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  1. Zhang R, Suwanarusk R, Malleret B, Cooke BM, Nosten F, Lau YL, et al.
    J Infect Dis, 2016 Jan 1;213(1):100-4.
    PMID: 26136472 DOI: 10.1093/infdis/jiv358
    Recent clinical trials revealed a surprisingly rapid clearance of red blood cells (RBCs) infected with malaria parasites by the spiroindolone KAE609. Here, we show that ring-stage parasite-infected RBCs exposed to KAE609 become spherical and rigid, probably through osmotic dysregulation consequent to the disruption of the parasite's sodium efflux pump (adenosine triphosphate 4). We also show that this peculiar drug effect is likely to cause accelerated splenic clearance of the rheologically impaired Plasmodium vivax- and Plasmodium falciparum-infected RBCs.
  2. Kuan CS, Chan CL, Yew SM, Toh YF, Khoo JS, Chong J, et al.
    PLoS One, 2015;10(6):e0131694.
    PMID: 26110649 DOI: 10.1371/journal.pone.0131694
    The outbreak of extensively drug-resistant tuberculosis (XDR-TB) has become an increasing problem in many TB-burdened countries. The underlying drug resistance mechanisms, including the genetic variation favored by selective pressure in the resistant population, are partially understood. Recently, the first case of XDR-TB was reported in Malaysia. However, the detailed genotype family and mechanisms of the formation of multiple drugs resistance are unknown. We sequenced the whole genome of the UM 1072388579 strain with a 2-kb insert-size library and combined with that from previously sequenced 500-bp-insert paired-end reads to produce an improved sequence with maximal sequencing coverage across the genome. In silico spoligotyping and phylogenetic analyses demonstrated that UM 1072388579 strain belongs to an ancestral-like, non-Beijing clade of East Asia lineage. This is supported by the presence of a number of lineage-specific markers, including fadD28, embA, nuoD and pks7. Polymorphism analysis showed that the drug-susceptibility profile is correlated with the pattern of resistance mutations. Mutations in drug-efflux pumps and the cell wall biogenesis pathway such as mmpL, pks and fadD genes may play an important role in survival and adaptation of this strain to its surrounding environment. In this work, fifty-seven putative promoter SNPs were identified. Among them, we identified a novel SNP located at -4 T allele of TetR/acrR promoter as an informative marker to recognize strains of East Asian lineage. Our work indicates that the UM 1072388579 harbors both classical and uncommon SNPs that allow it to escape from inhibition by many antibiotics. This study provides a strong foundation to dissect the biology and underlying resistance mechanisms of the first reported XDR M. tuberculosis in Malaysia.
  3. Tan MMC, Prina AM, Muniz-Terrera G, Mohan D, Ismail R, Assefa E, et al.
    BMJ Open, 2022 Dec 23;12(12):e068172.
    PMID: 36564121 DOI: 10.1136/bmjopen-2022-068172
    OBJECTIVES: To assess the prevalence and factors associated with multimorbidity in a community-dwelling general adult population on a large Health and Demographic Surveillance System (HDSS) scale.

    DESIGN: Population-based cross-sectional study.

    SETTING: South East Asia Community Observatory HDSS site in Malaysia.

    PARTICIPANTS: Of 45 246 participants recruited from 13 431 households, 18 101 eligible adults aged 18-97 years (mean age 47 years, 55.6% female) were included.

    MAIN OUTCOME MEASURES: The main outcome was prevalence of multimorbidity. Multimorbidity was defined as the coexistence of two or more chronic conditions per individual. A total of 13 chronic diseases were selected and were further classified into 11 medical conditions to account for multimorbidity. The conditions were heart disease, stroke, diabetes mellitus, hypertension, chronic kidney disease, musculoskeletal disorder, obesity, asthma, vision problem, hearing problem and physical mobility problem. Risk factors for multimorbidity were also analysed.

    RESULTS: Of the study cohort, 28.5% people lived with multimorbidity. The individual prevalence of the chronic conditions ranged from 1.0% to 24.7%, with musculoskeletal disorder (24.7%), obesity (20.7%) and hypertension (18.4%) as the most prevalent chronic conditions. The number of chronic conditions increased linearly with age (p<0.001). In the logistic regression model, multimorbidity is associated with female sex (adjusted OR 1.28, 95% CI 1.17 to 1.40, p<0.001), education levels (primary education compared with no education: adjusted OR 0.63, 95% CI 0.53 to 0.74; secondary education: adjusted OR 0.60, 95% CI 0.51 to 0.70; tertiary education: adjusted OR 0.65, 95% CI 0.54 to 0.80; p<0.001) and employment status (working adults compared with retirees: adjusted OR 0.70, 95% CI 0.60 to 0.82, p<0.001), in addition to age (adjusted OR 1.05, 95% CI 1.05 to 1.05, p<0.001).

    CONCLUSIONS: The current single-disease services in primary and secondary care should be accompanied by strategies to address complexities associated with multimorbidity, taking into account the factors associated with multimorbidity identified. Future research is needed to identify the most commonly occurring clusters of chronic diseases and their risk factors to develop more efficient and effective multimorbidity prevention and treatment strategies.

  4. Bourais I, Elmarrkechy S, Taha D, Badaoui B, Mourabit Y, Salhi N, et al.
    Molecules, 2022 Dec 16;27(24).
    PMID: 36558122 DOI: 10.3390/molecules27248989
    Leaves, husk, kernels, and bark methanolic extracts of Juglans regia L. were tested for their in vitro antidiabetic, anti-inflammatory, and antioxidant activities. For these purposes, α-amylase and α-glucosidase were used as the main enzymes to evaluate antidiabetic activities. Moreover, lipoxidase and tyrosinase activities were tested to estimate anti-inflammatory properties. Antioxidant properties of Juglans regia L., extracts were determined using three different assays. Leaves extract has an important radical scavenging activity and a-amylase inhibition. Similarly, husk extracts showed high total phenolic content (306.36 ± 4.74 mg gallic acid equivalent/g dry extract) with an important α-amylase inhibition (IC50 = 75.42 ± 0.99 µg/mL). Kernels exhibit significant tyrosinase (IC50 = 51.38 ± 0.81 µg/mL) correlated with antioxidant activities (p < 0.05). Husk and bark extracts also showed strong anti-lipoxidase activities with IC50 equal to 29.48 ± 0.28 and 28.58 ± 0.35 µg/mL, respectively. HPLC-DAD-ESI-MS/MS analysis highlights the phenolic profile of methanolic extracts of Juglans regia L. plant parts. The identified polyphenols were known for their antioxidant, antidiabetic (dicaffeoyl-quinic acid glycoside in kernels), and anti-inflammatory (3,4-dihydroxybenzoic acid in leaves) activities. Further investigations are needed to determine molecular mechanisms involved in these effects as well as to study the properties of the main identified compounds.
  5. Tan S, Zhou G, Yang Q, Ge S, Liu J, Cheng YW, et al.
    Sci Total Environ, 2023 Mar 15;864:160990.
    PMID: 36539095 DOI: 10.1016/j.scitotenv.2022.160990
    Traditional disposal of animal manures and lignocellulosic biomass is restricted by its inefficiency and sluggishness. To advance the carbon management and greenhouse gas mitigation, this review scrutinizes the effect of pyrolysis in promoting the sustainable biomass and manure disposal as well as stimulating the biochar industry development. This review has examined the advancement of pyrolysis of animal manure (AM) and lignocellulosic biomass (LB) in terms of efficiency, cost-effectiveness, and operability. In particular, the applicability of pyrolysis biochar in enhancing the crops yields via soil remediation is highlighted. Through pyrolysis, the heavy metals of animal manures are fixated in the biochar, thereby both soil contamination via leaching and heavy metal uptake by crops are minimized. Pyrolysis biochar is potentially use in soil remediation for agronomic and environmental co-benefits. Fast pyrolysis assures high bio-oil yield and revenue with better return on investment whereas slow pyrolysis has low revenue despite its minimum investment cost because of relatively low selling price of biochar. For future commercialization, both continuous reactors and catalysis can be integrated to pyrolysis to ameliorate the efficiency and economic value of pyrolysis biochar.
  6. Lu L, Fan W, Meng X, Xue L, Ge S, Wang C, et al.
    Sci Total Environ, 2023 Jan 15;856(Pt 1):158798.
    PMID: 36116663 DOI: 10.1016/j.scitotenv.2022.158798
    The rapid development of the textile industry and improvement of people's living standards have led to the production of cotton textile and simultaneously increased the production of textile wastes. Cotton is one of the most common textile materials, and the waste cotton accounts for 24% of the total textile waste. To effectively manage the waste, recycling and reusing waste cotton are common practices to reduce global waste production. This paper summarizes the characteristics of waste cotton and high-value products derived from waste cotton (e.g., yarns, composite reinforcements, regenerated cellulose fibers, cellulose nanocrystals, adsorptive materials, flexible electronic devices, and biofuels) via mechanical, chemical, and biological recycling methods. The advantages and disadvantages of making high-value products from waste cotton are summarized and discussed. New technologies and products for recycling waste cotton are proposed, providing a guideline and direction for merchants and researchers. This review paper can shed light on converting textile wastes other than cotton (e.g., bast, silk, wool, and synthetic fibers) into value-added products.
  7. Chai CY, Maran S, Thew HY, Tan YC, Rahman NMANA, Cheng WH, et al.
    Biology (Basel), 2022 Nov 02;11(11).
    PMID: 36358305 DOI: 10.3390/biology11111604
    The Harvey rat sarcoma (HRAS) proto-oncogene belongs to the RAS family and is one of the pathogenic genes that cause cancer. Deleterious nsSNPs might have adverse consequences at the protein level. This study aimed to investigate deleterious nsSNPs in the HRAS gene in predicting structural alterations associated with mutants that disrupt normal protein-protein interactions. Functional and structural analysis was employed in analyzing the HRAS nsSNPs. Putative post-translational modification sites and the changes in protein-protein interactions, which included a variety of signal cascades, were also investigated. Five different bioinformatics tools predicted 33 nsSNPs as "pathogenic" or "harmful". Stability analysis predicted rs1554885139, rs770492627, rs1589792804, rs730880460, rs104894227, rs104894227, and rs121917759 as unstable. Protein-protein interaction analysis revealed that HRAS has a hub connecting three clusters consisting of 11 proteins, and changes in HRAS might cause signal cascades to dissociate. Furthermore, Kaplan-Meier bioinformatics analyses indicated that the HRAS gene deregulation affected the overall survival rate of patients with breast cancer, leading to prognostic significance. Thus, based on these analyses, our study suggests that the reported nsSNPs of HRAS may serve as potential targets for different proteomic studies, diagnoses, and therapeutic interventions focusing on cancer.
  8. Lim AH, Ab Rahman N, Ong SM, Paraja J, Rashid R, Parmar IS, et al.
    Vaccine, 2022 Sep 16;40(39):5675-5682.
    PMID: 36030123 DOI: 10.1016/j.vaccine.2022.08.032
    There is a notable lack of vaccine effectiveness studies using test-negative case-controlled approach in low- and middle-income countries which have different logistic, demographic and socio-economic conditions from high-income countries. We aimed to estimate the effectiveness of BNT162b2 vaccine against COVID-19 infection over time, intensive care unit admission, severe or critical disease and death due to COVID-19. This study was conducted in the resident population of Labuan aged ≥18 years who had been tested for SARS-CoV-2 by Reverse-Transcriptase Polymerase Chain Reaction between 1 March 2021 and 31 October 2021. We used a test-negative case-control design where 2644 pairs of cases and controls were matched by age, sex, testing date, nationality and testing reason. Analysis was stratified by age group to estimate age effect (<60 years and ≥60 years). Of 22217 individuals tested by Reverse-Transcriptase Polymerase Chain Reaction, 5100 were positive for SARS-CoV-2 and aged 18 years and above. Overall vaccine effectiveness ≥ 14 days after the second dose was 65.2% (95% CI: 59.8-69.9%) against COVID-19 infection, 92.5% (95% CI: 72.3-98.8%) against intensive care unit admission, and 96.5% (95% CI: 82.3-99.8%) against COVID-19 deaths. Among infected individuals, vaccine effectiveness was 79.2% (95% CI: 42.3-94.1%) in preventing severe or critical disease due to COVID-19. Vaccine effectiveness for ≥60 years was 72.3% (95% CI: 53.4-83.9%) in fully vaccinated individuals, higher than 64.8% (95% CI: 49.3-59.1%) for those <60 years. Two doses of BNT162b2 were highly effective against COVID-19 infection, severe or critical disease, intensive care unit admission and death due to COVID-19. This study addresses a gap in literature on BNT162b2 vaccine effectiveness in low- and middle-income populations and demonstrates the feasibility of such a study design in a resource limited setting while supporting evidence of waning immunity.
  9. Closas AMFD, Lohmann K, Tan AH, Ibrahim NM, Lim JL, Tay YW, et al.
    J Mov Disord, 2023 Jan;16(1):91-94.
    PMID: 36537064 DOI: 10.14802/jmd.22109
    KMT2B-linked dystonia (DYT-KMT2B) is a childhood-onset dystonia syndrome typically beginning in the lower limbs and progressing caudocranially to affect the upper limbs with eventual prominent craniocervical involvement. Despite its recent recognition, it now appears to be one of the more common monogenic causes of dystonia syndromes. Here, we present an atypical case of DYT-KMT2B with oromandibular dystonia as the presenting feature, which remained restricted to this region three decades after symptom onset. This appears to be the first reported case of DYT-KMT2B from Southeast Asia and provides further supporting evidence for the pathogenic impact of the KMT2B c.6210_6213delTGAG variant.
  10. Raheem I, Mubarak NM, Karri RR, Solangi NH, Jatoi AS, Mazari SA, et al.
    Chemosphere, 2023 Jan;311(Pt 2):137056.
    PMID: 36332734 DOI: 10.1016/j.chemosphere.2022.137056
    Water consumption has grown in recent years due to rising urbanization and industry. As a result, global water stocks are steadily depleting. As a result, it is critical to seek strategies for removing harmful elements from wastewater once it has been cleaned. In recent years, many studies have been conducted to develop new materials and innovative pathways for water purification and environmental remediation. Due to low energy consumption, low operating cost, and integrated facilities, membrane separation has gained significant attention as a potential technique for water treatment. In these directions, MXene which is the advanced 2D material has been explored and many applications were reported. However, research on MXene-based membranes is still in its early stages and reported applications are scatter. This review provides a broad overview of MXenes and their perspectives, including their synthesis, surface chemistry, interlayer tuning, membrane construction, and uses for water purification. Application of MXene based membrane for extracting pollutants such as heavy metals, organic contaminants, and radionuclides from the aqueous water bodies were briefly discussed. Furthermore, the performance of MXene-based separation membranes is compared to that of other nano-based membranes, and outcomes are very promising. In order to shed more light on the advancement of MXene-based membranes and their operational separation applications, significant advances in the fabrication of MXene-based membranes is also encapsulated. Finally, future prospects of MXene-based materials for diverse applications were discussed.
  11. Wang L, Tan H, Yu J, ZhangBao J, Huang W, Chang X, et al.
    Eur J Neurol, 2023 Feb;30(2):443-452.
    PMID: 36286605 DOI: 10.1111/ene.15612
    BACKGROUND AND PURPOSE: The aim was to evaluate the potential of retinal nerve fiber layer thickness (RNFLT) measured with optical coherence tomography in predicting disease progression in relapsing-remitting multiple sclerosis (RRMS).

    METHODS: Analyses were conducted post hoc of this 24-month, phase III, double-blind study, in which RRMS patients were randomized (1:1:1) to once daily oral fingolimod 0.5 mg, 1.25 mg or placebo. The key outcomes were the association between baseline RNFLT and baseline clinical characteristics and clinical/imaging outcomes up to 24 months. Change of RNFLT with fingolimod versus placebo within 24 months and time to retinal nerve fiber layer (RNFL) thinning were evaluated.

    RESULTS: Altogether 885 patients were included. At baseline, lower RNFLT was correlated with higher Expanded Disability Status Scale score (r = -1.085, p = 0.018), lower brain volume (r = 0.025, p = 0.006) and deep gray matter volume (r = 0.731, p 

  12. Wong CY, Tham JS, Foo CN, Ng FL, Shahar S, Zahary MN, et al.
    Biosaf Health, 2023 Feb;5(1):37-44.
    PMID: 36588928 DOI: 10.1016/j.bsheal.2022.12.005
    Vaccination is crucial in controlling the spread of the coronavirus disease 2019 (COVID-19) that triggered the pandemic, but herd immunity can only work with high vaccination coverage in the population. This study aims to measure the COVID-19 knowledge level and determine the factors influencing COVID-19 vaccination intention among university students in Malaysia. A cross-sectional online survey was carried out with 1,274 Malaysian university students in July 2021. Univariate and multivariate analyses were employed to examine the relationships between the study variables. Results showed that the majority of university students had an acceptable level of knowledge of COVID-19. The knowledge, risk perception of COVID-19, social norms, and perceived benefit of COVID-19 vaccination were positively associated with vaccination intention. However, perceived trust in information sources of COVID-19 vaccination and the government's response to COVID-19 did not affect the university students' desire to receive the vaccination. These findings are essential for health policymakers and healthcare providers to implement evidence-based interventions to increase COVID-19 vaccination uptake among university students.
  13. Wang CC, Abdul Jalal MI, Song ZL, Teo YP, Tan CA, Heng KV, et al.
    Int J Environ Res Public Health, 2022 Oct 25;19(21).
    PMID: 36360757 DOI: 10.3390/ijerph192113878
    Early childhood nutritional deficiency has detrimental consequences on physical and cognitive development. We conducted a single-center, single-blind, two-arm pilot randomized no-treatment controlled trial (the Child of Urban Poverty Iron Project (CUPIP); NCT03819530) in a people’s housing project locale in Selangor, Malaysia, between September 2019 and February 2020, to assess the trial’s general feasibility and preliminary benefits of daily micronutrient supplementation for iron storage and anthropometric outcomes in under-5 children. Those with history of premature births, congenital abnormalities, or baseline hemoglobin <70 g/L were excluded. Participants received baseline deworming and were simply randomized in a 1:1 ratio to either micronutrient (4-month daily micronutrient packets) or control (no micronutrient supplementation) groups. Information on anthropometric, erythrocytic, and iron storage endpoints were collected. Overall, 45 (25 micronutrient and 20 controls) participants were enrolled and completed 4-month endpoint assessments. Micronutrient recipients demonstrated higher median mean corpuscular volume, serum ferritin level with no significant differences in all anthropometric endpoints. In conclusion, this pilot trial was implementable, demonstrating that micronutrient supplementation significantly improved hematological, but not anthropometric, endpoints, of under-5-year-old children living in an underprivileged environment. A definitive well-designed trial with larger sample sizes and greater attrition control should be contemplated in the future.
  14. Thien GSH, Ab Rahman M, Yap BK, Tan NML, He Z, Low PL, et al.
    ACS Omega, 2022 Nov 08;7(44):39472-39481.
    PMID: 36385870 DOI: 10.1021/acsomega.2c03206
    Due to their remarkable electrical and light absorption characteristics, hybrid organic-inorganic perovskites have recently gained popularity in several applications such as optoelectronics, lasers, and light-emitting diodes. Through this, there has recently been an increase in the use of halide perovskites (HPs) in resistive switching (RS) devices. However, lead-based (Pb-based) perovskites are notorious for being unstable and harmful to the environment. As a result, lead-free (Pb-free) perovskite alternatives are being investigated in achieving the long-term and sustainable use of RS devices. This work describes the characteristics of Pb-based and Pb-free perovskite RS devices. It also presents the recent advancements of HP RS devices, including the selection strategies of perovskite structures. In terms of resistive qualities, the directions of both HPs appear to be identical. Following that, the possible impact of switching from Pb-based to Pb-free HPs is examined to determine the requirement in RS devices. Finally, this work discusses the opportunities and challenges of HP RS devices in creating a stable, efficient, and sustainable memory storage technology.
  15. Pana TA, Kioh SH, Neal SR, Tan MP, Mat S, Moayyeri A, et al.
    Maturitas, 2023 Feb;168:71-77.
    PMID: 36502648 DOI: 10.1016/j.maturitas.2022.11.005
    BACKGROUND: This cohort study aimed to determine the association between body fat percentage (BF%), incident fractures and calcaneal broadband ultrasound attenuation (BUA).

    METHODS: Participants were drawn from the EPIC-Norfolk Prospective Population Cohort Study (median follow-up = 16.4 years). Cox models analysed the relationship between BF% and incident fractures (all and hip). Linear and restricted cubic spline (RCS) regressions modelled the relationship between BF% and BUA.

    RESULTS: 14,129 participants (56.2 % women) were included. There were 1283 and 537 incident all and hip fractures respectively. The participants had a mean (standard deviation) age of 61.5 (9.0) years for women and 62.9 (9.0) years for men. Amongst men, BF% was not associated with incident all fractures. While BF%  23 % was associated with increased risk of hip fractures by up to 50 % (hazard ratio (95 % confidence interval) = 1.49 (1.06-2.12)). In women, BF%  35 % was not associated with this outcome. Higher BF% was associated with lower risk of incident hip fractures in women. Higher BF% was associated with higher BUA amongst women. Higher BF% up to ~23 % was associated with higher BUA amongst men.

    CONCLUSIONS: Higher BF% is associated with lower risk of fractures in women. While there was no association between BF% and all fractures in men, increasing BF% >23 % was associated with higher risk of hip fractures in men. This appears to be independent of estimated bone mineral density. Fracture prevention efforts need to consider wider physical, clinical, and environmental factors.

  16. Tan MP, Sekawi Z, Abdul Manap R, Razali RM, Mahadzir H, Nordin N, et al.
    BMC Infect Dis, 2022 Dec 15;22(1):943.
    PMID: 36522615 DOI: 10.1186/s12879-022-07920-3
    BACKGROUND: Older persons are at high-risk of developing severe complications from influenza. This consensus statement was developed to provide guidance on appropriate influenza prevention strategies relevant to the Malaysian healthcare setting.

    METHODS: Under the initiative of the Malaysian Influenza Working Group (MIWG), a panel comprising 11 multi-speciality physicians was convened to develop a consensus statement. Using a modified Delphi process, the panellists reviewed published evidence on various influenza management interventions and synthesised 10 recommendations for the prevention of influenza among the aged population via group discussions and a blinded rating exercise.

    RESULTS: Overall, annual influenza vaccination is recommended for individuals aged ≥ 60 years, particularly those with specific medical conditions or residing in aged care facilities (ACFs). There is no preference for a particular vaccine type in this target population. Antiviral agents can be given for post-exposure chemoprophylaxis or when vaccine contraindication exists. Infection control measures should serve as adjuncts to prevent the spread of influenza, especially during Hajj.

    CONCLUSION: This consensus statement presents 10 evidence-based recommendations that can be adopted by healthcare providers to prevent influenza among the aged population in Malaysia. It could also serve as a basis for health policy planning in other lower- and middle-income countries.

  17. Burchert H, Lapidaire W, Williamson W, McCourt A, Dockerill C, Woodward W, et al.
    Am J Respir Crit Care Med, 2023 May 01;207(9):1227-1236.
    PMID: 36459100 DOI: 10.1164/rccm.202205-0858OC
    Rationale: Premature birth is an independent predictor of long-term cardiovascular risk. Individuals affected are reported to have a lower rate of [Formula: see text]o2 at peak exercise intensity ([Formula: see text]o2PEAK) and at the ventilatory anaerobic threshold ([Formula: see text]o2VAT), but little is known about their response to exercise training. Objectives: The primary objective was to determine whether the [Formula: see text]o2PEAK response to exercise training differed between preterm-born and term-born individuals; the secondary objective was to quantify group differences in [Formula: see text]o2VAT response. Methods: Fifty-two preterm-born and 151 term-born participants were randomly assigned (1:1) to 16 weeks of aerobic exercise training (n = 102) or a control group (n = 101). Cardiopulmonary exercise tests were conducted before and after the intervention to measure [Formula: see text]o2PEAK and the [Formula: see text]o2VAT. A prespecified subgroup analysis was conducted by fitting an interaction term for preterm and term birth histories and exercise group allocation. Measurements and Main Results: For term-born participants, [Formula: see text]o2PEAK increased by 3.1 ml/kg/min (95% confidence interval [CI], 1.7 to 4.4), and the [Formula: see text]o2VAT increased by 2.3 ml/kg/min (95% CI, 0.7 to 3.8) in the intervention group versus controls. For preterm-born participants, [Formula: see text]o2PEAK increased by 1.8 ml/kg/min (95% CI, -0.4 to 3.9), and the [Formula: see text]o2VAT increased by 4.6 ml/kg/min (95% CI, 2.1 to 7.0) in the intervention group versus controls. No significant interaction was observed with birth history for [Formula: see text]o2PEAK (P = 0.32) or the [Formula: see text]o2VAT (P = 0.12). Conclusions: The training intervention led to significant improvements in [Formula: see text]o2PEAK and [Formula: see text]o2VAT, with no evidence of a statistically different response based on birth history. Clinical trial registered with www.clinicaltrials.gov (NCT02723552).
  18. Nasaruddin NH, Ahmad SN, Sirat SS, Tan KW, Zakaria NA, Mohamad Nazam SS, et al.
    ACS Omega, 2022 Nov 29;7(47):42809-42818.
    PMID: 36467908 DOI: 10.1021/acsomega.2c04688
    A Schiff base bearing two methyl substituents, namely, 6,6'-((1E,1'E)-((2,2-dimethylpropane-1,3-diyl) bis(azanylylidene)) bis(methanylylidene)) bis(2-methylphenol) [H2AD1Me] was synthesized and characterized through physicochemical and spectroscopic analyses. Then, the Schiff base was complexed with Pd(II) and Ni(II) to form [Pd(AD1Me)] and [Ni(AD1Me)], respectively. Both metal complexes were successfully obtained and characterized through several analyses, viz., melting point, elemental analysis, molar conductivity, magnetic susceptibility, FTIR, 1H NMR, UV-vis, and single crystal X-ray diffraction. A quantitative analysis of the intermolecular interactions in the crystal structures has been performed using Hirshfeld surface analysis. Both metal complexes were crystallized in a monoclinic crystal system with the space group of P21/c. Additionally, the deprotonated phenolic oxygen atom (O1/O2) and azomethine nitrogen atom (N1/N2) of the ligand chelate the Pd(II) and Ni(II) ions, forming a slightly distorted square-planar complex containing three six-membered rings encircling the metal core with dsp2 hybridization. The shift of ν(C=N) to a higher frequency in FTIR by 26-28 cm-1 indicated that the complexation to Pd(II) and Ni(II) through the azomethine N was established. It was further supported through the shifting of the azomethine proton signal to higher or lower chemical shifts with Δδ = 0.43-1.15 ppm in 1H NMR. In addition, the shifting of the n-π*(C=N) band in UV-vis spectra with Δλ = 24-40 nm indicated the involvement of azomethine nitrogen in the complexation. All the compounds showed no significant antibacterial activity against three bacterial strains, namely, Staphylococcus aureus subsp. aureus Rosenbach (ATCC 6538), Streptococcus mutans Clarke (ATCC 700,610), and Proteus vulgaris (ATCC 6380), as the percent growth inhibition calculated was less than 90%.
  19. Ashrafizadeh M, Delfi M, Zarrabi A, Bigham A, Sharifi E, Rabiee N, et al.
    J Control Release, 2022 Nov;351:50-80.
    PMID: 35934254 DOI: 10.1016/j.jconrel.2022.08.001
    The site-specific delivery of antitumor agents is of importance for providing effective cancer suppression. Poor bioavailability of anticancer compounds and the presence of biological barriers prevent their accumulation in tumor sites. These obstacles can be overcome using liposomal nanostructures. The challenges in cancer chemotherapy and stimuli-responsive nanocarriers are first described in the current review. Then, stimuli-responsive liposomes including pH-, redox-, enzyme-, light-, thermo- and magneto-sensitive nanoparticles are discussed and their potential for delivery of anticancer drugs is emphasized. The pH- or redox-sensitive liposomes are based on internal stimulus and release drug in response to a mildly acidic pH and GSH, respectively. The pH-sensitive liposomes can mediate endosomal escape via proton sponge. The multifunctional liposomes responsive to both redox and pH have more capacity in drug release at tumor site compared to pH- or redox-sensitive alone. The magnetic field and NIR irradiation can be exploited for external stimulation of liposomes. The light-responsive liposomes release drugs when they are exposed to irradiation; thermosensitive-liposomes release drugs at a temperature of >40 °C when there is hyperthermia; magneto-responsive liposomes release drugs in presence of magnetic field. These smart nanoliposomes also mediate co-delivery of drugs and genes in synergistic cancer therapy. Due to lack of long-term toxicity of liposomes, they can be utilized in near future for treatment of cancer patients.
  20. Syed Sulaiman SZ, Tan WM, Radzi R, Shafie INF, Ajat M, Mansor R, et al.
    PeerJ, 2022;10:e12897.
    PMID: 35228907 DOI: 10.7717/peerj.12897
    BACKGROUND: Animal models are significant for understanding human osteoarthritis (OA). This study compared the synovial fluid proteomics changes in surgical and chemical induced OA models.

    METHODS: Thirty rabbits either had anterior cruciate ligament transection (ACLT) procedure or injected intra-articularly with monosodium iodoacetate (MIA, 8 mg) into the right knee. The joints were anatomically assessed, and the synovial fluid proteins analyzed using two-dimensional polyacrylamide gel electrophoresis (2DGE) and MALDI TOF/TOF mass spectrometry analysis at 4, 8 and 12 weeks. The proteins' upregulation and downregulation were compared with control healthy knees.

    RESULTS: Seven proteins (histidine-rich glycoprotein, beta-actin-like protein 2 isoform X1, retinol-binding protein-4, alpha-1-antiproteinase, gelsolin isoform, serotransferrin, immunoglobulin kappa-b4 chain-C-region) were significantly expressed by the surgical induction. They characterized cellular process (27%), organization of cellular components or biogenesis (27%), localization (27%) and biological regulation (18%), which related to synovitis, increased cellularity, and subsequently cartilage damage. Three proteins (apolipoprotein I-IV precursor, serpin peptidase inhibitor and haptoglobin precursor) were significantly modified by the chemical induction. They characterized stimulus responses (23%), immune responses (15%), biological regulations (15%), metabolism (15%), organization of cellular components or biogenesis (8%), cellular process (8%), biological adhesions (8%) and localization (8%), which related to chondrocytes glycolysis/death, neovascularization, subchondral bone necrosis/collapse and inflammation.

    CONCLUSIONS: The surgical induced OA model showed a wider range of protein changes, which were most upregulated at week 12. The biological process proteins expressions showed the chemical induced joints had slower OA progression compared to surgical induced joints. The chemical induced OA joints showed early inflammatory changes, which later decreased.

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