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1.
Article in English | MEDLINE | ID: mdl-38095128

ABSTRACT

AIM: Eating disorders (EDs) are associated with significant disease burden and unacceptably high mortality rates. Early intervention significantly improves prognosis and can prevent chronic suffering; however, large numbers of people with the illness are not being identified or managed in primary healthcare. The current study aimed to test the reliability of the face-to-face, clinician delivery of a previously validated, co-designed, online screening tool for eating disorders. METHODS: Individuals aged 14 and over who read, English were recruited from the community in either primary care (general practice) settings or headspace youth mental health centres. They completed the InsideOut Institute Screener (IOI-S) face-to-face, delivered verbally by the study researcher clinician and then online by self-report. The primary outcome was test-retest reliability as measured by two-way mixed effects model Intraclass Correlation Coefficient (ICC) with absolute agreement. RESULTS: A total of 83 participants aged 14-81 (M 36.2) completed the study in New South Wales and the Northern Territory, Australia, between April and November 2022. The ICC between successive iterations of the test was significantly positive (0.980), demonstrating strong internal validity and test-retest reliability of the scale. CONCLUSIONS: The IOI-S is an adaptive 6-item screening tool designed to 'start a conversation' and determine risk using gentle language conceived by individuals with lived experience. Originally designed for online use, the current study broadens its versatility to clinical settings. The screener performs equally well when delivered face-to-face in clinical practice. In conjunction with increased practitioner education and improved treatment referral pathways, broad implementation of the screener in early healthcare settings can support timely identification and intervention for those with EDs.

2.
Med J Malaysia ; 78(5): 602-608, 2023 09.
Article in English | MEDLINE | ID: mdl-37775486

ABSTRACT

INTRODUCTION: Previous trials and real-world studies have shown that nirmatrelvir/ritonavir (Paxlovid®) reduces hospitalisation and deaths in symptomatic, high-risk, nonsevere COVID-19 patients. However, there was a scarcity of data on its effectiveness in the local setting. This study aimed to determine the effectiveness of Paxlovid® in reducing hospitalisation and mortality among COVID-19 patients and to identify the types of adverse events that occur after taking Paxlovid®. MATERIALS AND METHODS: A two-arm prospective cohort study was conducted among adult patients with COVID-19 categories 2 and 3 treated with Paxlovid® and a matched control group. A standard risk-stratified scoring system was used to establish Paxlovid® eligibility. All patients who were prescribed Paxlovid® and took at least one dose of Paxlovid® were included in the study. The control patients were selected from a centralised COVID-19 patient registry and matched based on age, gender and COVID-19 stage severity. RESULTS: A total of 552 subjects were included in the study and evenly allocated to the treatment and control groups. There was no statistically significant difference in 28-day hospitalisation after diagnosis [Paxlovid®: 26 (9.4%), Control: 34 (12.3%), OR: 0.74; 95%CI, 0.43-1.27; p=0.274] or all-cause death [Paxlovid®: 2 (0.7%), Control: 3 (1.1%), OR 1.51; 95%CI, 0.25-9.09; p=0.999]. There was no significant reduction in hospitalisation duration, intensive care unit admission events or supplementary oxygen requirement in the treatment arm. Ethnicity, COVID-19 severity at diagnosis, comorbidities and vaccination status were predictors of hospitalisation events. CONCLUSION: In this two-arm study, Paxlovid® did not significantly lower the incidence of hospitalisation, all-cause death and the need for supplemental oxygen. Adverse effects were frequent but not severe. Paxlovid® efficacy varied across settings and populations, warranting further real-world investigations.


Subject(s)
COVID-19 , Ritonavir , Adult , Humans , Ritonavir/therapeutic use , COVID-19 Drug Treatment , Prospective Studies , Hospitalization
3.
Med J Malaysia ; 78(3): 336-343, 2023 05.
Article in English | MEDLINE | ID: mdl-37271843

ABSTRACT

INTRODUCTION: Effective smoking cessation programmes are essential for assisting smokers in quitting, indirectly lowering mortality and morbidity associated with smoking. Numerous studies have indicated positive outcomes when using mindfulness treatment (MT) to treat psychological or behavioural health issues. Although to date, no study has looked at the effectiveness of online MT for quitting smoking while addressing mental health, particularly among the Asian population. Therefore, this study compares the efficiency of online MT to traditional counselling therapy (CT) in aiding smoking cessation programmes while also addressing mental health. MATERIALS AND METHODS: A randomised control study with a two-group, single-blind design and baseline evaluation was selected. Social media sites were used to advertise for participants, who were then admitted after meeting the requirements. Participants who met the eligibility requirements were randomly split into two groups. Each group received a total of three sessions of online therapy (MT or CT), once every two weeks, as well as one phone call per week as reinforcement. At the beginning and end of the intervention, participants completed questionnaires (1st week and 5th week). Generalized Estimating Equation (GEE) statistical analysis was used to analyse all the variables. RESULTS: The MT group experienced a statistically significant decrease in cigarette consumption (ß: -3.50, 95% Wald CI: - 4.62, -2.39) compared to the CT group over time. Furthermore, the MT group demonstrated significant improvements in their scores for the AAQ-2, anxiety, stress, depression and mindfulness compared to the CT group. CONCLUSION: Online MT is more successful at assisting smokers in lowering their daily cigarette intake and supporting their mental health during the smoking cessation process. Further longitudinal comparisons of the effectiveness of online MT should be undertaken using online platforms in future studies.


Subject(s)
Mindfulness , Smoking Cessation , Humans , Smoking Cessation/psychology , Mental Health , Single-Blind Method , Smoking/psychology
4.
Malays Orthop J ; 17(1): 27-33, 2023 Mar.
Article in English | MEDLINE | ID: mdl-37064618

ABSTRACT

Introduction: Charcot arthropathy is a condition which is progressive, non-infectious, destructive and debilitating that commonly affect foot and ankle. This systematic review is to evaluate the occurrence of common outcomes associated with each intervention of Charcot neuroarthropathy in midfoot. Materials and methods: A systematic review on literatures that were published from Jan 2010 to Jan 2020 were collected, reviewed and selected regarding the surgical treatment procedures of Charcot neuroarthropathy in midfoot. Results: The initial search yielded 231 reports and after exclusion, nine out of the total studies were included in the outcome analysis for review. These were studies that included data concerning surgical reconstruction of Charcot arthropathy in the midfoot. Conclusion: It is suggested that soft tissue preparation and usage of combination of implants thus reduce the risk of infection as well as increase rigidity of construct, respectively. These factors will aid to improve outcome of midfoot Charcot arthropathy reconstruction.

5.
Blood ; 141(22): 2738-2755, 2023 06 01.
Article in English | MEDLINE | ID: mdl-36857629

ABSTRACT

Primary resistance to tyrosine kinase inhibitors (TKIs) is a significant barrier to optimal outcomes in chronic myeloid leukemia (CML), but factors contributing to response heterogeneity remain unclear. Using single-cell RNA (scRNA) sequencing, we identified 8 statistically significant features in pretreatment bone marrow, which correlated with either sensitivity (major molecular response or MMR) or extreme resistance to imatinib (eventual blast crisis [BC] transformation). Employing machine-learning, we identified leukemic stem cell (LSC) and natural killer (NK) cell gene expression profiles predicting imatinib response with >80% accuracy, including no false positives for predicting BC. A canonical erythroid-specifying (TAL1/KLF1/GATA1) regulon was a hallmark of LSCs from patients with MMR and was associated with erythroid progenitor [ERP] expansion in vivo (P < .05), and a 2- to 10-fold (6.3-fold in group A vs 1.09-fold in group C) erythroid over myeloid bias in vitro. Notably, ERPs demonstrated exquisite TKI sensitivity compared with myeloid progenitors (P < .001). These LSC features were lost with progressive resistance, and MYC- and IRF1-driven inflammatory regulons were evident in patients who progressed to transformation. Patients with MMR also exhibited a 56-fold expansion (P < .01) of a normally rare subset of hyperfunctional adaptive-like NK cells, which diminished with progressive resistance, whereas patients destined for BC accumulated inhibitory NKG2A+ NK cells favoring NK cell tolerance. Finally, we developed antibody panels to validate our scRNA-seq findings. These panels may be useful for prospective studies of primary resistance, and in assessing the contribution of predetermined vs acquired factors in TKI response heterogeneity.


Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Protein Kinase Inhibitors , Humans , Imatinib Mesylate/pharmacology , Imatinib Mesylate/therapeutic use , Prospective Studies , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism , Blast Crisis , Drug Resistance, Neoplasm/genetics
6.
Curr Hematol Malig Rep ; 17(6): 181-197, 2022 12.
Article in English | MEDLINE | ID: mdl-36258106

ABSTRACT

PURPOSE OF REVIEW: Despite the adoption of tyrosine kinases inhibitors (TKIs) as molecular targeted therapy in chronic myeloid leukemia, some patients do not respond to treatment and even experience disease progression. This review aims to give a broad summary of advances in understanding of the mechanisms of therapy resistance, as well as management strategies that may overcome or prevent the emergence of drug resistance. Ultimately, the goal of therapy is the cure of CML, which will also require an increased understanding of the leukemia stem cell (LSC). RECENT FINDINGS: Resistance to tyrosine kinase inhibitors stems from a range of possible causes. Mutations of the BCR-ABL1 fusion oncoprotein have been well-studied. Other causes range from cell-intrinsic factors, such as the inherent resistance of primitive stem cells to drug treatment, to mechanisms extrinsic to the leukemic compartment that help CML cells evade apoptosis. There exists heterogeneity in TKI response among different hematopoietic populations in CML. The abundances of these TKI-sensitive and TKI-insensitive populations differ from patient to patient and contribute to response heterogeneity. It is becoming clear that targeting the BCR-ABL1 kinase through TKIs is only one part of the equation, and TKI usage alone may not cure the majority of patients with CML. Considerable effort should be devoted to targeting the BCR-ABL1-independent mechanisms of resistance and persistence of CML LSCs.


Subject(s)
Fusion Proteins, bcr-abl , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Humans , Fusion Proteins, bcr-abl/genetics , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Drug Resistance, Neoplasm/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Disease Progression
7.
Oncogene ; 41(48): 5160-5175, 2022 11.
Article in English | MEDLINE | ID: mdl-36271030

ABSTRACT

Acute myeloid leukaemia (AML) is a rapidly fatal blood cancer that is characterised by the accumulation of immature myeloid cells in the blood and bone marrow as a result of blocked differentiation. Methods which identify master transcriptional regulators of AML subtype-specific leukaemia cell states and their combinations could be critical for discovering novel differentiation-inducing therapies. In this proof-of-concept study, we demonstrate a novel utility of the Mogrify® algorithm in identifying combinations of transcription factors (TFs) and drugs, which recapitulate granulocytic differentiation of the NB4 acute promyelocytic leukaemia (APL) cell line, using two different approaches. In the first approach, Connectivity Map (CMAP) analysis of these TFs and their target networks outperformed standard approaches, retrieving ATRA as the top hit. We identify dimaprit and mebendazole as a drug combination which induces myeloid differentiation. In the second approach, we show that genetic manipulation of specific Mogrify®-identified TFs (MYC and IRF1) leads to co-operative induction of APL differentiation, as does pharmacological targeting of these TFs using currently available compounds. We also show that loss of IRF1 blunts ATRA-mediated differentiation, and that MYC represses IRF1 expression through recruitment of PML-RARα, the driver fusion oncoprotein in APL, to the IRF1 promoter. Finally, we demonstrate that these drug combinations can also induce differentiation of primary patient-derived APL cells, and highlight the potential of targeting MYC and IRF1 in high-risk APL. Thus, these results suggest that Mogrify® could be used for drug discovery or repositioning in leukaemia differentiation therapy for other subtypes of leukaemia or cancers.


Subject(s)
Leukemia, Myeloid, Acute , Leukemia, Promyelocytic, Acute , Humans , Tretinoin/pharmacology , Tretinoin/therapeutic use , Network Pharmacology , Leukemia, Promyelocytic, Acute/drug therapy , Leukemia, Promyelocytic, Acute/genetics , Oncogene Proteins, Fusion/genetics , Oncogene Proteins, Fusion/metabolism , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Cell Differentiation/genetics , Transcription Factors/genetics
8.
Med J Malaysia ; 77(3): 292-299, 2022 05.
Article in English | MEDLINE | ID: mdl-35638484

ABSTRACT

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that is commonly associated with extra-articular manifestations. Pulmonary disease is frequently encountered, which causes serious morbidity and increases mortality. Among the pulmonary manifestations, interstitial lung disease (ILD) is the most common. We aimed to analyse the frequency and clinical characteristics of a cohort of patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD); describe the radiological features of ILD; identify predictive factors for developing ILD; and evaluate the impact of ILD on patient survival. MATERIALS AND METHODS: This retrospective study included all patients with RA who attended the rheumatology clinic of Kuala Lumpur Hospital from 2018 to 2021. RA-ILD was identified from high-resolution computed tomography (HRCT) thorax images evaluated by two thoracic radiologists. Descriptive and logistic regression analyses were conducted using SPSS version 26.0. RESULTS: Of the 732 patients with RA, 7.4% (54) had ILD. Univariate analysis identified Indian ethnicity, rheumatoid factor (RF) positivity, anti-cyclic citrullinated peptide antibody titre, and diabetes mellitus as risk factors for developing ILD. Multivariable logistic regression showed that RA-ILD was positively associated with female gender [Adjusted odds ratio (aOR)=3.40 (95% confidence interval (CI): 1.04, 11.17)], Indian ethnicity [aOR=2.03 (95% CI: 1.16, 3.57)], and positive RF [aOR=2.39 (95% CI: 1.18, 4.87)]. Nonspecific interstitial pneumonia (NSIP) was the predominant HRCT pattern. Majority of patients had limited disease (<20% of lung involvement) and good functional exercise capacity. There was significant improvement (p<0.05) in mean forced vital capacity (FVC) following treatment with immunosuppressive agents. No mortality occurred throughout the median follow-up period of 3.2 years. CONCLUSION: RA patients of Indian ethnicity had an increased risk for developing ILD, suggesting that genetics play a crucial role. Other independent predictors were female gender and RF positivity. The pattern of HRCT thorax and extent of lung involvement influenced prognosis and survival of patients with RA-ILD.


Subject(s)
Arthritis, Rheumatoid , Lung Diseases, Interstitial , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/diagnostic imaging , Cohort Studies , Ethnicity , Female , Humans , Lung Diseases, Interstitial/complications , Lung Diseases, Interstitial/etiology , Male , Retrospective Studies
10.
Int J Mol Sci ; 23(3)2022 Jan 21.
Article in English | MEDLINE | ID: mdl-35163134

ABSTRACT

Multiple myeloma (MM) is a hematological disease marked by abnormal growth of B cells in bone marrow. Inherent chromosomal instability and DNA damage are major hallmarks of MM, which implicates an aberrant DNA repair mechanism. Studies have implicated a role for CDK12 in the control of expression of DNA damage response genes. In this study, we examined the effect of a small molecule inhibitor of CDK12-THZ531 on MM cells. Treatment of MM cells with THZ531 led to heightened cell death accompanied by an extensive effect on gene expression changes. In particular, we observed downregulation of genes involved in DNA repair pathways. With this insight, we extended our study to identify synthetic lethal mechanisms that could be exploited for the treatment of MM cells. Combination of THZ531 with either DNA-PK inhibitor (KU-0060648) or PARP inhibitor (Olaparib) led to synergistic cell death. In addition, combination treatment of THZ531 with Olaparib significantly reduced tumor burden in animal models. Our findings suggest that using a CDK12 inhibitor in combination with other DNA repair inhibitors may establish an effective therapeutic regimen to benefit myeloma patients.


Subject(s)
Anilides/pharmacology , Biomarkers, Tumor/genetics , DNA Repair , Gene Expression Regulation, Neoplastic/drug effects , Multiple Myeloma/drug therapy , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Pyrimidines/pharmacology , Synthetic Lethal Mutations , Animals , Apoptosis , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Cell Proliferation , Drug Therapy, Combination , Humans , Mice , Mice, Inbred NOD , Mice, SCID , Multiple Myeloma/genetics , Multiple Myeloma/pathology , Prognosis , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
11.
Haematologica ; 107(2): 358-370, 2022 02 01.
Article in English | MEDLINE | ID: mdl-34615339

ABSTRACT

Cancer treatment is constantly evolving from a one-size-fits-all towards bespoke approaches for each patient. In certain solid cancers, including breast and lung, tumor genome profiling has been incorporated into therapeutic decision-making. For chronic phase chronic myeloid leukemia (CML), while tyrosine kinase inhibitor therapy is the standard treatment, current clinical scoring systems cannot accurately predict the heterogeneous treatment outcomes observed in patients. Biomarkers capable of segregating patients according to outcome at diagnosis are needed to improve management, and facilitate enrollment in clinical trials seeking to prevent blast crisis transformation and improve the depth of molecular responses. To this end, gene expression (GE) profiling studies have evaluated whether GE signatures at diagnosis are clinically informative. Patient material from a variety of sources has been profiled using microarrays, RNA sequencing and, more recently, single-cell RNA sequencing. However, differences in the cell types profiled, the technologies used, and the inherent complexities associated with the interpretation of genomic data pose challenges in distilling GE datasets into biomarkers with clinical utility. The goal of this paper is to review previous studies evaluating GE profiling in CML, and explore their potential as risk assessment tools for individualized CML treatment. We also review the contribution that acquired mutations, including those seen in clonal hematopoiesis, make to GE profiles, and how a model integrating contributions of genetic and epigenetic factors in resistance to tyrosine kinase inhibitors and blast crisis transformation can define a route to GE-based biomarkers. Finally, we outline a four-stage approach for the development of GE-based biomarkers in CML.


Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Biomarkers , Blast Crisis/drug therapy , Epigenesis, Genetic , Gene Expression , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use
12.
J Hazard Mater ; 424(Pt B): 127483, 2022 02 15.
Article in English | MEDLINE | ID: mdl-34673392

ABSTRACT

A novel bimetallic doped PAC (Fe-Mn/PAC) pellet was prepared with a facile sol-gel method and used as an ozone catalyst for phenolic wastewater (PWW) treatment. Adoption of Fe-Mn/PAC pellet in microbubble ozonation enhanced the 1-h chemical oxygen demand (COD) and phenol removal in PWW to 79% and 95%, respectively. With ozone dosage of 10 mg/L, 1 g/L Fe-Mn/PAC pellet exhibited ozone conversion of 92%. In comparison to microbubble ozonation process, Fe-Mn/PAC induced microbubble-catalytic ozonation process promoted ozone decomposition rate by 1.9 times. In terms of •OH production, Fe-Mn/PAC pellet enhanced •OH exposure by 10 times, with a Rct value of 2.92 × 10 -8. Rct kinetic model also suggested that Fe-Mn/PAC pellet obtained higher kinetic rate constants for initiating and promoting •OH generation. Usage of Fe-Mn/PAC pellet in microbubble ozonation for phenolic wastewater treatment also reduced the total ozone consumption by 70%. In Fe-Mn/PAC induced microbubble-catalytic ozonation process, the ratio between ozone consumption and COD removal (ΔO3/ΔCOD) was 0.91. Fe-Mn/PAC pellet characterization with X-ray photoelectron spectroscopy (XPS), Fourier-transform infrared (FT-IR) and X-ray powder diffraction (XRD) analysis revealed successful doping of Fe-Mn on PAC substrate and larger numbers of carbon-oxygen/hydroxyl surface groups, which played key roles in ozone decomposition and •OH production.


Subject(s)
Ozone , Water Pollutants, Chemical , Catalysis , Charcoal , Cost-Benefit Analysis , Phenol , Powders , Spectroscopy, Fourier Transform Infrared , Wastewater , Water Pollutants, Chemical/analysis
13.
Trials ; 22(1): 767, 2021 Nov 03.
Article in English | MEDLINE | ID: mdl-34732233

ABSTRACT

BACKGROUND: While it is well established that perioperative use of oral nutrition supplement (ONS) improves nutrition status among severely malnourished surgical cancer patients, the evidence requires further substantiation for non-severely malnourished patients with cancer. This protocol paper presents the rationale and design of a randomised controlled trial to evaluate the effectiveness of preoperative as well as an extended 90-day postoperative use of ONS on nutritional and clinical outcomes among patients undergoing elective surgery for breast and colorectal cancer. METHODS: Patients with primary breast and colorectal cancer undergoing elective surgery are recruited from two tertiary hospitals. Eligible patients are assigned into one of the three intervention arms: (i) Group SS will receive ONS in addition to their normal diet up to 14 days preoperatively and postoperatively up to discharge; (ii) Group SS-E will receive ONS in addition to their normal diet up to 14 days preoperatively, postoperatively up to discharge and for an extended 90 days after discharge; and (iii) Group DS will receive ONS in addition to their normal diet postoperatively up to discharge from the hospital. The ONS is a standard formula fortified with lactium to aid in sleep for recovery. The primary endpoints include changes in weight, body mass index (BMI), serum albumin and prealbumin levels, while secondary endpoints are body composition (muscle and fat mass), muscle strength (handgrip strength), energy and protein intake, sleep quality, haemoglobin, inflammatory markers (transferrin, high sensitivity C-reactive protein, interleukin-6), stress marker (saliva cortisol), length of hospital stay and postoperative complication rate. DISCUSSION: This trial is expected to provide evidence on whether perioperative supplementation in breast and colorectal cancer patients presenting with high BMI and not severely malnourished but undergoing the stress of surgery would be beneficial in terms of nutritional and clinical outcomes. TRIAL REGISTRATION: ClinicalTrial.gov NCT04400552. Registered on 22 May 2020, retrospectively registered.


Subject(s)
Colorectal Neoplasms , Malnutrition , Colorectal Neoplasms/surgery , Dietary Supplements , Hand Strength , Humans , Malnutrition/diagnosis , Malnutrition/etiology , Malnutrition/prevention & control , Nutritional Status , Patient Discharge , Randomized Controlled Trials as Topic
14.
Nature ; 598(7881): 510-514, 2021 10.
Article in English | MEDLINE | ID: mdl-34646013

ABSTRACT

Human epithelial tissues accumulate cancer-driver mutations with age1-9, yet tumour formation remains rare. The positive selection of these mutations suggests that they alter the behaviour and fitness of proliferating cells10-12. Thus, normal adult tissues become a patchwork of mutant clones competing for space and survival, with the fittest clones expanding by eliminating their less competitive neighbours11-14. However, little is known about how such dynamic competition in normal epithelia influences early tumorigenesis. Here we show that the majority of newly formed oesophageal tumours are eliminated through competition with mutant clones in the adjacent normal epithelium. We followed the fate of nascent, microscopic, pre-malignant tumours in a mouse model of oesophageal carcinogenesis and found that most were rapidly lost with no indication of tumour cell death, decreased proliferation or an anti-tumour immune response. However, deep sequencing of ten-day-old and one-year-old tumours showed evidence of selection on the surviving neoplasms. Induction of highly competitive clones in transgenic mice increased early tumour removal, whereas pharmacological inhibition of clonal competition reduced tumour loss. These results support a model in which survival of early neoplasms depends on their competitive fitness relative to that of mutant clones in the surrounding normal tissue. Mutant clones in normal epithelium have an unexpected anti-tumorigenic role in purging early tumours through cell competition, thereby preserving tissue integrity.


Subject(s)
Cell Competition , Cell Proliferation , Clone Cells/cytology , Clone Cells/metabolism , Epithelial Cells/cytology , Esophageal Neoplasms/pathology , Mutation , Animals , Carcinogenesis/immunology , Cell Death , Cell Survival , Disease Models, Animal , Epithelial Cells/immunology , Epithelial Cells/pathology , Epithelium/immunology , Esophageal Neoplasms/immunology , Female , Male , Mice , Time Factors
15.
Sci Total Environ ; 798: 149289, 2021 Dec 01.
Article in English | MEDLINE | ID: mdl-34340085

ABSTRACT

Reverse osmosis (RO) is being used in many water reclamation facilities to produce high quality water that can be reused for different purposes. As a part of the RO process, a reject stream is produced as the reverse osmosis concentrate (ROC), which contains elevated levels of contaminants compared to the source water. Effective treatment and safe disposal of ROC via cost-effective means is very challenging. This study aims to develop a robust microbubble ozonation-biological process for industrial ROC treatment with a target effluent chemical oxygen demand (COD) lower than 60 mg/L. As compared to macrobubble ozonation, microbubble ozonation exhibited better ozone dissolution and 29% higher COD removal efficiency with the same ozone dosage. Under the optimum operating conditions with ozone dosage of 30 mg/L, ROC natural pH of 8.67 and ozonation duration of 1 h, microbubble ozonation achieved 42% COD removal efficiency while increasing the BOD5/COD ratio (ratio of biological oxygen demand over 5 days to the corresponding chemical oxygen demand) in ROC from 0.042 to 0.216. A biological activated carbon (BAC) column with an empty bed contact time (EBCT) of 120 min was combined with microbubble ozonation for continuous ROC treatment. Over the 100-day operation, the combined system performed consistent organics removal with an average effluent COD of 45 mg/L. Both LC-OCD data and fluorescence EEM spectra confirmed humic substances were the dominant organic species in ROC. Ozone pre-treatment could achieve significant removal of humic substances in raw ROC. ATP analysis found that ozone pre-treatment enhanced BAC biofilm activity by around 5 folds. 5 min acute toxicity assessment with Aliivibrio fischeri showed 4 times reduction of bioluminescence inhibition in ozone treated ROC. From the environmental point of view, Life cycle assessment (LCA) results demonstrated that Ozone-BAC system had significant environmental burdens on climate change and human toxicity due to the electricity production process. These environmental impacts can be mitigated by optimizing the ozonation process with reduced ozone dosage or utilizing renewable energy sources for electricity generation.


Subject(s)
Ozone , Water Pollutants, Chemical , Charcoal , Environment , Humans , Microbubbles , Osmosis , Water Pollutants, Chemical/analysis
16.
Water Res ; 203: 117504, 2021 Sep 15.
Article in English | MEDLINE | ID: mdl-34388501

ABSTRACT

An integrated computational fluid dynamics (CFD)-kinetic model framework was developed to numerically describe the hydrodynamic and kinetic phenomena in a liquid-solid two phases Fluidized-bed reactor Fenton/granular activated carbon (FBR-Fenton/GAC) system. The model obtained excellent accuracy for predicting chemical oxygen demand (COD) removal in reverse osmosis concentrate (ROC) treatment under different operation conditions. Hydrodynamic evaluation demonstrated that under the quasi-steady state, the GAC particles were uniformly circulated in the bed region with two pairs of counter-rotating recirculation cells, and a clear interface layer formed between the solid and the liquid phases. Superficial liquid velocity highly affected the fluidized bed expansion and solid volume fraction, while its impact on the overall COD removal efficiency was negligible. Chemical evaluation revealed that GAC/H2O2 catalytic reaction enhanced the •OH production in FBR-Fenton/GAC process by 2.7 folds as compared to homogenous Fenton process. Fenton reaction mainly occurred in the upper liquid region and its kinetics for •OH generation significantly diminished by 75% within the first 10 min. GAC/H2O2 reaction took place in the fluidized bed region for continuous •OH generation with a relatively stable rate from 1.21 × 10-6 to 0.60 × 10-6 M/s. Along the ROC treatment with FBR-Fenton/GAC process, the simulated COD degradation rate decreased along the reaction time with 2.05 × 10-6 M/s and 2.93 × 10-7 M/s at 2 min and 60 min, respectively. Faster COD removal was attained in the fluidized bed region due to combining effects of •OH oxidation and GAC adsorption. The overall predicted COD concentration reduced from 122 to 35 mg/L, •OH oxidation and GAC adsorption contributed 59% and 41%, respectively, to the total COD removal.


Subject(s)
Water Pollutants, Chemical , Water Purification , Charcoal , Hydrodynamics , Hydrogen Peroxide , Kinetics , Waste Disposal, Fluid
17.
Med J Malaysia ; 76(4): 466-473, 2021 07.
Article in English | MEDLINE | ID: mdl-34305106

ABSTRACT

INTRODUCTION: Pregnancy in women with systemic lupus erythematosus (SLE) is known to be associated with adverse pregnancy outcomes (APO). We aimed to determine the frequency of APO, the associated variables and predictors. MATERIALS AND METHODS: This retrospective study included all pregnancies seen at the SLE Clinic, Kuala Lumpur Hospital from January 2008 to May 2020. Maternal outcomes included SLE flare during pregnancy, preeclampsia and eclampsia. Foetal outcomes included foetal loss, preterm birth and small-for-gestational age (SGA) neonates. Clinical and laboratory variables were examined. Variables from univariate analysis were entered into logistic regression model. Odds ratio and 95% confidence interval were reported. RESULTS: Of the 131 pregnancies, 106 (80.9%) were live births. Twenty-six (24.5%) babies were born preterm and 35 (33%) neonates were SGA. Twenty-four (18.3%) women had disease flare during pregnancy, with the majority (22/24) being mild to moderate flares. Four women experienced preeclampsia while none had eclampsia. Predictors of adverse maternal outcomes included high SLEDAI-2K score, proteinuria and hypocomplementemia within 6 months before conception and during pregnancy; history of lupus nephritis (LN), pre-existing hypertension, antiphospholipid syndrome (APS), antiphospholipid antibodies, anti-Ro antibody and anti-RNP antibody. Predictors of adverse foetal outcomes comprised APS, preeclampsia, anti-Sm antibody, history of neuropsychiatric systemic lupus erythematosus (NPSLE) and azathioprine use. CONCLUSION: Pregnancy in SLE women is best deferred until disease activity is in remission for at least 6 months before conception. A history of LN is associated with a 3-fold risk of renal flare during pregnancy. Haematological abnormalities are rare in disease flare during pregnancy.


Subject(s)
Lupus Erythematosus, Systemic , Pregnancy Complications , Premature Birth , Female , Humans , Infant, Newborn , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/epidemiology , Malaysia/epidemiology , Pregnancy , Pregnancy Complications/epidemiology , Pregnancy Outcome/epidemiology , Premature Birth/epidemiology , Premature Birth/etiology , Retrospective Studies
18.
J Nutr Health Aging ; 25(6): 774-782, 2021.
Article in English | MEDLINE | ID: mdl-34179933

ABSTRACT

OBJECTIVES: This study aims to address the knowledge gap and summarise the measurement for intrinsic capacity for the five WHO domains across different populations. It specifically aims to identify measurement tools, methods used for computation of a composite intrinsic capacity index and factors associated with intrinsic capacity among older adults. METHODS: We performed literature review in Medline, including search terms "aged" or "elderly" and "intrinsic capacity" for articles published from 2000 - 2020 in English. Studies which assessed intrinsic capacity in the five WHO domains were included. Information pertaining to study setting, methods used for measuring the domains of intrinsic capacity, computation methods for composite intrinsic capacity index, and details on tool validation were extracted. RESULTS: Seven articles fulfilling the inclusion criteria were included in the review. Of these, the majority were conducted in community settings (n=5) and were retrospective studies (n=6). The most commonly used tools for assessing intrinsic capacity were gait speed test and chair stand test (locomotion); handgrip-strength and mini-nutritional assessment (vitality); Mini-Mental State Examination (cognition); Geriatric Depression Scale (GDS) and Center for Epidemiological Studies Depression Scale (CES-D) (psychological), and self-reported vision and health questionnaires (sensory). Among the tools used to operationalise the domains, we found variations and non-concordance, especially in the vitality and psychological domains, which make inter-study comparison difficult. Validated scales were less commonly used for vitality and sensory domains. Biomarkers were used for locomotion, vitality, and sensory domains. Self-reported measures were mostly used in the psychological and sensory domains. Three studies operationalised a global score for intrinsic capacity, whereby scores from the individual domains were used to create a composite intrinsic capacity index, using two approaches: a) Structural equation modelling, and b) Sub-scores for each domain which were combined either by arithmetic sum or average. CONCLUSION: We identified considerable variations in measurement instruments and processes which are used to assess intrinsic capacity, especially among the vitality and psychological domains. A standardized intrinsic capacity composite score for clinical or community settings has not been operationalised yet. Further validation via prospective studies of the intrinsic capacity concept and computation of composite score using validated scales are needed.


Subject(s)
Hand Strength , Aged , Geriatric Assessment , Humans , Middle Aged , Retrospective Studies , Walking Speed
19.
Chemosphere ; 263: 127980, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33297029

ABSTRACT

Ozonation is a well-known and widely applied advanced oxidation process (AOP) for industrial wastewater treatment, while the ozonation efficiency might be limited by low mass transfer, poor solubility, and rapid decomposition rate of ozone molecules in the aqueous phase. The present study aims to investigate the feasibility of combined microbubble-catalytic ozonation process (M-O3/Fe/GAC) for improving the ozonation efficiency during treatment of petrochemical wastewater (PCW). M-O3/Fe/GAC process optimization was carried out with different pH conditions, ozone dosages and catalyst loadings. The optimum operating conditions were identified as 50 mg L-1 ozone dosage, real PCW pH (7.0-7.5) and 4 g L-1 catalyst loading. Among different ozonation processes, M-O3/Fe/GAC process achieved the highest chemical oxidation demand (COD) removal efficiency of 88%, which is 18% and 43% higher than those achieved by the microbubble and macrobubble ozonation processes, respectively. Phenolic compounds presented in PCW could be reduced by 63% within 15 min in M-O3/Fe/GAC treatment process. Long-term continuous flow studies suggested M-O3/Fe/GAC process to be the most cost-effective technology for PCW treatment with an operating cost of S$0.18 kg-1 COD and S$0.4 m-3 with good catalyst stability. Liquid size exclusion chromatography with organic carbon detection (LC-OCD) data suggested humic substances to be the dominant organic species in PCW, M-O3/Fe/GAC could achieve significant humic substances removal and biodegradability enhancement in PCW. Kinetics and mechanism studies revealed that organics removal in M-O3/Fe/GAC was 1.8 times higher than that in microbubble ozonation process, and hydroxyl radical (●OH) was the dominant oxidant specie for organics removal in M-O3/Fe/GAC process.


Subject(s)
Ozone , Water Pollutants, Chemical , Water Purification , Catalysis , Microbubbles , Oxidation-Reduction , Wastewater , Water Pollutants, Chemical/analysis
20.
Water Res ; 190: 116692, 2021 Feb 15.
Article in English | MEDLINE | ID: mdl-33279748

ABSTRACT

In recent years, fluidized-bed Fenton (FBR-Fenton) process has gained more attention in treating recalcitrant industrial wastewater. FBR-Fenton combines the effectiveness of homogeneous Fenton and sludge reduction of heterogeneous Fenton. Comparing to other modified Fenton processes, FBR-Fenton has greater economical and scaling up potential. However, large consumption of Fenton reagents and strict pH control are still the bottlenecks hampering the full-scale application of FBR-Fenton. While prior reviews mainly focused on the operation and performance of FBR-Fenton process, the present study critically discussed the challenges and bottlenecks for its full-scale industrial application. This study also comprehensively reviewed the development strategies for tackling these drawbacks, mainly over the recent five years. Homogeneous FBR-Fenton, heterogeneous FBR-Fenton and heterogeneous FBR-photo-Fenton processes were classified for the first time according to their reaction mechanisms and system designs. Important operational and design parameters affecting the cost-effectiveness of all FBR-Fenton technologies were reviewed, including the fundamentals, common practices and even innovative steps for enhancing the process performance. Up-to-date applications of FBR-Fenton technologies in recalcitrant wastewater/compounds treatment were also summarized, and it was found that upscaling of heterogeneous FBR-Fenton and heterogeneous FBR-photo-Fenton processes was still very challenging. Strategies to overcome the key technical limitations and enhance process cost-effectiveness were discussed in the future perspective part. Furthermore, modelling techniques such as computational fluid dynamics model and artificial neural network were suggested to be promising modelling techniques for speeding up the full-scale applications of FBR-Fenton technologies.


Subject(s)
Waste Disposal, Fluid , Water Purification , Hydrodynamics , Hydrogen Peroxide , Oxidation-Reduction , Sewage , Wastewater
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