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  1. Yean S, Prasetyo DB, Marcombe S, Hadi UK, Kazim AR, Tiawsirisup S, et al.
    PLoS Negl Trop Dis, 2024 Jul;18(7):e0012269.
    PMID: 38985826 DOI: 10.1371/journal.pntd.0012269
    BACKGROUND: Ticks, as critical vectors of a variety of pathogens, pose a significant public health challenge globally. In Southeast Asia (SEA), ticks are responsible for transmitting a diverse array of pathogens affecting humans and animals. The geographical and ecological diversity of SEA provides a unique environment that supports a wide range of tick species, which complicates the management and study of tick-borne diseases (TBDs).

    METHODOLOGY/PRINCIPAL FINDINGS: This article synthesizes findings from the first international symposium on ticks and TBDs in Southeast Asia, held in Phnom Penh on June 22 and 23, 2023. It highlights regional efforts to understand tick ecology and pathogen transmission. This paper proposes to present a summary of the various presentations given during the symposium following 3 main parts. The first one is devoted to the state of knowledge regarding ticks and TBDs in SEA countries, with presentations from 6 different countries, namely Cambodia, Indonesia, Laos, Malaysia, Thailand, and Vietnam. The second part focuses on the development of new research approaches on tick-borne pathogens (TBPs) and TBDs. The last part is a summary of the round table discussion held on the final day, with the aim of defining the most important challenges and recommendations for researches on TBP and TBD in the SEA region.

    CONCLUSIONS/SIGNIFICANCE: Key topics discussed include advancements in diagnostic tools, such as MALDI-TOF MS and proteomics, and the development of sustainable strategies for tick management and disease prevention. The symposium facilitated the exchange of knowledge and collaborative networks among experts from various disciplines, promoting a unified approach to tackling TBDs in the region. The symposium underscored the need for enhanced surveillance, diagnostics, and inter-regional cooperation to manage the threat of TBDs effectively. Recommendations include the establishment of a regional database for tick identification and the expansion of vector competence studies. These initiatives are crucial for developing targeted interventions and understanding the broader implications of climate change and urbanization on the prevalence of TBDs.

  2. Ng WL, Ng CJ, Teo CH, Ang TF, Lee YK, Abdul Hadi H, et al.
    Digit Health, 2024;10:20552076241277710.
    PMID: 39247097 DOI: 10.1177/20552076241277710
    OBJECTIVE: Most dengue cases are managed in an outpatient setting, where patients are advised to return to the clinic daily for monitoring. Some patients can develop severe dengue at home and fail to recognise the deterioration. An application called DengueAid was designed as a self-monitoring tool for patients to reduce delay in seeking timely treatment. This study aimed to assess the feasibility of conducting a randomised controlled trial to determine the effectiveness of the DengueAid application.

    METHODS: Dengue patients were recruited from a public health clinic in Malaysia and randomised to either use the DengueAid application plus standard care for dengue or receive only the standard care. The outcomes evaluated were the (1) feasibility of recruitment, data collection and follow-up procedures; (2) preliminary clinical outcome measures; and (3) acceptability of DengueAid. Qualitative interviews were conducted for participants in the intervention arm to assess the acceptability of DengueAid.

    RESULTS: Thirty-seven patients were recruited with 97% (n = 36) retention rates. The recruitment rate was low (63% refusal rate, n = 62/99) with difficulty in data collection and follow-up due to the variable interval of care for dengue in an outpatient setting. DengueAid application was acceptable to the participants, but preliminary clinical outcomes and qualitative data suggested limited utility of the application. Unwell conditions of patients and limited access to healthcare are important factors impacting the application's utility.

    CONCLUSION: The feasibility trial uncovered issues with recruitment, data collection and follow-up processes. Further research and modification to the application are needed to improve its utility and usability.

  3. Chong YM, Sam IC, Chong J, Kahar Bador M, Ponnampalavanar S, Syed Omar SF, et al.
    PLoS Negl Trop Dis, 2020 11;14(11):e0008744.
    PMID: 33253226 DOI: 10.1371/journal.pntd.0008744
    Malaysia had 10,219 confirmed cases of COVID-19 as of September 20, 2020. About 33% were associated with a Tablighi Jamaat religious mass gathering held in Kuala Lumpur between February 27 and March 3, 2020, which drove community transmission during Malaysia's second wave. We analysed genome sequences of SARS-CoV-2 from Malaysia to better understand the molecular epidemiology and spread. We obtained 58 SARS-CoV-2 whole genome sequences from patients in Kuala Lumpur and performed phylogenetic analyses on these and a further 57 Malaysian sequences available in the GISAID database. Nine different SARS-CoV-2 lineages (A, B, B.1, B.1.1, B.1.1.1, B.1.36, B.2, B.3 and B.6) were detected in Malaysia. The B.6 lineage was first reported a week after the Tablighi mass gathering and became predominant (65.2%) despite being relatively rare (1.4%) globally. Direct epidemiological links between lineage B.6 viruses and the mass gathering were identified. Increases in reported total cases, Tablighi-associated cases, and community-acquired B.6 lineage strains were temporally linked. Non-B.6 lineages were mainly travel-associated and showed limited onward transmission. There were also temporally correlated increases in B.6 sequences in other Southeast Asian countries, India and Australia, linked to participants returning from this event. Over 95% of global B.6 sequences originated from Asia Pacific. We also report a nsp3-C6310A substitution found in 47.3% of global B.6 sequences which was associated with reduced sensitivity using a commercial diagnostic real-time PCR assay. Lineage B.6 became the predominant cause of community transmission in Malaysia after likely introduction during a religious mass gathering. This event also contributed to spikes of lineage B.6 in other countries in the Asia-Pacific. Mass gatherings can be significant causes of local and global spread of COVID-19. Shared genomic surveillance can be used to identify SARS-CoV-2 transmission chains to aid prevention and control, and to monitor diagnostic molecular assays. Clinical Trial Registration: COVID-19 paper.
  4. Lee HC, Md Yusof HH, Leong MP, Zainal Abidin S, Seth EA, Hewitt CA, et al.
    Int J Neurosci, 2019 Sep;129(9):871-881.
    PMID: 30775947 DOI: 10.1080/00207454.2019.1580280
    Aims: The JAK-STAT signalling pathway is one of the key regulators of pro-gliogenesis process during brain development. Down syndrome (DS) individuals, as well as DS mouse models, exhibit an increased number of astrocytes, suggesting an imbalance of neurogenic-to-gliogenic shift attributed to dysregulated JAK-STAT signalling pathway. The gene and protein expression profiles of JAK-STAT pathway members have not been characterised in the DS models. Therefore, we aimed to profile the expression of Jak1, Jak2, Stat1, Stat3 and Stat6 at different stages of brain development in the Ts1Cje mouse model of DS. Methods: Whole brain samples from Ts1Cje and wild-type mice at embryonic day (E)10.5, E15, postnatal day (P)1.5; and embryonic cortex-derived neurospheres were collected for gene and protein expression analysis. Gene expression profiles of three brain regions (cerebral cortex, cerebellum and hippocampus) from Ts1Cje and wild-type mice across four time-points (P1.5, P15, P30 and P84) were also analysed. Results: In the developing mouse brain, none of the Jak/Stat genes were differentially expressed in the Ts1Cje model compared to wild-type mice. However, Western blot analyses indicated that phosphorylated (p)-Jak2, p-Stat3 and p-Stat6 were downregulated in the Ts1Cje model. During the postnatal brain development, Jak/Stat genes showed complex expression patterns, as most of the members were downregulated at different selected time-points. Notably, embryonic cortex-derived neurospheres from Ts1Cje mouse brain expressed lower Stat3 and Stat6 protein compared to the wild-type group. Conclusion: The comprehensive expression profiling of Jak/Stat candidates provides insights on the potential role of the JAK-STAT signalling pathway during abnormal development of the Ts1Cje mouse brains.
  5. Chong YM, Sam IC, Ponnampalavanar S, Syed Omar SF, Kamarulzaman A, Munusamy V, et al.
    Microbiol Resour Announc, 2020 May 14;9(20).
    PMID: 32409547 DOI: 10.1128/MRA.00383-20
    We sequenced four severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from Malaysia during the second wave of infection and found unique mutations which suggest local evolution. Circulating Malaysian strains represent introductions from different countries, particularly during the first wave of infection. Genome sequencing is important for understanding local epidemiology.
  6. Shafie SNA, Md Nordin NAH, Bilad MR, Misdan N, Sazali N, Putra ZA, et al.
    Membranes (Basel), 2021 May 19;11(5).
    PMID: 34069683 DOI: 10.3390/membranes11050371
    This study focuses on the effect of modified silica fillers by [EMIN][Tf2N] via physical adsorption on the CO2 separation performance of a mixed matrix membrane (MMM). The IL-modified silica was successfully synthesized as the presence of fluorine element was observed in both Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectrometer (XPS) analyses. The prepared MMMs with different loadings of the IL-modified silica were then compared with an unmodified silica counterpart and neat membrane. The morphology of IL-modified MMMs was observed to have insignificant changes, while polymer chains of were found to be slightly more flexible compared to their counterpart. At 2 bar of operating pressure, a significant increase in performance was observed with the incorporation of 3 wt% Sil-IL fillers compared to that of pure polycarbonate (PC). The permeability increased from 353 to 1151 Barrer while the CO2/CH4 selectivity increased from 20 to 76. The aforementioned increment also exceeded the Robeson upper bound. This indicates that the incorporation of fillers surface-modified with ionic liquid in an organic membrane is worth exploring for CO2 separation.
  7. Langhoff R, Arjumand J, Waliszewski M, Reimer P, Härtel D, Hohl C, et al.
    Angiology, 2021 Sep;72(8):724-732.
    PMID: 33779291 DOI: 10.1177/0003319721997314
    We evaluated the safety and efficacy of a resveratrol-paclitaxel-coated peripheral balloon catheter in an all-comer patient cohort undergoing endovascular treatment of above-the-knee and below-the-knee peripheral artery disease. CONSEQUENT ALL COMERS (Clinical Post-Market Clinical Follow-up [PMCF] on Peripheral Arteries treated with SeQuent Please OTW [Over-the Wire]) is a prospective, single-arm, multicenter observational study (ClinicalTrials Identifier: NCT02460042). The primary end point was the 12-month target lesion revascularization (TLR) rate. Secondary end points included vessel patency, target vessel revascularization, and all-cause mortality. A total of 879 lesions in 784 consecutive patients (71.3 ± 10.4 years old, 57.7% male) were analyzed; 53.3% had claudication, whereas the remaining 46.7% exhibited critical limb ischemia (CLI). Substantial comorbidities were present, including diabetes mellitus (41.2%), smoking (66.1%), and coronary artery disease (33.9%). Lesion length (879 lesions) was 12.0 ± 9.3 cm and 31.8% were Transatlantic Inter-Society Consensus II C/D lesions. The overall technical success rate of the 1269 drug-coated balloon (DCB)'s used was 99.6% (1.60 ± 0.79 DCB's/patient). At 12 months, the TLR rates were 6.3% in patients with CLI and 9.6% in claudicants, with a primary patency rate of 89.9% and 87.1%, respectively. All-cause mortality was 4.3% (28/658). The most important predictors for TLR were female gender, in-stent restenosis at baseline and lesion length.
  8. Heidari MH, Movafagh A, Abdollahifar MA, Abdi S, Barez MM, Azimi H, et al.
    Anat Cell Biol, 2017 Mar;50(1):69-72.
    PMID: 28417057 DOI: 10.5115/acb.2017.50.1.69
    Prostate cancer is the most common cancer type in men and is the second cause of death, due to cancer, in patients over 50, after lung cancer. Prostate specific antigen (PSA) is a widely used tumor marker for prostate cancer. Recently, PSA is discovered in non-prostatic cancer tissues in men and women raising doubts about its specificity for prostatic tissues. PSA exists in low serum level in healthy men and in higher levels in many prostate disorders, including prostatitis and prostate cancer. Thus, a supplementary tumor marker is needed to accurately diagnose the cancer and to observe the patient after treatment. Recently, soluble human leukocyte antigen-G (sHLA-G) has been introduced as a new tumor marker for different cancer types, including colorectal, breast, lung, and ovary. The present descriptive-experimental study was carried out including patients with malignant prostate tumor, patients with benign prostate tumor, and a group of health men as the control group, as judged by an oncologist as well as a pathologist. After sterile blood sampling, sHLA-G was measured by enzyme-linked immunosorbent assay in each group. The data was then analyzed using one-way ANOVA. P≤0.05 was considered as statistically significant. The results showed that the mean of sHLA-G level was high in patients. Also, it was found that there was a significant difference in sHLA serum level between the three groups. The data revealed that sHLA-G can be a novel supplementary tumor marker in addition to PSA to diagnose prostate cancer.
  9. Tan YC, Abdul Sattar M, Ahmeda AF, Abdul Karim Khan N, Murugaiyah V, Ahmad A, et al.
    PLoS One, 2020;15(4):e0231472.
    PMID: 32298299 DOI: 10.1371/journal.pone.0231472
    Oxidative stress is involved in the pathogenesis of a number of diseases including hypertension and renal failure. There is enhanced expression of nicotinamide adenine dinucleotide (NADPH oxidase) and therefore production of hydrogen peroxide (H2O2) during renal disease progression. This study investigated the effect of apocynin, an NADPH oxidase inhibitor and catalase, an H2O2 scavenger on Cyclosporine A (CsA) nephrotoxicity in Wistar-Kyoto rats. Rats received CsA (25mg/kg/day via gavage) and were assigned to vehicle, apocynin (2.5mmol/L p.o.), catalase (10,000U/kg/day i.p.) or apocynin plus catalase for 14 days. Renal functional and hemodynamic parameters were measured every week, and kidneys were harvested at the end of the study for histological and NADPH oxidase 4 (NOX4) assessment. Oxidative stress markers and blood urea nitrogen (BUN) were measured. CsA rats had higher plasma malondialdehyde (by 340%) and BUN (by 125%), but lower superoxide dismutase and total antioxidant capacity (by 40%, all P<0.05) compared to control. CsA increased blood pressure (by 46mmHg) and decreased creatinine clearance (by 49%, all P<0.05). Treatment of CsA rats with apocynin, catalase, and their combination decreased blood pressure to near control values (all P<0.05). NOX4 mRNA activity was higher in the renal tissue of CsA rats by approximately 63% (P<0.05) compared to controls but was reduced in apocynin (by 64%), catalase (by 33%) and combined treatment with apocynin and catalase (by 84%) compared to untreated CsA rats. Treatment of CsA rats with apocynin, catalase, and their combination prevented hypertension and restored renal functional parameters and tissue Nox4 expression in this model. NADPH inhibition and H2O2 scavenging is an important therapeutic strategy during CsA nephrotoxicity and hypertension.
  10. Nemati F, Rezaie M, Tabesh H, Eid K, Xu G, Ganjali MR, et al.
    Environ Res, 2022 Jan 06;208:112685.
    PMID: 34999024 DOI: 10.1016/j.envres.2022.112685
    Graphene-based nanomaterials with remarkable properties, such as good biocompatibility, strong mechanical strength, and outstanding electrical conductivity, have dramatically shown excellent potential in various applications. Increasing surface area and porosity percentage, improvement of adsorption capacities, reduction of adsorption energy barrier, and also prevention of agglomeration of graphene layers are the main advantages of functionalized graphene nanocomposites. On the other hand, Cerium nanostructures with remarkable properties have received a great deal of attention in a wide range of fields; however, in some cases low conductivity limits their application in different applications. Therefore, the combination of cerium structures and graphene networks has been widely invesitaged to improve properties of the composite. In order to have a comprehensive information of these nanonetworks, this research reviews the recent developments in cerium functionalized graphene derivatives (graphene oxide (GO), reduced graphene oxide (RGO), and graphene quantum dot (GQD) and their industrial applications. The applications of functionalized graphene derivatives have also been successfully summarized. This systematic review study of graphene networks decorated with different structure of Cerium have potential to pave the way for scientific research not only in field of material science but also in fluorescent sensing, electrochemical sensing, supercapacitors, and catalyst as a new candidate.
  11. Yusof HH, Lee HC, Seth EA, Wu X, Hewitt CA, Scott HS, et al.
    J Mol Neurosci, 2019 Apr;67(4):632-642.
    PMID: 30758748 DOI: 10.1007/s12031-019-01275-2
    Notch signalling pathway is involved in the proliferation of neural progenitor cells (NPCs), to inhibit neuronal cell commitment and to promote glial cell fate. Notch protein is cleaved by gamma-secretase, a multisubunit transmembrane protein complex that releases the Notch intracellular domain (NICD) and subsequently activates the downstream targets. Down syndrome (DS) individuals exhibit an increased number of glial cells (particularly astrocytes), and reduced number of neurons suggesting the involvement of Notch signalling pathway in the neurogenic-to-gliogenic shift in DS brain. Ts1Cje is a DS mouse model that exhibit similar neuropathology to human DS individuals. To date, the spatiotemporal gene expression of the Notch and gamma-secretase genes have not been characterised in Ts1Cje mouse brain. Understanding the expression pattern of Notch and gamma-secretase genes may provide a better understanding of the underlying mechanism that leads to the shift. Gene expression analysis using RT-qPCR was performed on early embryonic and postnatal development of DS brain. In the developing mouse brain, mRNA expression analysis showed that gamma-secretase members (Psen1, Pen-2, Aph-1b, and Ncstn) were not differentially expressed. Notch2 was found to be downregulated in the developing Ts1Cje brain samples. Postnatal gene expression study showed complex expression patterns and Notch1 and Notch2 genes were found to be significantly downregulated in the hippocampus at postnatal day 30. Results from RT-qPCR analysis from E15.5 neurosphere culture showed an increase of expression of Psen1, and Aph-1b but downregulation of Pen-2 and Ncstn genes. Gamma-secretase activity in Ts1Cje E15.5 neurospheres was significantly increased by fivefold. In summary, the association and the role of Notch and gamma-secretase gene expression throughout development with neurogenic-to-gliogenic shift in Ts1Cje remain undefined and warrant further validation.
  12. Raji YO, Othman MHD, Nordin NAHSM, Adam MR, Said KAM, Abdulyekeen KA, et al.
    Membranes (Basel), 2021 Dec 01;11(12).
    PMID: 34940457 DOI: 10.3390/membranes11120956
    This research aimed to investigate the ultrafiltration of water from emulsified oily wastewater through the application of surface-functionalized ceramic membrane to enhance its water permeability based on optimized parameters using a cross-flow filtration system. The interactive effects of feed concentration (10-1000 ppm), pH (4-10), and pressure (0-3 bar) on the water flux and oil rejection were investigated. Central composite design (CCD) from response surface methodology (RSM) was employed for statistical analysis, modeling, and optimization of operating conditions. The analysis of variance (ANOVA) results showed that the oil rejection and water flux models were significant with p-values of 0.0001 and 0.0075, respectively. In addition, good correlation coefficients of 0.997 and 0.863 were obtained for the oil rejection and water flux models, respectively. The optimum conditions for pressure, pH, and feed concentration were found to be 1.5 bar, pH 8.97, and 10 ppm, respectively with water flux and oil rejection maintained at 152 L/m2·h and 98.72%, respectively. Hence, the functionalized ultrafiltration ceramic membrane enables the separation efficiency of the emulsified oil in water to be achieved.
  13. Zainordin NA, Eddy Warman NA, Mohamad AF, Abu Yazid FA, Ismail NH, Chen XW, et al.
    PLoS One, 2021;16(10):e0258507.
    PMID: 34644368 DOI: 10.1371/journal.pone.0258507
    INTRODUCTION: There is limited data on the effects of low carbohydrate diets on renal outcomes particularly in patients with underlying diabetic kidney disease. Therefore, this study determined the safety and effects of very low carbohydrate (VLCBD) in addition to low protein diet (LPD) on renal outcomes, anthropometric, metabolic and inflammatory parameters in patients with T2DM and underlying mild to moderate kidney disease (DKD).

    MATERIALS AND METHODS: This was an investigator-initiated, single-center, randomized, controlled, clinical trial in patients with T2DM and DKD, comparing 12-weeks of low carbohydrate diet (<20g daily intake) versus standard low protein (0.8g/kg/day) and low salt diet. Patients in the VLCBD group underwent 2-weekly monitoring including their 3-day food diaries. In addition, Dual-energy x-ray absorptiometry (DEXA) was performed to estimate body fat percentages.

    RESULTS: The study population (n = 30) had a median age of 57 years old and a BMI of 30.68kg/m2. Both groups showed similar total calorie intake, i.e. 739.33 (IQR288.48) vs 789.92 (IQR522.4) kcal, by the end of the study. The VLCBD group showed significantly lower daily carbohydrate intake 27 (IQR25) g vs 89.33 (IQR77.4) g, p<0.001, significantly higher protein intake per day 44.08 (IQR21.98) g vs 29.63 (IQR16.35) g, p<0.05 and no difference in in daily fat intake. Both groups showed no worsening of serum creatinine at study end, with consistent declines in HbA1c (1.3(1.1) vs 0.7(1.25) %) and fasting blood glucose (1.5(3.37) vs 1.3(5.7) mmol/L). The VLCBD group showed significant reductions in total daily insulin dose (39(22) vs 0 IU, p<0.001), increased LDL-C and HDL-C, decline in IL-6 levels; with contrasting results in the control group. This was associated with significant weight reduction (-4.0(3.9) vs 0.2(4.2) kg, p = <0.001) and improvements in body fat percentages. WC was significantly reduced in the VLCBD group, even after adjustments to age, HbA1c, weight and creatinine changes. Both dietary interventions were well received with no reported adverse events.

    CONCLUSION: This study demonstrated that dietary intervention of very low carbohydrate diet in patients with underlying diabetic kidney disease was safe and associated with significant improvements in glycemic control, anthropometric measurements including weight, abdominal adiposity and IL-6. Renal outcomes remained unchanged. These findings would strengthen the importance of this dietary intervention as part of the management of patients with diabetic kidney disease.

  14. Heidari MH, Movafagh A, Abdollahifar MA, Abdi S, Barez MM, Azimi H, et al.
    Anat Cell Biol, 2017 Jun;50(2):162.
    PMID: 28713622 DOI: 10.5115/acb.2017.50.2.162
    [This corrects the article on p. 69 in vol. 50, PMID: 28417057.].
  15. Chong YM, Chan YF, Jamaluddin MFH, Hasan MS, Pang YK, Ponnampalavanar S, et al.
    J Clin Virol, 2021 Dec;145:105000.
    PMID: 34739838 DOI: 10.1016/j.jcv.2021.105000
    BACKGROUND: Reports of co-circulation of respiratory viruses during the COVID-19 pandemic and co-infections with SARS-CoV-2 vary. However, limited information is available from developing countries.

    OBJECTIVES: We aimed to investigate the incidence of respiratory viruses in adult patients with suspected COVID-19 in Kuala Lumpur, Malaysia.

    STUDY DESIGN: We collected 198 respiratory samples from adult patients hospitalized with suspected COVID-19 in a single teaching hospital in Kuala Lumpur in February-May 2020 and tested combined oro-nasopharyngeal swabs with the NxTAG Respiratory Pathogen Panel (Luminex) and Allplex RV Essential (Seegene) assays. Forty-five negative samples further underwent viral metagenomics analysis.

    RESULTS: Of the 198 samples, 74 (37.4%) had respiratory pathogens, including 56 (28.3%) with SARS-CoV-2 and 18 (9.1%) positive for other respiratory pathogens. There were five (2.5%) SARS-CoV-2 co-infections, all with rhinovirus/enterovirus. Three samples (6.7%; 3/45) had viruses identified by metagenomics, including one case of enterovirus D68 and one of Saffold virus genotype 6 in a patient requiring ICU care. Most of the COVID-19 patients (91.1%; 51/56) had mild symptoms but 5.4% (3/56) died.

    CONCLUSION: During the early COVID-19 period, common respiratory viruses other than SARS-CoV-2 only accounted for 9.1% of hospitalization cases with ARI and co-infections with SARS-CoV-2 were rare. Continued surveillance is important to understand the impact of COVID-19 and its associated public health control measures on circulation of other respiratory viruses. Metagenomics can identify unexpected or rare pathogens, such as Saffold virus, which is rarely described in adults.

  16. Shamsi S, Abdul Ghafor AAH, Norjoshukrudin NH, Ng IMJ, Abdullah SNS, Sarchio SNE, et al.
    Int J Nanomedicine, 2022;17:5781-5807.
    PMID: 36474524 DOI: 10.2147/IJN.S369373
    BACKGROUND: The impetuous usage of antibiotics has led to the perpetual rise of methicillin-resistant Staphylococcus aureus (MRSA), which has garnered the interest of potential drug alternatives, including nanomaterials.

    PURPOSE: The present study investigates the stability, toxicity, and antibacterial potential of gallic acid-loaded graphene oxide (GAGO) on several MRSA strains.

    METHODS: The stability of a synthesized and characterized GAGO was monitored in different physiological media. The toxicity profile of GAGO was evaluated in 3T3 murine fibroblast cells and the embryonic zebrafish model. The antibacterial activity of GAGO against MRSA, methicillin-susceptible S. aureus (MSSA), and community-acquired MRSA; with or without Panton-valentine leucocidin gene (MRSA-pvl+ and MRSA-pvl-) was investigated through disk diffusion, CFU counting method, time-kill experiment, and high-resolution transmission electron microscopy (HRTEM) observation.

    RESULTS: A stable GAGO nanocomposite has shown an improved toxicity profile in 3T3 murine fibroblast cells and zebrafish embryos, besides exhibiting normal ROS levels than graphene oxide (GO) and GA (gallic acid). The nanocomposite inhibited the growth of all bacterial strains employed. The effectiveness of the GAGO nanocomposite was comparable to cefoxitin (CFX), at ≥150 µg/mL in MRSA and MSSA. GAGO exhibited a significantly delayed response towards MRSA-pvl+ and MRSA-pvl-, with increased inhibition following 8 to 24 h of exposure, while comparable activity to native GA was only achieved at 24 h. Meanwhile, for MRSA and MSSA, GAGO had a comparable activity with native GA and GO as early as 2 h of exposure. HRTEM observation further reveals that GAGO-exposed cells were membrane compromised.

    CONCLUSION: In summary, the present study indicates the antibacterial potential of GAGO against MRSA strains, but further study is warranted to understand the mechanism of action of GAGO and its resistance in MRSA strains.

  17. Naini AA, Mayanti T, Harneti D, Darwati, Nurlelasari, Maharani R, et al.
    Phytochemistry, 2023 Jan;205:113477.
    PMID: 36283447 DOI: 10.1016/j.phytochem.2022.113477
    Two undescribed sesquiterpenoids, namely dysoticans A and B, and three undescribed sesquiterpenoid dimers, namely dysoticans C-E, together with six analogs, were isolated from the stem bark of Dysoxylum parasiticum (Osbeck) Kosterm. (Meliaceae), growing in West Java, Indonesia. Their structures were elucidated based on extensive spectroscopic analysis and theoretical simulations of ECD spectra and 13C NMR shifts. Dysoticans A and B possessed undescribed cadinanes with minor modifications, while C and D featured unprecedented pseudo-sesquiterpenoid dimers through O-ether linkages of cadinanes and guaianes, respectively. Dysotican E was also characterized as the true-sesquiterpenoid dimer featuring eudesmane-germacrene hybrid framework from the Meliaceae family. Furthermore, A-C and E showed moderate activities against the human breast cancer MCF-7 and cervical cancer HeLa cell lines with IC50 values ranging from 22.15 to 45.14 μM. D selectively exhibited significant cytotoxicity against the HeLa cell line with an IC50 value of 13.00 ± 0.13 μM.
  18. Schwalm JR, McCready T, Lamelas P, Musa H, Lopez-Jaramillo P, Yusoff K, et al.
    Am Heart J, 2018 09;203:57-66.
    PMID: 30015069 DOI: 10.1016/j.ahj.2018.06.004
    BACKGROUND: Cardiovascular disease is the leading cause of death throughout the world, with the majority of deaths occurring in low- and middle-income countries. Despite clear evidence for the benefits of blood pressure reduction and availability of safe and low-cost medications, most individuals are either unaware of their condition or not adequately treated.

    OBJECTIVE: The primary objective of this study is to evaluate whether a community-based, multifaceted intervention package primarily provided by nonphysician health workers can improve long-term cardiovascular risk in people with hypertension by addressing identified barriers at the patient, health care provider, and health system levels.

    METHODS/DESIGN: HOPE-4 is a community-based, parallel-group, cluster randomized controlled trial involving 30 communities (1,376 participants) in Colombia and Malaysia. Participants ≥50 years old and with newly diagnosed or poorly controlled hypertension were included. Communities were randomized to usual care or to a multifaceted intervention package that entails (1) detection, treatment, and control of cardiovascular risk factors by nonphysician health workers in the community, who use tablet-based simplified management algorithms, decision support, and counseling programs; (2) free dispensation of combination antihypertensive and cholesterol-lowering medications, supervised by local physicians; and (3) support from a participant-nominated treatment supporter (either a friend or family member). The primary outcome is the change in Framingham Risk Score after 12 months between the intervention and control communities. Secondary outcomes including change in blood pressure, lipid levels, and Interheart Risk Score will be evaluated.

    SIGNIFICANCE: If successful, the study could serve as a model to develop low-cost, effective, and scalable strategies to reduce cardiovascular risk in people with hypertension.

  19. Tharwani ZH, Bilal W, Khan HA, Kumar P, Butt MS, Hamdana AH, et al.
    Inquiry, 2023;60:469580231167024.
    PMID: 37085986 DOI: 10.1177/00469580231167024
    Over the years, several developing countries have been suffering from high infant and child mortality rates, however, according to the recent statistics, Pakistan falls high on the list. Our narrative review of copious research on this topic highlights that several factors, such as complications associated with premature births, high prevalence of birth defects, lack of vaccination, unsafe deliveries, poor breastfeeding practices, complications during delivery, sudden infant death syndrome (SIDS), poor socioeconomic conditions, and a struggling healthcare system, have influenced these rates. Bearing in mind the urgency of addressing the increased infant and child mortality rate in Pakistan, multiple steps must be taken in order to prevent unnecessary deaths. An effective initiative could be spreading awareness and education among women, as a lack of education among women has been indirectly linked to increased child mortality in Pakistan across many researches conducted on the issue. Furthermore, the government should invest in healthcare by hiring more physicians and providing better supplies and improving infrastructure, especially in underdeveloped areas, to decrease child mortality due to lack of clean water and poor hygiene. Lastly, telemedicine should be made common in order to provide easy access to women who cannot visit the hospital.
  20. Hamdana AH, Mohsin H, Habib Tharwani Z, Masood W, Furqana AQ, Sohail A, et al.
    Inquiry, 2023;60:469580231175437.
    PMID: 37190997 DOI: 10.1177/00469580231175437
    Monkeypox (MPX) is a zoonotic disease caused by the MPX virus from the poxviridae family of orthopoxviruses. Typically, endemic in central and west Africa, it has now become a matter of concern since cases have been reported in non-endemic countries around mid-June 2022, especially in the European region, with the transmission not related to travel. The diagnosis is made by PCR testing of the skin lesions. Even though treatment is symptomatic, antiretrovirals, such as tecovirimat, are used in severe cases. Vaccination with second and third generation vaccines is approved for prophylaxis in high risk individuals. Unfortunately, these options of treatment and prevention are only available in high income countries at the moment. This review, through a thorough literature search of articles from 2017 onward, focuses on epidemiology, clinical manifestations, challenges, treatment, prevention and control of MPX virus and how they can be corelated with other viral outbreaks including COVID-19, Acute Hepatitis of unknown origin, Measles and Dengue, to better predict and therefore prevent its transmission. The previous COVID-19 pandemic increased the disease burden on healthcare infrastructure of low-middle income countries, therefore, this recent MPX outbreak calls for a joint effort from healthcare authorities, political figures, and NGOs to combat the disease and prevent its further spread not only in high income but also in middle- and low-income countries.
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