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Sagittal sinus thrombosis in a patient with familial Protein C deficiency: Highlighting the impact of thrombophilia testing

Wan Ab Rahman WS, Abdullah WZ, Hassan MN, Ahmed S, Zulkafli Z, Wan Ahmed WA, et al.

Malays J Pathol, 2021 Dec;43(3):449-452.
PMID: 34958066

Plasma protein-C is a natural anticoagulant that inactivates factors Va and VIIIa. Familial protein C deficiency is inherited as an autosomal dominant disorder. The homozygous or compound heterozygous type may present early as purpura fulminant, while the heterozygous type can present as thromboembolism later in life. Presented in this report is a case of a 21-year-old female patient with protein-C deficiency, confirmed by thrombophilia investigations. She experienced recurrent deep vein thrombosis and cerebral sinus thrombosis due to thrombotic occlusion. She had a family history of deep vein thrombosis. Hence, high-risk cases should be seriously considered for long term anticoagulation therapy. The utility versus futility of thrombophilia testing in a particular situation is discussed to address and ensure safe practice among patients with thromboembolism.
Prevalence of Clostridium difficile infection and colonization in a tertiary hospital and elderly community of North-Eastern Peninsular Malaysia

Zainul NH, Ma ZF, Besari A, Siti Asma H, Rahman RA, Collins DA, et al.

Epidemiol Infect, 2017 Oct;145(14):3012-3019.
PMID: 28891459 DOI: 10.1017/S0950268817002011

Little is known about Clostridium difficile infection (CDI) in Asia. The aims of our study were to explore (i) the prevalence, risk factors and molecular epidemiology of CDI and colonization in a tertiary academic hospital in North-Eastern Peninsular Malaysia; (ii) the rate of carriage of C. difficile among the elderly in the region; (iii) the awareness level of this infection among the hospital staffs and students. For stool samples collected from hospital inpatients with diarrhea (n = 76) and healthy community members (n = 138), C. difficile antigen and toxins were tested by enzyme immunoassay. Stool samples were subsequently analyzed by culture and molecular detection of toxin genes, and PCR ribotyping of isolates. To examine awareness among hospital staff and students, participants were asked to complete a self-administered questionnaire. For the hospital and community studies, the prevalence of non-toxigenic C. difficile colonization was 16% and 2%, respectively. The prevalence of CDI among hospital inpatients with diarrhea was 13%. Out of 22 C. difficile strains from hospital inpatients, the toxigenic ribotypes 043 and 017 were most common (both 14%). In univariate analysis, C. difficile colonization in hospital inpatients was significantly associated with greater duration of hospitalization and use of penicillin (both P < 0·05). Absence of these factors was a possible reason for low colonization in the community. Only 3% of 154 respondents answered all questions correctly in the awareness survey. C. difficile colonization is prevalent in a Malaysian hospital setting but not in the elderly community with little or no contact with hospitals. Awareness of CDI is alarmingly poor.
Fulltext Silica and graphene mediate arsenic detection in mature rice grain by a newly patterned current-volt aptasensor

Uda MNA, Gopinath SCB, Hashim U, Halim NH, Parmin NA, Uda MNA, et al.

Sci Rep, 2021 Jul 19;11(1):14688.
PMID: 34282233 DOI: 10.1038/s41598-021-94145-0

Arsenic is a major global threat to the ecosystem. Here we describe a highly accurate sensing platform using silica nanoparticles/graphene at the surface of aluminum interdigitated electrodes (Al IDE), able to detect trace amounts of arsenic(III) in rice grain samples. The morphology and electrical properties of fabricated Al IDEs were characterized and standardized using AFM, and SEM with EDX analyses. Micrometer scale Al IDEs were fabricated with silicon, aluminum, and oxygen as primary elements. Validation of the bare Al IDE with electrolyte fouling was performed at different pH levels. The sensing surface was stable with no electrolyte fouling at pH 7. Each chemical modification step was monitored with current-volt measurement. The surface chemical bonds were characterized by fourier transform infrared spectroscopy (FTIR) and revealed different peaks when interacting with arsenic (1600-1000 cm-1). Both silica nanoparticles and graphene presented a sensitive limit of detection as measured by slope calibration curves at 0.0000001 pg/ml, respectively. Further, linear regression was established using ΔI (A) = 3.86 E-09 log (Arsenic concentration) [g/ml] + 8.67 E-08 [A] for silica nanoparticles, whereas for graphene Y = 3.73 E-09 (Arsenic concentration) [g/ml] + 8.52 E-08 on the linear range of 0.0000001 pg/ml to 0.01 pg/ml. The R2 for silica (0.96) and that of graphene (0.94) was close to the maximum (1). Modification with silica nanoparticles was highly stable. The potential use of silica nanoparticles in the detection of arsenic in rice grain extract can be attributed to their size and stability.
Stress distributions in maxillary central incisors restored with various types of post materials and designs

Madfa AA, Kadir MR, Kashani J, Saidin S, Sulaiman E, Marhazlinda J, et al.

Med Eng Phys, 2014 Jul;36(7):962-7.
PMID: 24834856 DOI: 10.1016/j.medengphy.2014.03.018

Different dental post designs and materials affect the stability of restoration of a tooth. This study aimed to analyse and compare the stability of two shapes of dental posts (parallel-sided and tapered) made of five different materials (titanium, zirconia, carbon fibre and glass fibre) by investigating their stress transfer through the finite element (FE) method. Ten three-dimensional (3D) FE models of a maxillary central incisor restored with two different designs and five different materials were constructed. An oblique loading of 100 N was applied to each 3D model. Analyses along the centre of the post, the crown-cement/core and the post-cement/dentine interfaces were computed, and the means were calculated. One-way ANOVAs followed by post hoc tests were used to evaluate the effectiveness of the post materials and designs (p=0.05). For post designs, the tapered posts introduced significantly higher stress compared with the parallel-sided post (p<0.05), especially along the centre of the post. Of the materials, the highest level of stress was found for stainless steel, followed by zirconia, titanium, glass fibre and carbon fibre posts (p<0.05). The carbon and glass fibre posts reduced the stress distribution at the middle and apical part of the posts compared with the stainless steel, zirconia and titanium posts. The opposite results were observed at the crown-cement/core interface.
Atrovirinone inhibits pro-inflammatory mediator release from murine macrophages and human whole blood

Syahida A, Israf DA, Permana D, Lajis NH, Khozirah S, Afiza AW, et al.

Immunol Cell Biol, 2006 Jun;84(3):250-8.
PMID: 16509831

Many plant-derived natural compounds have been reported previously to inhibit the production of important pro-inflammatory mediators such as nitric oxide, prostaglandin E2, TNF-alpha and reactive oxygen species by suppressing inducible enzyme expression via inhibition of the mitogen-activated protein kinase pathway and nuclear translocation of critical transcription factors. This study evaluates the effects of atrovirinone [2-(1-methoxycarbonyl-4,6-dihydroxyphenoxy)-3-methoxy-5,6-di-(3-methyl-2-butenyl)-1,4-benzoquinone)], a benzoquinone that we have previously isolated from Garcinia atroviridis, on two cellular systems that are repeatedly used in the analysis of anti-inflammatory bioactive compounds, namely, RAW 264.7 macrophage cells and whole blood. Atrovirinone inhibited the production of both nitric oxide and prostaglandin E2 from LPS-induced and IFN-gamma-induced RAW 264.7 cells and whole blood, with inhibitory concentration (IC)50 values of 4.62 +/- 0.65 and 9.33 +/- 1.47 micromol/L, respectively. Analysis of thromboxane B2 (TXB2) secretion from whole blood stimulated by either the cyclooxygenase (COX)-1 or the COX-2 pathway showed that atrovirinone inhibits the generation of TXB2 by both pathways, with IC50 values of 7.41 +/- 0.92 and 2.10 +/- 0.48 micromol/L, respectively. Analysis of IC50 ratios showed that atrovirinone was more COX-2 selective in its inhibition of TXB2, with a ratio of 0.32. Atrovirinone also inhibited the generation of intracellular reactive oxygen species and the secretion of TNF-alpha from RAW 264.7 cells in a dose-responsive manner, with IC50 values of 5.99 +/- 0.62 and 11.56 +/- 0.04 micromol/L, respectively. Lipoxygenase activity was also moderately inhibited by atrovirinone. Our results suggest that atrovirinone acts on important pro-inflammatory mediators possibly by the inhibition of the nuclear factor-kappaB pathway and also by the inhibition of the COX/lipoxygenase enzyme activity.
Differentiation of dental pulp stem cells into islet-like aggregates

Govindasamy V, Ronald VS, Abdullah AN, Nathan KR, Ab Aziz ZA, Abdullah M, et al.

J Dent Res, 2011 May;90(5):646-52.
PMID: 21335539 DOI: 10.1177/0022034510396879

The post-natal dental pulp tissue contains a population of multipotent mesenchymal progenitor cells known as dental pulp stromal/stem cells (DPSCs), with high proliferative potential for self-renewal. In this investigation, we explored the potential of DPSCs to differentiate into pancreatic cell lineage resembling islet-like cell aggregates (ICAs). We isolated, propagated, and characterized DPSCs and demonstrated that these could be differentiated into adipogenic, chondrogenic, and osteogenic lineage upon exposure to an appropriate cocktail of differentiating agents. Using a three-step protocol reported previously by our group, we succeeded in obtaining ICAs from DPSCs. The identity of ICAs was confirmed as islets by dithiozone-positive staining, as well as by expression of C-peptide, Pdx-1, Pax4, Pax6, Ngn3, and Isl-1. There were several-fold up-regulations of these transcription factors proportional to days of differentiation as compared with undifferentiated DPSCs. Day 10 ICAs released insulin and C-peptide in a glucose-dependent manner, exhibiting in vitro functionality. Our results demonstrated for the first time that DPSCs could be differentiated into pancreatic cell lineage and offer an unconventional and non-controversial source of human tissue that could be used for autologous stem cell therapy in diabetes.
Self-reported bone fracture among Malaysian adults: Baseline findings of PURE Malaysia cohort study

Zaleha MI, Noor Hassim I, Azmi MT, Hasni MJ, Rosnah I, Abdul-Hamid H, et al.

Med J Malaysia, 2023 Nov;78(6):787-792.
PMID: 38031222

INTRODUCTION: In Malaysia, studies on self-reported bone fractures are scarce. Due to the fact that bone fractures may serve as an indicator of osteoporosis in the community, this study aimed to identify the factors associated with their occurrence among adults in Malaysia.
MATERIALS AND METHODS: Epidemiological data for selfreported bone fractures were obtained through direct interviews using a validated questionnaire from the Prospective Urban and Rural Epidemiology (PURE) study.
RESULTS: Of 15,378 respondents, 6.63% (n=1019) reported bone fractures, with a higher proportion of men (65.8%, n=671) than women (34.2%, n=348). Higher odds of selfreporting bone fractures were seen in males (aOR, 2.12; 95%CI: 1.69, 2.65), those with a history of injury (aOR 5.01; 95%CI: 3.10, 6.32) and those who were obese (aOR: 1.46; 95% CI: 1.13, 1.89), highly active (aOR 1.25; 95%CI: 1.02, 1.53), smokers (aOR 1.35; 95%CI: 1.11, 1.65) and alcohol consumers (aOR 1.67; 95%CI: 1.20,2.32).
CONCLUSION: Adopting a healthier lifestyle that includes a balanced diet and moderate physical activity is critical for weight loss, increased muscle and bone mass and better stability, which reduces the likelihood of fractures following a fall.
Review of MR spectroscopy analysis and artificial intelligence applications for the detection of cerebral inflammation and neurotoxicity in Alzheimer's disease

Seriramulu VP, Suppiah S, Lee HH, Jang JH, Omar NF, Mohan SN, et al.

Med J Malaysia, 2024 Jan;79(1):102-110.
PMID: 38287765

INTRODUCTION: Magnetic resonance spectroscopy (MRS) has an emerging role as a neuroimaging tool for the detection of biomarkers of Alzheimer's disease (AD). To date, MRS has been established as one of the diagnostic tools for various diseases such as breast cancer and fatty liver, as well as brain tumours. However, its utility in neurodegenerative diseases is still in the experimental stages. The potential role of the modality has not been fully explored, as there is diverse information regarding the aberrations in the brain metabolites caused by normal ageing versus neurodegenerative disorders.
MATERIALS AND METHODS: A literature search was carried out to gather eligible studies from the following widely sourced electronic databases such as Scopus, PubMed and Google Scholar using the combination of the following keywords: AD, MRS, brain metabolites, deep learning (DL), machine learning (ML) and artificial intelligence (AI); having the aim of taking the readers through the advancements in the usage of MRS analysis and related AI applications for the detection of AD.
RESULTS: We elaborate on the MRS data acquisition, processing, analysis, and interpretation techniques. Recommendation is made for MRS parameters that can obtain the best quality spectrum for fingerprinting the brain metabolomics composition in AD. Furthermore, we summarise ML and DL techniques that have been utilised to estimate the uncertainty in the machine-predicted metabolite content, as well as streamline the process of displaying results of metabolites derangement that occurs as part of ageing.
CONCLUSION: MRS has a role as a non-invasive tool for the detection of brain metabolite biomarkers that indicate brain metabolic health, which can be integral in the management of AD.
Parametric study of coagulant recovery from water treatment sludge towards water circular economy

Shawal NBM, Razali NA, Hairom NHH, Yatim NII, Rasit N, Harun MHC, et al.

Water Sci Technol, 2023 Dec;88(12):3142-3150.
PMID: 38154800 DOI: 10.2166/wst.2023.398

This study aims to recover the used coagulants from two water treatment plants via acidification technique. The water treatment sludge (WTS) was acidified with sulfuric acid (H2SO-4) at variable normalities (0.5, 1, 1.5, 2.0 and 2.5 N). The surface morphology and functionalities of both recovered coagulants were analysed using scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR). The performance of recovered coagulants was tested for turbidity removal in surface water treatment at different coagulant dosages and pH. It was found that the optimum normality of H2SO4 for recovered alum was 1.5 N, where 66% turbidity removal was recorded. The recovered PAC treated with 1.0 N H2SO4 indicated high turbidity removal percentage, which was 50.5%. The turbidity removal increased with increasing coagulant dosage. More than 80% turbidity removal was achieved with 40 mg/L dosage of recovered alum and recovered PAC. Maximum removal (85%) was observed with 50 mg/L dosage of recovered alum. For commercial coagulant, the turbidity removal was higher, with a difference of up to 6% in favor of recovered alum. The potential reuse of coagulants can be explored in order to reduce the operating costs and promotes the reduction of WTS disposal.
Distinguishing features of COVID-19 and non-COVID-19 febrile seizures in hospitalised children

Mahendran S, Ng BH, Lim HY, Zailanalhuddin NE, Chandran Y, Wong WF, et al.

Med J Malaysia, 2024 Jul;79(4):408-413.
PMID: 39086337

INTRODUCTION: Febrile seizures in children can be associated with various underlying conditions, including COVID-19. Differentiating COVID-19 and non-COVID-19 related febrile seizures is crucial for tailored patient management and for implementing appropriate infection control measures to prevent nosocomial transmission. This study aimed to describe the clinical features of children hospitalised for COVID-19 and non-COVID-19 febrile seizures and to identify factors that differentiate between the two groups.
MATERIALS AND METHODS: This retrospective cross-sectional study involved children aged 6 months to 6 years who were hospitalised for febrile seizures in Hospital Tuanku Ja'afar Seremban (HTJS) from January 2021 to June 2022. Descriptive statistics were used to summarise the differences in demographics and clinical presentations. Logistic regression analyses were performed to identify factors associated with COVID-19 and non-COVID-19 febrile seizures.
RESULTS: Of the 345 patients (median age 22 months, IQR 15- 32; 59.7% were males) included in the study, 130 (37.7%) tested positive for COVID-19, while 215 (62.3%) tested negative. There were no significant differences between both groups based on age, comorbidities, history of febrile seizures, seizure types, temperature on arrival, cough and rhinorrhoea. Multivariate analysis revealed that a family history of febrile seizures and leucocytosis were associated with increased odds of non-COVID-19 febrile seizures. In contrast, lymphopenia was associated with decreased odds.
CONCLUSION: The clinical presentation of COVID-19 and non- COVID-19 febrile seizures are remarkably similar, highlighting the importance of including COVID-19 screening in febrile seizures workup. Full blood count readings may be potentially useful for differentiating between these conditions.
A rare case of compound heterozygous Southeast Asian double α-globin gene deletion and Haemoglobin Quong Sze in a Malay proband

Vijian D, Wan Ab Rahman WS, Kannan TP, Zulkafli Z, Mohd Noor NH, Bahar R, et al.

Malays J Pathol, 2024 Aug;46(2):321-324.
PMID: 39207010

INTRODUCTION: Haemoglobin (Hb) Quong Sze is a non-deletional α-thalassaemia subtype that occurs due to missense mutation at codon 125 of the HBA2 gene. Interaction between Hb QS with Southeast Asian double α-globin gene deletion results in non-deletional HbH disease, which is more severe than deletional HbH.
CASE REPORT: A 3-month-old baby boy was presented with neonatal anaemia and mild hepatomegaly. Full blood count revealed severe hypochromic microcytic anaemia. There was an abundance of HbH inclusion bodies in his red blood cells. High-performance liquid chromatography showed a reduced HbA2 level with the presence of pre-run peak. Capillary electrophoresis showed the presence of HbH and Hb Barts. Molecular analysis found a common α0-thalassaemia (--SEA) in one allele and mutation in codon 125 in the other allele.
DISCUSSION: Non-deletional HbH disease due to a combination of deletional and non-deletional mutations may present with severe clinical manifestations than those with deletion mutations, which warrants accurate diagnosis using molecular techniques.
Fulltext Hepatitis A virus: declining seroprevalence in children and adolescents in Southeast Asia

Kunasol P, Cooksley G, Chan VF, Isahak I, John J, Loleka S, et al.

Southeast Asian J Trop Med Public Health, 1998 Jun;29(2):255-62.
PMID: 9886108

The prevalence of hepatitis A virus (HAV) in a country largely reflects its standards of hygiene and socioeconomic conditions. Countries which undergo socioeconomic development show major change in HAV prevalence from high to low endemicity, and this is largely reflected in patterns of age-related seroprevalence. This paper presents age-related HAV seroprevalence patterns of SE Asian countries, and highlights how these patterns have changed over recent decades. Singapore, Thailand and Malaysia have experienced a decline in childhood and adolescent HAV seroprevalence, typical of countries which undergo socioeconomic development. By contrast, India has remained a country of high endemicity, with almost universal seroconversion in childhood. The Philippines and Vietnam show age-related seroprevalence patterns typical of high to moderate endemicity, while Indonesia shows significant regional variation in HAV seroprevalence. Populations within countries which exhibit major improvements in endemicity and age related HAV seroprevalence patterns are at risk of HAV epidemics, and a paradoxical increase in incidence tends to occur as seroconversion shifts from children to adults. The residents of these countries, a significant number of whom are at-risk, would benefit from a program of vaccination, as would non-infected individuals visiting high-risk areas.
Variation of the crystal growth of mesoporous silica nanoparticles and the evaluation to ibuprofen loading and release

Kamarudin NH, Jalil AA, Triwahyono S, Artika V, Salleh NF, Karim AH, et al.

J Colloid Interface Sci, 2014 May 1;421:6-13.
PMID: 24594025 DOI: 10.1016/j.jcis.2014.01.034

Mesoporous silica nanoparticles (MSNs) were synthesized with variable microwave power in the range of 100-450 W, and the resulting enhancement of MSN crystal growth was evaluated for the adsorption and release of ibuprofen. X-ray diffraction (XRD) revealed that the MSN prepared under the highest microwave power (MSN450) produced the most crystallized and prominent mesoporous structure. Enhancement of the crystal growth improved the hexagonal order and range of silica, which led to greater surface area, pore width and pore volume. MSN450 exhibited higher ibuprofen adsorption (98.3 mg/g), followed by MSN300(81.3 mg/g) and MSN100(74.1 mg/g), confirming that more crystallized MSN demonstrated higher adsorptivity toward ibuprofen. Significantly, MSN450 also contained more hydroxyl groups that provided more adsorption sites. In addition, MSN450 exhibited comparable ibuprofen adsorption with conventionally synthesized MSN, indicating the potential of microwave treatment in the synthesis of related porous materials. In vitro drug release was also investigated with simulated biological fluids and the kinetics was studied under different pH conditions. MSN450 showed the slowest release rate of ibuprofen, followed by MSN300 and MSN100. This was due to the wide pore diameter and longer range of silica order of the MSN450. Ibuprofen release from MSN450 at pH 5 and 7 was found to obey a zero-order kinetic model, while release at pH 2 followed the Kosmeyer-Peppas model.
Utilization of bivalve shell-treated Zea mays L. (maize) husk leaf as a low-cost biosorbent for enhanced adsorption of malachite green

Jalil AA, Triwahyono S, Yaakob MR, Azmi ZZ, Sapawe N, Kamarudin NH, et al.

Bioresour Technol, 2012 Sep;120:218-24.
PMID: 22820110 DOI: 10.1016/j.biortech.2012.06.066

In this work, two low-cost wastes, bivalve shell (BS) and Zea mays L. husk leaf (ZHL), were investigated to adsorb malachite green (MG) from aqueous solutions. The ZHL was treated with calcined BS to give the BS-ZHL, and its ability to adsorb MG was compared with untreated ZHL, calcined BS and Ca(OH)(2)-treated ZHL under several different conditions: pH (2-8), adsorbent dosage (0.25-2.5 g L(-1)), contact time (10-30 min), initial MG concentration (10-200 mg L(-1)) and temperature (303-323 K). The equilibrium studies indicated that the experimental data were in agreement with the Langmuir isotherm model. The use of 2.5 g L(-1) BS-ZHL resulted in the nearly complete removal of 200 mg L(-1) of MG with a maximum adsorption capacity of 81.5 mg g(-1) after 30 min of contact time at pH 6 and 323 K. The results indicated that the BS-ZHL can be used to effectively remove MG from aqueous media.
Anti-inflammatory effect of zerumbone on acute and chronic inflammation models in mice

Sulaiman MR, Perimal EK, Akhtar MN, Mohamad AS, Khalid MH, Tasrip NA, et al.

Fitoterapia, 2010 Oct;81(7):855-8.
PMID: 20546845 DOI: 10.1016/j.fitote.2010.05.009

The anti-inflammatory activity of zerumbone (1), a natural cyclic sesquiterpene isolated from Zingiber zerumbet Smith was investigated using carrageenan-induced paw edema and cotton pellet-induced granuloma tissue formation test in mice. It was demonstrated that intraperitoneal administration of 1 at a dose of 5, 10, 50 and 100 mg/kg produced significant dose-dependent inhibition of paw edema induced by carrageenan. It was also demonstrated that 1 at similar doses significantly suppressed granulomatous tissue formation in cotton pellet-induced granuloma test.
Antinociceptive activity of a synthetic chalcone, flavokawin B on chemical and thermal models of nociception in mice

Mohamad AS, Akhtar MN, Zakaria ZA, Perimal EK, Khalid S, Mohd PA, et al.

Eur J Pharmacol, 2010 Nov 25;647(1-3):103-9.
PMID: 20826146 DOI: 10.1016/j.ejphar.2010.08.030

The present study examined the potential antinociceptive activity of flavokawin B (6'-hydroxy-2',4'-dimethoxychalcone), a synthetic chalcone using chemical- and thermal-induced nociception models in mice. It was demonstrated that flavokawin B (FKB; 0.3, 1, 3 and 10 mg/kg) administered via both oral (p.o.) and intraperitoneal (i.p.) routes produced significant and dose-dependent inhibition in the abdominal constrictions induced by acetic acid, with the i.p. route producing antinociception of approximately 7-fold more potent than the p.o. route. It was also demonstrated that FKB produced significant inhibition in the two phases of the formalin-induced paw licking test. In addition, the same treatment of flavokawin B (FKB) exhibited significant inhibition of the neurogenic nociceptive induced by intraplantar injections of glutamate and capsaicin. Likewise, this compound also induced a significant increase in the response latency period to thermal stimuli in the hot plate test and its antinociceptive effect was not related to muscle relaxant or sedative action. Moreover, the antinociception effect of the FKB in the formalin-induced paw licking test and the hot plate test was not affected by pretreatment of non-selective opioid receptor antagonist, naloxone. The present results indicate that FKB produced pronounced antinociception effect against both chemical and thermal models of pain in mice that exhibited both peripheral and central analgesic activity.
Fulltext Natural history of asymptomatic gallstones: differential behaviour in male and female subjects

Sood S, Winn T, Ibrahim S, Gobindram A, Arumugam AA, Razali NC, et al.

Med J Malaysia, 2015 Dec;70(6):341-5.
PMID: 26988206 MyJurnal

OBJECTIVE: The natural history of asymptomatic (silent) gallstones has been inadequately studied. Existing information derives from studies based on oral cholecystography or relatively small sample sizes. We planned a retrospective cohort study in subjects with gallstones to determine conversion rates from asymptomatic to symptomatic.
METHODS: We extracted data from computerised databases of one government hospital and two private clinics in Malaysia. Files were scrutinised to ensure that criteria for asymptomatic gallstones were fulfilled. Patients were called on telephone, further questioned to confirm that the gallstones at detection were truly asymptomatic, and asked about symptoms that were consistent with previously defined criteria for biliary colic. Appropriate ethical clearances were taken.
RESULTS: 213 (112 males) patients fulfilled the criteria for asymptomatic gallstones and could be contacted. 23 (10.8%) developed pain after an average follow up interval of 4.02 years (range 0.1-11 years). Conversion rates from asymptomatic to symptomatic gallstones were high in the first two years of follow up, averaging 4.03±0.965 per year. Over time the conversion rates slowed, and by year 10 the annual conversion rate averaged only 1.38±0.29. Conversion rates were much higher for females compared to males (F:M hazard ratio 3.23, SE 1.54, p>z 0.014). The lifetime risks for conversion approached 6.15% for males, and 22.1% for females.
CONCLUSION: In conclusion, asymptomatic gallstones are much more likely to convert to symptomatic in females than in males. Males in whom asymptomatic stones are discovered should be advised conservative treatment. Surgery may be preferable to conservative management if the subject is a young female.
m radiology records of Hospital
Study site: Computerised database, Hospital Selayang, Selangor; private clinics, Kuala Lumpur, Malaysia
Fulltext Visualising functional 5-HT3 receptors containing A and C subunits at or near the cell surface

Abad IPL, Fam RL, Nguyen DT, Nowell CJ, Trinh PNH, Manallack DT, et al.

Biomed Pharmacother, 2020 Dec;132:110860.
PMID: 33059258 DOI: 10.1016/j.biopha.2020.110860

Five different subunits of the human serotonin 3 (5-hydroxytrptamine 3; 5-HT3) receptor exist and these are present in both central and peripheral systems. Different subunits alter the efficacy of 5-HT3 receptor antagonists used to treat diarrhoea predominant-irritable bowel syndrome, chemotherapy induced nausea and vomiting and depression. Cell surface arrangement of 5-HT3 receptor complexes and the contribution of C, D and E subunits to receptor function is poorly understood. Here, we examine interactions of A and C subunits using 5-HT3 receptor subunits containing fluorescent protein inserts between the 3rd and 4th transmembrane spanning region. HEK293T cells that do not normally express 5-HT3 receptor subunits, were transiently transfected with A or C or both subunits. Patch clamp experiments show that cells transfected with either fluorescent protein tagged A or A and C subunits generate whole cell currents in response to 5-HT. These findings correlate with the apparent distribution of fluorescent protein tagged A and C subunits at or near cell surfaces detected using TIRF microscopy. In co-transfected cells, the A and C subunits are associated forming AC heteromer complexes at or near the cell surface and a proportion can also form A or C homomers. In conclusion, it is likely that both A homomers and AC heteromers contribute to whole cell currents in response to 5-HT with minimal contribution from C homomers.
Multiplex sequencing of SARS-Cov-2 genome directly from clinical samples using the Ion Personal Genome Machine (PGM)

Tan KK, Tiong V, Tan JY, Wong JE, Teoh BT, Abd-Jamil J, et al.

Trop Biomed, 2021 Sep 01;38(3):283-288.
PMID: 34362871 DOI: 10.47665/tb.38.3.069

Various methods have been developed for rapid and high throughput full genome sequencing of SARS-CoV-2. Here, we described a protocol for targeted multiplex full genome sequencing of SARS-CoV-2 genomic RNA directly extracted from human nasopharyngeal swabs using the Ion Personal Genome Machine (PGM). This protocol involves concomitant amplification of 237 gene fragments encompassing the SARS-CoV-2 genome to increase the abundance and yield of viral specific sequencing reads. Five complete and one near-complete genome sequences of SARS-CoV-2 were generated with a single Ion PGM sequencing run. The sequence coverage analysis revealed two amplicons (positions 13 751-13 965 and 23 941-24 106), which consistently gave low sequencing read coverage in all isolates except 4Apr20-64- Hu. We analyzed the potential primer binding sites within these low covered regions and noted that the 4Apr20-64-Hu possess C at positions 13 730 and 23 929, whereas the other isolates possess T at these positions. The genome nucleotide variations observed suggest that the naturally occurring variations present in the actively circulating SARS-CoV-2 strains affected the performance of the target enrichment panel of the Ion AmpliSeq™ SARS CoV 2 Research Panel. The possible impact of other genome nucleotide variations warrants further investigation, and an improved version of the Ion AmpliSeq™ SARS CoV 2 Research Panel, hence, should be considered.
Fulltext Characterisation of a New Fungal Immunomodulatory Protein from Tiger Milk mushroom, Lignosus rhinocerotis

Pushparajah V, Fatima A, Chong CH, Gambule TZ, Chan CJ, Ng ST, et al.

Sci Rep, 2016 07 27;6:30010.
PMID: 27460640 DOI: 10.1038/srep30010

Lignosus rhinocerotis (Tiger milk mushroom) is an important folk medicine for indigenous peoples in Southeast Asia. We previously reported its de novo assembled 34.3 Mb genome encoding a repertoire of proteins including a putative bioactive fungal immunomodulatory protein. Here we report the cDNA of this new member (FIP-Lrh) with a homology range of 54-64% to FIPs from other mushroom species, the closest is with FIP-glu (LZ-8) (64%) from Ganoderma lucidum. The FIP-Lrh of 112 amino acids (12.59 kDa) has a relatively hydrophobic N-terminal. Its predicted 3-dimensional model has identical folding patterns to FIP-fve and contains a partially conserved and more positively charged carbohydrates binding pocket. Docking predictions of FIP-Lrh on 14 glycans commonly found on cellular surfaces showed the best binding energy of -3.98 kcal/mol to N-acetylgalactosamine and N-acetylglucosamine. Overexpression of a 14.9 kDa soluble 6xHisFIP-Lrh was achieved in pET-28a(+)/BL21 and the purified recombinant protein was sequence verified by LC-MS/MS (QTOF) analysis. The ability to haemagglutinate both mouse and human blood at concentration ≥0.34 μM, further demonstrated its lectin nature. In addition, the cytotoxic effect of 6xHisFIP-Lrh on MCF-7, HeLa and A549 cancer cell lines was detected at IC50 of 0.34 μM, 0.58 μM and 0.60 μM, respectively.

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