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Fulltext Nasopharyngeal Mantle Cell Lymphoma: An Extremely Rare Entity

Paul M, Asmi NH, Omar EK, Abdullah S, Mohamad I

Oman Med J, 2019 Jan;34(1):74-77.
PMID: 30671189 DOI: 10.5001/omj.2019.13

Mantle cell lymphoma (MCL) is a rare, aggressive subtype of non-Hodgkin lymphoma with a poor prognosis and high recurrence rate. It seldom affects the Waldeyer's ring let alone the nasopharynx. Patients usually present at late stages of the disease leading to poor failure-free and overall survival rates. Intensive chemotherapy regimes and autologous stem cell transplantation have reported increased survival rates. We report a relapsed case of nasopharyngeal MCL, which previously occurred in the gastrointestinal tract. The patient had undergone a hemicolectomy for colon intussusception secondary to the intraluminal lymphoma mass. He was unable to complete the treatment regime for MCL due to the adverse side effects. Oropharyngeal mass was discovered during routine outpatient follow-up, which was confirmed as nasopharyngeal MCL. We discuss the prognosis, disease progression, and possible treatments.
Endothelium dependent hyperpolarization-type relaxation compensates for attenuated nitric oxide-mediated responses in subcutaneous arteries of diabetic patients

Mokhtar SS, Vanhoutte PM, Leung SW, Yusof MI, Wan Sulaiman WA, Mat Saad AZ, et al.

Nitric Oxide, 2016 Feb 29;53:35-44.
PMID: 26768833 DOI: 10.1016/j.niox.2015.12.007

Diabetes impairs endothelium-dependent relaxations. The present study evaluated the contribution of different endothelium-dependent relaxing mechanisms to the regulation of vascular tone in subcutaneous blood vessels of humans with Type 2 diabetes mellitus. Subcutaneous arteries were isolated from tissues of healthy controls and diabetics. Vascular function was determined using wire myography. Expressions of proteins were measured by Western blotting and immunostaining. Endothelium-dependent relaxations to acetylcholine were impaired in arteries from diabetics compared to controls (P = 0.009). Acetylcholine-induced nitric oxide (NO)-mediated relaxations [in the presence of an inhibitor of cyclooxygenases (COX; indomethacin) and small and intermediate conductance calcium-activated potassium channel blockers (UCL1684 and TRAM 34, respectively)] were attenuated in arteries from diabetics compared to controls (P
Fulltext Circulating MicroRNAs in Young Patients with Acute Coronary Syndrome

Tong KL, Mahmood Zuhdi AS, Wan Ahmad WA, Vanhoutte PM, de Magalhaes JP, Mustafa MR, et al.

Int J Mol Sci, 2018 May 15;19(5).
PMID: 29762500 DOI: 10.3390/ijms19051467

Circulating microRNAs (miRNAs) hold great potential as novel diagnostic markers for acute coronary syndrome (ACS). This study sought to identify plasma miRNAs that are differentially expressed in young ACS patients (mean age of 38.5 ± 4.3 years) and evaluate their diagnostic potentials. Small RNA sequencing (sRNA-seq) was used to profile plasma miRNAs. Discriminatory power of the miRNAs was determined using receiver operating characteristic (ROC) analysis. Thirteen up-regulated and 16 down-regulated miRNAs were identified in young ACS patients. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) validation showed miR-183-5p was significantly up-regulated (8-fold) in ACS patients with non-ST-segment elevated myocardial infarction (NSTEMI) whereas miR-134-5p, miR-15a-5p, and let-7i-5p were significantly down-regulated (5-fold, 7-fold and 3.5-fold, respectively) in patients with ST-segment elevated myocardial infarction (STEMI), compared to the healthy controls. MiR-183-5p had a high discriminatory power to differentiate NSTEMI patients from healthy controls (area under the curve (AUC) of ROC = 0.917). The discriminatory power for STEMI patients was highest with let-7i-5p (AUC = 0.833) followed by miR-134-5p and miR-15a-5p and this further improved (AUC = 0.935) with the three miRNAs combination. Plasma miR-183-5p, miR-134-5p, miR-15a-5p and let-7i-5p are deregulated in STEMI and NSTEMI and could be potentially used to discriminate the two ACS forms.
Fulltext Citation Classics on Dental Caries: A Systematic Review

Arshad AI, Ahmad P, Dummer PMH, Alam MK, Asif JA, Mahmood Z, et al.

Eur J Dent, 2020 Feb;14(1):128-143.
PMID: 32189321 DOI: 10.1055/s-0040-1703419

OBJECTIVE: A systematic search was performed for the identification and analysis of the 100 most often cited articles on dental caries and to highlight the changing trends in the field of dentistry over time.
MATERIALS AND METHODS: The search was performed without any restriction on the study design, publication year, or language using the Web of Science (WoS) group of Clarivate Analytics enabling the search through "All Databases." Based on the citation count as available in WoS, the articles were sorted in a descending manner. Information regarding each article was then extracted, which included its authorship, counts of citation (in other databases), citation density, current citation index (2019), publication year, country of publication, journal of article, evidence level based on study design, and keywords description.
RESULTS: The count of citation for each article varied in each database, that is, 175 to 2,003 in WoS, 89 to 1,981 in Scopus, and 126 to 3,492 when searched in Google Scholar. The highest number of articles (n = 10) related to dental caries were published in 2004. A total of 301 authors made valuable contributions to this field, out of which J.D. Featherstone had coauthored 6 articles. A significant negative correlation (p < 0.01) was found between the age of the article and the citation density (r =-0.545). However, a nonsignificant correlation (p = 0.952) occurred between the age of publication and the citation count (r = 0.006).
CONCLUSION: The results of this systematic review provide a critical appraisal of the context underpinning scientific developments in the field of dental caries and also highlighted trends in clinical management and research.
Methodological quality assessment criteria for the evaluation of laboratory-based studies included in systematic reviews within the specialty of Endodontology: A development protocol

Nagendrababu V, Abbott PV, Boutsioukis C, Duncan HF, Faggion CM, Kishen A, et al.

Int Endod J, 2022 Jan 18.
PMID: 35043398 DOI: 10.1111/iej.13682

High-quality systematic reviews in the field of Dentistry provide the most definitive overarching evidence for clinicians, guideline developers and healthcare policy makers to judge the foreseeable risks, anticipated benefits, and potential harms of dental treatment. In the process of carrying out a systematic review, it is essential that authors appraise the methodological quality of the primary studies they include, because studies which follow poor methodology will have a potentially serious negative impact on the overall strength of the evidence and the recommendations that can be drawn. In Endodontology, systematic reviews of laboratory studies have used quality assessment criteria developed subjectively by the individual authors as there are no comprehensive, well-structured, and universally accepted criteria that can be applied objectively and universally to individual studies included in reviews. Unfortunately, these subjective criteria are likely to be inaccurately defined, unreliably applied, inadequately analysed, unreasonably biased, defective, and non-repeatable. The aim of the present paper is to outline the process to be followed in the development of comprehensive methodological quality assessment criteria to be used when evaluating laboratory studies, that is research not conducted in vivo on humans or animals, included in systematic reviews within Endodontology. The development of new methodological quality assessment criteria for appraising the laboratory-based studies included in systematic reviews within Endodontology will follow a three-stage process. First, a steering committee will be formed by the project leaders to develop a preliminary list of assessment criteria by modifying and adapting those already available, but with the addition of several new items relevant for Endodontology. The initial draft assessment criteria will be reviewed and refined by a Delphi Group (n = 40) for their relevance and inclusion using a nine-point Likert scale. Second, the agreed items will then be discussed in an online or face-to-face meeting by a group of experts (n = 10) to further refine the assessment criteria. Third, based on the feedback received from the online/face-to-face meeting, the steering committee will revise the quality assessment criteria and subsequently a group of authors will be selected to pilot the new system. Based on the feedback collected, the criteria may be revised further before being approved by the steering committee. The assessment criteria will be published in relevant journals, presented at national and international congresses/meetings, and will be freely available on a dedicated website. The steering committee will update the assessment criteria periodically based on feedback received from end-users.
Fulltext CD10 marks non-canonical PPARγ-independent adipocyte maturation and browning potential of adipose-derived stem cells

Chakraborty S, Ong WK, Yau WWY, Zhou Z, Bhanu Prakash KN, Toh SA, et al.

Stem Cell Res Ther, 2021 02 04;12(1):109.
PMID: 33541392 DOI: 10.1186/s13287-021-02179-y

BACKGROUND: Effective stem cell therapy is dependent on the stem cell quality that is determined by their differentiation potential, impairment of which leads to poor engraftment and survival into the target cells. However, limitations in our understanding and the lack of reliable markers that can predict their maturation efficacies have hindered the development of stem cells as an effective therapeutic strategy. Our previous study identified CD10, a pro-adipogenic, depot-specific prospective cell surface marker of human adipose-derived stem cells (ASCs). Here, we aim to determine if CD10 can be used as a prospective marker to predict mature adipocyte quality and play a direct role in adipocyte maturation.
METHODS: We first generated 14 primary human subject-derived ASCs and stable immortalized CD10 knockdown and overexpression lines for 4 subjects by the lentiviral transduction system. To evaluate the role of CD10 in adipogenesis, the adipogenic potential of the human subject samples were scored against their respective CD10 transcript levels. Assessment of UCP1 expression levels was performed to correlate CD10 levels to the browning potential of mature ASCs. Quantitative polymerase chain reaction (qPCR) and Western blot analysis were performed to determine CD10-dependent regulation of various targets. Seahorse analysis of oxidative metabolism and lipolysis assay were studied. Lastly, as a proof-of-concept study, we used CD10 as a prospective marker for screening nuclear receptor ligands library.
RESULTS: We identified intrinsic CD10 levels as a positive determinant of adipocyte maturation as well as browning potential of ASCs. Interestingly, CD10 regulates ASC's adipogenic maturation non-canonically by modulating endogenous lipolysis without affecting the classical peroxisome proliferator-activated receptor gamma (PPARγ)-dependent adipogenic pathways. Furthermore, our CD10-mediated screening analysis identified dexamethasone and retinoic acid as stimulator and inhibitor of adipogenesis, respectively, indicating CD10 as a useful biomarker for pro-adipogenic drug screening.
CONCLUSION: Overall, we establish CD10 as a functionally relevant ASC biomarker, which may be a prerequisite to identify high-quality cell populations for improving metabolic diseases.
Postmenopausal hormone therapy and Alzheimer's disease, dementia, and Parkinson's disease: A systematic review and time-response meta-analysis

Wu M, Li M, Yuan J, Liang S, Chen Z, Ye M, et al.

Pharmacol Res, 2020 05;155:104693.
PMID: 32057896 DOI: 10.1016/j.phrs.2020.104693

Hormone therapy continues to be a favourable option in the management of menopausal symptomatology, but the associated risk-benefit ratios with respect to neurodegenerative diseases remain controversial. The study aim was to determine the relation between menopausal hormone therapy and Alzheimer's disease, dementia, and Parkinson's disease in human subjects. A literature search was performed in PubMed/Medline, Cochrane collaboration, and Scopus databases from onset of the database to September 2019. Random-effects model was used to estimate pooled odd ratio (OR) and 95 % confidence intervals (CI). Subgroup analysis was performed based on the type and formulation of hormone. In addition, the time-response effect of this relationship was also assessed based on duration of hormone therapy. Associations between hormone therapy and Alzheimer's disease, dementia, and Parkinson's disease in menopausal women were reported in 28 studies. Pooled results with random effect model showed a significant association between hormone therapy and Alzheimer's disease (OR 1.08, 95 % CI 1.03-1.14, I2: 69 %). This relationship was more pronounced in patients receiving the combined estrogen-progestogen formulation. Moreover, a significant non-linear time-response association between hormone therapy and Alzheimer's disease was also identified (Coef1 = 0.0477, p1<0.001; Coef2 = -0.0932, p2<0.001). Similarly, pooled analysis revealed a significant association between hormone therapy and all-cause dementia (OR 1.16, 95 % CI 1.02-1.31, I2: 19 %). Interestingly, no comparable relationship was uncovered between hormone therapy as a whole and Parkinson's disease (OR 1.14, 95 % CI 0.95-1.38, I2: 65 %); however, sub-group analysis revealed a significant relationship between the disease and progestogen (OR 3.41, 95 % CI 1.23-9.46) or combined estrogen-progestogen formulation use (OR 1.49, 95 % CI 1.34-1.65). Indeed, this association was also found to be driven by duration of exposure (Coef1 = 0.0626, p1 = 0.04). This study reveals a significant direct relationship between the use of certain hormonal therapies and Alzheimer's disease, all-cause dementia, and Parkinson's disease in menopausal women. However, the association appears to shift in direct after five years in the context of Alzheimer's disease, adding further weight to the critical window or timing hypothesis of neurodegeneration and neuroprotection.
Fulltext A miR-335/COX-2/PTEN axis regulates the secretory phenotype of senescent cancer-associated fibroblasts

Kabir TD, Leigh RJ, Tasena H, Mellone M, Coletta RD, Parkinson EK, et al.

Aging (Albany NY), 2016 08;8(8):1608-35.
PMID: 27385366 DOI: 10.18632/aging.100987

Senescent cancer-associated fibroblasts (CAF) develop a senescence-associated secretory phenotype (SASP) that is believed to contribute to cancer progression. The mechanisms underlying SASP development are, however, poorly understood. Here we examined the functional role of microRNA in the development of the SASP in normal fibroblasts and CAF. We identified a microRNA, miR-335, up-regulated in the senescent normal fibroblasts and CAF and able to modulate the secretion of SASP factors and induce cancer cell motility in co-cultures, at least in part by suppressing the expression of phosphatase and tensin homologue (PTEN). Additionally, elevated levels of cyclo-oxygenase 2 (PTGS2; COX-2) and prostaglandin E2 (PGE2) secretion were observed in senescent fibroblasts, and inhibition of COX-2 by celecoxib reduced the expression of miR-335, restored PTEN expression and decreased the pro-tumourigenic effects of the SASP. Collectively these data demonstrate the existence of a novel miRNA/PTEN-regulated pathway modulating the inflammasome in senescent fibroblasts.
PROBE 2023 guidelines for reporting observational studies in endodontics: Explanation and elaboration

Nagendrababu V, Duncan HF, Fouad AF, Kirkevang LL, Parashos P, Pigg M, et al.

Int Endod J, 2023 Feb 27.
PMID: 36851874 DOI: 10.1111/iej.13909

Observational studies play a critical role in evaluating the prevalence and incidence of conditions or diseases in populations as well as in defining the benefits and potential hazards of health-related interventions. There are currently no reporting guidelines for observational studies in the field of Endodontics. The Preferred Reporting Items for study Designs in Endodontology (PRIDE) team has developed and published new reporting guidelines for observational-based studies called the 'Preferred Reporting items for OBservational studies in Endodontics (PROBE) 2023' guidelines. The PROBE 2023 guidelines were developed exclusively for the speciality of Endodontics by integrating and adapting the 'STrengthening the Reporting of OBservational studies in Epidemiology (STROBE)' checklist and the 'Clinical and Laboratory Images in Publications (CLIP)' principles. The recommendations of the Guidance for Developers of Health Research Reporting Guidelines were adhered to throughout the process of developing the guidelines. The purpose of this document is to serve as a guide for authors by providing an explanation for each of the items in the PROBE 2023 checklist along with relevant examples from the literature. The document also offers advice to authors on how they can address each item in their manuscript before submission to a journal. The PROBE 2023 checklist is freely accessible and downloadable from the PRIDE website (http://pride-endodonticguidelines.org/probe/).
Fulltext Deep Mining Generation of Lung Cancer Malignancy Models from Chest X-ray Images

Horry M, Chakraborty S, Pradhan B, Paul M, Gomes D, Ul-Haq A, et al.

Sensors (Basel), 2021 Oct 07;21(19).
PMID: 34640976 DOI: 10.3390/s21196655

Lung cancer is the leading cause of cancer death and morbidity worldwide. Many studies have shown machine learning models to be effective in detecting lung nodules from chest X-ray images. However, these techniques have yet to be embraced by the medical community due to several practical, ethical, and regulatory constraints stemming from the "black-box" nature of deep learning models. Additionally, most lung nodules visible on chest X-rays are benign; therefore, the narrow task of computer vision-based lung nodule detection cannot be equated to automated lung cancer detection. Addressing both concerns, this study introduces a novel hybrid deep learning and decision tree-based computer vision model, which presents lung cancer malignancy predictions as interpretable decision trees. The deep learning component of this process is trained using a large publicly available dataset on pathological biomarkers associated with lung cancer. These models are then used to inference biomarker scores for chest X-ray images from two independent data sets, for which malignancy metadata is available. Next, multi-variate predictive models were mined by fitting shallow decision trees to the malignancy stratified datasets and interrogating a range of metrics to determine the best model. The best decision tree model achieved sensitivity and specificity of 86.7% and 80.0%, respectively, with a positive predictive value of 92.9%. Decision trees mined using this method may be considered as a starting point for refinement into clinically useful multi-variate lung cancer malignancy models for implementation as a workflow augmentation tool to improve the efficiency of human radiologists.
Fulltext Factors determining generalization in deep learning models for scoring COVID-CT images

Horry MJ, Chakraborty S, Pradhan B, Fallahpoor M, Chegeni H, Paul M

Math Biosci Eng, 2021 10 27;18(6):9264-9293.
PMID: 34814345 DOI: 10.3934/mbe.2021456

The COVID-19 pandemic has inspired unprecedented data collection and computer vision modelling efforts worldwide, focused on the diagnosis of COVID-19 from medical images. However, these models have found limited, if any, clinical application due in part to unproven generalization to data sets beyond their source training corpus. This study investigates the generalizability of deep learning models using publicly available COVID-19 Computed Tomography data through cross dataset validation. The predictive ability of these models for COVID-19 severity is assessed using an independent dataset that is stratified for COVID-19 lung involvement. Each inter-dataset study is performed using histogram equalization, and contrast limited adaptive histogram equalization with and without a learning Gabor filter. We show that under certain conditions, deep learning models can generalize well to an external dataset with F1 scores up to 86%. The best performing model shows predictive accuracy of between 75% and 96% for lung involvement scoring against an external expertly stratified dataset. From these results we identify key factors promoting deep learning generalization, being primarily the uniform acquisition of training images, and secondly diversity in CT slice position.
Fulltext Malay Version of Nijmegen Cochlear Implant Questionnaire and Quality of Life of Patients with Post-lingual Deafness

Paul M, Abdullah A, Hashim ND, Ismail NFM, Shah SA

Medeni Med J, 2023 Jun 20;38(2):128-139.
PMID: 37338914 DOI: 10.4274/MMJ.galenos.2023.60980

OBJECTIVE: The Nijmegen Cochlear Implant questionnaire (NCIQ) was used to gauge the quality of life (QOL) improvement among cochlear implant (CI) users who suffered from post-lingual deafness. This study aimed to determine the consistency and reliability of the Malay version of the Nijmegen Cochlear Implant questionnaire (NCIQ-M) and to report the QOL of patients using NCIQ-M.
METHODS: This study has two phases: Phase I involves the translation of the NCIQ from English to Malay, followed by internal consistency and test-retest reliability assessment of the final version of NCIQ-M. Phase II involves QOL assessment of post-lingual deafness using NCIQ-M.
RESULTS: Twenty CI users and 20 non-CI users answered the NCIQ-M. Test-retest reliability analysis of the NCIQ-M was performed using an intraclass correlation coefficient, achieving scores of more than 0.85. Internal consistency was analysed with Cronbach α of more than 0.70 in all subdomains. Scores between the two groups of subjects were analyzed using an independent sample t-test. Good internal consistency, intraclass correlation, and test-retest reliability were obtained. Scores in all six subdomains of the NCIQ-M are significantly higher in the CI user group than in the non-CI user group.
CONCLUSIONS: The NCIQ-M is a consistent and reliable subjective questionnaire to determine the QOL of CI users concerning physical, psychological, and social functioning.
Fulltext Development of Debiasing Technique for Lung Nodule Chest X-ray Datasets to Generalize Deep Learning Models

Horry MJ, Chakraborty S, Pradhan B, Paul M, Zhu J, Loh HW, et al.

Sensors (Basel), 2023 Jul 21;23(14).
PMID: 37514877 DOI: 10.3390/s23146585

Screening programs for early lung cancer diagnosis are uncommon, primarily due to the challenge of reaching at-risk patients located in rural areas far from medical facilities. To overcome this obstacle, a comprehensive approach is needed that combines mobility, low cost, speed, accuracy, and privacy. One potential solution lies in combining the chest X-ray imaging mode with federated deep learning, ensuring that no single data source can bias the model adversely. This study presents a pre-processing pipeline designed to debias chest X-ray images, thereby enhancing internal classification and external generalization. The pipeline employs a pruning mechanism to train a deep learning model for nodule detection, utilizing the most informative images from a publicly available lung nodule X-ray dataset. Histogram equalization is used to remove systematic differences in image brightness and contrast. Model training is then performed using combinations of lung field segmentation, close cropping, and rib/bone suppression. The resulting deep learning models, generated through this pre-processing pipeline, demonstrate successful generalization on an independent lung nodule dataset. By eliminating confounding variables in chest X-ray images and suppressing signal noise from the bone structures, the proposed deep learning lung nodule detection algorithm achieves an external generalization accuracy of 89%. This approach paves the way for the development of a low-cost and accessible deep learning-based clinical system for lung cancer screening.
Fulltext Ankrd11 is a chromatin regulator involved in autism that is essential for neural development

Gallagher D, Voronova A, Zander MA, Cancino GI, Bramall A, Krause MP, et al.

Dev. Cell, 2015 Jan 12;32(1):31-42.
PMID: 25556659 DOI: 10.1016/j.devcel.2014.11.031

Ankrd11 is a potential chromatin regulator implicated in neural development and autism spectrum disorder (ASD) with no known function in the brain. Here, we show that knockdown of Ankrd11 in developing murine or human cortical neural precursors caused decreased proliferation, reduced neurogenesis, and aberrant neuronal positioning. Similar cellular phenotypes and aberrant ASD-like behaviors were observed in Yoda mice carrying a point mutation in the Ankrd11 HDAC-binding domain. Consistent with a role for Ankrd11 in histone acetylation, Ankrd11 was associated with chromatin and colocalized with HDAC3, and expression and histone acetylation of Ankrd11 target genes were altered in Yoda neural precursors. Moreover, the Ankrd11 knockdown-mediated decrease in precursor proliferation was rescued by inhibiting histone acetyltransferase activity or expressing HDAC3. Thus, Ankrd11 is a crucial chromatin regulator that controls histone acetylation and gene expression during neural development, thereby providing a likely explanation for its association with cognitive dysfunction and ASD.
Fulltext Mutant p53 cooperates with the SWI/SNF chromatin remodeling complex to regulate VEGFR2 in breast cancer cells

Pfister NT, Fomin V, Regunath K, Zhou JY, Zhou W, Silwal-Pandit L, et al.

Genes Dev., 2015 Jun 15;29(12):1298-315.
PMID: 26080815 DOI: 10.1101/gad.263202.115

Mutant p53 impacts the expression of numerous genes at the level of transcription to mediate oncogenesis. We identified vascular endothelial growth factor receptor 2 (VEGFR2), the primary functional VEGF receptor that mediates endothelial cell vascularization, as a mutant p53 transcriptional target in multiple breast cancer cell lines. Up-regulation of VEGFR2 mediates the role of mutant p53 in increasing cellular growth in two-dimensional (2D) and three-dimensional (3D) culture conditions. Mutant p53 binds near the VEGFR2 promoter transcriptional start site and plays a role in maintaining an open conformation at that location. Relatedly, mutant p53 interacts with the SWI/SNF complex, which is required for remodeling the VEGFR2 promoter. By both querying individual genes regulated by mutant p53 and performing RNA sequencing, the results indicate that >40% of all mutant p53-regulated gene expression is mediated by SWI/SNF. We surmise that mutant p53 impacts transcription of VEGFR2 as well as myriad other genes by promoter remodeling through interaction with and likely regulation of the SWI/SNF chromatin remodeling complex. Therefore, not only might mutant p53-expressing tumors be susceptible to anti VEGF therapies, impacting SWI/SNF tumor suppressor function in mutant p53 tumors may also have therapeutic potential.
Impact of Covid-19 on the therapeutic plasma exchange service within the South East Asian region: Consensus recommendations and global perspectives

Viswanathan S, Hiew FL, Siritho S, Apiwattanakul M, Tan K, Quek AML, et al.

J Clin Apher, 2021 Dec;36(6):849-863.
PMID: 34694652 DOI: 10.1002/jca.21937

INTRODUCTION: Therapeutic plasma exchange (TPE) for neuroimmunological disorders has played an increasingly important role within the Southeast Asian (SEA) region. The South East Asian Therapeutic Plasma exchange Consortium (SEATPEC) was formed in 2018 to promote education and research on TPE within the region. The advent of the Covid-19 pandemic has produced challenges for the development and expansion of this service.
METHODOLOGY: A qualitative and semi-quantitative questionnaire-based survey was conducted by SEATPEC member countries from January to June 2020 (Phase 1) and then from July 2020 to January 2021 in (Phase 2) to assess the impact of Covid-19 on regional TPE.
OBJECTIVES: The study's main objectives were to explore the challenges experienced and adaptations/adjustments taken by SEATPEC countries in order to continue safe and efficient TPE during the Covid-19 pandemic.
RESULTS: The pandemic was found to disrupt the delivery of TPE services in all SEATPEC countries. Contributing factors were multifactorial due to overstretched medical services, staff shortages, quarantines and redeployments, fear of acquiring Covid-19, movement restriction orders, and patient's psychological fear of attending hospitals/testing for Covid-19. All SEATPEC countries practiced careful stratification of cases for TPE (electives vs emergencies, Covid-19 vs non-Covid-19 cases). SEATPEC countries had to modify TPE treatment protocols to include careful preprocedure screening of patient's for Covid-19, use of personal protective equipment (PPE) and post-TPE sanitization of machines and TPE suites.
CONCLUSION: Based on the responses of the survey, SEATPEC countries produced a consensus statement with five recommendations for safe and effective TPE within the region.
Facilities, selection, outcome measurement, and limitations of therapeutic plasma exchange for neuroimmunological disorders: The South East Asian survey study

Rattanathamsakul N, Siritho S, Viswanathan S, Hiew FL, Apiwattanakul M, Tan K, et al.

J Clin Apher, 2023 Aug;38(4):437-446.
PMID: 36896493 DOI: 10.1002/jca.22047

INTRODUCTION: Therapeutic plasma exchange (TPE) for neuroimmunological disorders has played an important role in the Southeast Asian region. This study investigates the challenges of performing TPE within the region.
METHOD: A questionnaire-based survey was conducted and launched to 15 South East Asian Therapeutic Plasma Exchange Consortium (SEATPEC) members from seven countries in January 2021. It included demographics, TPE techniques, indications, challenges, timing, outcome measurement, and access to laboratory testing in each local center.
RESULTS: A total of 15 neurologists from 12 participating centers were included. They usually perform five sessions of TPE (100.0%), with 1 to 1.5 plasma volume (93.3%), and exchanges via the central catheter (100.0%). Acute relapses of neuromyelitis optica spectrum disorder and myasthenia gravis are the most common indications. They used a combination of normal saline and 5% albumin (60.0%) as replacement fluid. Most (66.7%) used TPE as an add-on treatment in steroid-refractory cases or as first-line treatment for severe attacks. They suggested assessing the TPE efficacy of TPE by the interval to the next attack, post-TPE relapse rates, and TPE-related complications. The major challenges within our region are expense, reimbursibility, and access to TPE.
CONCLUSION: Although countrywise differences exist, all share similarities regarding methods, indications, timing, obstacles, and challenges of TPE for neuroimmunological conditions. Regional collaboration will be essential to identify strategies to reduce these barriers to access to TPE in the future.
Fulltext Tryptophan-metabolizing gut microbes regulate adult neurogenesis via the aryl hydrocarbon receptor

Wei GZ, Martin KA, Xing PY, Agrawal R, Whiley L, Wood TK, et al.

Proc Natl Acad Sci U S A, 2021 Jul 06;118(27).
PMID: 34210797 DOI: 10.1073/pnas.2021091118

While modulatory effects of gut microbes on neurological phenotypes have been reported, the mechanisms remain largely unknown. Here, we demonstrate that indole, a tryptophan metabolite produced by tryptophanase-expressing gut microbes, elicits neurogenic effects in the adult mouse hippocampus. Neurogenesis is reduced in germ-free (GF) mice and in GF mice monocolonized with a single-gene tnaA knockout (KO) mutant Escherichia coli unable to produce indole. External administration of systemic indole increases adult neurogenesis in the dentate gyrus in these mouse models and in specific pathogen-free (SPF) control mice. Indole-treated mice display elevated synaptic markers postsynaptic density protein 95 and synaptophysin, suggesting synaptic maturation effects in vivo. By contrast, neurogenesis is not induced by indole in aryl hydrocarbon receptor KO (AhR-/-) mice or in ex vivo neurospheres derived from them. Neural progenitor cells exposed to indole exit the cell cycle, terminally differentiate, and mature into neurons that display longer and more branched neurites. These effects are not observed with kynurenine, another AhR ligand. The indole-AhR-mediated signaling pathway elevated the expression of β-catenin, Neurog2, and VEGF-α genes, thus identifying a molecular pathway connecting gut microbiota composition and their metabolic function to neurogenesis in the adult hippocampus. Our data have implications for the understanding of mechanisms of brain aging and for potential next-generation therapeutic opportunities.
Increased utilization of peritoneal dialysis to cope with mounting demand for renal replacement therapy--perspectives from Asian countries

Li PK, Lui SL, Leung CB, Yu AW, Lee E, Just PM, et al.

Perit Dial Int, 2007 Jun;27 Suppl 2:S59-61.
PMID: 17556331

With the number of end-stage renal disease (ESRD) patients growing, one of the crucial questions facing health care professionals and funding agencies in Asia is whether funding for dialysis will be sufficient to keep up with demand. During the ISPD's 2006 Congress, academic nephrologists and government officials from China, Hong Kong, India, Indonesia, Japan, Macau, Malaysia, Philippines, Singapore, Taiwan, Thailand, and Vietnam participated in a roundtable discussion on dialysis economics in Asia. The focus was policy and health care financing. The roundtable addressed ESRD growth in Asia and how to obtain enough funding to keep up with the growth in patient numbers. Various models were presented: the "peritoneal dialysis (PD) first" policy model, incentive programs, nongovernmental organizations providing PD, and PD reimbursement in a developing economy. This article summarizes the views of the participant nephrologists on how to increase the utilization of PD to improve on clinical and financial management of patients with ESRD.
Mode-locked thulium-bismuth codoped fiber laser using graphene saturable absorber in ring cavity

Zen DI, Saidin N, Damanhuri SS, Harun SW, Ahmad H, Ismail MA, et al.

Appl Opt, 2013 Feb 20;52(6):1226-9.
PMID: 23434993 DOI: 10.1364/AO.52.001226

We demonstrate mode locking of a thulium-bismuth codoped fiber laser (TBFL) operating at 1901.6 nm, using a graphene-based saturable absorber (SA). In this work, a single layer graphene is mechanically exfoliated using the scotch tape method and directly transferred onto the surface of a fiber pigtail to fabricate the SA. The obtained Raman spectrum characteristic indicates that the graphene on the core surface has a single layer. At 1552 nm pump power of 869 mW, the mode-locked TBFL self starts to generate an optical pulse train with a repetition rate of 16.7 MHz and pulse width of 0.37 ps. This is a simple, low-cost, stable, and convenient laser oscillator for applications where eye-safe and low-photon-energy light sources are required, such as sensing and biomedical diagnostics.

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