Poverty related diseases amongst Malaysia's low-income community: a review.

Poverty, as proven by several studies, is a driving force behind poor health and hygiene practices. This review attempts to outline common communicable and non-communicable diseases that disproportionately affect Malaysia's 2.91 million low-income households. The current study also looks into the government's housing and healthcare programmes for this demographic to improve their health and well-being. The initial examination yielded incredibly little research on this marginalised community, with event reporting typically generalised to the Malaysian community as a whole rather than analysing disease incidences based on household income, which would better reflect povertydriven diseases. As a result, there is an acute need for more accurate information on the epidemiology of diseases among the poor in order to address this public health issue and provide conclusions that can drive policy designs.

Single-nucleus RNA sequencing of pre-malignant liver reveals disease-associated hepatocyte state with HCC prognostic potential.

Current approaches to staging chronic liver diseases have limited utility for predicting liver cancer risk. Here, we employed single-nucleus RNA sequencing (snRNA-seq) to characterize the cellular microenvironment of healthy and pre-malignant livers using two distinct mouse models. Downstream analyses unraveled a previously uncharacterized disease-associated hepatocyte (daHep) transcriptional state. These cells were absent in healthy livers but increasingly prevalent as chronic liver disease progressed. Copy number variation (CNV) analysis of microdissected tissue demonstrated that daHep-enriched regions are riddled with structural variants, suggesting these cells represent a pre-malignant intermediary. Integrated analysis of three recent human snRNA-seq datasets confirmed the presence of a similar phenotype in human chronic liver disease and further supported its enhanced mutational burden. Importantly, we show that high daHep levels precede carcinogenesis and predict a higher risk of hepatocellular carcinoma development. These findings may change the way chronic liver disease patients are staged, surveilled, and risk stratified.

TWEAK/Fn14 Signalling Regulates the Tissue Microenvironment in Chronic Pancreatitis.

Chronic pancreatitis increases the risk of developing pancreatic cancer through the upregulation of pathways favouring proliferation, fibrosis, and sustained inflammation. We established in previous studies that the ligand tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) signals through its cognate receptor fibroblast growth factor-inducible 14 (Fn14) to regulate these underlying cellular processes in the chronic liver injury niche. However, the role of the TWEAK/Fn14 signalling pathway in pancreatic disease is entirely unknown. An analysis of publicly available datasets demonstrated that the TWEAK receptor Fn14 is upregulated in pancreatitis and pancreatic adenocarcinoma, with single cell RNA sequencing revealing pancreatic ductal cells as the main Fn14 producers. We then used choline-deficient, ethionine-supplemented (CDE) diet feeding of wildtype C57BL/6J and Fn14 knockout littermates to (a) confirm CDE treatment as a suitable model of chronic pancreatitis and (b) to investigate the role of the TWEAK/Fn14 signalling pathway in pancreatic ductal proliferation, as well as fibrotic and inflammatory cell dynamics. Our time course data obtained at three days, three months, and six months of CDE treatment reveal that a lack of TWEAK/Fn14 signalling significantly inhibits the establishment and progression of the tissue microenvironment in CDE-induced chronic pancreatitis, thus proposing the TWEAK/Fn14 pathway as a novel therapeutic target.

Poverty related diseases amongst Malaysia’s low-income community: a review

@#Poverty, as proven by several studies, is a driving force behind poor health and hygiene practices. This review attempts to outline common communicable and non-communicable diseases that disproportionately affect Malaysia’s 2.91 million low-income households. The current study also looks into the government’s housing and healthcare programmes for this demographic to improve their health and well-being. The initial examination yielded incredibly little research on this marginalised community, with event reporting typically generalised to the Malaysian community as a whole rather than analysing disease incidences based on household income, which would better reflect povertydriven diseases. As a result, there is an acute need for more accurate information on the epidemiology of diseases among the poor in order to address this public health issue and provide conclusions that can drive policy designs.

Association between fatty acids and coronary heart disease: A scoping review.

INTRODUCTION: High intakes of total fat are long known as a risk factor for coronary heart disease (CHD), but the association between fatty acids and CHD remains unclear. This scoping review aims to collate and analyze the association between types of fatty acid and risk of CHD. MATERIALS AND METHODS: This review uses the methodological framework of Arksey and O'Malley. A total of 19 studies were selected from 9456 studies screened from the electronic databases. RESULTS: Majority of the studies reported no association between saturated fat (SFA) and monounsaturated fat (MUFA) with CHD. Meanwhile, seven out of 12 studies reported inverse association between polyunsaturated fat (PUFA) and risk of CHD whilst 67% of the studies found that trans-fat intake was positively associated with CHD risk. CONCLUSIONS: This review finds that all the types of dietary fat have different effects on the risk of CHD. Nevertheless, intakes of healthy fat such as MUFA and PUFA in controlled amounts are expected to reduce CHD risk. In addition, the divergence of findings found between studies might be due to the methodological inconsistencies. More robust research is needed to determine the actual dietary determinants of CHD as it will provide important information for future development of dietary intervention.

Influence of various Cu/Fe ratios on the surface properties of green synthesized Cu-Fe-BTC and it`s relation to methylene blue adsorption.

The incorporation of different percentages of Fe2+ into copper benzene-1,3,5-tricarboxylate (CuBTC) was successfully carried out at room-temperature synthesis with water as the only solvent. The XRD and XPS analysis shows that the Fe2+ were substituted into the paddlewheel structure. The incorporation of 18% Fe2+ into CuBTC can increase the surface area and porosity of the framework. The BET surface area of Cu82Fe18BTC (1240 m2/g) was significantly higher than CuBTC (708 m2/g). Further increase in the Fe2+ percentage will reduce the surface area of the compound. The presence of Fe2+ in the framework successfully disturbs the pore formation and widens the pore size on the surface of these compounds. This as well as the pHpzc, which is related to the surface acidity of the resulting bimetallic organic framework (BMOF), play an important role in the adsorption process. Cu53Fe47BTC with an adsorption capacity of 94.42 mg/g shows approximately 6 times greater adsorption capacity against MB compared to CuBTC. This shows that by utilizing a different ratio of Cu and a second metal, it is possible to effectively design the surface morphology of BMOF for specific applications.

Previous liver regeneration induces fibro-protective mechanisms during thioacetamide-induced chronic liver injury.

Chronic liver injury is characterised by continuous or repeated epithelial cell loss and inflammation. Hepatic wound healing involves matrix deposition through activated hepatic stellate cells (HSCs) and the expansion of closely associated Ductular Reactions and liver progenitor cells (LPCs), which are thought to give rise to new epithelial cells. In this study, we used the murine thioacetamide (TAA) model to reliably mimic these injury and regeneration dynamics and assess the impact of a recovery phase on subsequent liver injury and fibrosis. Age-matched naïve or 6-week TAA-treated/4-week recovered mice (C57BL/6 J, n = 5-9) were administered TAA for six weeks (C57BL/6 J, n = 5-9). Sera and liver tissues were harvested at key time points to assess liver injury biochemically, by real-time PCR for fibrotic mediators, Sirius Red staining and hydroxyproline assessment for collagen deposition as well as immunofluorescence for inflammatory, HSC and LPC markers. In addition, primary HSCs and the HSC cell line LX-2 were co-cultured with the well-characterised LPC line BMOL and analysed for potential changes in expression of fibrogenic mediators. Our data demonstrate that recovery from a previous TAA insult, with LPCs still present on day 0 of the second treatment, led to a reduced TAA-induced disease progression with less severe fibrosis than in naïve TAA-treated animals. Importantly, primary activated HSCs significantly reduced pro-fibrogenic gene expression when co-cultured with LPCs. Taken together, previous TAA injury established a fibro-protective molecular and cellular microenvironment. Our proof-of principle HSC/LPC co-culture data demonstrate that LPCs communicate with HSCs to regulate fibrogenesis, highlighting a key role for LPCs as regulatory cells during chronic liver disease.

Comparative study of chemically synthesized and low temperature bio-inspired Musa acuminata peel extract mediated zinc oxide nanoparticles for enhanced visible-photocatalytic degradation of organic contaminants in wastewater treatment.

Zinc oxide (ZnO) photocatalysts were successfully synthesized via chemical and green, environmentally-benign methods. The work highlights the valorization of banana peel (BP) waste extract as the reducing and capping agents to produce pure, low temperature, highly crystalline, and effective ZnO nanoparticles with superior photocatalytic activities for the removal of hazardous Basic Blue 9 (BB9), crystal violet (CV), and cresol red (CR) dyes in comparison to chemically synthesized ZnO. Their formation and morphologies were verified by various optical spectroscopic and electron microscopic techniques. XRD results revealed that the biosynthesized ZnO exhibited 15.3 nm crystallite size when determined by Scherrer equation, which was smaller than the chemically synthesized ZnO. The FTIR spectra confirmed the presence of biomolecules in the green-mediated catalyst. EDX and XPS analyses verified the purity and chemical composition of ZnO. Nitrogen sorption analysis affirmed the high surface area of bio-inspired ZnO. Maximum removal efficiencies were achieved with 30 mg green ZnO catalyst, 2.0 × 10-5 M BB9 solution, alkaline pH 12, and irradiation time 90 min. Green-mediated ZnO showed superior photodegradation efficiency and reusability than chemically synthesized ZnO. Therefore, this economical, environment-friendly photocatalyst is applicable for the removal of organic contaminants in wastewater treatment under visible light irradiation.

The acetone crude extract of Quercus infectoria (Olivier) galls alters pH of the digestive vacuole of the malaria parasite, Plasmodium falciparum

@#The reduced efficacy of the mainstay antimalarial drugs due to the widespread of drugresistant Plasmodium falciparum has necessitated efforts to discover new antimalarial drugs with new targets. Quercus infectoria (Olivier) has long been used to treat various ailments including fever. The acetone extract of the plant galls has recently been reported to have a promising antimalarial activity in vitro. This study was aimed to determine the effect of the Q. infectoria gall acetone crude extract on pH of the digestive vacuole of Plasmodium falciparum. A ratiometric fluorescent probe, fluorescein isothiocyanate-dextran (FITC-dextran) was used to facilitate a quantitative measurement of the digestive vacuole pH by flow cytometry. Mid trophozoite stage malaria parasites grown in resealed erythrocytes containing FITC-dextran were treated with different concentrations of the acetone extract based on the 50% inhibitory concentration (IC50). Saponin-permeabilized parasites were analyzed to obtain the ratio of green/yellow fluorescence intensity (Rgy) plotted as a function of pH in a pH calibration curve of FITC-dextran. Based on the pH calibration curve, the pH of the digestive vacuole of the acetone extract-treated parasites was significantly altered (pH values ranged from 6.35- 6.71) in a concentration-dependent manner compared to the untreated parasites (pH = 5.32) (p < 0.001). This study provides a valuable insight into the potential of the Q. infectoria galls as a promising antimalarial candidate with a novel mechanism of action.

Sub-lethal concentrations of artemisinin alter pH of the digestive vacuole of the malaria parasite, Plasmodium falciparum.

An appropriate pH maintenance within a membrane-enclosed organelle is vital for the occurrence of biological processes. Artemisinin (ART), a potent antimalarial drug has been reported to target the digestive vacuole (DV) of Plasmodium falciparum, which might alter the pH of the organelle, thereby impairing the hemoglobin degradation and subsequent heme detoxification. Hence, a flow cytometry-based technique using fluorescein isothiocyanate-dextran (FITC-dextran) as a ratiometric pH probe was employed to measure the pH of the DV of the malaria parasite treated with ART. Based on the pH calibration curve generated, the steady-state pH of the acidic DV of the non-treated parasites was 5.42 ± 0.11, indicating that FITC-dextran is suitable for detection of physiological pH of the organelle. The alteration of the DV pH occurred when the parasites were treated with ART even at the sub-lethal concentrations (15 and 30 nM) used. The similar effect was shown by the parasites treated with a standard proton pump inhibitor, concanamycin A. This suggests that ART might have altered the DV pH at lower levels than the level needed to kill the parasite. This study has important implications in designing new ART treatment strategies and in generating new endoperoxide-based antimalarial drugs pertaining to the interruption of the pH regulation of the malaria parasite's DV.

Sub-lethal concentrations of artemisinin alter pH of the digestive vacuole of the malaria parasite, Plasmodium falciparum

@#An appropriate pH maintenance within a membrane-enclosed organelle is vital for the occurrence of biological processes. Artemisinin (ART), a potent antimalarial drug has been reported to target the digestive vacuole (DV) of Plasmodium falciparum, which might alter the pH of the organelle, thereby impairing the hemoglobin degradation and subsequent heme detoxification. Hence, a flow cytometry-based technique using fluorescein isothiocyanate-dextran (FITC-dextran) as a ratiometric pH probe was employed to measure the pH of the DV of the malaria parasite treated with ART. Based on the pH calibration curve generated, the steady-state pH of the acidic DV of the non-treated parasites was 5.42 ± 0.11, indicating that FITC-dextran is suitable for detection of physiological pH of the organelle. The alteration of the DV pH occurred when the parasites were treated with ART even at the sub-lethal concentrations (15 and 30 nM) used. The similar effect was shown by the parasites treated with a standard proton pump inhibitor, concanamycin A. This suggests that ART might have altered the DV pH at lower levels than the level needed to kill the parasite. This study has important implications in designing new ART treatment strategies and in generating new endoperoxide-based antimalarial drugs pertaining to the interruption of the pH regulation of the malaria parasite’s DV.

Effects of prolonged isolation in a confined space on status of oxidative stress and prothrombogenesis: In preparation for possible future manned space expedition to Mars.

INTRODUCTION: Apart from inflammation and endothelial dysfunction, other key components in the development of atherogenesis include prothrombogenesis and oxidative stress. The effects of long-term confinement and isolation, exposure to radiation and different gravity forces during space travel could potentially increase the long-term risk of atherosclerosis. To the best of our knowledge, this is the first study determining the status of prothrombogenesis and oxidative stress in six cosmonauts subjected to the longest duration of confined isolation period of 520 days in preparation for prospective undetermined manned space travel to Mars. MATERIALS AND METHODS: This collaborative research between the National Space Agency (ANGKASA), Universiti Teknologi MARA, Malaysia and Institute of Biomedical Problems (IBMP), Russia was conducted at the Russian Academy of Sciences IBMP, Moscow, Russia. Six multi-national cosmonauts were assigned to live in a ground-based confined module for 520 days. Standard exercise and diet regime were instituted throughout the isolation phase. Six age, ethnic and gender-matched healthy, free-living ground controls were recruited in parallel. Serial serum and whole blood were analysed for biomarkers of prothrombogenesis [plasminogen activator inhibitor-1 (PAI-1) and homocysteine] and oxidative stress [oxidised low-density lipoprotein (ox-LDL) and malondialdehyde (MDA)]. RESULTS: There were significantly lower concentrations of PAI-1 and homocysteine in cosmonauts during confinement compared to the controls. There were no significant differences seen in the concentrations of biomarkers of oxidative stress during confinement but there was a significant percentage change increment for serum MDA in cosmonauts. CONCLUSION: Long-term confinement decreased the risk of prothrombogenesis and this could be attributed to the exercise and diet regime which includes omega-3 fatty acids supplementation given to the crew members during their confinement period. However, oxidative damage could not be excluded and may be attributed to the influence of psychological stress during this prolonged confinement.

Influence of Mg/CTAB ratio on the structural, physicochemical properties and catalytic activity of amorphous mesoporous magnesium silicate catalysts.

This study investigated the physicochemical and catalytic properties of mesoporous magnesium silicate catalysts prepared at various Mg/CTAB ratios (0.25, 0.50, 0.75 and 1.00). The XPS analysis detected a mixture of enstatite and magnesium carbonate species when the Mg/CTAB ratio was 0.25, and 0.50. A mixture of forsterite and magnesium carbonate species were detected when the Mg/CTAB ratio was 0.75 whereas for the Mg/CTAB ratio of 1.00, enstatite and magnesium metasilicate species were detected. A catalyst with the Mg/CTAB ratio of 1.00 demonstrated the highest catalytic activity in the oxidation of styrene. The styrene conversion rate was 59.0%, with 69.2% styrene oxide (StO) selectivity. The H2O2 molecules were activated regio-specifically by the magnesium species to prevent rapid self-decomposition while promoting selective interaction with styrene. All the parameters that influence the styrene conversion and product selectivity were evaluated using analysis of variance (ANOVA) with Tukey's test. The ANOVA analysis showed that the reaction time (h), Mg/CTAB ratio, styrene/H2O2 ratio, catalyst loading (mg) and temperature (°C) affect styrene conversion and product selectivity (StO) significantly (p < 0.05). The oxidation of styrene was well fitted to the pseudo-first-order model. The activation energy, E a of the catalysed styrene epoxidation reaction was calculated to be 27.7 kJmol-1. The catalyst can be reused several times without any significant loss in its activity and selectivity. The results from this study will be useful in designing and developing low cost, high activity catalysts from alkaline earth metals.

Primary follicular lymphoma of the pancreas: A rare tumour mimicking pancreatic carcinoma.

INTRODUCTION: Primary pancreatic lymphomas are extremely rare. Clinically, primary pancreatic lymphoma mimics symptoms of carcinoma of the pancreatic head. Clinical and radiological features may overlap with other pancreatic conditions such as carcinoma, neuroendocrine tumours and autoimmune pancreatitis. CASE REPORT: We report a case of a 75-year-old man who presented with symptoms of obstructive jaundice. Ultrasonography and computed tomography (CT) showed an ill-defined lobulated soft tissue lesion at the head/uncinate process of the pancreas measuring 4.5 x 4.9 x 5.8 cm. The patient underwent pancreaticoduodenectomy for suspected pancreatic head/uncinate process carcinoma. Histopathology and immunohistochemical assessment of the pancreatic lesion established the diagnosis of a low-grade follicular lymphoma. DISCUSSION: Clinical and imaging features of primary pancreatic lymphoma may often overlap with pancreatic carcinoma. There is a value of obtaining preoperative tissue diagnosis such as tissue biopsy and fine needle aspiration (FNA) cytology with or without flow cytometry to make an accurate diagnosis of non-Hodgkin lymphoma and alleviate the need of more radical surgery in pancreatic lymphoma.

Sialic acid catabolism by N-acetylneuraminate pyruvate lyase is essential for muscle function.

Sialic acids are important components of glycoproteins and glycolipids essential for cellular communication, infection, and metastasis. The importance of sialic acid biosynthesis in human physiology is well illustrated by the severe metabolic disorders in this pathway. However, the biological role of sialic acid catabolism in humans remains unclear. Here, we present evidence that sialic acid catabolism is important for heart and skeletal muscle function and development in humans and zebrafish. In two siblings, presenting with sialuria, exercise intolerance/muscle wasting, and cardiac symptoms in the brother, compound heterozygous mutations [chr1:182775324C>T (c.187C>T; p.Arg63Cys) and chr1:182772897A>G (c.133A>G; p.Asn45Asp)] were found in the N-acetylneuraminate pyruvate lyase gene (NPL). In vitro, NPL activity and sialic acid catabolism were affected, with a cell-type-specific reduction of N-acetyl mannosamine (ManNAc). A knockdown of NPL in zebrafish resulted in severe skeletal myopathy and cardiac edema, mimicking the human phenotype. The phenotype was rescued by expression of wild-type human NPL but not by the p.Arg63Cys or p.Asn45Asp mutants. Importantly, the myopathy phenotype in zebrafish embryos was rescued by treatment with the catabolic products of NPL: N-acetyl glucosamine (GlcNAc) and ManNAc; the latter also rescuing the cardiac phenotype. In conclusion, we provide the first report to our knowledge of a human defect in sialic acid catabolism, which implicates an important role of the sialic acid catabolic pathway in mammalian muscle physiology, and suggests opportunities for monosaccharide replacement therapy in human patients.

PGM1 deficiency: Substrate use during exercise and effect of treatment with galactose.

Mutations in PGM1 (phosphoglucomutase 1) cause Glycogen Storage Disease type XIV, which is also a congenital disorder of protein N-glycosylation. It presents throughout life as myopathy with additional systemic symptoms. We report the effect of oral galactose treatment during five months in a patient with biochemically and genetically confirmed PGM1 deficiency. The 12-minute-walking distance increased by 225 m (65%) and transferrin glycosylation was restored to near-normal levels. The exercise assessments showed a severe exercise intolerance due to a block in skeletal muscle glycogenolytic capacity and that galactose treatment tended to normalize skeletal muscle substrate use from fat to carbohydrates during exercise.

Sensitivity of artemisinin towards different stages of development of the malaria parasite, Plasmodium falciparum.

Artemisinin-based combination therapies (ACTs) serve as a first line of defence against malaria infection. The success of malaria treatment depends closely on the timing of action and the target of this drug. The early inhibitory effect of artemisinin associated with the integrity and pH of the digestive vacuole (DV) of the malaria parasite was investigated. Using the malaria SYBR Green I based-fluorescence assay, artemisinin showed activity against the chloroquine-sensitive strains of 3D7 and D10 higher than that against the chloroquineresistant strain of Dd2. A significant inhibition of parasite growth with marked changes in parasite morphology was seen following treatment with 0.2-60 times the IC50 value of artemisinin for a period of 4 hours was observed at mid ring, late trophozoite and late schizont stages. The drug had no obvious alterations in the distribution of a pH-sensitive probe, LysoSensor Blue labelling of the DV even at the highest concentration examined. Using a ratiometric pH probe, SNARF-1-dextran, the DV pH of treated trophozoites remained acidic, suggesting the loss of DV pH is probably not the mode of action of artemisinin that causes parasite killing.

Draft Genome Sequence of Erwinia mallotivora BT-MARDI, Causative Agent of Papaya Dieback Disease.

Erwinia mallotivora was isolated from papaya trees infected with dieback disease, which were planted at the Malaysian Agricultural Research and Development Institute (MARDI), Malaysia. Here, we report a draft genome sequence of E. mallotivora BT-MARDI, which offers an important source of information for understanding pathogen and host interaction during papaya dieback development.

Greater occipital nerve blocks in chronic cluster headache: a prospective open-label study.

BACKGROUND AND PURPOSE: Greater occipital nerve blockade (GONB) has been shown to be effective in episodic cluster headache. However, its use in chronic cluster headache (CCH) is less certain. The study aims to prospectively assess the efficacy and consistency of response to GONB in a large series of CCH patients. METHODS: CCH patients who had a unilateral GONB and were referred to the National Hospital for Neurology and Neurosurgery were studied prospectively. Headache characteristics were collected using headache diaries. Responders were considered to be patients with a complete or partial response lasting at least 7 days. In a subgroup of responders the outcomes of serial GONB performed at 3-monthly intervals were also analysed. RESULTS: Eighty-three CCH patients were studied. After the first GONB, a positive response was observed in 47 (57%) patients: 35 (42%) were rendered pain free, 12 (15%) had a partial benefit and one patient obtained <50% improvement. The duration of a positive response lasted a median of 21 days (range 7-504 days). There was a transient worsening of condition in 6% of patients. The overall rate and average duration of response remained consistent after the second [n = 37; 31 responders (84%); median duration 21 days], third [n = 28; 20 responders (71%); median duration 25 days] and fourth [n = 14; 10 responders (71%); median duration 23 days] injections. CONCLUSION: GONB seems to be an efficacious treatment with reproducible effects in CCH patients. Performed three monthly, GONB may have a useful role in the management of CCH.

Optimization of a greener method for removal phenol species by cloud point extraction and spectrophotometry.

A greener method based on cloud point extraction was developed for removing phenol species including 2,4-dichlorophenol (2,4-DCP), 2,4,6-trichlorophenol (2,4,6-TCP) and 4-nitrophenol (4-NP) in water samples by using the UV-Vis spectrophotometric method. The non-ionic surfactant DC193C was chosen as an extraction solvent due to its low water content in a surfactant rich phase and it is well-known as an environmentally-friendly solvent. The parameters affecting the extraction efficiency such as pH, temperature and incubation time, concentration of surfactant and salt, amount of surfactant and water content were evaluated and optimized. The proposed method was successfully applied for removing phenol species in real water samples.