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Fulltext Preparation, characterization, and in ovo vaccination of dextran-spermine nanoparticle DNA vaccine coexpressing the fusion and hemagglutinin genes against Newcastle disease

Firouzamandi M, Moeini H, Hosseini SD, Bejo MH, Omar AR, Mehrbod P, et al.

Int J Nanomedicine, 2016;11:259-67.
PMID: 26834470 DOI: 10.2147/IJN.S92225

Plasmid DNA (pDNA)-based vaccines have emerged as effective subunit vaccines against viral and bacterial pathogens. In this study, a DNA vaccine, namely plasmid internal ribosome entry site-HN/F, was applied in ovo against Newcastle disease (ND). Vaccination was carried out using the DNA vaccine alone or as a mixture of the pDNA and dextran-spermine (D-SPM), a nanoparticle used for pDNA delivery. The results showed that in ovo vaccination with 40 μg pDNA/egg alone induced high levels of antibody titer (P<0.05) in specific pathogen-free (SPF) chickens at 3 and 4 weeks postvaccination compared to 2 weeks postvaccination. Hemagglutination inhibition (HI) titer was not significantly different between groups injected with 40 μg pDNA + 64 μg D-SPM and 40 μg pDNA at 4 weeks postvaccination (P>0.05). Higher antibody titer was observed in the group immunized with 40 μg pDNA/egg at 4 weeks postvaccination. The findings also showed that vaccination with 40 μg pDNA/egg alone was able to confer protection against Newcastle disease virus strain NDIBS002 in two out of seven SPF chickens. Although the chickens produced antibody titers 3 weeks after in ovo vaccination, it was not sufficient to provide complete protection to the chickens from lethal viral challenge. In addition, vaccination with pDNA/D-SPM complex did not induce high antibody titer when compared with naked pDNA. Therefore, it was concluded that DNA vaccination with plasmid internal ribosome entry site-HN/F can be suitable for in ovo application against ND, whereas D-SPM is not recommended for in ovo gene delivery.

Matched MeSH terms: Newcastle Disease/genetics; Newcastle Disease/immunology; Newcastle Disease/prevention & control*; Newcastle disease virus/immunology
Fulltext Copy number variation in exportin-4 (XPO4) gene and its association with histological severity of non-alcoholic fatty liver disease

Zain SM, Mohamed Z, Pirmohamed M, Tan HL, Alshawsh MA, Mahadeva S, et al.

Sci Rep, 2015 Aug 21;5:13306.
PMID: 26293807 DOI: 10.1038/srep13306

A recent genome-wide copy number (CNV) scan identified a 13q12.11 duplication in the exportin-4 (XPO4) gene to be associated with non-alcoholic steatohepatitis (NASH). We sought to confirm the finding in a larger cohort and to assess the serum XPO4 pattern in a broad spectrum of non-alcoholic fatty liver disease (NAFLD) cases. We analysed 249 NAFLD patients and 232 matched controls using TaqMan assay and serum XPO4 was measured. Copy number distribution was as follows: copy number neutral (NAFLD: 53.8%, controls: 68.6%), copy number losses (NAFLD: 13.3%, controls: 12.9%), copy number gains (NAFLD: 32.9%, controls: 18.5%). CNV gain was significantly associated with a greater risk of NAFLD (adjusted OR 2.22, 95% CI 1.42-3.46, P = 0.0004) and NASH (adjusted OR 2.33, 95% CI 1.47-3.68, P = 0.0003). Interestingly, subjects carrying extra copy number showed significantly higher serum ALT and triglyceride (P

Matched MeSH terms: Genetic Predisposition to Disease*; Non-alcoholic Fatty Liver Disease/blood; Non-alcoholic Fatty Liver Disease/genetics*; Non-alcoholic Fatty Liver Disease/pathology*
Fulltext HDSS Profile: The South East Asia Community Observatory Health and Demographic Surveillance System (SEACO HDSS)

Partap U, Young EH, Allotey P, Soyiri IN, Jahan N, Komahan K, et al.

Int J Epidemiol, 2017 Oct 01;46(5):1370-1371g.
PMID: 29024948 DOI: 10.1093/ije/dyx113
Matched MeSH terms: Disease*
Fulltext A sudden paediatric death due to hand, foot and mouth disease: the importance of vigilance

Rahimi R, Omar E, Tuan Soh TS, Mohd Nawi SFA, Md Noor S

Malays J Pathol, 2017 Aug;39(2):167-170.
PMID: 28866699 MyJurnal

BACKGROUND: Hand, foot and mouth disease (HFMD) is caused by enteroviruses such as Coxsackie virus A16 (CVA16) and Enterovirus 71 (EV71). The diagnostic hallmarks are oral ulcers and maculo-papular or vesicular rash on the hands and feet. Severe form of this disease can lead to death due to neurological and cardiopulmonary complications. This case report aims to describe a fatal case of HFMD with minimal oral and skin manifestations.
CASE REPORT: A four-year-old girl was brought to a hospital after suddenly becoming unresponsive at home. She had a history of fever and lethargy for three days prior to her demise. The patient, and f ive other children in her neighbourhood had been diagnosed to have HFMD at a local health clinic; the other children had recovered without complications.
RESULTS: Autopsy revealed a few punctate, sub-epidermal vesicles measuring 1 to 2 mm on the palm of her right hand and sole of the right foot, visible only with a magnifying glass. Internal examination revealed prominent nodularity at the oro- and hypopharynxes. The lungs were markedly congested and oedematous. Histopathology of the lung showed marked oedema and haemorrhage with mild pneumonic changes. Oedema with increase in macroglia and astrocytic proliferation were seen in the cerebral tissue, but no lymphocytic infiltration was evident. Enterovirus EV71 was detected by polymerase chain reaction in samples from the lung, cerebrospinal fluid and serum. The cause of death was given as HFMD complicated by pneumonia.
CONCLUSION: Fatal HFMD may have minimal signs. A complete history, careful physical examination and relevant investigations lead to a diagnosis at post mortem examination. Awareness of the subtle signs and rapid deterioration associated with a fatal case of HFMD is a challenge to clinicians who encounter these cases.

Matched MeSH terms: Hand, Foot and Mouth Disease/pathology*
Fulltext What are the direct medical costs of managing type 2 diabetes mellitus in Malaysia?

Feisul IM, Azmi S, Mohd Rizal AM, Zanariah H, Nik Mahir NJ, Fatanah I, et al.

Med J Malaysia, 2017 10;72(5):271-277.
PMID: 29197881 MyJurnal

INTRODUCTION: An economic analysis was performed to estimate the annual cost of diabetes mellitus to Malaysia.

METHODS: We combined published data and clinical pathways to estimate cost of follow-up and complications, then calculated the overall national cost. Costs consisted of diabetes follow-up and complications costs.

RESULTS: Patient follow-up was estimated at RM459 per year. Complications cost were RM42,362 per patient per year for nephropathy, RM4,817 for myocardial infarction, RM5,345 for stroke, RM3,880 for heart failure, RM5,519 for foot amputation, RM479 for retinopathy and RM4,812 for cataract extraction.

CONCLUSION: Overall, we estimated the total cost of diabetes as RM2.04 billion per year for year 2011 (both public and private sector). Of this, RM1.40 billion per year was incurred by the government. Despite some limitations, we believe our study provides insight to the actual cost of diabetes to the country. The high cost to the nation highlights the importance of primary and secondary prevention.

Matched MeSH terms: Disease Management*
Fulltext Can Helminth Infection Reverse Microbial Dysbiosis?

Loke P, Lim YAL

Trends Parasitol, 2015 Nov;31(11):534-535.
PMID: 26604162 DOI: 10.1016/j.pt.2015.10.001

There is growing interest in treating inflammatory conditions with helminth infection. Recently, Loukas and colleagues have reported promising results from using experimental hookworm infection to reduce gluten sensitivity in celiac disease patients. Analysis of microbiota samples from the trial is contributing to our understanding of the complexity underlying helminth–microbiota–host relationships.

Matched MeSH terms: Celiac Disease/etiology*
Fulltext Factors determining dengue outbreak in Malaysia

Ahmad R, Suzilah I, Wan Najdah WMA, Topek O, Mustafakamal I, Lee HL

PLoS One, 2018;13(2):e0193326.
PMID: 29474401 DOI: 10.1371/journal.pone.0193326

A large scale study was conducted to elucidate the true relationship among entomological, epidemiological and environmental factors that contributed to dengue outbreak in Malaysia. Two large areas (Selayang and Bandar Baru Bangi) were selected in this study based on five consecutive years of high dengue cases. Entomological data were collected using ovitraps where the number of larvae was used to reflect Aedes mosquito population size; followed by RT-PCR screening to detect and serotype dengue virus in mosquitoes. Notified cases, date of disease onset, and number and type of the interventions were used as epidemiological endpoint, while rainfall, temperature, relative humidity and air pollution index (API) were indicators for environmental data. The field study was conducted during 81 weeks of data collection. Correlation and Autoregressive Distributed Lag Model were used to determine the relationship. The study showed that, notified cases were indirectly related with the environmental data, but shifted one week, i.e. last 3 weeks positive PCR; last 4 weeks rainfall; last 3 weeks maximum relative humidity; last 3 weeks minimum and maximum temperature; and last 4 weeks air pollution index (API), respectively. Notified cases were also related with next week intervention, while conventional intervention only happened 4 weeks after larvae were found, indicating ample time for dengue transmission. Based on a significant relationship among the three factors (epidemiological, entomological and environmental), estimated Autoregressive Distributed Lag (ADL) model for both locations produced high accuracy 84.9% for Selayang and 84.1% for Bandar Baru Bangi in predicting the actual notified cases. Hence, such model can be used in forestalling dengue outbreak and acts as an early warning system. The existence of relationships among the entomological, epidemiological and environmental factors can be used to build an early warning system for the prediction of dengue outbreak so that preventive interventions can be taken early to avert the outbreaks.

Matched MeSH terms: Disease Outbreaks*
Combating oxidative stress disorders with citrus flavonoid: Naringenin

Zaidun NH, Thent ZC, Latiff AA

Life Sci, 2018 Sep 01;208:111-122.
PMID: 30021118 DOI: 10.1016/j.lfs.2018.07.017

The incidence of diseases related to oxidative stress disorders have been increased dramatically. Alternatives medicine or the active compound extracted from the natural products received great attention among researches at the present era. Naringenin (NG), a common dietary flavanone, found in the citrus fruits such as oranges, bergamots, lemons and grapefruit. It is used in the several oxidative stress disorders as the nutraceutical value of the compound emerges. Functionally, the antioxidants effect of NG is primarily attributed by reducing the free radical like reactive oxygen species (ROS) and enhancing the antioxidants activity such as superoxide dismutase (SOD), catalase, glutathione (GSH) in chronic diseases such as cardiovascular, neurodegenerative, diabetes, pulmonary, cancer and nephropathy. The present review article summarised the antioxidant property of NG and its molecular mechanism towards such diseases. Pubmed, Science Direct, Scopus, Web of Science and Google scholar were searched using the terms 'naringenin', 'oxidative stress disorders', 'naringenin and cardiovascular diseases', 'naringenin and diabetes mellitus', 'naringenin and neurodegenerative diseases', 'naringenin and pulmonary diseases', 'naringenin and cancer' and 'naringenin and nephropathy'. There has been special attention on evaluating anti-oxidative effect of NG on neurodegenerative diseases. Although some mechanisms of action remain vague, the current review highlighted the potential use of NG as a oxidative stress reliever which can be used as next prophylaxis compound in the treatment of the various oxidative stress disorders.

Matched MeSH terms: Chronic Disease/drug therapy*
Fulltext Isolation and molecular detection of Newcastle Disease virus from an imported meat sample

Leow, B.L., Syamsiah, A.S., Ong, G.H., Faizul, F.M.Y., Muhammad, R.S., Basirah, M.A., et al.

Jurnal Veterinar Malaysia, 2016;28(2):17-20.
MyJurnal

Infected poultry meat plays an important role in the spread of Newcastle Disease (ND). In this study, an imported meat product was found to be positive for ND by both virus isolation and molecular characterization. Analysis of the deduced amino acid sequences of the F protein cleavage site showed that the isolate was virulent as indicated by the sequence 112RRQKR116 for the Cterminus of the F2 protein and phenylanine (F) at the N-terminus of the F1 protein, residue 117. Basic Local Alignment Search Tool (BLAST) analysis showed the isolate was 98% identical with China Hebei ND strain. Though the regulations for the importation of poultry meat for human consumption into Malaysia are strict, the possibility of the persistence of ND virus in imported meat is prevalent. Strict enforcement of importing regulations and screening the disease in imported poultry meat is important to ensure food safety and prevent introducing ND strain fInfected poultry meat plays an important role in the spread of Newcastle Disease (ND). In this study, an imported meat product was found to be positive for ND by both virus isolation and molecular characterization. Analysis of the deduced amino acid sequences of the F protein cleavage site showed that the isolate was virulent as indicated by the sequence 112RRQKR116 for the Cterminus of the F2 protein and phenylanine (F) at the N-terminus of the F1 protein, residue 117. Basic Local Alignment Search Tool (BLAST) analysis showed the isolate was 98% identical with China Hebei ND strain. Though the regulations for the importation of poultry meat for human consumption into Malaysia are strict, the possibility of the persistence of ND virus in imported meat is prevalent. Strict enforcement of importing regulations and screening the disease in imported poultry meat is important to ensure food safety and prevent introducing ND strain from other countries into Malaysiarom other countries into Malaysia.

Matched MeSH terms: Newcastle Disease; Newcastle disease virus
AN OUTBREAK OF TETRODOTOXIN POISONING FROM CONSUMING HORSESHOE CRABS IN SABAH

Suleiman M, Muhammad J, Jelip J, William T, Chua TH

Southeast Asian J Trop Med Public Health, 2017 Jan;48(1):197-203.
PMID: 29644840

The horseshoe crab (Carcinoscorpius rotundicauda) is consumed by those
residing near the coastal areas of Kota Marudu District in Malaysia, as it is considered
a delicacy. During June to August, 2011 thirty cases of tetrodotoxin poisoning
were reported from Kota Marudu District following ingestion of horseshoe
crabs caught in Kota Marudu Bay. The purpose of this study is to describe this
case series in order to determine risk factors to prevent further outbreaks. There
were six confirmed and 24 probable cases of tetrodotoxin poisoning identified in
the study area during the study period as diagnosed by clinical presentation and
laboratory findings. Symptoms included dizziness (80%), circumoral and lingual
numbness (80%), hand and feet numbness (63.3%), nausea and vomiting (30%)
and weakness and difficulty in breathing (26.6%). Three cases (10%) died while 27
cases recovered. Forty-seven percent of the cases had onset of symptoms within
30 minutes of ingestion and 14% 31-60 minutes after ingestion of horseshoe crab
meat. Urine samples were collected from the cases, while horseshoe crabs, cockles
and sea water from the epidemic area were also taken for analysis. Tetrodotoxin
was detected in the urine of six cases; the highest concentrations recorded were
among the three cases who died. High tetrodotoxin concentrations were found
in the hepatic cecum and eggs of the tested horseshoe crabs. Dinoflagellates were
not detected in the sea water or cockle samples. Intensive health education was
initiated quickly to stop other members of the Marudu Bay community from
consuming the horseshoe crabs. This is the first documented epidemic of tetrodotoxin
poisoning in Sabah.

Matched MeSH terms: Disease Outbreaks*
The Global Spine Care Initiative: World Spine Care executive summary on reducing spine-related disability in low- and middle-income communities

Haldeman S, Nordin M, Chou R, Côté P, Hurwitz EL, Johnson CD, et al.

Eur Spine J, 2018 09;27(Suppl 6):776-785.
PMID: 30151809 DOI: 10.1007/s00586-018-5722-x

PURPOSE: Spinal disorders, including back and neck pain, are major causes of disability, economic hardship, and morbidity, especially in underserved communities and low- and middle-income countries. Currently, there is no model of care to address this issue. This paper provides an overview of the papers from the Global Spine Care Initiative (GSCI), which was convened to develop an evidence-based, practical, and sustainable, spinal healthcare model for communities around the world with various levels of resources.
METHODS: Leading spine clinicians and scientists around the world were invited to participate. The interprofessional, international team consisted of 68 members from 24 countries, representing most disciplines that study or care for patients with spinal symptoms, including family physicians, spine surgeons, rheumatologists, chiropractors, physical therapists, epidemiologists, research methodologists, and other stakeholders.
RESULTS: Literature reviews on the burden of spinal disorders and six categories of evidence-based interventions for spinal disorders (assessment, public health, psychosocial, noninvasive, invasive, and the management of osteoporosis) were completed. In addition, participants developed a stratification system for surgical intervention, a classification system for spinal disorders, an evidence-based care pathway, and lists of resources and recommendations to implement the GSCI model of care.
CONCLUSION: The GSCI proposes an evidence-based model that is consistent with recent calls for action to reduce the global burden of spinal disorders. The model requires testing to determine feasibility. If it proves to be implementable, this model holds great promise to reduce the tremendous global burden of spinal disorders. These slides can be retrieved under Electronic Supplementary Material.

Matched MeSH terms: Global Burden of Disease*
The Global Spine Care Initiative: methodology, contributors, and disclosures

Johnson CD, Haldeman S, Nordin M, Chou R, Côté P, Hurwitz EL, et al.

Eur Spine J, 2018 09;27(Suppl 6):786-795.
PMID: 30151808 DOI: 10.1007/s00586-018-5723-9

PURPOSE: The purpose of this report is to describe the Global Spine Care Initiative (GSCI) contributors, disclosures, and methods for reporting transparency on the development of the recommendations.
METHODS: World Spine Care convened the GSCI to develop an evidence-based, practical, and sustainable healthcare model for spinal care. The initiative aims to improve the management, prevention, and public health for spine-related disorders worldwide; thus, global representation was essential. A series of meetings established the initiative's mission and goals. Electronic surveys collected contributorship and demographic information, and experiences with spinal conditions to better understand perceptions and potential biases that were contributing to the model of care.
RESULTS: Sixty-eight clinicians and scientists participated in the deliberations and are authors of one or more of the GSCI articles. Of these experts, 57 reported providing spine care in 34 countries, (i.e., low-, middle-, and high-income countries, as well as underserved communities in high-income countries.) The majority reported personally experiencing or having a close family member with one or more spinal concerns including: spine-related trauma or injury, spinal problems that required emergency or surgical intervention, spinal pain referred from non-spine sources, spinal deformity, spinal pathology or disease, neurological problems, and/or mild, moderate, or severe back or neck pain. There were no substantial reported conflicts of interest.
CONCLUSION: The GSCI participants have broad professional experience and wide international distribution with no discipline dominating the deliberations. The GSCI believes this set of papers has the potential to inform and improve spine care globally. These slides can be retrieved under Electronic Supplementary Material.

Matched MeSH terms: Global Burden of Disease*
Genetics of inflammatory bowel disease in Asia: systematic review and meta-analysis

Ng SC, Tsoi KK, Kamm MA, Xia B, Wu J, Chan FK, et al.

Inflamm Bowel Dis, 2012 Jun;18(6):1164-76.
PMID: 21887729 DOI: 10.1002/ibd.21845

BACKGROUND: Inflammatory bowel diseases (IBD) result from an interaction between genetic and environmental factors. Preliminary findings suggest that susceptibility genes differ between IBD patients in Asia and the West. We aimed to evaluate disease-predisposing genes in Asian IBD patients.
METHODS: A systematic review and meta-analysis were performed of published studies from 1950 to 2010 using keyword searches in MEDLINE, EMBASE, EBM Reviews, and BIOSIS Previews.
RESULTS: In all, 477 abstracts were identified and data extracted from 93 studies, comprising 17,976 IBD patients and 27,350 age- and sex-matched controls. Major nucleotide oligomerization domain (NOD)-2 variants in Western Crohn's disease (CD) patients were not associated with CD in Han Chinese, Japanese, South Korean, Indian, and Malaysian populations. New NOD2 mutations were, however, associated with CD in Malaysians (JW1), Han Chinese, and Indians (P268S). Autophagy-related protein 16-linked 1 (ATG16L1) was not associated with CD in East Asians (odds ratio [OR] 0.97; 95% confidence interval [CI] 0.84-1.13). Interleukin (IL)-23R was associated with CD in South Koreans (OR 1.8; 95% CI 1.16-2.82) and a single nucleotide polymorphism in IL-23R (Gly149Arg) was protective of CD in Han Chinese (OR 0.3; 95% CI 0.15-0.60). Tumor necrosis factor (TNF) superfamily gene-15 (SF15) polymorphisms were associated with CD (OR 2.68; 95% CI 1.86-3.86), while TNF-308 polymorphisms (OR 1.82; 95% CI 1.15-2.9), cytotoxic T lymphocyte antigen (CTLA)-4 (OR 2.75; 95% CI 1.22-6.22) and MICA allele (OR 2.41; 95% CI 1.89-3.07) were associated with ulcerative colitis in Asians.
CONCLUSIONS: Genetic mutations of IBD in Asians differ from Caucasians. New mutations and susceptibility genes identified in Asian IBD patients provide an opportunity to explore new disease-associated mechanisms in this population of rising incidence.

Matched MeSH terms: Genetic Predisposition to Disease*
Fulltext Mutation Study of Malaysian Patients with Ornithine Transcarbamylase Deficiency: Clinical, Molecular, and Bioinformatics Analyses of Two Novel Missense Mutations of the OTC Gene

Ali EZ, Zakaria Y, Mohd Radzi MA, Ngu LH, Jusoh SA

Biomed Res Int, 2018;2018:4320831.
PMID: 30175132 DOI: 10.1155/2018/4320831

Ornithine transcarbamylase deficiency (OTCD), an X-linked disorder that results from mutations in the OTC gene, causes hyperammonemia and leads to various clinical manifestations. Mutations occurring close to the catalytic site of OTCase can cause severe OTCD phenotypes compared with those caused by mutations occurring on the surface of this protein. In this study, we report two novel OTC missense mutations, Q171H and N199H, found in Malaysian patients. Q171H and N199H caused neonatal onset OTCD in a male and late OTCD in a female, respectively. In silico predictions and molecular docking were performed to examine the effect of these novel mutations, and the results were compared with other 30 known OTC mutations. In silico servers predicted that Q171H and N199H, as well as 30 known missense mutations, led to the development of OTCD. Docking analysis indicated that N-(phosphonoacetyl)-L-ornithine (PALO) was bound to the catalytic site of OTCase mutant structure with minimal conformational changes. However, the mutations disrupted interatomic interactions in the catalytic site. Therefore, depending on the severity of disruption occurring at the catalytic site, the mutation may affect the efficiency of mechanism and functions of OTCase.

Matched MeSH terms: Ornithine Carbamoyltransferase Deficiency Disease/genetics*
Fulltext T Cell Immunity To Enterovirus 71 Infection In Humans And Implications For Vaccine Development

Yee PTI, Poh CL

Int J Med Sci, 2018;15(11):1143-1152.
PMID: 30123051 DOI: 10.7150/ijms.26450

Enterovirus 71 (EV-A71) is one of the major pathogens causing hand, foot and mouth disease (HFMD). Some strains can lead to neurological disease and fatality in children. Up to date, there is no FDA-approved vaccine to prevent severe HFMD and mortality. Although the inactivated vaccine has advanced to production in China, lack of long-term protection and the requirement of multiple boosters have necessitated the development of other types of vaccines. Recent studies indicate that cellular and not humoral immunity determines the clinical outcome of EV-A71 infections. High levels of cytokines such as IL-1β, IL-6, IL-10 and IFN-γ tend to correlate with clinical severity in patients with pulmonary edema and encephalitis. The live attenuated vaccine may serve as the preferred choice as it can induce excellent humoral and cellular immunity as well as live-long immunity. Expression of certain HLA alleles such as TNF-α promoter type II (-308 allele), HLA-A33 and HLA-DR17 responses have been linked to severe HFMD. However, the high variability of MHC genes could restrict T cell recognition and be a major obstacle in the design of peptide vaccines. Hence, the development of a T cell universal vaccine (incorporating both CD4+ and CD8+ T cell epitopes) that induces broad, multifunctional and cross-reactive CD8+ T cell responses maybe desirable.

Matched MeSH terms: Hand, Foot and Mouth Disease/immunology
The 2016 Singapore Zika virus outbreak did not cause a surge in Guillain-Barré syndrome

Umapathi T, Kam YW, Ohnmar O, Ng BCJ, Ng Y, Premikha M, et al.

J Peripher Nerv Syst, 2018 09;23(3):197-201.
PMID: 30070025 DOI: 10.1111/jns.12284

Although individuals with Zika virus (ZIKV) antibodies were reported in Malaya in mid-1950s, entomological and human surveillance in Singapore did not identify autochthonous transmission until the outbreak of August-November, 2016. A total of 455 cases from 15 separate clusters were identified. We asked if this ZIKV outbreak increased the incidence of Guillain-Barré syndrome (GBS) and aimed to characterize these cases. Eleven GBS cases, consecutively enrolled into our prospective GBS database from onset to 4 weeks after outbreak, and six controls, comprising three GBS patients enrolled before outbreak and three non-GBS patients, were examined for evidence of recent ZIKV infection. We performed serum, urine ZIKV RT-PCR, ZIKV serology, and virus neutralization assays, accounting for cross-reaction and co-infection with dengue (DENV). We found five GBS cases with only serological evidence of recent ZIKV infection (including one ZIKV-DENV co-infection). A temporal relationship with ZIKV outbreak was unlikely as two cases were GBS controls enrolled 3 months before outbreak. None reported symptoms of ZIKV infection. In addition, compared to last 10 years the national number of GBS hospitalizations did not increase during and immediately after outbreak. We conclude the 2016 Singapore ZIKV outbreak did not cause a change in GBS epidemiology.

Matched MeSH terms: Disease Outbreaks*
Fulltext Delineating inflammatory bowel disease through transcriptomic studies: current review of progress and evidence

Chan SN, Low END, Raja Ali RA, Mokhtar NM

Intest Res, 2018 Jul;16(3):374-383.
PMID: 30090036 DOI: 10.5217/ir.2018.16.3.374

Inflammatory bowel disease (IBD), which comprises of Crohn's disease and ulcerative colitis, is an idiopathic relapsing and remitting disease in which the interplay of different environment, microbial, immunological and genetic factors that attribute to the progression of the disease. Numerous studies have been conducted in multiple aspects including clinical, endoscopy and histopathology for the diagnostics and treatment of IBD. However, the molecular mechanism underlying the aetiology and pathogenesis of IBD is still poorly understood. This review tries to critically assess the scientific evidence at the transcriptomic level as it would help in the discovery of RNA molecules in tissues or serum between the healthy and diseased or different IBD subtypes. These molecular signatures could potentially serve as a reliable diagnostic or prognostic biomarker. Researchers have also embarked on the study of transcriptome to be utilized in targeted therapy. We focus on the evaluation and discussion related to the publications reporting the different approaches and techniques used in investigating the transcriptomic changes in IBD with the intention to offer new perspectives to the landscape of the disease.

Matched MeSH terms: Crohn Disease; Disease Progression
Fulltext Development of a New Molecular Marker for the Resistance to Tomato Yellow Leaf Curl Virus

Nevame AYM, Xia L, Nchongboh CG, Hasan MM, Alam MA, Yongbo L, et al.

Biomed Res Int, 2018;2018:8120281.
PMID: 30105248 DOI: 10.1155/2018/8120281

Tomato yellow leaf curl virus (TYLCV) responsible for tomato yellow leaf curl disease (TYLCD) causes a substantial decrease in tomato (Solanum lycopersicum L.) yield worldwide. The use of resistant variety as a sustainable management strategy has been advocated. Tremendous progress has been made in genetically characterizing the resistance genes (R gene) in tomato. Breeding tomato for TYLCV resistance has been based mostly on Ty-3 as a race-specific resistance gene by introgression originating from wild tomato species relatives. Improvement or development of a cultivar is achievable through the use of marker-assisted selection (MAS). Therefore, precise and easy use of gene-targeted markers would be of significant importance for selection in breeding programs. The present study was undertaken to develop a new marker based on Ty-3 gene sequence that can be used for MAS in TYLCV resistant tomato breeding program. The new developed marker was named ACY. The reliability and accuracy of ACY were evaluated against those of Ty-3 linked marker P6-25 through screening of commercial resistant and susceptible tomato hybrids, and genetic segregation using F2 population derived from a commercial resistant hybrid AG208. With the use of bioinformatics and DNA sequencing analysis tools, deletion of 10 nucleotides was observed in Ty-3 gene sequence for susceptible tomato variety. ACY is a co-dominant indel-based marker that produced clear and strong polymorphic band patterns for resistant plant distinguishing it from its susceptible counterpart. The obtained result correlates with 3:1 segregation ratio of single resistant dominant gene inheritance, which depicted ACY as gene-tag functional marker. This marker is currently in use for screening 968 hybrids varieties and one thousand breeding lines of tomato varieties stocked in Jiangsu Green Port Modern Agriculture Development Company (Green Port). So far, ACY has been used to identify 56 hybrids and 51 breeding lines. These newly detected breeding lines were regarded as potential source of resistance for tomato breeding. This work exploited the sequence of Ty-3 and subsequently contributed to the development of molecular marker ACY to aid phenotypic selection. We thus recommend this marker to breeders, which is suitable for marker-assisted selection in tomato.

Matched MeSH terms: Disease Resistance/genetics*
Fulltext Tocotrienol Rich Fraction Supplementation Modulate Brain Hippocampal Gene Expression in APPswe/PS1dE9 Alzheimer's Disease Mouse Model

Wan Nasri WN, Makpol S, Mazlan M, Tooyama I, Wan Ngah WZ, Damanhuri HA

J Alzheimers Dis, 2019;70(s1):S239-S254.
PMID: 30507571 DOI: 10.3233/JAD-180496

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by loss of memory and other cognitive abilities. AD is associated with aggregation of amyloid-β (Aβ) deposited in the hippocampal brain region. Our previous work has shown that tocotrienol rich fraction (TRF) supplementation was able to attenuate the blood oxidative status, improve behavior, and reduce fibrillary-type Aβ deposition in the hippocampus of an AD mouse model. In the present study, we investigate the effect of 6 months of TRF supplementation on transcriptome profile in the hippocampus of APPswe/PS1dE9 double transgenic mice. TRF supplementation can alleviate AD conditions by modulating several important genes in AD. Moreover, TRF supplementation attenuated the affected biological process and pathways that were upregulated in the AD mouse model. Our findings indicate that TRF supplementation can modulate hippocampal gene expression as well as biological processes that can potentially delay the progression of AD.

Matched MeSH terms: Alzheimer Disease; Disease Progression
Fulltext A rare cause of unilateral tinnitus

Nik Mohd Syukra Nik Abd Ghani, Nik Adilah Nik Othman, Amran Mohamad

International Medical Journal Malaysia, 2018;17(1):145-148.
MyJurnal

Tinnitus is not a disease per se but it is a symptom. It can be either subjective or objective type and the
underlying cause varies such as tumour, infection, vascular abnormality or Meniere’s disease. Foreign body in the external ear is a common presentation especially in children. However, foreign body in the middle ear manifested with only symptom of tinnitus is a rare and unexpected presentation. Foreign body in the middle ear are commonly due to iatrogenic cause such as complication of myringotomy and ventilation tube insertion surgery. There are reported cases of complications of myringotomy and ventilation tube insertion, and they typically presented with the ear infection manifestation, myringosclerosis or permanent perforation of tympanic membrane. Currently, there are only few reported cases in literatures of foreign body in the middle ear following complication of medial migration of ventilation tube into a middle ear with intact tympanic membrane.

Matched MeSH terms: Iatrogenic Disease; Meniere Disease

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