Browse publications by year: 2021

  1. Subramaniam P, Ho JJ, Davis PG
    Cochrane Database Syst Rev, 2021 Oct 18;10(10):CD001243.
    PMID: 34661278 DOI: 10.1002/14651858.CD001243.pub4
    BACKGROUND: Cohort studies have suggested that nasal continuous positive airway pressure (CPAP) starting in the immediate postnatal period before the onset of respiratory disease (prophylactic CPAP) may be beneficial in reducing the need for intubation and intermittent positive pressure ventilation (IPPV), and in preventing bronchopulmonary dysplasia (BPD), in preterm or low birth weight infants.

    OBJECTIVES: To determine if prophylactic nasal CPAP (started within the first 15 minutes) or very early nasal CPAP regardless of respiratory status (started within the first hour of life), reduces the use of mechanical ventilation and the incidence of bronchopulmonary dysplasia without any adverse effects in preterm infants.

    SEARCH METHODS: A comprehensive search was run on 6 November 2020 in the Cochrane Central Register of Controlled Trials (CENTRAL via CRS Web) and MEDLINE via Ovid. We also searched the reference lists of retrieved studies.

    SELECTION CRITERIA: We included all randomised controlled trials (RCTs) and quasi-RCTs in preterm infants (under 37 weeks of gestation). We included trials if they compared prophylactic nasal CPAP (started within the first 15 minutes) or very early nasal CPAP (started within the first hour of life) in infants with minimal signs of respiratory distress with 'supportive care', such as supplemental oxygen therapy, standard nasal cannula, or mechanical ventilation. We excluded studies where prophylactic CPAP was compared with CPAP along with co-interventions.

    DATA COLLECTION AND ANALYSIS: We used the standard methods of Cochrane Neonatal, including independent study selection, assessment of trial quality, and extraction of data by two review authors.

    MAIN RESULTS: We included eight trials (seven from the previous version of the review and one new study), recruiting 3201 babies, in the meta-analysis. Four trials, involving 765 babies, compared CPAP with supportive care, and three trials (2364 babies) compared CPAP with mechanical ventilation. One trial (72 babies) compared prophylactic CPAP with very early CPAP. Apart from a lack of blinding of the intervention, we judged seven studies to have a low risk of bias. However, one study had a high risk of selection bias. Prophylactic or very early CPAP compared to supportive care There may be a reduction in failed treatment (risk ratio (RR) 0.6, 95% confidence interval (CI) 0.49 to 0.74; risk difference (RD) -0.16, 95% CI -0.34 to 0.02; 4 studies, 765 infants; very low certainty evidence). CPAP possibly reduces BPD at 36 weeks (RR 0.76, 95% CI 0.51 to 1.14; 3 studies, 683 infants, moderate certainty evidence); there may be little or no difference in death (RR 1.04, 95% CI 0.56 to 1.93; 4 studies, 765 infants; moderate certainty evidence). Prophylactic CPAP may reduce the composite outcome of death or BPD (RR 0.69, 95% CI 0.40 to 1.19; 1 study, 256 infants; low certainty evidence). There may be no difference in pulmonary air leak (pneumothorax) (RR 0.75, 95% CI 0.35 to 1.16; 3 studies, 568 infants; low certainty evidence), or intraventricular haemorrhage (IVH) Grade 3 or 4 (RR 0.96, 95% CI 0.39 to 2.37; 2 studies, 486 infants; moderate certainty evidence). Neurodevelopmental impairment was not reported in any of the studies. Prophylactic or very early CPAP compared to mechanical ventilation There was probably a reduction in the incidence of BPD at 36 weeks (RR 0.89, 95% CI 0.8 to 0.99; RD -0.04, 95% CI -0.08 to 0.00; 3 studies, 2150 infants; moderate certainty evidence); and death or BPD (RR 0.89, 95% CI 0.81 to 0.97; RD -0.05, 95% CI -0.09 to 0.01; 3 studies, 2358 infants; moderate certainty evidence). There was also probably a reduction in the need for mechanical ventilation (failed treatment) (RR 0.49, 95% CI 0.45 to 0.54; RD -0.50, 95% CI -0.54 to -0.45; 2 studies, 1042 infants; moderate certainty evidence). There was probably a reduction in the incidence of death (RR 0.82, 95% CI 0.66 to 1.03; 3 studies, 2358 infants; moderate certainty evidence); pulmonary air leak (pneumothorax) (RR 1.24, 95% CI 0.91 to 1.69; 3 studies, 2357 infants; low certainty evidence); and IVH Grade 3 or 4 (RR 1.09, 95% CI 0.86 to 1.39; 3 studies, 2301 infants; moderate certainty evidence). One study in this comparison reported that there was probably little or no difference between the groups in the incidence of neurodevelopmental impairment at 18 to 22 months (RR 0.91, 95% CI 0.62 to 1.32; 976 infants; moderate certainty evidence). Prophylactic CPAP compared with very early CPAP There was one study in this comparison. We are very uncertain whether there is any difference in the incidence of BPD (RR 0.5, 95% CI 0.05 to 5.27; very low certainty evidence). The combined outcome of death and BPD was not reported, and failed treatment was reported but without data. There may have been little to no effect on death (RR 0.75, 95% CI 0.29 to1.94; 1 study, 72 infants; very low certainty evidence). Intraventricular haemorrhage Grade 3 or 4 and neurodevelopmental outcomes were not reported in this study. Pulmonary air leak (pneumothorax) was reported in this study, but there were no events in either group.

    AUTHORS' CONCLUSIONS: For preterm and very preterm infants, there is insufficient evidence to evaluate prophylactic CPAP compared to oxygen therapy and other supportive care. When compared to mechanical ventilation, prophylactic nasal CPAP in very preterm infants reduces the incidence of BPD, the combined outcome of death and BPD, and mechanical ventilation. There is probably no difference in neurodevelopmental impairment at 18 to 22 months of age. When prophylactic CPAP is compared to early CPAP, we are very uncertain about whether there is any difference between prophylactic and very early CPAP. There is no information about the effect of prophylactic or very early CPAP in late preterm infants. There is one study awaiting classification.

    MeSH terms: Humans; Infant; Infant, Newborn; Infant, Premature; Intermittent Positive-Pressure Ventilation; Infant, Very Low Birth Weight; Continuous Positive Airway Pressure*
  2. Salari N, Jafari S, Darvishi N, Valipour E, Mohammadi M, Mansouri K, et al.
    Diabetol Metab Syndr, 2021 Oct 18;13(1):110.
    PMID: 34663429 DOI: 10.1186/s13098-021-00733-5
    BACKGROUND: Obesity is a complex disease with an increasing prevalence worldwide. There are different weight-management options for obesity treatment, including dietary control, exercise, surgery, and medication. Medications are always associated with different responses from different people. More safety and efficacy of drugs with fewer side effects are valuable for any clinical condition. In this systematic review and network meta-analysis, different anti-obesity drugs are compared to identify the most effective drug.

    METHODS: All relevant studies were extracted by searching national and international databases of SID, MagIran, ProQuest, PubMed, Science Direct, Scopus, Web of Science (WoS), and Google Scholar without time limit until October 2020. Finally, the meta-analysis was performed with the 11 remaining studies containing 14 different drug supplements. The standardized mean difference (SMD) was calculated at a 95% confidence interval (CI) to evaluate the effects of each treatment group compared with placebo. A random-effect model was used to evaluate the effect of individual studies on the final result. Heterogeneity and incompatibility of the network were assessed by Cochran's Q and Higgins I2, and the Net Heat chart, respectively. Data analysis was performed using R software.

    RESULTS: Our results showed that there were significant mean effects in people intervened with Phentermine 15.0 mg + Topiramate 92.0 mg, Phentermine 7.5 mg + Topiramate 46.0 mg, Pramlintide, Naltrexone + Bupropion 32, and Liraglutide, with SMD effects size = - 9.1, - 7.4, - 6.5, - 5.9, - 5.35, respectively.

    CONCLUSION: This study was performed to compare the effect of different drugs used for weight loss in obese patients. The most effective drugs for weight loss were phentermine and topiramate, pramlintide, naltrexone, bupropion, and liraglutide compared to placebo treatment, respectively. This study provides new insights into anti-obesity drugs and hopes to shed new light on future research to manage and treat obesity.

  3. Chuah SL, Jobli AT, Wan SA, Teh CL
    J Med Case Rep, 2021 Oct 19;15(1):526.
    PMID: 34663471 DOI: 10.1186/s13256-021-03103-x
    BACKGROUND: Cerebellar degeneration is a rare and severe presentation of primary Sjögren syndrome. There are few case reports of cerebellar degeneration associated with different autoimmune diseases, especially with systemic lupus erythematosus and neuro-Behcet's disease. There are only six patients reported worldwide to be affected by cerebellar atrophy associated with primary Sjögren syndrome. In this report, we describe a patient with primary Sjögren syndrome who presented with ataxia due to cerebellar degeneration.

    CASE PRESENTATION: We report the case of a 37-year-old Chinese woman with primary Sjögren syndrome who presented with ataxia over 3 months associated with tremor of the limbs. Magnetic resonance imaging of the brain revealed bilateral cerebellar atrophy. Based on the presence of cerebellar signs with magnetic resonance imaging brain findings, she was diagnosed as cerebellar degeneration secondary to primary Sjögren syndrome. She was treated with methylprednisolone, hydroxychloroquine, and two cycles of monthly intravenous cyclophosphamide. Subsequently, she refused further treatment, and her neurological symptoms remained the same upon the last clinic review. Primary cerebellar degeneration is rarely associated with primary Sjögren syndrome. The pathogenesis of the neurological manifestations in primary Sjögren syndrome is unclear. Treatment involves corticosteroids and immunosuppressive agents with no consensus of a specific therapy for the management of primary Sjögren syndrome with central nervous system involvement.

    CONCLUSIONS: Cerebellar degeneration is a rare presentation of primary Sjögren syndrome. Early diagnosis and treatment of this condition is needed to ensure a good outcome.

    MeSH terms: Adult; Cerebellar Ataxia*; Female; Humans; Magnetic Resonance Imaging; Spinocerebellar Degenerations*
  4. Law KB, M Peariasamy K, Mohd Ibrahim H, Abdullah NH
    Sci Rep, 2021 10 18;11(1):20574.
    PMID: 34663839 DOI: 10.1038/s41598-021-00013-2
    The conventional susceptible-infectious-recovered (SIR) model tends to magnify the transmission dynamics of infectious diseases, and thus the estimated total infections and immunized population may be higher than the threshold required for infection control and eradication. The study developed a new SIR framework that allows the transmission rate of infectious diseases to decline along with the reduced risk of contact infection to overcome the limitations of the conventional SIR model. Two new SIR models were formulated to mimic the declining transmission rate of infectious diseases at different stages of transmission. Model A utilized the declining transmission rate along with the reduced risk of contact infection following infection, while Model B incorporated the declining transmission rate following recovery. Both new models and the conventional SIR model were then used to simulate an infectious disease with a basic reproduction number (r0) of 3.0 and a herd immunity threshold (HIT) of 0.667 with and without vaccination. Outcomes of simulations were assessed at the time when the total immunized population reached the level predicted by the HIT, and at the end of simulations. Further, all three models were used to simulate the transmission dynamics of seasonal influenza in the United States and disease burdens were projected and compared with estimates from the Centers for Disease Control and Prevention. For the simulated infectious disease, in the initial phase of the outbreak, all three models performed expectedly when the sizes of infectious and recovered populations were relatively small. As the infectious population increased, the conventional SIR model appeared to overestimate the infections even when the HIT was achieved in all scenarios with and without vaccination. For the same scenario, Model A appeared to attain the level predicted by the HIT and in comparison, Model B projected the infectious disease to be controlled at the level predicted by the HIT only at high vaccination rates. For infectious diseases with high r0, and at low vaccination rates, the level at which the infectious disease was controlled cannot be accurately predicted by the current theorem. Transmission dynamics of infectious diseases with herd immunity can be accurately modelled by allowing the transmission rate of infectious diseases to decline along with the reduction of contact infection risk after recovery or vaccination. Model B provides a credible framework for modelling infectious diseases with herd immunity in a randomly mixed population.
    MeSH terms: Communicable Diseases/genetics; Communicable Diseases/transmission*; Disease Outbreaks; Humans; Models, Theoretical; Vaccination; Immunity, Herd/immunology; Immunity, Herd/physiology*; Basic Reproduction Number
  5. Brohan MA, Dom NC, Ishak AR, Abdullah S, Salim H, Ismail SNS, et al.
    Environ Sci Pollut Res Int, 2021 Dec;28(46):66501-66509.
    PMID: 34665420 DOI: 10.1007/s11356-021-17049-6
    This study intends to deal with the environmental consequences of the COVID-19 pandemic in Malaysia, by providing a summary of the effects of COVID-19 on municipal solid waste (MSW). In this analysis, the data on domestic waste collection were collected from the Solid Waste Management and Public Cleaning Corporation (SWCorp) from 1 January 2020 to 31 December 2020 to evaluate the relative changes in MSW percentage via a waste weighing method. The data consisted of the cumulative tonnage of MSW for every local authority in Peninsular Malaysia and was classified according to MCO phases; before the MCO, during the MCO, during the conditional MCO (CMCO) and during the recovery MCO (RMCO) phases. The results indicated that the enforcement of the early MCO showed a positive effect by decreasing the volume of MSW. This decrease was noted across 41 local authorities, which accounts for 87.23% of Peninsular Malaysia. However, the amount of MSW began to increase again when the MCO reached the conditional and recovery stages. From this, it can be concluded that the implementation of the MCO, in its various incarnations, has shown us that our lifestyles can have a harmful impact on our environment. While the pandemic was still spreading and limitations were still in place in Malaysia, local governments and waste management companies had to quickly alter their waste management systems and procedures. The current circumstance allows us to rethink our social and economic structures while improving environmental and social inclusion.
  6. Mohammad Yusof NAD, Karupiah K, Mohd Tamrin SB, Rasdi I, How V, Sambasivam S, et al.
    PLoS One, 2021;16(10):e0258796.
    PMID: 34665845 DOI: 10.1371/journal.pone.0258796
    Traffic police riders are exposed to prolonged static postures causing significant angular deviation of the musculoskeletal, including the lumbar angle (L1-L5). This postural alteration contributes to awkward posture, musculoskeletal disorders and spinal injury, especially in the lower back area, as it is one of the most severe modern diseases nowadays. Thus, the study aimed to evaluate the effect of lumbar support with a built-in massager system on spinal angle profiles among traffic police riders. A randomised controlled trial (pre-testpost-test control design) was used to assess spinal angle pattern while riding the high-powered motorcycle for 20 minutes. Twenty-four traffic police riders were randomly selected to participate and 12 riders were assigned to the control group and 12 riders to the experimental group. The pre-test and post-test were conducted at a one-week interval. Each participant was required to wear a TruPosture Smart Shirt (to monitor spinal posture). The TruPosture Apps recorded the spinal angle pattern. The data indicated that the police riders using motorcycle seat with lumbar support and built-in massager system showed a huge improvement in maintaining posture which only involves slight spinal angle deviation changes from the spinal reference angle throughout the 20 minutes ride. The data collected then were analysed using the Mann-Whitney test and Wilcoxon signed-ranked test to verify a statistically significant difference between and within the control and experimental groups. There were significant differences in all sensors between the control group and experimental groups (p<0.05) and within the experimental group. According to the findings, it can be said that the ergonomic intervention prototype (lumbar support with built-in massager system) successfully helps to maintain and improve the natural curve of the spinal posture. This indirectly would reduce the risk of developing musculoskeletal disorders and spinal injury among traffic police riders.
    MeSH terms: Adult; Equipment Design; Female; Humans; Human Engineering/instrumentation*; Male; Massage/instrumentation*; Motorcycles*; Posture/physiology*; Spine/anatomy & histology*; Spine/physiology; Police; Young Adult; Wireless Technology; Mobile Applications
  7. Abdul Wahab NA, Makmor Bakry M, Ahmad M, Mohamad Noor Z, Mhd Ali A
    Patient Prefer Adherence, 2021;15:2249-2265.
    PMID: 34675490 DOI: 10.2147/PPA.S319469
    Background: Hypertension is one of the major risk factors of stroke and leading risk factors for global death. Inadequate control of blood pressure due to medication non-adherence remains a challenge and identifying the underlying causes will provide useful information to formulate suitable interventions.

    Purpose: This study aimed to explore the roles of culture, religiosity, and spirituality on adherence to anti-hypertensive medications.

    Methodology: A semi-structured qualitative interview was used to explore promoters and barriers to medication adherence among hypertensive individuals residing in urban and rural areas of Perak State, West Malaysia. Study participants were individuals who are able to comprehend either in Malay or English, above 18 years old and on antihypertensive medications. Interview transcriptions from 23 participants were coded inductively and analyzed thematically. Codes generated were verified by three co-investigators who were not involved in transcribing process. The codes were matched with quotations and categorized using three levels of themes named as organizing, classifying and general themes.

    Results: Cultural aspects categorized as societal and communication norms were related to non-adherence. The societal norms related to ignorance, belief in testimony and anything "natural is safe" affected medication adherence negatively. Communication norms manifested as superficiality, indirectness and non-confrontational were also linked to medication non-adherence. Internal and organizational religiosity was linked to increased motivation to take medication. In contrast, religious misconception about healing and treatment contributed towards medication non-adherence. The role of spirituality remains unclear and seemed to be understood as related to religiosity.

    Conclusion: Culture and religiosity (C/R) are highly regarded in many societies and shaped people's health belief and behaviour. Identifying the elements and mechanism through which C/R impacted adherence would be useful to provide essential information for linking adherence assessment to the interventions that specifically address causes of medication non-adherence.

  8. Binmaeil H, Hanafiah A, Mohamed Rose I, Raja Ali RA
    Infect Drug Resist, 2021;14:4129-4145.
    PMID: 34675558 DOI: 10.2147/IDR.S325056
    AIMS AND OBJECTIVES: More than half of the world's population is infected with Helicobacter pylori, which can cause chronic gastritis. WHO has regarded clarithromycin-resistant H. pylori as a high priority pathogen. Hence, accurate diagnosis and detection of clarithromycin- and levofloxacin-resistant H. pylori strains is essential for proper management of infection. The objective of this study was to develop and optimize multiplex quantitative PCR assay for detection of mutations associated with clarithromycin and levofloxacin resistance in H. pylori directly from the gastric biopsies.

    MATERIALS AND METHODS: Specific primers and probes were designed to amplify ureA and mutations in 23S rRNA and gyrA genes. Singleplex and triplex qPCR assays were optimized and the assay's sensitivities and specificities were determined. The optimized multiplex qPCR assay was performed on 571 gastric biopsies.

    RESULTS: In this study, 14.7% (84/571) of the gastric biopsies were positive for H. pylori by conventional methods and 23.8% (136/571) were positive by the ureA-qPCR with 96.4% sensitivity and 88.5% specificity, while the +LR and -LR were 8.72 and 0.04, respectively. The ureA-positive samples (n=136) were subjected to multiplex qPCR which detected A2142G and A2143G mutations in the 23S rRNA gene (20.6%, 28/136) conferring clarithromycin resistance and gyrA mutations N87K, N87I, D91N, and D91Y (11.8%, 16/136) leading to levofloxacin resistance. The sensitivity and specificity of qPCR of 23S rRNA gene were 100% and 98.7%, respectively, while 100% and 99.8% for qPCR of gyrA, respectively.

    CONCLUSION: The effectiveness of this qPCR is that it is sensitive in detecting low bacterial load and will help in timely detection of clarithromycin- and levofloxacin-resistant strains, especially in case of mixed infections. Since it is culture independent, it can inform clinicians about antibiotics to be included in the first-line therapy, thereby improving the management of H. pylori infection at a much greater pace.

  9. Mahmoud MA, Islam MA, Ahmed M, Bashir R, Ibrahim R, Al-Nemiri S, et al.
    Risk Manag Healthc Policy, 2021;14:4235-4241.
    PMID: 34675717 DOI: 10.2147/RMHP.S325184
    Objective: The aim of this study was to validate the Arabic version of General Medication Adherence Scale (GMAS) in Sudanese patients with type 2 diabetes mellitus (T2DM).

    Methods: A 3-month cross-sectional study was conducted among patients with T2DM at Al-Daraja Health Center, located in Wad Medani, Sudan. A convenient sample of patients was selected, and the study sample size was calculated using the item response ratio. Factorial, known group, and construct validities were determined. Internal consistency and reliability were also determined.

    Results: Responses were provided by 500 patients. The average medication adherence score was 30 (median 31). The normed fit index (NFI) was 0.950, the comparative fit index (CFI) was 0.963, the incremental fit index (IFI) was 0.963, and the root-mean-square error of approximation (RMSEA) was 0.071. The results from these fit indices indicated a good model. Factorial, known group and construct validities were all established. A significant association was found between adherence score and age (P = 0.03) since a larger proportion of older patients were found to have high adherence compared to patients in other age groups. The reliability (α) of the questionnaire was 0.834.

    Conclusion: The Arabic version of GMAS was validated in Sudanese patients with T2DM making it a suitable scale to be used in this population.

  10. Rosli NA, Teow YH, Mahmoudi E
    Sci Technol Adv Mater, 2021;22(1):885-907.
    PMID: 34675754 DOI: 10.1080/14686996.2021.1978801
    Infectious diseases of bacterial and viral origins contribute to substantial mortality worldwide. Collaborative efforts have been underway between academia and the industry to develop technologies for a more effective treatment for such diseases. Due to their utility in various industrial applications, nanoparticles (NPs) offer promising potential as antimicrobial agents against bacterial and viral infections. NPs have been established to possess potent antimicrobial activities against various types of pathogens due to their unique characteristics and cell-damaging ability through several mechanisms. The recently accepted antimicrobial mechanisms possessed by NPs include metal ion release, oxidative stress induction, and non-oxidative mechanisms. Another merit of NPs lies in the low likelihood of the development of microbial tolerance towards NPs, given the multiple simultaneous mechanisms of action against the pathogens targeting numerous gene mutations in these pathogens. Moreover, NPs provide a fascinating opportunity to curb microbial growth before infections: this outstanding feature has led to their utilization as active antimicrobial agents in different industrial applications, e.g. the coating of medical devices, incorporation in food packaging, promoting wound healing and encapsulation with other potential materials for wastewater treatment. This review discusses the progress and achievements in the antimicrobial applications of NPs, factors contributing to their actions, mechanisms underlying their efficiency, and risks of their applications, including the antimicrobial action of metal nanoclusters (NCs). The review concludes with a discussion of the restrictions on present studies and future prospects of nanotechnology-based NPs development.
  11. She L, Ma L, Jan A, Sharif Nia H, Rahmatpour P
    Front Psychol, 2021;12:743936.
    PMID: 34675851 DOI: 10.3389/fpsyg.2021.743936
    The aim of this study was to investigate the relationship between interaction and online learning satisfaction, whether this relationship is mediated by academic self-efficacy and student engagement among Chinese university students during the COVID-19 pandemic. A serial mediation model was developed to examine the proposed relationship. This study employed a cross-sectional, questionnaire-based research design. A sample of 1,504 Chinese university students (M age=19.89years, SD age=1.93) from five provinces in China completed an online survey questionnaire from December 2020 to January 2021 to respond to questions on demographic characteristics and items to measure the variables in the research model. The partial least squares structural equation modeling was used to assess the measurement model and proposed serial mediation model. Data were analyzed using SmartPLS software version 3.3.2. The results of the measurement model showed good reliability and validity for all constructs. The results of the structural model and hypothesis testing showed that all hypotheses were supported in this study. Particularly, there was a significant positive relationship between interaction and online learning satisfaction (Q1), interaction and academic self-efficacy (Q2), academic self-efficacy and student engagement (Q3), and the student engagement and online learning satisfaction (Q4). In addition, the results showed that academic self-efficacy and student engagement serial mediated the relationship between interaction and online learning satisfaction (Q5). The serial mediation model explained 34.6% of the variance of online learning satisfaction. The findings shed light on the underlying mechanisms that explain students' online learning satisfaction during the COVID-19 pandemic. Universities and policymakers need to make better decisions that ultimately could lead to students' academic outcomes and achievement.
  12. Saad HKM, Taib WRW, Ismail I, Johan MF, Al-Wajeeh AS, Al-Jamal HAN
    Exp Ther Med, 2021 Dec;22(6):1402.
    PMID: 34675995 DOI: 10.3892/etm.2021.10838
    Iron homeostasis is regulated by hepcidin (HEPC) that controls the dietary iron absorption and iron recycling. HEPC deficiency contributes to iron overload in β-thalassemia patients. The present study aimed to investigate the correlation between HEPC concentration and serum iron status among hemoglobin E (HbE)/β-thalassemia patients and their parents (HbE trait and β-thalassemia trait) compared with healthy controls. This study is a comparative cross-sectional study in which iron profile and HEPC level were examined in 65 HbE/β-thalassemia patients (pretransfusion) and 65 parents at the Hospital Sultanah Nur Zahirah and in 130 students as healthy controls from Univesiti Sultan Zainal Abidin, Terengganu, Malaysia. Furthermore, six samples from each group (HbE/β-thalassemia patients, parents and healthy controls) were randomly selected for gene expression analysis of HEPC and ferroportin1 (FPN1) using reverse transcription quantitative PCR. The results demonstrated that serum HEPC level were significantly decreased in HbE/β-thalassemia patients and their parents (P<0.001) compared with healthy controls. In addition, the gene expression analysis showed a dramatically downregulated HEPC in HbE/β-thalassemia patients and their parents (P=0.001) compared with healthy controls. However, there was a marked upregulation of FPN1 in HbE/β-thalassemia patients and their parents (P=0.001) compared with healthy controls. Iron profiling results revealed a significantly increased serum ferritin in HbE/β-thalassemia patients and their parents compared with healthy controls (P<0.001). In summary, the present study demonstrated that HEPC expression level and serum level were significantly decreased in HbE/β-thalassemia patients and their parents, which was combined with a marked increased FPN1 expression level and serum ferritin level compared with healthy volunteers. These findings supported the hypothesis that downregulated HEPC could lose its function as a negative regulator of FPN1, resulting in iron overload in HbE/β-thalassemia patients. Subsequently, assessing HEPC and FPN1 gene expression may be a useful tool to determine the risk of iron toxicity in patients with HbE/β-thalassemia and their parents, and could therefore be considered as a therapeutic target in the management of iron burden in these patients.
  13. Godman B, Wladysiuk M, McTaggart S, Kurdi A, Allocati E, Jakovljevic M, et al.
    Biomed Res Int, 2021;2021:9996193.
    PMID: 34676266 DOI: 10.1155/2021/9996193
    BACKGROUND: Diabetes mellitus rates and associated costs continue to rise across Europe enhancing health authority focus on its management. The risk of complications is enhanced by poor glycaemic control, with long-acting insulin analogues developed to reduce hypoglycaemia and improve patient convenience. There are concerns though with their considerably higher costs, but moderated by reductions in complications and associated costs. Biosimilars can help further reduce costs. However, to date, price reductions for biosimilar insulin glargine appear limited. In addition, the originator company has switched promotional efforts to more concentrated patented formulations to reduce the impact of biosimilars. There are also concerns with different devices between the manufacturers. As a result, there is a need to assess current utilisation rates for insulins, especially long-acting insulin analogues and biosimilars, and the rationale for patterns seen, among multiple European countries to provide future direction. Methodology. Health authority databases are examined to assess utilisation and expenditure patterns for insulins, including biosimilar insulin glargine. Explanations for patterns seen were provided by senior-level personnel.

    RESULTS: Typically increasing use of long-acting insulin analogues across Europe including both Western and Central and Eastern European countries reflects perceived patient benefits despite higher prices. However, activities by the originator company to switch patients to more concentrated insulin glargine coupled with lowering prices towards biosimilars have limited biosimilar uptake, with biosimilars not currently launched in a minority of European countries. A number of activities were identified to address this. Enhancing the attractiveness of the biosimilar insulin market is essential to encourage other biosimilar manufacturers to enter the market as more long-acting insulin analogues lose their patents to benefit all key stakeholder groups.

    CONCLUSIONS: There are concerns with the availability and use of insulin glargine biosimilars among European countries despite lower costs. This can be addressed.

    MeSH terms: Insulin Glargine/economics; Insulin Glargine/therapeutic use*; Cost-Benefit Analysis/trends*; Diabetes Mellitus/diagnosis; Diabetes Mellitus/drug therapy*; Diabetes Mellitus/economics; Europe; Humans; Hypoglycemic Agents/economics; Hypoglycemic Agents/therapeutic use*; Patient Education as Topic/methods*; Insulin, Long-Acting/economics; Insulin, Long-Acting/therapeutic use*; Biosimilar Pharmaceuticals/economics; Biosimilar Pharmaceuticals/therapeutic use*
  14. Chen SP, Lin SR, Chen TH, Ng HS, Yim HS, Leong MK, et al.
    Biomed Pharmacother, 2021 Dec;144:112333.
    PMID: 34678724 DOI: 10.1016/j.biopha.2021.112333
    Diabetes mellitus (DM) is concomitant with significant morbidity and mortality and its prevalence is accumulative in worldwide. The conventional antidiabetic agents are known to mitigate the symptoms of diabetes; however, they may also cause side and adverse effects. There is an imperative necessity to conduct preclinical and clinical trials for the discovery of alternative therapeutic agents that can overcome the drawbacks of current synthetic antidiabetic drugs. This study aimed to investigate the efficacy of lowering blood glucose and underlined mechanism of γ-mangostin, mangosteen (Garcinia mangostana) xanthones. The results showed γ-Mangostin had a antihyperglycemic ability in short (2 h)- and long-term (28 days) administrations to diet-induced diabetic mice. The long-term administration of γ-mangostin attenuated fasting blood glucose of diabetic mice and exhibited no hepatotoxicity and nephrotoxicity. Moreover, AMPK, PPARγ, α-amylase, and α-glucosidase were found to be the potential targets for simulating binds with γ-mangostin after molecular docking. To validate the docking results, the inhibitory potency of γ-mangostin againstα-amylase/α-glucosidase was higher than Acarbose via enzymatic assay. Interestingly, an allosteric relationship between γ-mangostin and insulin was also found in the glucose uptake of VSMC, FL83B, C2C12, and 3T3-L1 cells. Taken together, the results showed that γ-mangostin exerts anti-hyperglycemic activity through promoting glucose uptake and reducing saccharide digestion by inhibition of α-amylase/α-glucosidase with insulin sensitization, suggesting that γ-mangostin could be a new clue for drug discovery and development to treat diabetes.
    MeSH terms: alpha-Amylases/antagonists & inhibitors; alpha-Amylases/metabolism; Animals; Blood Glucose/drug effects*; Blood Glucose/metabolism; Diabetes Mellitus/blood; Diabetes Mellitus/drug therapy*; Diabetes Mellitus/enzymology; Disease Models, Animal; Insulin Resistance*; Male; Mice, Inbred ICR; Plant Extracts/isolation & purification; Plant Extracts/pharmacology*; Plant Extracts/toxicity; Time Factors; Signal Transduction; Biomarkers/blood; Down-Regulation; 3T3-L1 Cells; Xanthones/pharmacology*; Xanthones/toxicity; PPAR gamma/metabolism*; Mice; AMP-Activated Protein Kinases/metabolism*; Diet, High-Fat; Glycoside Hydrolase Inhibitors/isolation & purification; Glycoside Hydrolase Inhibitors/pharmacology*; Glycoside Hydrolase Inhibitors/toxicity
  15. Lim CK, Lim JH, Ibrahim I, Chan YM, Zakaria NF, Yahya R, et al.
    Diagnostics (Basel), 2021 Sep 23;11(10).
    PMID: 34679443 DOI: 10.3390/diagnostics11101745
    Protein-energy wasting (PEW) is a devastating metabolic derangement that leads to increased morbidity and mortality in hemodialysis (HD) patients. This study aimed to determine the diagnostic test accuracy of bioelectrical impedance analysis derived-phase angle (PhA) in detecting PEW among HD patients. This was a multi-centre, cross-sectional study conducted amongst 152 multi-ethnic HD patients in Klang Valley, Malaysia. PEW was assessed using the International Society of Renal Nutrition and Metabolism criteria as the reference method. PhA was measured using a multi-frequency bioelectrical impedance spectroscopy at 50 kHz. Multiple and logistic regressions were used to determine factors associated with PhA and PEW diagnosis, respectively. A receiver operating characteristics curve analysis was used to establish the gender-specific PhA cut-offs to detect PEW. PEW existed in 21.1% of the HD patients. PhA was found as an independent predictor of PEW (adjOR = 0.308, p = 0.001), with acceptable to excellent discriminative performance (adjAUCmale = 0.809; adjAUCfemale = 0.719). Male patients had higher PhA cut-off compared to female patients (4.26° vs. 3.30°). We concluded that PhA is a valid and pragmatic biomarker to detect PEW in multi-ethnic Malaysian HD patients and a gender-specific cut-off is necessary, attributed to the gender differences in body composition.
  16. Kalafi EY, Jodeiri A, Setarehdan SK, Lin NW, Rahmat K, Taib NA, et al.
    Diagnostics (Basel), 2021 Oct 09;11(10).
    PMID: 34679557 DOI: 10.3390/diagnostics11101859
    The reliable classification of benign and malignant lesions in breast ultrasound images can provide an effective and relatively low-cost method for the early diagnosis of breast cancer. The accuracy of the diagnosis is, however, highly dependent on the quality of the ultrasound systems and the experience of the users (radiologists). The use of deep convolutional neural network approaches has provided solutions for the efficient analysis of breast ultrasound images. In this study, we propose a new framework for the classification of breast cancer lesions with an attention module in a modified VGG16 architecture. The adopted attention mechanism enhances the feature discrimination between the background and targeted lesions in ultrasound. We also propose a new ensembled loss function, which is a combination of binary cross-entropy and the logarithm of the hyperbolic cosine loss, to improve the model discrepancy between classified lesions and their labels. This combined loss function optimizes the network more quickly. The proposed model outperformed other modified VGG16 architectures, with an accuracy of 93%, and also, the results are competitive with those of other state-of-the-art frameworks for the classification of breast cancer lesions. Our experimental results show that the choice of loss function is highly important and plays a key role in breast lesion classification tasks. Additionally, by adding an attention block, we could improve the performance of the model.
  17. Badmus KA, Idrus Z, Meng GY, Sazili AQ, Mamat-Hamidi K
    Animals (Basel), 2021 Sep 22;11(10).
    PMID: 34679783 DOI: 10.3390/ani11102759
    This study was designed to characterize telomere length and its regulatory genes and to evaluate their potential as well-being biomarkers. Chickens were fed a diet containing corticosterone (CORT) for 4 weeks and performances, organ weight, plasma CORT levels, telomere lengths and regulatory genes were measured and recorded. Body weights of CORT-fed chickens were significantly suppressed (p < 0.05), and organ weights and circulating CORT plasma levels (p < 0.05) were altered. Interaction effect of CORT and duration was significant (p < 0.05) on heart and liver telomere length. CORT significantly (p < 0.05) shortened the telomere length of the whole blood, muscle, liver and heart. The TRF1, chTERT, TELO2 and HSF1 were significantly (p < 0.05) upregulated in the liver and heart at week 4 although these genes and TERRA were downregulated in the muscles at weeks 2 and 4. Therefore, telomere lengths and their regulators are associated and diverse, so they can be used as novel biomarkers of stress in broiler chickens fed with CORT.
  18. Hashmi SF, Rathore HA, Sattar MA, Johns EJ, Gan CY, Chia TY, et al.
    Biomolecules, 2021 Oct 19;11(10).
    PMID: 34680182 DOI: 10.3390/biom11101549
    Our main objective was to investigate the effect of chronic administration of hydrogen sulphide donor (sodium hydrosulphide) on the expression of intercellular adhesion molecule-1 (ICAM-1) and concentration of nuclear factor-kappa B (NF-kB) in a renal ischemia-reperfusion injury (IRI) model of WKY and L-nitro-arginine-methyl-ester (L-NAME)-induced hypertensive rats. Sodium hydrosulphide (NaHS) was administered intraperitoneally (i.p.) for 35 days while cystathionine gamma lyase (CSE) inhibitor dL-propargylglycine (PAG) was administered at a single dose of 50 mg/kg. Animals were anesthetised using sodium pentobarbitone (60 mg/kg) and then prepared to induce renal ischemia by clamping the left renal artery for 30 min followed by 3 h of reperfusion. Pre-treatment with NaHS improved the renal functional parameters in both WKY and L-NAME-induced hypertensive rats along with reduction of blood pressure in hypertensive groups. Oxidative stress markers like malondialdehyde (MDA), total superoxide dismutase (T-SOD) and glutathione (GSH) were also improved by NaHS treatment following renal IRI. Levels of ICAM-1 and NF-kB concentration were reduced by chronic treatment with NaHS and increased by PAG administration after renal IRI in plasma and kidney. Treatment with NaHS improved tubular morphology and glomerulus hypertrophy. Pre-treatment with NaHS reduced the degree of renal IRI by potentiating its antioxidant and anti-inflammatory mechanism, as evidenced by decreased NF-kB concentration and downregulation of ICAM-1 expression.
    MeSH terms: Animals; Gene Expression Regulation/drug effects; Humans; Hydrogen Sulfide/pharmacology*; Reperfusion Injury/drug therapy*; Reperfusion Injury/genetics; Reperfusion Injury/pathology; NF-kappa B/genetics; Intercellular Adhesion Molecule-1/genetics*; Rats, Inbred Dahl; Rats; Acute Kidney Injury/drug therapy*; Acute Kidney Injury/genetics; Acute Kidney Injury/pathology
  19. Rajasegaran Y, Azlan A, Rosli AA, Yik MY, Kang Zi K, Yusoff NM, et al.
    Biomedicines, 2021 Oct 19;9(10).
    PMID: 34680611 DOI: 10.3390/biomedicines9101494
    MicroRNAs (miRNAs) are short non-coding RNAs involved in post-transcriptional gene regulation. Over the past years, various studies have demonstrated the role of aberrant miRNA expression in the onset of cancer. The mechanisms by which miRNA exerts its cancer-promoting or inhibitory effects are apparent through the various cancer hallmarks, which include selective proliferative advantage, altered stress response, vascularization, invasion and metastasis, metabolic rewiring, the tumor microenvironment and immune modulation; therefore, this review aims to highlight the association between miRNAs and the various cancer hallmarks by dissecting the mechanisms of miRNA regulation in each hallmark separately. It is hoped that the information presented herein will provide further insights regarding the role of cancer and serve as a guideline to evaluate the potential of microRNAs to be utilized as biomarkers and therapeutic targets on a larger scale in cancer research.
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