background and Objectives: Chronic Obstructive Pulmonary Disease (COPD) is the third most common cause of death globally. Pulmonary rehabilitation (PR) programmes are important to reduce COPD symptoms and improve the quality of life of people with COPD. Digital health interventions have recently been adopted in PR programmes, which allow people with COPD to participate in such programmes with low barriers. The aim of this study is to review and discuss the reported effects of digital health interventions on PR outcomes in people with COPD. Materials and Methods: To achieve the study goals, a systematic literature search was conducted using PubMed (MEDLINE), CINAHL, AMED, SPORTDiscus and the Physiotherapy Evidence Database. Randomised clinical trials (RCTs) were included if they met specified criteria. Two reviewers independently checked titles, abstracts, and performed full-text screening and data extraction. The quality assessment and risk of bias were performed in accordance with the PEDRO scale and Cochrane Risk of Bias tool 2, respectively. Results: Thirteen RCTs were included in this systematic review with 1525 participants with COPD. This systematic review showed the potential positive effect of digital health PR on the exercise capacity—measured by 6- and 12-min walking tests, pulmonary function, dyspnoea and health-related quality of life. There was no evidence for advantages of digital health PR in the improvement of anxiety, depression, and self-efficacy. Conclusions: Digital health PR is more effective than traditional PR in improving the pulmonary and physical outcomes for people with COPD, but there was no difference between the two PR programmes in improving the psychosocial outcomes. The certainty of the findings of this review is affected by the small number of included studies.

Abstract Trauma is the number one cause of death among Americans between the ages of 1 and 46 years, costing more than $670 billion a year. Following death related to central nervous system injury, hemorrhage accounts for the majority of remaining traumatic fatalities. Among those with severe trauma that reach the hospital alive, many may survive if the hemorrhage and traumatic injuries are diagnosed and adequately treated in a timely fashion. This article aims to review the recent advances in pathophysiology management following a traumatic hemorrhage as well as the role of diagnostic imaging in identifying the source of hemorrhage. The principles of damage control resuscitation and damage control surgery are also discussed. The chain of survival for severe hemorrhage begins with primary prevention; however, once trauma has occurred, prehospital interventions and hospital care with early injury recognition, resuscitation, definitive hemostasis, and achieving endpoints of resuscitation become paramount. An algorithm is proposed for achieving these goals in a timely fashion as the median time from onset of hemorrhagic shock and death is 2 h.

Cancer is a serious health problem, with a rising trend in its occurrence documented globally. Female breast cancer is the most common type of cancer worldwide with treatment consisting of different strategies like mastectomy, chemotherapy, and radiotherapy. Anticancer property has been studied in withaferin-A (WA), a bioactive compound of Withania somnifera. Another natural substance derived from bees, propolis, has been investigated for many beneficial effects on human diseases. The current study aims to investigate the ameliorative efficacy and antiproliferative potential of combinational drug therapy of withaferin-A and propolis on breast cancer cells. By evaluating the levels of glycoproteins, nucleic acids, and the marker enzymes in benzo[a]pyrene-induced breast cancer-bearing female Wistar rats, the pharmacodynamic effects of withaferin-A and propolis drug combination were examined. Biochemical analysis of DNA, RNA, and protein levels in the liver demonstrated typical results after propolis therapy. Withaferin-A and propolis drug combination treatment significantly decreased nucleic acid synthesis, indicating that combination chemotherapy has increased breast tumoricidal efficiency. The pharmacological combination therapy exhibited the capacity to control glycoproteins associated with tumor growth (hexose, hexosamine, and sialic acid), with a considerable decrease in their levels detected. Histopathological analysis of the mammary glands demonstrated a decrease in hyperplasia and cell proliferation, indicating that the treatment has the ability to reverse architectural and morphological abnormalities associated with breast cancer. This study found that natural drug compounds in combination have shown regenerative and regulating effects when given to rats carrying the breast cancer gene.

In almost all cultures medicinal plants are used as a rich source of phytochemicals and nutraceuticals components and have played promising role in maintaining and improving human health. The current study was aimed to unveil biological evaluation of Centaurea iberica. Plant extracts were prepared in five different solvents viz. methanol, ethanol, n-hexane, ethyl acetate and chloroform. The antioxidant potentials (2,2-diphenyl, 1-picrylhydrazine scavenging activity, total reducing power) of the plant revealed that the methanolic extract showed significant DPPH (2,2-diphenyl, 1-picrylhydrazine) scavenging activity (IC50 value 77.20 ± 8.81), reducing power (20.45 ± 0.54 AAE mg/g). In case of antibacterial assay, highest zone of inhibition (20 ± 1.5 mm) was recorded in methanolic extract against Klebsiella pneumonia. Likewise, for antifungal activity the highest zone of inhibition was recorded for methanolic extract (18 ± 2.4 mm) against Aspergillus niger. Moreover, 50 % inhibition was observed for methanolic extract against targated PC3 (prostate cancer cell line) cell lines and 3T3 cell lines. In the light of present study, it is recommended that further in vitro and in vivo studies should be performed using different animal models and characterization should be done to isolate different compounds that could be used to treat different types of ailments.

Pulicaria arabica has been traditionally utilized in folk medicine for various purposes such as ulcer treatments as well as antidiarrheal agent. Herein, the chemical profiles of Pulicaria arabica essential oils (PAEOs) and the in vitro antiproliferative effect of PAEOs were investigated. Hydrodistillation was employed to prepare PAEOs which were then characterized by GC/MS, while the antiproliferative effects were investigated by MTT assay as well as flow cytometric and RT-PCR analysis. Sixty-four (99.99 %) constituents were recognized from PAEOs. Carvotanacetone (36.97 %), (-)-carvomenthone (27.20 %) and benzene, 2-(1,1-dimethylethyl)-1,4-dimethoxy- (6.92 %) were the main components. PAEOs displayed IC50 values ranging from 30 to 50 μg/mL. DNA content analysis revealed that A549 cells exposed to PAEOs exhibited an increase in G1 cells population. The flow cytometry analysis results also showed that the PAEOs antiproliferative effect was mediated via apoptosis induction. Furthermore, a modulation in the pro-apoptotic markers (caspase-3 and Bax) and anti-apoptotic (Bcl-2) was also observed. In conclusion, PAEOs exhibited a moderate anti-proliferative effect on A549 cells through modulating the cell cycle progression and apoptosis initiation. These findings could offer a potential therapeutic use of PAEOs in lung cancer treatment.

Objectives: Anthraquinones (9,10-dioxoantracenes) with a wide range of applications constitute an important class of natural and synthetic compounds. Moreover, there is an increasing interest in developing new anthraquinone derivatives with biological activity. These findings suggested that due to the qualities of anthraquinone, it may be employed in the pharmaceutical and food industries. Methods: The synthesis of anthraquinone derivatives (compound 1 and 2) was performed using the Mannich base reaction, and the compounds were characterised via FT-IR, 1H and 13C NMR spectra, and mass spectral analysis. Through the use of spectroscopic analytical techniques, the in vitro antioxidant capacity of anthraquinone was examined. These techniques included DPPH free radical scavenging, hydrogen peroxide (H2O2) scavenging, ABTS•+ scavenging activity, ferrous ion (Fe2+). Results: At a concentration of 100 µg/mL, compound 2 shows that 65.2 % inhibited to DPPH assays compared with butylated hydroxyl toluene (BHT) at 45.7 % activity. Moreover, compound 2 shows that more potential of activity against DPPH, ABTS•+, hydrogen peroxide, ferric ion (Fe3+), and ferrous ion (Fe2+) chelating, reducing, and antioxidant properties when compared with compound 1 and standard BHT. The compounds 1 and 2 where checked for tyrosinase activity, the compound 2 shows that significant of activity compared with compound 1 and standard kojic acid. Conclusion: Kinetics studies were analysed compounds 1 and 2 through all antioxidant assays and activity of tyrosinase inhibition. The compound 2 was highly active against all the activities. Based on the aforementioned findings, it can be used to maintain nutritional quality, extend the shelf life of food and medicine, delay the development of hazardous oxidation products, and minimise or stop the oxidation of lipids in dietary items.

Objective: Phaleria macrocarpa fruit has been reported to be effectively used in Malaysia and neighboring countries to prevent obesity. Despite its anti-obesity potential, no research has ever predicted the compound-lipase, compound-HMG-CoA reductase interactions and in vivo investigations to further confirm its anti-obesity properties. Thus, the purpose of this study was to assess the anti-obesity and antihyperlipidemic effects of P. macrocarpa by in vitro, computational (in silico), and in vivo assays. Method: Initially, fruit was extracted through liquid CO2 and heating under reflux extraction methods to obtain liquid CO2 extracts (LCE-1 and LCE-2) and heating under reflux extract (HRE), respectively. Subsequently, all three extracts were assessed for antioxidant potentials through in vitro bioassays and FTIR analysis to identify different types of functional groups present in the existing bioactive compounds. Successively, the most active fraction (LCE-2) was subjected to GCMS analysis for the identification of lipid lowering and lipase inhibitors through molecular docking approach. Finally, anti-obesity and lipid lowering effects were further confirmed through an in vivo assay using mice. Result: LCE-2 exhibited higher DPPH (IC50 = 0.172 mg/mL) and FRAP (78.98 AAEmg/g) antioxidant activities and showed more potent peaks in FTIR chromatograms than LCE-1 and HRE. Among the identified tentative bioactive compounds viz. methyl palmitate, palmitic acid, ethyl palmitate, methyl oleate, oleic acid, cis-vaccenic acid, 3-deoxyestradiol and phenol, 2,2′-methylenebis[6-(1,1-dimethylethyl)-4-methyl- were found as an anti-obesity and lipid lowering compounds whose protein–ligand interaction was confirmed by binding affinity, amino acid residues and bonding interactions. Similarly, anti-obesity and lipid lowering findings were also found in a mice model after 6 weeks treatment at a dose of 250 mg/kg b.w. Conclusion: Based on the aforementioned in vitro, in silico and in vivo findings, it is concluded that the LCE-2 possesses lipase and HMG-CoA reductase inhibitors that can assist to develop this plant’s extract as an alternative safe lipid lowering herbal medicine in future.

Alzheimer's disease (AD) is a complicated neurodegenerative disorder that presents significant challenges for the development of effective therapeutic interventions. Understanding disease mechanisms and exploring potential treatments require the use of animal models that accurately replicate the pathology of AD. In this study, we investigated the potential of two neurotoxin inducers, aluminium chloride (AlCl3) and okadaic acid (OKA), to validate the zebrafish as a model organism for AD. AD can impact locomotor activity and induce anxiety-like behaviors. To assess these behaviors, a 6-minute novel tank test was conducted. Zebrafish were administered with low, medium, or high doses of neurotoxic agent (AlCl3 or OKA) intraperitoneally twice weekly for 21 days. Behavioral activities were recorded at three time points: day 7 (short duration), day 14 (moderate duration), and day 21 (extended duration). The behavioral task required the evaluation of four endpoints. Methanolic extract of Litsea garciae bark was selected as a potential plant for the treatment of AD in this study, based on its previously demonstrated antioxidant effect. However, the acute toxicity of this plant has not been previously assessed. Therefore, this research was aimed to investigate the acute toxicity of the L. garciae bark’s methanolic extract in adult zebrafish. The extract was immersed in a static system following OECD Test Guideline No. 203, and the acute toxicity test involved monitoring the adult zebrafish for 96 h for any deaths or apparent abnormalities. Regarding the behavioural task, the groups induced with 100 nM of OKA demonstrated significant differences in all measured parameters compared to the control group at the 21-day time point. In contrast, none of the parameters were significantly different between the AlCl3-induced groups and the control group at any of the three time points (7, 14, or 21 days). Regarding acute toxicity, neither the test group (100 mg/L) nor the control group recorded any deaths or abnormalities. Therefore, no LC50 value could be determined. These findings confirm the acceptance of OKA as an inducer in the zebrafish model of AD and highlight the significance of the safe and non-toxic nature of L. garciae bark's methanolic extract for future ethnopharmacological investigations.

Background: Few studies investigated the impact of particulate matter (PM2.5) on some symptom exacerbations that are not perceived as severe enough to search for medical assistance. We aimed to study the association of short-term daily total PM2.5 exposure with work loss due to sickness among adults living in California. Methods: We included 44,544 adult respondents in the workforce from 2015 to 2018 California Health Interview Survey data. Daily total PM2.5 concentrations were linked to respondents’ home addresses from continuous spatial surfaces of PM2.5 generated by a geostatistical surfacing algorithm. We estimated the effect of a 2-week average of daily total PM2.5 exposure on work loss using logistic regression models. Results: About 1.69% (weighted percentage) of adult respondents reported work loss in the week before the survey interview. The odds ratio of work loss was 1.45 (odds ratio [OR] = 1.45, 95% confidence interval [CI]: 1.03, 2.03) when a 2-week average of daily total PM2.5 exposure was higher than 12 µg/m3. The OR for work loss was 1.05 (95% CI: 0.98, 1.13) for each 2.56ug/m3 increase in the 2-week average of daily total PM2.5 exposure, and became stronger among those who were highly exposed to wildfire smoke (OR = 1.06, 95% CI: 1.00, 1.13), compared to those with lower wildfire smoke exposure (OR = 1.04, 95% CI: 0.79, 1.39). Conclusions: Our findings suggest that short-term ambient PM2.5 exposure is positively associated with work loss due to sickness and the association was stronger among those with higher wildfire smoke exposure. It also indicated that the current federal and state PM2.5 standards (annual average of 12 µg/m3) could be further strengthened to protect the health of the citizens of California.

The Siddha system of medicine is an ancient medical lineage that is practiced primarily in the southern part of India. Siddha system of medicine has been in practice for thousands of years with documented evidence dating back to the 6th century BCE. According to siddha system of medicine’s basic fundamental principle, the human body is made up of 96 thathuvam (primary components), which encompass physical, physiological, psychological, and intellectual aspects. Medicine (marunthu) is classified as a wide range of internal and external medicines. The major components of its medical formulations include plant parts, minerals and animal products. Various methods were carried out for the purification process to eliminate the toxins. Choornam, Guligai, Tailam, Parpam, Chendooram, Kattu, Pasai and Poochu are the most common medicines used in Siddha system of medicine for the treatment of various diseases. The pathophysiological classification of diseases is elaborated in detail in the classical Siddha literature. Siddha system of medicine plays an important role in protecting people from diseases such as COVID-19 by providing immune-protecting and immune-boosting medicines in today's world. Mathan tailam and maha megarajanga tailam are the two unique preparations used widely for various skin diseases including chronic wounds and burns. Scientific validation of both medicines will help in understanding their effectiveness against a typical wound condition. In the present study physio-chemical and phytochemical, HPTLC, and GC–MS analyses were carried out and discussed in detail on the multifunctional properties exhibited in the patient communities.

Traumatic brain injury (TBI) is a leading cause of mortality and long-term impairment globally. TBI has a dynamic pathology, encompassing a variety of metabolic and molecular events that occur in two phases: primary and secondary. A forceful external blow to the brain initiates the primary phase, followed by a secondary phase that involves the release of calcium ions (Ca2+) and the initiation of a cascade of inflammatory processes, including mitochondrial dysfunction, a rise in oxidative stress, activation of glial cells, and damage to the blood–brain barrier (BBB), resulting in paracellular leakage. Currently, there are no FDA-approved drugs for TBI, but existing approaches rely on delivering micro- and macromolecular treatments, which are constrained by the BBB, poor retention, off-target toxicity, and the complex pathology of TBI. Therefore, there is a demand for innovative and alternative therapeutics with effective delivery tactics for the diagnosis and treatment of TBI. Tissue engineering, which includes the use of biomaterials, is one such alternative approach. Biomaterials, such as hydrogels, including self-assembling peptides and electrospun nanofibers, can be used alone or in combination with neuronal stem cells to induce neurite outgrowth, the differentiation of human neural stem cells, and nerve gap bridging in TBI. This review examines the inclusion of biomaterials as potential treatments for TBI, including their types, synthesis, and mechanisms of action. This review also discusses the challenges faced by the use of biomaterials in TBI, including the development of biodegradable, biocompatible, and mechanically flexible biomaterials and, if combined with stem cells, the survival rate of the transplanted stem cells. A better understanding of the mechanisms and drawbacks of these novel therapeutic approaches will help to guide the design of future TBI therapies.

The purpose of this narrative review is to summarize the utility of augmented reality (AR) and virtual reality (VR) in neurosurgery in both enhancing surgical performance and subsequently improving patient outcomes. We identified papers that cover the use of AR/VR in neurosurgeries in a variety of clinical settings and surgical dilemmas, particularly highlighting how these advancements have improved tumor resections for neurosurgical oncologists and have aided in accurate placement of pedicle screws during spine cases. As a result of such improvements, patients may reap better postsurgical outcomes with shorter lengths of hospital stay. We also identified papers on resident education and communication among surgeons, identifying yet another fruitful avenue for these technologies. Despite such promising outcomes, challenges remain prior to acceptance into mainstream practice and widespread availability of these technologies, thus further research and development are crucial for future implementation.

Meningiomas are the most prevalent primary intracranial tumors. The majority are benign but can undergo dedifferentiation into advanced grades classified by World Health Organization (WHO) into Grades 1 to 3. Meningiomas’ tremendous variability in tumor behavior and slow growth rates complicate their diagnosis and treatment. A deeper comprehension of the molecular pathways and cellular microenvironment factors implicated in meningioma survival and pathology is needed. This review summarizes the known genetic and epigenetic aberrations involved in meningiomas, with a focus on neurofibromatosis type 2 (NF2) and non-NF2 mutations. Novel potential biomarkers for meningioma diagnosis and prognosis are also discussed, including epigenetic-, RNA-, metabolomics-, and protein-based markers. Finally, the landscape of available meningioma-specific animal models is overviewed. Use of these animal models can enable planning of adjuvant treatment, potentially assisting in pre-operative and post-operative decision making. Discovery of novel biomarkers will allow, in combination with WHO grading, more precise meningioma grading, including meningioma identification, subtype determination, and prediction of metastasis, recurrence, and response to therapy. Moreover, these biomarkers may be exploited in the development of personalized targeted therapies that can distinguish between the 15 diverse meningioma subtypes.

Shamsul Azhar Shah,1 Nazarudin Safian,1 Zulkefley Mohammad,1 Siti Rohani Nurumal,1 Wan Abdul Hannan Wan Ibadullah,1 Juliana Mansor,1 Saharuddin Ahmad,2 Mohd Rohaizat Hassan,1 Yugo Shobugawa3 1Department of Community Health, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, 56000, Malaysia; 2Department of Family Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, 56000, Malaysia; 3Department of Active Aging, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, JapanCorrespondence: Shamsul Azhar Shah, Department of Community Health, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, 56000, Malaysia, Tel +60 3-9145 8787, Fax +60 3-91456670, Email drsham@ppukm.ukm.edu.myPurpose: Handgrip strength (HGS) is indicative of overall physical health among older adults. A decrease in HGS may be associated with an increased risk of disease. The aim of this study is to determine the factors associated with HGS among older adults in Malaysia.Patients and Methods: One thousand two hundred four (1204) participants from urban and rural areas in Selangor state, Malaysia, were recruited. Sociodemographic and health-related conditions were gathered through a comprehensive face-to-face interview, followed by HGS assessments by a handgrip dynamometer. Subsequently, multiple linear regression was used to test the main association with the HGS.Results: A total of 691 participants (57.4%) were male, and 513 (42.6%) were female. Males had a mean HGS of 30.0 (SD 7.53) kg, and females had a mean HGS of 19.4 (SD 5.28) kg. Males’ handgrip strength was significantly reduced with increasing age, physically inactive, and diabetes (all at the level p< 0.001) after adjusting for social-demographic characteristics and health-related variables. Meanwhile, for females, the HGS was significantly decreased with age (p< 0.001), physically inactive (p< 0.001) and hypertension (p=0.03). However, female HGS was positively related to BMI (p< 0.001).Conclusion: The study contributed to a better understanding of factors associated with HGS, and thus, the HGS is recommended as a section in the health evaluation among high-risk older adults as the strategy of disease control and prevention.Keywords: handgrip strength, elderly, risk factors

BackgroundType-1 diabetes mellitus (T1DM) is a complex multifactorial disease with an autoimmune etiology and is thought to result from an interaction between genetic and non-genetic factors. Cytokines play a crucial role in the pathogenesis of autoimmune diseases due to their effector and regulatory functions in immune responses. Interleukin-4 (IL4) and Interleukin-13 (IL13) are anti-inflammatory cytokines and are considered as important mediators in pathology of the autoimmune diseases.MethodsWe have determined the genotype frequency of IL4 gene promoter polymorphism (−590C/T, rs2243250), IL13 gene polymorphism p.(Arg130Glu, rs20541) and human leukocyte antigen, HLA-DQ and DR genotypes in Kuwaiti children with T1DM to investigate their role in genetic susceptibility. This study included 261 Kuwaiti children with T1DM and 214 healthy controls. The genotypes for IL4 (−590C/T) and IL13 p.(Arg130Glu) gene polymorphisms were detected by PCR-RFLP methods. HLA-DQ and DR genotypes were determined by sequence-specific PCR methods.ResultsThe CC genotype of IL4 gene polymorphism (−590C/T) was significantly related to the risk for T1DM in Kuwaiti patients (OR 1.64). The homozygous AA (QQ) and heterozygous AG (RQ) genotypes of IL13 gene polymorphism p.(Arg130Glu), also manifested a statistically significant association with T1DM (OR 2.92 and 4.79). In 55% T1DM patients, the HLA genotype was either DQ2/DQ2 or in combination with a DQ8 allele. Collectively, 91% Kuwaiti T1DM patients had either DQ2 or DQ8 alleles in different combinations highlighting them as the high risk-genotypes in comparison to the controls. In the case of HLA-DR, the genotypes DR3/DRB5, DR3/DR4, DR3/DR7 and DR4/DR4 showed highest frequency amongst the Kuwaiti T1DM patients and thus can be considered as high-risk genotypes when compared to the controls. A high degree of co-inheritance (>80%) was detected between IL4 and IL13 gene polymorphism genotypes (CC and QQ) and the high-risk HLA-DQ and DR genotypes amongst the Kuwaiti T1DM patients.ConclusionsWe have identified the association of IL4 and IL13 gene polymorphisms with susceptibility to T1DM in Kuwaiti children and the co-inheritance of these polymorphisms with high-risk HLA genotypes. The findings may contribute to early identification of childhood diabetes.

BackgroundIn the last couple of years, viral infections have been leading the globe, considered one of the most widespread and extremely damaging health problems and one of the leading causes of mortality in the modern period. Although several viral infections are discovered, such as SARS CoV-2, Langya Henipavirus, there have only been a limited number of discoveries of possible antiviral drug, and vaccine that have even received authorization for the protection of human health. Recently, another virial infection is infecting worldwide (Monkeypox, and Smallpox), which concerns pharmacists, biochemists, doctors, and healthcare providers about another epidemic. Also, currently no specific treatment is available against Monkeypox. This research gap encouraged us to develop a new molecule to fight against monkeypox and smallpox disease. So, firstly, fifty different curcumin derivatives were collected from natural sources, which are available in the PubChem database, to determine antiviral capabilities against Monkeypox and Smallpox.Material and methodPreliminarily, the molecular docking experiment of fifty different curcumin derivatives were conducted, and the majority of the substances produced the expected binding affinities. Then, twelve curcumin derivatives were picked up for further analysis based on the maximum docking score. After that, the density functional theory (DFT) was used to determine chemical characterizations such as the highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), softness, and hardness, etc.ResultsThe mentioned derivatives demonstrated docking scores greater than 6.80 kcal/mol, and the most significant binding affinity was at -8.90 kcal/mol, even though 12 molecules had higher binding scores (-8.00 kcal/mol to -8.9 kcal/mol), and better than the standard medications. The molecular dynamic simulation is described by root mean square deviation (RMSD) and root-mean-square fluctuation (RMSF), demonstrating that all the compounds might be stable in the physiological system.ConclusionIn conclusion, each derivative of curcumin has outstanding absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics. Hence, we recommended the aforementioned curcumin derivatives as potential antiviral agents for the treatment of Monkeypox and Smallpox virus, and more in vivo investigations are warranted to substantiate our findings.

Air pollutants, especially particulate matter, and other meteorological factors serve as important carriers of infectious microbes and play a critical role in the spread of disease. However, there remains uncertainty about the relationship among particulate matter, other air pollutants, meteorological conditions and climate change and the spread of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), hereafter referred to as COVID-19. A systematic review was conducted using PRISMA guidelines to identify the relationship between air quality, meteorological conditions and climate change, and COVID-19 risk and outcomes, host related factors, co-morbidities and disparities. Out of a total of 170,296 scientific publications screened, 63 studies were identified that focused on the relationship between air pollutants and COVID-19. Additionally, the contribution of host related-factors, co-morbidities, and health disparities was discussed. This review found a preponderance of evidence of a positive relationship between PM2.5, other air pollutants, and meteorological conditions and climate change on COVID-19 risk and outcomes. The effects of PM2.5, air pollutants, and meteorological conditions on COVID-19 mortalities were most commonly experienced by socially disadvantaged and vulnerable populations. Results however, were not entirely consistent, and varied by geographic region and study. Opportunities for using data to guide local response to COVID-19 are identified.

We synthesised a new series of sulphonamide-bearing quinazolinone derivatives 5-18 and evaluated their in vitro cytotoxicity in various cancer cell lines (A549, HepG-2, LoVo and MCF-7) and in normal human cells (HUVEC). Compounds 6 and 10 exhibited the higher activity against all the cancer cell lines compared with 5-flourourcil as positive control. The ability of the most promising compounds 6 and 10 to induce cell cycle arrest and apoptosis in breast cancer (MCF-7) cells was evaluated by flow cytometry. Reverse transcriptase-polymerase chain reaction and western blotting were used to evaluate the expression of apoptosis-related markers. We found that the 2-tolylthioacetamide derivative 6 and the 3-ethyl phenyl thioacetamide derivative 10 exhibited cytotoxic activity comparable to that of 5-fluorouracil as reference drug in MCF-7 and LoVo colon cancer cells. Cell cycle analysis showed a concentration-dependent accumulation of cells in the sub-G1 phase upon treatment with both compounds. The Annexin V-fluorescein isothiocyanate/propidium iodide assay showed that the compounds 6 and 10 increased the early and late apoptosis cell death modes in a dose-dependent manner. These compounds downregulated the expression of B-cell lymphoma-2 (Bcl-2), while increasing that of p53, Bcl-2-like protein 4, and caspase-7, at the mRNA and protein levels. Molecular docking of compounds 6 and 10 with Bcl-2 predicted them to show moderate − high binding affinity (6: −7.5 kcal/mol, 10: −7.9 kcal/mol) and interactions with key central substrate cavity residues. Overall, compounds 6 and 10 were found to be promising anticancer and apoptosis-inducing agents.

Diabetic Retinopathy (DR) is a degenerative disease that impacts the eyes and is a consequence of Diabetes mellitus, where high blood glucose levels induce lesions on the eye retina. Diabetic Retinopathy is regarded as the leading cause of blindness for diabetic patients, especially the working-age population in developing nations. Treatment involves sustaining the patient’s current grade of vision since the disease is irreversible. Early detection of Diabetic Retinopathy is crucial in order to sustain the patient’s vision effectively. The main issue involved with DR detection is that the manual diagnosis process is very time, money, and effort consuming and involves an ophthalmologist’s examination of eye retinal fundus images. The latter also proves to be more difficult, particularly in the early stages of the disease when disease features are less prominent in the images. Machine learning-based medical image analysis has proven competency in assessing retinal fundus images, and the utilization of deep learning algorithms has aided the early diagnosis of Diabetic Retinopathy (DR). This paper reviews and analyzes state-of-the-art deep learning methods in supervised, self-supervised, and Vision Transformer setups, proposing retinal fundus image classification and detection. For instance, referable, non-referable, and proliferative classifications of Diabetic Retinopathy are reviewed and summarized. Moreover, the paper discusses the available retinal fundus datasets for Diabetic Retinopathy that are used for tasks such as detection, classification, and segmentation. The paper also assesses research gaps in the area of DR detection/classification and addresses various challenges that need further study and investigation.

Acute kidney injury (AKI) poses a significant challenge in critically ill patients. To determine the prevalence, risk factors, and mortality rate of AKI among nonsurgical critically ill patients in Jordan University Hospital, we conducted a retrospective study using a consecutive sampling method, including 457 nonsurgical critically ill patients admitted to the medical intensive care unit (MICU) from January to June 2021. The mean age was 63.8 ± 18 years, with 196 (42.8%) developing AKI during their stay in the MICU. Among AKI nonsurgical patients, pulmonary diseases (n = 52; 34.5%) emerged as the primary cause for admission, exhibiting the highest prevalence, followed by sepsis (n = 40; 20.4%). Furthermore, we found that older age (adjusted OR (AOR): 1.04; 95% confidence interval (CI): 1.04–1.06; p=0.003), preadmission use of diuretics (AOR: 2.12; 95% CI: 1.06–4.25; p=0.03), use of ventilators (2.19; 95% CI: 1.12–2.29; p=0.02), and vasopressor use during MICU stay (AOR: 4.25; 95% CI: 2.1308.47; p=0.001) were observed to have higher mortality rates. Prior utilization of statins before admission exhibited a significant association with reduced mortality rate (AOR: 0.42; 95% CI: 0.2–0.85; p=0.02). Finally, AKI was associated with a higher mortality rate during MICU stay (AOR: 2.44; 95% CI: 1.07–5.56; p=0.03). The prevalence of AKI among nonsurgical patients during MICU stay is higher than what has been reported previously in the literature, which highlights the nuanced importance of identifying more factors contributing to AKI in developing countries, and hence providing preventive measures and adhering to global strategies are recommended.

Abstract Bioengineered tissues or organs produced using matrix proteins or components derived from xenogeneic sources pose risks of allergic responses, immune rejection, or even autoimmunity. Here, we report successful xeno‐free isolation, expansion, and cryopreservation of human endothelial cells (EC), fibroblasts (FBs), pericytes (PCs), and keratinocytes (KCs). We further demonstrate the bioprinting of a human skin substitute with a dermal layer containing xeno‐free cultured human EC, FBs, and PCs in a xeno‐free bioink containing human collagen type I and fibronectin layered in a biocompatible polyglycolic acid mesh and subsequently seeded with xeno‐free human KCs to form an epidermal layer. Following implantation of such bilayered skin grafts on the dorsum of immunodeficient mice, KCs form a mature stratified epidermis with rete ridge‐like structures. The ECs and PCs form human EC‐lined perfused microvessels within 2 weeks after implantation, preventing graft necrosis, and eliciting further perfusion of the graft by angiogenic host microvessels. As proof‐of‐concept, we generated 12 individual grafts using a single donor of all four cell types. In summary, we describe the fabrication of a bioprinted vascularized bilayered skin substitute under completely xeno‐free culture conditions demonstrating feasibility of a xeno‐free approach to complex tissue engineering.

Fine particulate matter (PM2.5) exposure can cause premature death and harmful chronic disease such as diabetes. The U.S. Environmental Protection Agency (EPA) sets annual PM2.5 standards to reduce these negative health effects. Currently, annual average exposure over 12 µg/m3 is considered unhealthy. This study tests whether individuals living in locations exposed to elevated ambient levels of PM2.5 concentrations were more likely to self-report diabetes. We examined the association of long-term exposure to PM2.5 and diabetes at enrollment (2002–2009) in a cohort of 44,610 individuals residing in 12 states, recruited into the Southern Community Cohort Study (SCCS). Annual average PM2.5 was estimated using remotely sensed satellite data integrated with ground monitoring data at participants’ residence in urban and rural locations. We used multilevel mixed-effects logistic regression models to estimate the associations between self-reported diabetes and historical exposure to elevated ambient levels of PM2.5. We found a 10.1% increase in odds of reported diabetes with exposure to unhealthful levels of PM2.5 exposure (>12 µg/m3 at enrollment) compared to respondents living in areas with lower annual PM2.5 concentrations. Participants with medical histories of hypertension, hypercholesterolemia, and smoking had an overall 384% higher odds of reported diabetes than those without these clinical risk factors. Black participants were more likely to live in locations with higher ambient PM2.5 concentrations, report high levels of clinical risk factors, and had a 29.1% increase in odds of reported diabetes than Whites. In SCCS participants, exposures to high ambient levels of PM2.5 were associated with self-reported diabetes at enrollment. Reduction in PM2.5 standards for the U.S. are recommended.

Shamsul Azhar Shah,1 Nazarudin Safian,1 Saharuddin Ahmad,2 Siti Rohani Nurumal,1 Zulkefley Mohammad,1 Juliana Mansor,1 Wan Abdul Hannan Wan Ibadullah,1 Yugo Shobugawa,3 Megumi Rosenberg4 1Department of Community Health, Faculty of Medicine, National University of Malaysia, Kuala Lumpur, Malaysia; 2Department of Family Medicine, Faculty of Medicine, National University of Malaysia, Kuala Lumpur, Malaysia; 3Department of Active Aging, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; 4Centre for Health Development, World Health Organization, Kobe, JapanCorrespondence: Shamsul Azhar ShahDepartment of Community Health, Faculty of Medicine, National University of Malaysia, Cheras, Kuala Lumpur, 56000, MalaysiaTel +60 3-9145 8787Fax +60 3-91456670Email drsham@ppukm.ukm.edu.myPurpose: Older people often have chronic diseases which require a continuity of care over the long term. Countries undergoing population aging need to ensure that older people are receiving the care they need. This study assesses the prevalence of, reasons for, and factors associated with unmet healthcare needs among older people individuals in Malaysia.Patients and Methods: This cross-sectional study used data collected during 2018– 2020 from 1204 older adults aged 60 and older selected from Selangor state, Malaysia. A comprehensive face-to-face interview based on the Bahasa Malaysia version of the Japan Gerontological Evaluation Study (JAGES-BM) questionnaire was administered to gain information on unmet healthcare needs, socioeconomic factors, health-related factors, and measures of function (activities of daily living, depression, visual impairment, hearing impairment, memory impairment, and walking impairment). Multivariate logistic regression was used to analyze factors associated with their unmet healthcare needs.Results: Overall, the percentage of older people respondents with unmet healthcare needs is 6.6%. The most reported reasons for forgoing or delaying healthcare were lack of knowledge about healthcare and financial barriers to care. The inability to travel alone (adjusted odds ratio [aOR] 2.51), being overweight (aOR 1.88), and having self-reported depression (aOR 2.23) were each associated with a higher likelihood of having unmet healthcare needs in their daily life.Conclusion: The prevalence of unmet healthcare needs among older people in this part of Malaysia is lower than that reported in some other countries. However, it is possible to further reduce unmet healthcare needs by improving people’s knowledge and attitudes about appropriate healthcare utilization, strengthening financial protection measures and providing support to people at high risk of having unmet healthcare needs.Keywords: healthcare needs, old age, Malaysia

Doxorubicin (Dox) is an anthracycline antibiotic that is primarily used for treating various solid tumors including that of pulmonary, ovary, breast, uterine, cervix, and several blood cancers. However, nephrotoxicity associated with Dox treatment limits its clinical use. Administration of Dox in combination with compounds exhibiting antioxidant properties are being used to minimize the side effects of Dox. Diosmin is a flavonoid glycoside with numerous beneficial properties that is found in the pericarp of many citrus fruits. Diosmin has demonstrated antioxidant, anti-inflammatory, and anti-apoptotic effects in response to various insults, although the exact mechanism remains unknown. Therefore, this study was designed to evaluate the effect of diosmin in preventing kidney damage in response to Dox treatment. Male Wistar rats were randomly divided into four groups: control group, Dox group (20 mg/kg, i.p.), Dox plus low-dose diosmin group (100 mg/kg orally), and Dox plus high-dose diosmin group (200 mg/kg orally). A single intraperitoneal injection of Dox resulted in kidney damage as evidenced by significant alterations in kidney markers, histological abnormalities, and the attenuation of antioxidant defense mechanisms (GSH, SOD, and CAT). Moreover, Dox treatment significantly altered the expression of oxidative stress, inflammatory, and anti-apoptotic protein markers. Diosmin pretreatment alleviated Dox-induced nephrotoxicity by ameliorating the antioxidant mechanism, decreasing inflammation and apoptosis, and restoring kidney architecture. In conclusion, our results indicate that diosmin is a promising therapeutic agent for the prevention of nephrotoxicity associated with DOX.

Objectives: In recent years, biological precursor-based synthesis, particularly plant-based green synthesis, has piqued attention in the area of nanotechnology. The goal of this work is to look into the antibacterial, antifungal, antioxidant, and antiproliferation activity of silver nanoparticles (AgNPs) made from ethanolic extract of Salacia chinensis L. were investigated. Methods: This study can be broadly separated into three parts: the first extraction from Salacia chinensis L. roots, The second characterization of NPs by UV-Vis, DLS, FTIR and SEM, and the third analysis of its antimicrobial; antioxidant and antiproliferative properties. UV–Vis absorption indicated the synthesis of AgNPs, and the spectrum was seen at 401 and 447 nm. The existence of functional groups in the produced AgNPs was verified by FT-IR spectral peaks at 3423.83 cm−1. In three planes, XRD was calculated to investigate the crystallinity and consistent spherical size (peaks at 2θ values of at 28.78, 32.18, 38.04, 54.63, and 77.08°) of the particles. Results: The results of antibacterial, antifungal and antiproliferative effect of synthesized AgNPs with Salacia chinensis L. ethanolic root extract have admirable antimicrobial (19.5 mm), antioxidant (IC50 values 117.3, 59.61 g mL−1) and antiproliferative activity against HEK293 cell lines protect up to 90.3 % respectively. Conclusions: As a consequence, biosynthesized Salacia chinensis L. AgNPs shown outstanding effects and have the potential to be used as antibacterial, antioxidant, and antiproliferative agents.

Background: Immigrants represent over one-fifth (21.9%) of the Canadian population, which is an increasing trend. Primary care is a gateway to accessing the healthcare system for the majority of Canadians seeking medical services; however, Canada reported a growing shortage of healthcare providers, mainly primary care practitioners. Canadians, including immigrants, encounter many unmet healthcare needs due to various reasons. This study aimed to assess unmet healthcare (UHC) needs and associated factors among Nepalese immigrants residing in Calgary. Methods: A cross-sectional study using a self-administered questionnaire was conducted in 2019. UHC needs were measured based on a single-item question: “During the past 12 months, was there ever a time that you felt you needed medical help, but you did not receive it”. A follow-up question was asked to learn about associated unmet needs factors, and the responses were categorized into availability, accessibility, and acceptability. Descriptive and multivariable logistic regression was employed to assess the association between UHC needs and its predictors by using STATA version 14.2. Results: Of 401 study participants, nearly half of the participants (n = 187; 46.63%) reported UHC needs, which was not significantly different among male and female participants (p = 0.718). UHC needs were nearly two times higher among those aged 26–45 (AOR 1.93) and those ≥56 years (AOR 2.17) compared to those under 25 years of age. The top reasons reported for unmet needs were long waits to access care (67.91%), healthcare costs (57.22%), and lack of knowing where to get help (31.55%). Overall, “services availability when required” was a leading obstacle that accounted for UHC needs (n = 137, 73.26%). Nearly two-thirds (n = 121, 64.71%) of participants reported that “accessibility of services” was a barrier, followed by “acceptability (n = 107, 57.22%). Those who reported UHC needs also reported an impact on their lives personally and economically. The most commonly reported personal impact was mental health impact, including worry, anxiety, and stress (67.38%). The most common economic impact reported due to UHC needs was increased use of over-the-counter drugs (33.16%) and increased healthcare costs (17.20%). Conclusions: UHC needs are presented in the Nepalese immigrant population. Accessibility to healthcare is limited for several reasons: waiting time, cost, distance, and unavailability of services. UHC needs impact individuals’ personal health, daily life activities, and financial capacity. Strategies to improve access to PHC for disadvantaged populations are crucial and need to be tackled effectively.

Collagen, along with proteoglycans, glycosaminoglycans, glycoproteins, and various growth factors, forms the extracellular matrix (ECM) and contributes to the complexity and diversity of different tissues. Herein, we compared the physicochemical and biological properties of ECM hydrogels derived from four different human tissues: skin, bone, fat, and birth. Pure human collagen type I hydrogels were used as control. Physical characterization of ECM hydrogels and assessment of cell response of cord-tissue mesenchymal stem cells (CMSCs) were performed. Decellularization efficiency was found to be >90% for all ECM. Hydroxyproline quantification assay showed that collagen content in birth ECM was comparable to collagen control and significantly greater than other sources of ECM. Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed the presence of γ, β, α1 and α2 collagen chains in all ECMs. Gelation kinetics of ECM hydrogels was significantly slower than collagen control. Compressive modulus of skin ECM was the highest and birth ECM was the lowest. Skin and birth ECM hydrogels were more stable than bone and fat ECM hydrogels. CMSCs encapsulated in birth ECM hydrogels exhibited the highest metabolic activity. Rheological characterization revealed that all ECM-derived inks exhibited shear thinning properties, and skin-derived ECM inks were most suitable for extrusion-based bioprinting for the concentration and printing conditions used in this study. Overall, results demonstrate that the physicochemical and biological properties of ECM hydrogels vary significantly depending on the tissue source. Therefore, careful selection of tissue source is important for development of ECM-based biomimetic tissue constructs for regenerative medicine applications.

Malaria is a potentially fatal disease caused by protozoan parasites of the genus Plasmodium. It is responsible for significant morbidity and mortality in endemic countries of the tropical and subtropical world, particularly in Africa, Southeast Asia, and South America. It is estimated that 247 million malaria cases and 619,000 deaths occurred in 2021 alone. The World Health Organization’s (WHO) global initiative aims to reduce the burden of disease but has been massively challenged by the emergence of parasitic strains resistant to traditional and emerging antimalarial therapy. Therefore, development of new antimalarial drugs with novel mechanisms of action that overcome resistance in a safe and efficacious manner is urgently needed. Based on the evolving understanding of the physiology of Plasmodium, identification of potential targets for drug intervention has been made in recent years, resulting in more than 10 unique potential anti-malaria drugs added to the pipeline for clinical development. This review article will focus on current therapies as well as novel targets and therapeutics against malaria.

Abstract Purpose: To compare the outcomes of accelerated versus standard corneal cross-linking for the treatment of progressive keratoconus. Methods: In this retrospective comparative study, 63 eyes of 40 patients with progressive keratoconus were divided into two groups; 27 eyes in group one were treated with an accelerated protocol (10 mW/cm 2 , 9 min) and 36 eyes in group two were treated with the standard method (3 mW/cm 2 , 30 min). Visual acuity, refraction, corneal topography, corneal tomography, and anterior and posterior corneal higher-order aberrations (HOAs) were assessed preoperatively and 18–30 months postoperatively. Results: The LogMAR uncorrected and corrected distance visual acuity values were improved in both groups postoperatively. However, the improvement was significantly higher in group one (P < 0.05, all). The flattening in the anterior keratometry readings, flat K, steep K, and average K were significantly higher in group two (P < 0.001, all). The maximum anterior keratometry (AKf) values significantly decreased in both groups, whereas the maximum posterior keratometry (AKb) values increased. The reduction in the minimum corneal thickness (ThKmin) was significantly greater (36.49um) in group two, compared to 10.85um in group one. There was a significant increase in the posterior average keratometry, and a significant decrease in the posterior astigmatism, along 3 mm meridian in S-CXL (P = 0.03, P = 0.008, respectively), while the corresponding values showed no statistical significance in group one (P > 0.05). The anterior corneal trefoil was significantly reduced in group one (P = 0.002), whereas anterior total HOAs and coma were significantly improved in group two (P < 0.0014, all). The posterior corneal spherical aberration decreased significantly in group one (P = 0.02), while group two revealed significant reduction in the posterior trefoil values (P = 0.011). The change in the anterior maximum keratometry was significantly and positively correlated to the preoperative maximum keratometry in group two (P = 0.53, P = 0.003). Conclusion: An accelerated cross-linking protocol using 10 mW/cm 2 for 9 min showed more visual improvement and less pachymetric reduction when compared to the standard protocol, however, anterior corneal flattening, posterior corneal steepening, and the change in the posterior astigmatism were significantly higher in the standard protocol; while corneal HOAs were improved in both protocols.

Abstract Cigarette smoking has a negative effect on respiratory and skeletal muscle function and is a risk factor for various chronic diseases. To assess the effects of 14 days of smoking cessation on respiratory and skeletal muscle function, markers of inflammation and oxidative stress in humans. Spirometry, skeletal muscle function, circulating carboxyhaemoglobin levels, advanced glycation end products (AGEs), markers of oxidative stress and serum cytokines were measured in 38 non-smokers, and in 48 cigarette smokers at baseline and after 14 days of smoking cessation. Peak expiratory flow (p = 0.004) and forced expiratory volume in 1 s/forced vital capacity (p = 0.037) were lower in smokers compared to non-smokers but did not change significantly after smoking cessation. Smoking cessation increased skeletal muscle fatigue resistance (p

Background: The emergence and spread of SARS-CoV-2 throughout the world has created an enormous socioeconomic impact. Although there are several promising drug candidates in clinical trials, none is available clinically. Thus, the drug repurposing approach may help to overcome the current pandemic. Methods: The main protease (Mpro) of SARS-CoV-2 is crucial for cleaving nascent polypeptide chains. Here, FDA-approved antiviral and anti-infection drugs were screened by high-throughput virtual screening (HTVS) followed by re-docking with standard-precision (SP) and extra-precision (XP) molecular docking. The most potent drug's binding was further validated by free energy calculations (Prime/MM-GBSA) and molecular dynamics (MD) simulation. Results: Out of 1397 potential drugs, 157 showed considerable affinity toward Mpro. After HTVS, SP, and XP molecular docking, four high-affinity lead drugs (Iodixanol, Amikacin, Troxerutin, and Rutin) with docking energies −10.629 to −11.776 kcal/mol range were identified. Among them, Amikacin exhibited the lowest Prime/MM-GBSA energy (−73.800 kcal/mol). It led us to evaluate other aminoglycosides (Neomycin, Paramomycin, Gentamycin, Streptomycin, and Tobramycin) against Mpro. All aminoglycosides were bound to the substrate-binding site of Mpro and interacted with crucial residues. Altogether, Amikacin was found to be the most potent inhibitor of Mpro. MD simulations of the Amikacin-Mpro complex suggested the formation of a complex stabilized by hydrogen bonds, salt bridges, and van der Waals interactions. Conclusion: Aminoglycosides may serve as a scaffold to design potent drug molecules against COVID-19. However, further validation by in vitro and in vivo studies is required before using aminoglycosides as an anti-COVID-19 agent.

Abstract Objective To investigate local short‐term neuroplasticity elicited by subthalamic, thalamic, and pallidal deep brain stimulation (DBS) for movement disorders. Methods During DBS surgery, we delivered pairs of stimulus pulses with both circular and directional leads across 90 interstimulus intervals in 17 participants and recorded local field potentials from unused contacts on the implanted electrode array. We removed the stimulus artifact, validated the neural origin of the underlying signals, and examined short‐term plasticity as a function of interstimulus interval and DBS target, using linear mixed effects models. Results DBS evokes short latency local field potentials that are readily detected with both circular and directional leads at all stimulation targets (0.31 ± 0.10 msec peak latency, mean ± SD). Peak amplitude, area, and latency are modified strongly by interstimulus interval (P

Alzheimer's disease (AD) is a neurodegenerative disease and the most prevalent form of dementia. The generation of oxygen free radicals and oxidative damage is believed to be involved in the pathogenesis of AD. It has been suggested that date palm, a plant rich in phenolic compounds and flavonoids, can provide an alternative treatment to fight memory loss and cognitive dysfunction due to its potent antioxidant activity. Thus, we studied the effect of flavonoids present in date palm on Aβ1−40 amyloid formation using molecular docking and molecular dynamics simulation. AutoDock. Myricetin was used as a positive control drug. The flavonoids Diosmetin, Luteolin, and Rutin were found to be potent inhibitors of aggregation (docking energies ≤ −8.05 kcal mol−1) targeting Aβ1−40 fibrils (both 2LMO and 6TI5), simultaneously. Further screening by physicochemical properties and drug-likeness analysis suggested that all flavonoids except Rutin followed Lipinski's rule of five. Rutin was, thus, taken as a negative control (due to its violation of Lipinski's rule) to compare its dynamics with Diosmetin. Diosmetin exhibited the highest positive scores for drug likeness. Since Luteolin exhibited moderate drug-likeness and better absorption properties, it was also included in molecular dynamics simulation. Molecular dynamics of shortlisted compounds (Rutin, Diosmetin, and Luteolin) were performed for 200 ns, and the results were analyzed by monitoring root mean square deviations (RMSD), root mean square fluctuation (RMSF) analysis, the radius of gyration (Rg), and solvent accessible surface area (SASA). The results proved the formation of a stable protein-compound complex. Based on binding energies and non-bonded interactions, Rutin and Luteolin emerged as better lead molecules than Diosmetin. However, high MW (610.5), lowest absorption rate (16.04%), and more than one violation of Lipinski's rule make Rutin a less likely candidate as an anti-amyloidogenic agent. Moreover, among non-violators of Lipinski's rule, Diosmetin exhibited a greater absorption rate than Luteolin as well as the highest positive scores for drug-likeness. Thus, we can conclude that Diosmetin and Luteolin may serve as a scaffold for the design of better inhibitors with higher affinities toward the target proteins. However, these results warrant in-vitro and in-vivo validation before practical use.

Background and aim: COVID-19 emerged by the end of 2019 in Wuhan, China. It spreaded and became a public health emergency all over the world by mid of April 2020. Flavonoids are specialized metabolites that have antimicrobial properties including anti-viral activity. Rutin, a medicinally important flavonoid belongs to one of the best natural antioxidant classes. It has antiprotozoal, antibacterial, and antiviral properties. Keeping the antimicrobial potential of rutin in mind, we studied its role in the inhibition of essential proteins of SARS-CoV-2 including main protease (Mpro), RNA-dependent RNA polymerase (RdRp), papain-like protease (PLpro), and spike (S)-protein through different in silico approaches. Experimental procedure: Molecular docking, inhibition constant, hydrogen bond calculations, and ADMET-properties prediction were performed using different softwares. Results and conclusion: Molecular docking study showed significant binding of rutin with Mpro, RdRp, PLpro, and S-proteins of SARS-CoV-2. Out of these four proteins, Mpro exhibited the strongest binding affinity with the least binding energy (−8.9 kcal/mol) and stabilized through hydrogen bonds with bond lengths ranging from 1.18 Å to 3.17 Å as well as hydrophobic interactions. The predicted ADMET and bioactivity showed its optimal solubility, non-toxic, and non-carcinogenic properties. The values of the predicted inhibitory constant of the rutin with SARS-CoV-2 vital proteins ranged between 5.66 μM and 6.54 μM which suggested its promising drug candidature. This study suggested rutin alone or in combination as a dietary supplement may be used to fight against COVID-19 after detailed in vitro and in vivo studies.

Euphorbia plants have a significant place in traditional medicine due to their numerous therapeutic properties, including their anti-tumor effects, which have been observed in several species. In the current study, a phytochemical investigation of Euphorbia saudiarabica methanolic extract led to the isolation and characterization of four secondary metabolites from the chloroform (CHCl3) and ethyl acetate (EtOAc) fractions, which are reported for the first time in this species. One of the constituents, saudiarabicain F (2), is a rare C-19 oxidized ingol-type diterpenoid that has not been previously reported. The structures of these compounds were determined by extensive spectroscopic (HR-ESI-MS, 1D and 2D NMR) analyses. The anticancer properties of the E. saudiarabica crude extract, its fractions and its isolated compounds were examined against several cancer cells. The active fractions were evaluated for their effects on cell-cycle progression and apoptosis induction using flow cytometry. Furthermore, RT-PCR was employed to estimate the gene-expression levels of the apoptosis-related genes. It was demonstrated that the E. saudiarabica CHCl3 and EtOAc fractions suppressed the proliferation of the cancer cells. The MCF-7 cells were the most sensitive to both fractions, with IC50 values of 22.6 and 23.2 µg/mL, respectively. Notably, both fractions caused cell-cycle arrest in the G2/M phase of the treated MCF-7 cells. The inhibition of the MCF-7 cells’ proliferation was also linked with apoptosis induction by flow-cytometry analysis. Additionally, the activation of apoptosis by both fractions was demonstrated by an increase in the ratio of Bax to Bcl-2, with an increase in the expression of caspase-7. Among the isolated compounds, glutinol (1) showed potent activity against the MCF-7 cell line, with an IC50 value of 9.83 µg/mL. Our findings suggest that E. saudiarabica has apoptosis-inducing effects and shows promise as a potential source of new chemotherapeutic drugs.