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Harm reduction in Asia: a successful response to hidden epidemics. The Asian Harm Reduction Network

Crofts N, Costigan G, Narayanan P, Gray J, Dorabjee J, Langkham B, et al.

AIDS, 1998;12 Suppl B:S109-15.
PMID: 9679636
Kimura's disease: a report of three cases with a brief review of literature

Madhavan M, Othman NH, Singh MS, Indudharan R, Sharma HS, Shamsuddin AR

Acta Otorhinolaryngol Ital, 2000 Aug;20(4):284-9.
PMID: 11234448

Kimura's disease (KD) is an uncommon chronic inflammatory condition of unknown aetiology involving subcutaneous tissue, presenting as a tumor like lesion with a predilection for the head and neck region. Clinically it is often confused with parotid tumor with lymph node metastasis. It is difficult to diagnose before tissue biopsy. Fine needle aspiration cytology has only limited value. Unless the pathologists are aware of this entity, it might be misdiagnosed. Surgery, radiotherapy and steroid therapy have been tried but none is proved best and recurrence is common. Three cases of KD seen in our hospital and the problems encountered in them are presented.
Reye and Reye-like syndromes: results of a pilot study in Peninsular Malaya, 1986

Sinniah D, Sinniah R, Yap YF, Singh M, George R, Lim NL, et al.

Acta Paediatr Jpn, 1990 Aug;32(4):385-90.
PMID: 2288220

A pilot epidemiologic study of all cases of Reye and Reye-like syndromes was undertaken at 8 representative major hospitals in Peninsular Malaya from January 1st to December 31st 1986. The cases were classified as definitive Reye's syndrome, clinical Reye's syndrome and encephalo-hepatopathies. Less than 50% of cases reviewed fulfilled the National Center for Disease Control criteria for clinical Reye's syndrome. Causes of Reye-like syndromes/encephalo-hepatopathies included fulminant hepatitis, Japanese B encephalitis, dengue, septicaemia, and complex febrile fits. It was not possible to differentiate clinical Reye's syndrome from the other encephalo-hepatopathies by either the clinical features (except for jaundice) or biochemical parameters. Liver biopsy is necessary for a definitive diagnosis of Reye's syndrome in Malaysia, because of the high prevalence of Reye-like diseases. The mortality rate in the 2 groups of patients is similar. Ingestion of salicylates was not found to be significantly associated with Reye and Reye-like syndromes in this study.
Fulltext Isolation, identification and quantification of differentially expressed proteins from cancerous and normal breast tissues

Othman MI, Majid MI, Singh M, Man CN, Lay-Harn G

Ann. Clin. Biochem., 2008 May;45(Pt 3):299-306.
PMID: 18482919 DOI: 10.1258/acb.2007.007104

Infiltrating ductal carcinoma (IDCA) is the most common type of breast cancer accounting for 85% of all invasive breast cancers.
Pharmaceutical Aspects of Green Synthesized Silver Nanoparticles: A Boon to Cancer Treatment

Mishra V, Nayak P, Singh M, Tambuwala MM, Aljabali AA, Chellappan DK, et al.

Anticancer Agents Med Chem, 2021;21(12):1490-1509.
PMID: 32951580 DOI: 10.2174/1871520620666200918111024

BACKGROUND: Silver nanoparticles (AgNPs) are among the most investigated nanostructures in recent years, which exhibit more challenging and promising qualities in different biomedical applications. The AgNPs synthesized by the green approach provide potential healthcare benefits over chemical approaches, including improvement of tissue restoration, drug delivery, diagnosis, being environmentally friendly, and a boon to cancer treatment.
OBJECTIVE: In the current scenario, the development of safe and effective drug delivery systems is the utmost concern of formulation development scientists as well as clinicians.
METHODS: Google, Web of Science, and PubMed portals have been searched for potentially relevant literature to get the latest developments and updated information related to different aspects of green synthesized AgNPs along with their biomedical applications, especially in the treatment of different types of cancers.
RESULTS: The present review highlights the latest published research regarding the different green approaches for the synthesis of AgNPs, their characterization techniques as well as various biomedical applications, particularly in cancer treatment. In this context, environment-friendly AgNPs are proving themselves as better candidates in terms of size, drug loading and release efficiency, targeting efficiency, minimal drug-associated side effects, pharmacokinetic profiling, and biocompatibility issues.
CONCLUSION: With continuous efforts by multidisciplinary team approaches, nanotechnology-based AgNPs will shed new light on diagnostics and therapeutics in various disease treatments. However, the toxicity issues of AgNPs need greater attention as unanticipated toxic effects must be ruled out for their diversified applications.
Analysis of differentially expressed proteins in colorectal cancer using hydroxyapatite column and SDS-PAGE

Lim SR, Gooi BH, Singh M, Gam LH

Appl Biochem Biotechnol, 2011 Nov;165(5-6):1211-24.
PMID: 21863284 DOI: 10.1007/s12010-011-9339-3

Limitation on two dimensional (2D) gel electrophoresis technique causes some proteins to be under presented, especially the extreme acidic, basic, or membrane proteins. To overcome the limitation of 2D electrophoresis, an analysis method was developed for identification of differentially expressed proteins in normal and cancerous colonic tissues using self-pack hydroxyapatite (HA) column. Normal and cancerous colon tissues were homogenized and proteins were extracted using sodium phosphate buffer at pH 6.8. Protein concentration was determined and the proteins were loaded unto the HA column. HA column reduced the complexity of proteins mixture by fractionating the proteins according to their ionic strength. Further protein separation was accomplished by a simple and cost effective sodium dodecyl sulfate-polyacrylamide gel electrophoresis method. The protein bands were subjected to in-gel digestion and protein analysis was performed using electrospray ionization (ESI) ion trap mass spectrometer. There were 17 upregulated proteins and seven downregulated proteins detected with significant differential expression. Some of these proteins were low abundant proteins or proteins with extreme pH that were usually under presented in 2D gel analysis. We have identified brain mitochondrial carrier protein 1, T-cell surface glycoprotein CD1a, SOSS complex subunit B2, and Protein Jade 1 which were previously not detected in 2D gel analysis method.
Fulltext Rationale and protocol paper for the Asia Pacific Network for inherited eye diseases

Wong WM, Tham YC, Simunovic MP, Chen FK, Luu CD, Chen H, et al.

Asia Pac J Ophthalmol (Phila), 2024;13(1):100030.
PMID: 38233300 DOI: 10.1016/j.apjo.2023.100030

PURPOSE: There are major gaps in our knowledge of hereditary ocular conditions in the Asia-Pacific population, which comprises approximately 60% of the world's population. Therefore, a concerted regional effort is urgently needed to close this critical knowledge gap and apply precision medicine technology to improve the quality of lives of these patients in the Asia-Pacific region.
DESIGN: Multi-national, multi-center collaborative network.
METHODS: The Research Standing Committee of the Asia-Pacific Academy of Ophthalmology and the Asia-Pacific Society of Eye Genetics fostered this research collaboration, which brings together renowned institutions and experts for inherited eye diseases in the Asia-Pacific region. The immediate priority of the network will be inherited retinal diseases (IRDs), where there is a lack of detailed characterization of these conditions and in the number of established registries.
RESULTS: The network comprises 55 members from 35 centers, spanning 12 countries and regions, including Australia, China, India, Indonesia, Japan, South Korea, Malaysia, Nepal, Philippines, Singapore, Taiwan, and Thailand. The steering committee comprises ophthalmologists with experience in consortia for eye diseases in the Asia-Pacific region, leading ophthalmologists and vision scientists in the field of IRDs internationally, and ophthalmic geneticists.
CONCLUSIONS: The Asia Pacific Inherited Eye Disease (APIED) network aims to (1) improve genotyping capabilities and expertise to increase early and accurate genetic diagnosis of IRDs, (2) harmonise deep phenotyping practices and utilization of ontological terms, and (3) establish high-quality, multi-user, federated disease registries that will facilitate patient care, genetic counseling, and research of IRDs regionally and internationally.
Specimen shrinkage and its influence on margin assessment in breast cancer

Yeap BH, Muniandy S, Lee SK, Sabaratnam S, Singh M

Asian J Surg, 2007 Jul;30(3):183-7.
PMID: 17638637

The determination of tumour-free margin in breast cancer is crucial in deciding subsequent patient management. To exemplify the phenomenon of margin contraction during specimen preparation for histopathological analysis, we quantified the shrinkage of breast specimens as a result of formalin fixation.
Fulltext Early results of a rotation flap to treat chronic anal fissures

Singh M, Sharma A, Duthie G, Balasingh D, Kandasamy P

Asian J Surg, 2005 Jul;28(3):189-91.
PMID: 16024313

Treatment of anal fissures has changed dramatically in the past decade. This is primarily due to a better understanding of its pathophysiology and the implications of the various available options. Only a few anal fissures fail to respond to medical therapy. Sphincterotomy and anal dilatation have fallen out of favour due to the risk of incontinence. Island flaps have been proposed to address this, but 60-70% of the flap donor sites break down with complications. We propose using a rotation flap to overcome this problem.
Partial superficial parotidectomy for pleomorphic adenoma of the parotid gland

Bhattacharya A, Singh M, Shah A, Varghese LL

BMJ Case Rep, 2021 Jun 14;14(6).
PMID: 34127499 DOI: 10.1136/bcr-2020-238759

Pleomorphic adenoma, otherwise called as benign mixed tumour, is the most common salivary gland tumour which accounts for 60% of all benign salivary gland tumours. The clinical, radiological and histopathological presentations are varied. The tumour occurs in diverse anatomical sites and can consist of epithelial and mesenchymal components. In this case report, the patient reported with an asymptomatic swelling on the face. CT scan with contrast was advised. The clinical, roentgenographic findings and Fine Needle Aspiration Cytology were indicative of pleomorphic adenoma of the parotid gland. Treatment included partial superficial parotidectomy under general anaesthesia using the modified Blair's incision. The facial nerve was not involved. Part of the gland along with the tumour was resected completely superficial to the facial nerve with a margin of normal tissue all around. Histopathologic examination of tissue specimen confirmed the lesion as pleomorphic adenoma. The patient was asymptomatic at 6-month follow-up.
Fulltext Supplementing hand washing with proper use of alcoholic hand rub in a special neonatal care unit in a large academic public health institute at Jabalpur, Madhya Pradesh, India

Singh M, Agrawal A, Sisodia D, Kasar PK, Kaur A, Datta V, et al.

BMJ Open Qual, 2021 11;10(4).
PMID: 34759034 DOI: 10.1136/bmjoq-2020-001131

OBJECTIVE: The purpose was to increase use of alcoholic hand rub (AHR) in specialised newborn care unit (SNCU) to improve hand hygiene in order to reduce neonatal sepsis and mortality at Netaji Subhash Chandra Bose Medical College and Hospital, Jabalpur.
DESIGN: A prospective interventional and observational study.
METHODOLOGY: We formed a quality improvement (QI) team in our SNCU consisting of doctors, nurses, auxiliary staff and parents (a floating member) to improve proper use of AHR. To identify the barriers to the problem, we used fishbone analysis tool. The barriers which were not allowing the health providers to use AHR properly identified were amount of AHR in millilitres to be used per day per baby, how much and when the amount of AHR to be indented from the main store and what is the proper site to place the bottle. We used plan-do-study-act cycles to test and adapt solutions to these problems. Within 5-6 weeks of starting our project, AHR use increased from 44 mL to 92 mL per baby per day and this is sustained around 100 mL per baby per day for over 2 years now.
RESULTS: Significant decrease in neonatal mortality was observed (reduced from median of 41.0 between August 2016 and April 2018 to 24.0 between May 2018 and December 2019). The neonates discharged alive improved from 41.2 to 52.3 as a median percentage value. The percentage of babies who were referred out and went Left Against Medical Advice (LAMA) deceased too.
CONCLUSION: Multiple factors can lead to neonatal deaths, but the important factors are always contextual to facilities. QI methodology provides health workers with the skills to identify the major factors contributing to mortality and develop strategies to deal with them. Improving processes of care can lead to improved hand hygiene and saves lives.
Proteomics of Grade 3 infiltrating ductal carcinoma in Malaysian Chinese breast cancer patients

Othman MI, Majid MI, Singh M, Subathra S, Seng L, Gam LH

Biotechnol Appl Biochem, 2009 Mar;52(Pt 3):209-19.
PMID: 18564057 DOI: 10.1042/BA20070271

Breast cancer is the leading cause of cancer-related mortality and morbidity among women worldwide and IDC (infiltrating ductal carcinoma) is the most common type of invasive breast cancer. The changes in the biological behaviour of cancer tissue can be predicted by measuring the differential protein expression of normal and cancerous tissues. Using a combination of SDS/PAGE and LC (liquid chromatography)-MS/MS (tandem MS), we identified 82 common and differentially expressed proteins from normal and cancerous breast tissues in 20 Malaysian Chinese patients with IDC. These proteins are extracted from the normal and cancerous tissue of patients and therefore represent the actual proteins involved in cancer development. Proteins identified possibly have significant roles in the development of breast cancer in Malaysian Chinese patients in view of their consistent expression in most of the patients, although some of the proteins had not been detected in earlier studies that were mostly carried out in Western countries. This observation suggests that molecular mechanisms leading to breast cancer development in this region may not be identical with those leading to IDC in Western regions.
Combinational effect of angiotensin receptor blocker and folic acid therapy on uric acid and creatinine level in hyperhomocysteinemia-associated hypertension

Singh Y, Samuel VP, Dahiya S, Gupta G, Gillhotra R, Mishra A, et al.

Biotechnol Appl Biochem, 2019 Sep;66(5):715-719.
PMID: 31314127 DOI: 10.1002/bab.1799

Homocysteine [HSCH2 CH2 CH(NH2 )COOH] (Hcy) is a sulfur-containing amino acid of 135.18 Da of molecular weight, generated during conversion of methionine to cysteine. If there is a higher accumulation of Hcy in the blood, that is usually above 15 µmol/L, it leads to a condition referred to as hyperhomocysteinemia. A meta-analysis of observational study suggested an elevated concentration of Hcy in blood, which is termed as the risk factors leading to ischemic heart disease and stroke. Further experimental studies stated that Hcy can lead to an increase in the proliferation of vascular smooth muscle cells and functional impairment of endothelial cells. The analyses confirmed some of the predictors for Hcy presence, such as serum uric acid (UA), systolic blood pressure, and hematocrit. However, angiotensin-converting enzyme inhibitors angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) alone are inadequate for controlling UA and creatinine level, although the addition of folic acid may be beneficial in hypertensive patients who are known to have a high prevalence of elevated Hcy. We hypothesized that combination therapy with an ARB (olmesartan) and folic acid is a promising treatment for lowering the UA and creatinine level in hyperhomocysteinemia-associated hypertension.
Potential hydrophobic protein markers of breast cancer in Malaysian Chinese, Malay and Indian patients

Liang S, Singh M, Gam LH

Cancer Biomark, 2010;8(6):319-30.
PMID: 22072120 DOI: 10.3233/CBM-2011-0221

Breast cancer is a leading cause of worldwide mortality in females. In Malaysia, breast cancer is the most commonly diagnosed cancer in women. Of these, the Chinese had the most number of breast cancer cases, followed by the Indian and the Malay. The most common type of breast cancer is infiltrating ductal carcinoma (IDC). A proteomic approach was used to identify protein profile changes in cancerous tissues compared with the normal tissues, the tissues were collected from patients of three different ethnicities, i.e. Chinese, Malay and Indian. Ten differentially expressed hydrophobic proteins were identified. We had evaluated the potential of these proteins as biomarker for infiltrating ducal carcinoma (IDC) and the ethnic-specific expression of these proteins was also determined. The data showed that peroxiredoxin-2, heat shock protein 60, protein disulfide isomerase and calreticulin may serve as ethnic-related potential markers for either one or combination of Chinese, Malay and Indian cohorts as their expression levels were significantly high in the cancerous tissues compared to the normal tissues in the ethnic group tested.
Publication year=2010-2011
Uncovering the complex role of interferon-gamma in suppressing type 2 immunity to cancer

Bhat AA, Goyal A, Thapa R, Almalki WH, Kazmi I, Alzarea SI, et al.

Cytokine, 2023 Nov;171:156376.
PMID: 37748333 DOI: 10.1016/j.cyto.2023.156376

Cancer involves cells' abnormal growth and ability to invade or metastasize to different body parts. Cancerous cells can divide uncontrollably and spread to other areas through the lymphatic or circulatory systems. Tumors form when malignant cells clump together in an uncontrolled manner. In this context, the cytokine interferon-gamma (IFN-γ) is crucial in regulating immunological responses, particularly malignancy. While IFN-γ is well-known for its potent anti-tumor effects by activating type 1 immunity, recent research has revealed its ability to suppress type 2 immunity, associated with allergy and inflammatory responses. This review aims to elucidate the intricate function of IFN-γ in inhibiting type 2 immune responses to cancer. We explore how IFN-γ influences the development and function of immune cells involved in type 2 immunity, such as mast cells, eosinophils, and T-helper 2 (Th2) cells. Additionally, we investigate the impact of IFN-mediated reduction of type 2 immunity on tumor development, metastasis, and the response to immunotherapeutic interventions. To develop successful cancer immunotherapies, it is crucial to comprehend the complex interplay between type 2 and type 1 immune response and the regulatory role of IFN-γ. This understanding holds tremendous promise for the development of innovative treatment approaches that harness the abilities of both immune response types to combat cancer. However, unraveling the intricate interplay between IFN-γ and type 2 immunity in the tumor microenvironment will be essential for achieving this goal.
Fulltext The PCA and LDA analysis on the differential expression of proteins in breast cancer

Liang S, Singh M, Dharmaraj S, Gam LH

Dis Markers, 2010;29(5):231-42.
PMID: 21206008 DOI: 10.3233/DMA-2010-0753

Breast cancer is a leading cause of mortality in women. In Malaysia, it is the most common cancer to affect women. The most common form of breast cancer is infiltrating ductal carcinoma (IDC). A proteomic approach was undertaken to identify protein profile changes between cancerous and normal breast tissues from 18 patients. Two protein extracts; aqueous soluble and membrane associated protein extracts were studied. Thirty four differentially expressed proteins were identified. The intensities of the proteins were used as variables in PCA and reduced data of six principal components (PC) were subjected to LDA in order to evaluate the potential of these proteins as collective biomarkers for breast cancer. The protein intensities of SEC13-like 1 (isoform b) and calreticulin contributed the most to the first PC while the protein intensities of fibrinogen beta chain precursor and ATP synthase D chain contributed the most to the second PC. Transthyretin precursor and apolipoprotein A-1 precursor contributed the most to the third PC. The results of LDA indicated good classification of samples into normal and cancerous types when the first 6 PCs were used as the variables. The percentage of correct classification was 91.7% for the originally grouped tissue samples and 88.9% for cross-validated samples.
Fulltext The differential expression of aqueous soluble proteins in breast normal and cancerous tissues in relation to ethnicity of the patients; Chinese, Malay and Indian

Liang S, Singh M, Gam LH

Dis Markers, 2010;28(3):149-65.
PMID: 20534901 DOI: 10.3233/DMA-2010-0694

Female breast cancer is one of the leading causes of female mortality worldwide. In Malaysia, breast cancer is the most commonly diagnosed cancer in women. Of the women in Malaysia, the Chinese have the highest number of breast cancer cases, followed by the Indian and the Malay. The most common type of breast cancer is infiltrating ductal carcinoma (IDC). A proteomic approach was applied in this study to identify changes in the protein profile of cancerous tissues compared with normal tissues from 18 patients; 8 Chinese, 6 Malay and 4 Indian were analysed. Twenty-four differentially expressed hydrophilic proteins were identified. We evaluated the potential of these proteins as biomarkers for infiltrating ductal carcinoma based on their ethnic-specific expressions. Three of the upregulated proteins, calreticulin, 14-3-3 protein zeta and 14-3-3 protein eta, were found to be expressed at a significantly higher level in the cancerous breast tissues when compared with the normal tissues in cases of infiltrating ductal carcinoma. The upregulation in expression was particularly dominant in the Malay cohort.
Disruption of the biological activity of protease-activated receptors2/4 in adults rather than children in SARS CoV-2 virus-mediated mortality in COVID-19 infection

Singh Y, Fuloria NK, Fuloria S, Subramaniyan V, Almalki WH, Gupta G, et al.

Drug Dev Res, 2021 Dec;82(8):1075-1078.
PMID: 34469011 DOI: 10.1002/ddr.21874

One of the most remarkable results in 2019 is the reduced prevalence and death of children from coronavirus infection (COVID-19). In 2019, a worldwide pandemic impacted around 0.1 billion individuals, with over 3.5 million mortality reported in the literature. There is minimal knowledge on SARS-CoV-2 infection immunological responses in kids. Studies have been focused mostly on adults and children since the course of pediatric sickness is often short. In adults, severe COVID-19 is related to an excessive inflammatory reaction. Macrophages and monocytes are well known to contribute to this systemic response, although numerous lines are indicative of the importance of neutrophils. An increased number of neutrophils and neutrophil to lymphocyte ratios are early signs of SARS-CoV-2 and a worse prognosis. In this study that it is crucial to monitor PAR2 and PAR4 expression and function (since nursing children have elevated levels) and the inhibiting the normal physiology through the use of anticoagulants may exacerbate the problem in adults. Thus, in COVID-19 infection, we propose the use of antiplatelet (thromboxane A2 inhibitors), if required rather than anticoagulants (FXa and thrombin Inhibitors).
Fulltext Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer

Im SA, Gennari A, Park YH, Kim JH, Jiang ZF, Gupta S, et al.

ESMO Open, 2023 Jun;8(3):101541.
PMID: 37178669 DOI: 10.1016/j.esmoop.2023.101541

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer (MBC) was published in 2021. A special, hybrid guidelines meeting was convened by ESMO and the Korean Society of Medical Oncology (KSMO) in collaboration with nine other Asian national oncology societies in May 2022 in order to adapt the ESMO 2021 guidelines to take into account the differences associated with the treatment of MBC in Asia. These guidelines represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with MBC representing the oncological societies of China (CSCO), India (ISMPO), Indonesia (ISHMO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO). The voting was based on the best available scientific evidence and was independent of drug access or practice restrictions in the different Asian countries. The latter were discussed when appropriate. The aim of these guidelines is to provide guidance for the harmonisation of the management of patients with MBC across the different regions of Asia, drawing from data provided by global and Asian trials whilst at the same time integrating the differences in genetics, demographics and scientific evidence, together with restricted access to certain therapeutic strategies.
Fulltext Therapeutic Potential of Phytoconstituents in Management of Alzheimer's Disease

Singh AK, Rai SN, Maurya A, Mishra G, Awasthi R, Shakya A, et al.

Evid Based Complement Alternat Med, 2021;2021:5578574.
PMID: 34211570 DOI: 10.1155/2021/5578574

Since primitive times, herbs have been extensively used in conventional remedies for boosting cognitive impairment and age-associated memory loss. It is mentioned that medicinal plants have a variety of dynamic components, and they have become a prominent choice for synthetic medications for the care of cognitive and associated disorders. Herbal remedies have played a major role in the progression of medicine, and many advanced drugs have already been developed. Many studies have endorsed practicing herbal remedies with phytoconstituents, for healing Alzheimer's disease (AD). All the information in this article was collated from selected research papers from online scientific databases, such as PubMed, Web of Science, and Scopus. The aim of this article is to convey the potential of herbal remedies for the prospect management of Alzheimer's and related diseases. Herbal remedies may be useful in the discovery and advancement of drugs, thus extending new leads for neurodegenerative diseases such as AD. Nanocarriers play a significant role in delivering herbal medicaments to a specific target. Therefore, many drugs have been described for the management of age-linked complaints such as dementia, AD, and the like. Several phytochemicals are capable of managing AD, but their therapeutic claims are restricted due to their lower solubility and metabolism. These limitations of natural therapeutics can be overcome by using a targeted nanocarrier system. This article will provide the primitive remedies as well as the development of herbal remedies for AD management.

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