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Re-emergence of Chikungunya virus in South-east Asia: virological evidence from Sri Lanka and Singapore

Hapuarachchi HC, Bandara KB, Sumanadasa SD, Hapugoda MD, Lai YL, Lee KS, et al.

J Gen Virol, 2010 Apr;91(Pt 4):1067-76.
PMID: 19955565 DOI: 10.1099/vir.0.015743-0

Chikungunya fever swept across many South and South-east Asian countries, following extensive outbreaks in the Indian Ocean Islands in 2005. However, molecular epidemiological data to explain the recent spread and evolution of Chikungunya virus (CHIKV) in the Asian region are still limited. This study describes the genetic Characteristics and evolutionary relationships of CHIKV strains that emerged in Sri Lanka and Singapore during 2006-2008. The viruses isolated in Singapore also included those imported from the Maldives (n=1), India (n=2) and Malaysia (n=31). All analysed strains belonged to the East, Central and South African (ECSA) lineage and were evolutionarily more related to Indian than to Indian Ocean Islands strains. Unique genetic characteristics revealed five genetically distinct subpopulations of CHIKV in Sri Lanka and Singapore, which were likely to have emerged through multiple, independent introductions. The evolutionary network based on E1 gene sequences indicated the acquisition of an alanine to valine 226 substitution (E1-A226V) by virus strains of the Indian sublineage as a key evolutionary event that contributed to the transmission and spatial distribution of CHIKV in the region. The E1-A226V substitution was found in 95.7 % (133/139) of analysed isolates in 2008, highlighting the widespread establishment of mutated CHIKV strains in Sri Lanka, Singapore and Malaysia. As the E1-A226V substitution is known to enhance the transmissibility of CHIKV by Aedes albopictus mosquitoes, this observation has important implications for the design of vector control strategies to fight the virus in regions at risk of chikungunya fever.
Fulltext Establishing an international awareness day for paediatric rheumatic diseases: reflections from the inaugural World Young Rheumatic Diseases (WORD) Day 2019

Smith EMD, Ainsworth S, Beresford MW, Buys V, Costello W, Egert Y, et al.

Pediatr Rheumatol Online J, 2020 Sep 11;18(1):71.
PMID: 32917217 DOI: 10.1186/s12969-020-00465-2

There is a lack of awareness of paediatric rheumatic diseases (PRDs), among the public, and certain groups of healthcare professionals (HCPs), including general practitioners. To help improve international awareness and understanding of PRDs, World yOung Rheumatic Diseases (WORD) Day was established on 18 March 2019. Its aim was to raise awareness of PRDs and the importance of timely referral plus early diagnosis and access to appropriate treatment and support. A steering committee was established, and an external agency provided digital support. A social media campaign was launched in December 2018 to promote it, and analytics were used to measure its impact. Face-to-face and virtual events took place globally on or around WORD Day 2019, with 34 countries reporting events. Examples included lectures, social gatherings and media appearances. A total of 2585 and 660 individuals followed the official Facebook and Twitter accounts respectively, up until WORD Day. The official #WORDDay2019 hashtag was seen by 533,955 unique accounts on 18 March 2019 alone, with 3.3 million impressions. WORD Day 2019 was the first international campaign focused solely on PRDs. It demonstrated that despite awareness events being often resource-light, they can be implemented across a range of diverse settings. WORD Day has now become an annual global awareness event, facilitated by a growing network of patient, parent and professional community supporters.
Fulltext Body mass index (BMI) of adults: Findings of the Malaysian Adult Nutrition Survey (MANS)

Azmi MY, Junidah R, Siti Mariam A, Safiah MY, Fatimah S, Norimah AK, et al.

Malays J Nutr, 2009 Sep;15(2):97-119.
PMID: 22691810 MyJurnal

The Malaysian Adults Nutrition Survey (MANS) was carried out between October 2002 and July 2003, involving 6,775 men and 3,441 women aged 18 - 59 years. Anthropometric assessment showed that the overall mean body weight and BMI were 62.65 kg (CI: 62.20, 63.09) and 24.37 kg/m2 (CI: 24.21, 24.53) respectively. Based on the WHO (1998) classification of BMI, 12.15% (CI: 11.26, 13.10) were obese (BMI > 30 kg/m2), and 26.71% (CI: 25.50, 27.96) overweight (BMI > 25 - 29.9 kg/m2). Significantly, more women were obese [14.66% (CI: 13.37, 16.04)] while significantly more men were overweight [28.55% (CI: 26.77, 30.40)]. Ethnicitywise, prevalence of obesity was highest among the Malays [15.28% (CI: 13.91, 16.77)] while overweight was highest for the Indians [31.01% (CI: 26.64, 35.76)]. Both obesity and overweight were highest among those aged 40 - 49 years. Obesity was highest for those whose household income was between RM1,500 - 3,500 while overweight was more prevalent for those whose household income exceeded RM3,500. The prevalence of overweight was highest for those with primary education [31.90% (CI: 29.21, 34.72)]. There was no significant urban rural differential in both obesity and overweight. The study found 9.02% (CI:8.82, 10.61) with chronic energy deficiency (CED) (BMI < 18.5 kg/m2). The prevalence of CED was relatively higher in the indigenous population (Orang Asli) [14.53% (CI: 5.14, 34.77)], subjects aged 18-19 years [26.24% (CI: 21.12, 32.09)], and with monthly household income of < RM1,500 [10.85% (CI: 9.63, 12.20)]. The prevalence of CED was not significantly different among the geographical zones and educational levels, and between urban/rural areas and sexes. The results call for priority action to address the serious problem of overweight and obesity among Malaysian adults as it poses a grave burden to the country's resources and development.
Study name: Malaysian Adult Nutrition Survey (MANS-2003)
Fulltext Meal patterns of Malaysian adults: findings from the Malaysian adults nutrition survey (MANS)

Wan Abdul Manan WM, Nur Firdaus I, Safiah MY, Siti Haslinda MD, Poh BK, Norimah AK, et al.

Malays J Nutr, 2012 Aug;18(2):221-30.
PMID: 24575668 MyJurnal

INTRODUCTION: Meal patterns have received little attention in nutrition studies. The aim of this study is to present the findings on general meal patterns of Malaysian adults.
METHODS: The Malaysian Adults Nutrition Survey (MANS), carried out in 2002 and 2003, involved 6,928 adults selected by stratified random sampling from all households by zone in Peninsular Malaysia, Sabah and Sarawak.
RESULTS: In general, the results showed that most respondents (74.16%) ate three meals per day; 89.20% of the respondents consumed breakfast, while 88.57% consumed lunch and 91.97% consumed dinner with no significant difference in terms of sex. In Peninsular Malaysia, the Northern Zone had the highest number of people consuming breakfast compared to other zones. Meanwhile, the population in Sarawak had the largest proportion of people consuming lunch and dinner, but the smallest proportion of people consuming breakfast. A significantly higher number of the rural population consumed breakfast and lunch than urbanites; however there was no significant difference in dinner consumption. Generally, breakfast consumption increased with age whereby significant difference existed between the 18 to 19 years age group and the age group of 30 years and older. Lunch intake among the age groups showed no significant difference. In contrast, dinner consumption was significantly lower among the 18 to 19 years age group compared to all other age groups. Comparison among the ethnic groups showed that the Indian population had the lowest percentage of having breakfast and lunch while the Orang Asli had the lowest percentage of consuming dinner. However, the Orang Asli recorded the highest percentage for taking breakfast and lunch while the Chinese had the highest percentage of taking dinner.
CONCLUSION: Considering that Malaysian adults consumed their conventional breakfast, lunch and dinner, these findings indicatethat Malaysians are maintaining their traditional meal patterns.
Study name: Malaysian Adult Nutrition Survey (MANS-2003)
The superoxide dismutase mimetic tempol blunts diabetes-induced upregulation of NADPH oxidase and endoplasmic reticulum stress in a rat model of diabetic nephropathy

De Blasio MJ, Ramalingam A, Cao AH, Prakoso D, Ye JM, Pickering R, et al.

Eur J Pharmacol, 2017 Jul 15;807:12-20.
PMID: 28438648 DOI: 10.1016/j.ejphar.2017.04.026

Endoplasmic reticulum (ER) stress contributes to progression of diabetic nephropathy, which promotes end-stage renal failure in diabetic patients. This study was undertaken to investigate the actions of tempol and ramipril, pharmacological agents that target the consequences of NADPH oxidase, on diabetic nephropathy in a rat model of type 1 diabetes, with an emphasis on markers of ER stress. Male Sprague-Dawley rats were injected intravenously with a single bolus of streptozotocin (55mg/kg) to induce type 1 diabetes. An additional age-matched group of rats was administered with citrate vehicle as controls. After 4 weeks of untreated diabetes, rats received tempol (1.5mM/kg/day subcutaneously, n=8), ramipril (1mg/kg/day in drinking water, n=8) or remained untreated for an additional 4 weeks (n=7). After 8 weeks of diabetes in total, kidneys were collected for histological analysis, gene expression and protein abundance. Tempol and ramipril blunted diabetes-induced upregulation of NADPH oxidase isoforms (Nox4, Nox2, p47phox), accompanied by an amelioration of diabetes-induced glomerular injury (podocin, nephrin, Kim-1), tubulo-interstitial fibrosis (TGFβ1, TGFβ-R2, pSMAD3, α-SMA) and pro-inflammatory cytokines (TNFα, MCP-1, ANX-A1, FPR2) expression. In addition, the diabetes-induced renal ER stress, evidenced by increased expression of GRP-78 chaperone and stress-associated markers ATF4, TRB3, as well as XBP1s, phospho-p38 mitogen-activated protein kinase (MAPK) and 3-nitrotyrosination, were all attenuated by tempol and ramipril. These observations suggest that antioxidant approaches that blunt NADPH upregulation may attenuate diabetic nephropathy, at least in part by negatively regulating ER stress and inflammation, and hence ameliorating kidney damage.
Tackling membrane fouling in microalgae filtration using nylon 6,6 nanofiber membrane

Bilad MR, Azizo AS, Wirzal MDH, Jia Jia L, Putra ZA, Nordin NAHM, et al.

J Environ Manage, 2018 Oct 01;223:23-28.
PMID: 29885561 DOI: 10.1016/j.jenvman.2018.06.007

Microalgae technology, if managed properly, has promising roles in solving food-water-energy nexus. The Achilles' heel is, however, to lower the costs associated with cultivation and harvesting. As a favorable technique, application of membrane process is strongly limited by membrane fouling. This study evaluates performance of nylon 6,6 nanofiber membrane (NFM) to a conventional polyvinylidene fluoride phase inverted membrane (PVDF PIM) for filtration of Chlorella vulgaris. Results show that nylon 6,6 NFM is superhydrophilic, has higher size of pore opening (0.22 vs 0.18 μm) and higher surface pore density (23 vs 18 pores/μm2) leading to higher permeance (1018 vs 493 L/m2hbar) and better fouling resistant. Such advantages help to outperform the filterability of PVDF PIM by showing much higher steady-state permeance (286 vs 120 L/m2hbar), with comparable biomass retention. In addition, unlike for PVDF PIM, imposing longer relaxation cycles further enhances the performance of the NFM (i.e., 178 L/m2hbar for 0.5 min and 236 L/m2hbar for 5 min). Overall findings confirm the advantages of nylon 6,6 NFM over the PVDF PIM. Such advantages can help to reduce required membrane area and specific aeration demand by enabling higher flux and lowering aeration rate. Nevertheless, developments of nylon 6,6 NFM material with respect to its intrinsic properties, mechanical strength and operational conditions of the panel can still be explored to enhance its competitiveness as a promising fouling resistant membrane material for microalgae filtration.
Fulltext An extendable optical fibre probe survey meter for naturally occurring radioactive material (NORM) and other weak emitters

Zubair HT, Bradley DA, Khairina MD, Oresegun A, Basaif A, Othman J, et al.

Sci Rep, 2023 Jul 24;13(1):11918.
PMID: 37488183 DOI: 10.1038/s41598-023-39180-9

We have developed a radioluminescence-based survey meter for use in industries in which there is involvement in naturally occurring radioactive material (NORM), also in support of those needing to detect other weak emitters of radiation. The functionality of the system confronts particular shortcomings of the handheld survey meters that are currently being made use of. The device couples a LYSO:Ce scintillator with a photodetector via a polymer optical fibre waveguide, allowing for "intrinsically safe" inspection within pipework, separators, valves and other such component pieces. The small-diameter optical fibre probe is electrically passive, immune to electromagnetic interference, and chemically inert. The readout circuit is entirely incorporated within a handheld casing housing a silicon photomultiplier (SiPM) detection circuit and a microprocessor circuit connected to an LCD display. A 15 m long flexible PMMA optical fibre waveguide is butt coupled to an ABS plastic probe that retains the LYSO:Ce scintillator. Initial tests have included the use of lab-based mixed gamma-ray sources, measurements being made in concert with a reference conventional GM survey-meter. Characterization, via NORM sources at a decontamination facility, has shown useful sensitivity, covering the dose-rate range 0.10- to 28 µSv h-1 (R-squared 0.966), extending to 80 µSv/h as demonstrated in use of a Cs-137 source. The system is shown to provide an effective tool for detection of radioactivity within hard to access locations, in particular for sources emitting at low radiation levels, down to values that approach background.
Fulltext Methanol outbreak: a Malaysian tertiary hospital experience

Md Noor J, Hawari R, Mokhtar MF, Yussof SJ, Chew N, Norzan NA, et al.

Int J Emerg Med, 2020 Feb 07;13(1):6.
PMID: 32028888 DOI: 10.1186/s12245-020-0264-5

INTRODUCTION: Methanol poisoning usually occurs in a cluster and initial diagnosis can be challenging. Mortality is high without immediate interventions. This paper describes a methanol poisoning outbreak and difficulties in managing a large number of patients with limited resources.
METHODOLOGY: A retrospective analysis of a methanol poisoning outbreak in September 2018 was performed, describing patients who presented to a major tertiary referral centre.
RESULT: A total of 31 patients were received over the period of 9 days. Thirty of them were males with a mean age of 32 years old. They were mostly foreigners. From the 31 patients, 19.3% were dead on arrival, 3.2% died in the emergency department and 38.7% survived and discharged. The overall mortality rate was 61.3%. Out of the 12 patients who survived, two patients had toxic optic neuropathy, and one patient had uveitis. The rest of the survivors did not have any long-term complications. Osmolar gap and lactate had strong correlations with patient's mortality. Serum pH, bicarbonate, lactate, potassium, anion gap, osmolar gap and measured serum osmolarity between the alive and dead patients were significant. Post-mortem findings of the brain were unremarkable.
CONCLUSION: The mortality rate was higher, and the morbidity includes permanent visual impairment and severe neurological sequelae. Language barrier, severity of illness, late presentation, unavailability of intravenous ethanol and fomipezole and delayed dialysis may have been the contributing factors. Patient was managed based on clinical presentation. Laboratory parameters showed difference in median between group that survived and succumbed for pH, serum bicarbonate, lactate, potassium and osmolar and anion gap. Management of methanol toxicity outbreak in resource-limited area will benefit from a well-designed guideline that is adaptable to the locality.
A review on titanium oxide nanoparticles modified metal-organic frameworks for effective CO2 conversion and efficient wastewater remediation

Zango ZU, Khoo KS, Garba A, Garba ZN, Danmallam UN, Aldaghri O, et al.

Environ Res, 2024 Apr 30;252(Pt 3):119024.
PMID: 38692419 DOI: 10.1016/j.envres.2024.119024

Environmental pollution has been increasing since last decade due to increasing industrialisation and urbanisation. Various kinds ofenvironmental pollutants including carbon dioxide (CO2), dyes, pharmaceuticals, phenols, heavy metals along with many organic and inorganic species have been discovered in the various environmental compartments which possess harmful impacts tox human health, wildlife, and ecosystems. Thus, various efforts have been made through regulations, technological advancements, and public awareness campaigns to reduce the impact of the pollution. However, finding suitable alternatives to mitigate their impacts remained a challenge. Metal-organic frameworks (MOFs) are one of the advanced materials with unique features such as high porosity and stability which exhibit versatile applications in environmental remediation. Their composites with titanium oxide nanoparticles (TiO2) have been discovered to offer potential feature such as light harvesting capacity and catalytic activity. The composite integration and properties have been confirmed through characterization using surface area analysis, scanning electron/transmission electron microscopy, atomic force microscopy, fourier transformed infrared spectroscopy, X-ray diffraction analysis, X-ray photoelectron spectroscopy, thermogravimetric analysis, and others. Thus, this work rigorously discussed potential applications of the MOF@TiO2 nanomaterials for the CO2 capture and effective utilization in methanol, ethanol, acetone, acetaldehyde, and other useful products that served as fuel to various industrial processes. Additionally, the work highlights the effective performance of the materials towards photocatalytic degradation of both organic and inorganic pollutants with indepth mechanistic insights. The article will offer significant contribution for the development of sustainable and efficient technologies for the environmental monitoring and pollution mitigation.
Single-cell classification, analysis, and its application using deep learning techniques

Premkumar R, Srinivasan A, Harini Devi KG, M D, E G, Jadhav P, et al.

Biosystems, 2024 Mar;237:105142.
PMID: 38340976 DOI: 10.1016/j.biosystems.2024.105142

Single-cell analysis (SCA) improves the detection of cancer, the immune system, and chronic diseases from complicated biological processes. SCA techniques generate high-dimensional, innovative, and complex data, making traditional analysis difficult and impractical. In the different cell types, conventional cell sequencing methods have signal transformation and disease detection limitations. To overcome these challenges, various deep learning techniques (DL) have outperformed standard state-of-the-art computer algorithms in SCA techniques. This review discusses DL application in SCA and presents a detailed study on improving SCA data processing and analysis. Firstly, we introduced fundamental concepts and critical points of cell analysis techniques, which illustrate the application of SCA. Secondly, various effective DL strategies apply to SCA to analyze data and provide significant results from complex data sources. Finally, we explored DL as a future direction in SCA and highlighted new challenges and opportunities for the rapidly evolving field of single-cell omics.
Fulltext Spread of carbapenem-resistant Acinetobacter baumannii global clone 2 in Asia and AbaR-type resistance islands

Kim DH, Choi JY, Kim HW, Kim SH, Chung DR, Peck KR, et al.

Antimicrob Agents Chemother, 2013 Nov;57(11):5239-46.
PMID: 23939892 DOI: 10.1128/AAC.00633-13

In this surveillance study, we identified the genotypes, carbapenem resistance determinants, and structural variations of AbaR-type resistance islands among carbapenem-resistant Acinetobacter baumannii (CRAB) isolates from nine Asian locales. Clonal complex 92 (CC92), corresponding to global clone 2 (GC2), was the most prevalent in most Asian locales (83/108 isolates; 76.9%). CC108, or GC1, was a predominant clone in India. OXA-23 oxacillinase was detected in CRAB isolates from most Asian locales except Taiwan. blaOXA-24 was found in CRAB isolates from Taiwan. AbaR4-type resistance islands, which were divided into six subtypes, were identified in most CRAB isolates investigated. Five isolates from India, Malaysia, Singapore, and Hong Kong contained AbaR3-type resistance islands. Of these, three isolates harbored both AbaR3- and AbaR4-type resistance islands simultaneously. In this study, GC2 was revealed as a prevalent clone in most Asian locales, with the AbaR4-type resistance island predominant, with diverse variants. The significance of this study lies in identifying the spread of global clones of carbapenem-resistant A. baumannii in Asia.
Fulltext Quality of benzathine penicillin G: A multinational cross-sectional study

Hand RM, Senarathna SMDKG, Page-Sharp M, Gray K, Sika-Paotonu D, Sheel M, et al.

Pharmacol Res Perspect, 2020 12;8(6):e00668.
PMID: 33090729 DOI: 10.1002/prp2.668

Benzathine penicillin G (BPG) is used as first-line treatment for most forms of syphilis and as secondary prophylaxis against rheumatic heart disease (RHD). Perceptions that poor quality of BPG is linked to reported adverse effects and therapeutic failure may impact syphilis and RHD control programs. Clinical networks and web-based advertising were used to obtain vials of BPG from a wide range of countries. The quality of BPG was assessed using a high performance liquid chromatography assay capable of detecting relevant impurities and degradation products. Tests for water content, presence of heavy metals and physical characteristics of BPG, including particle size analysis and optical microscopy, also were conducted. Thirty-five batches of BPG were sourced from 16 countries across 4 WHO regions. All batches passed the US Pharmacopeia requirements for BPG injection (content), with no evidence of breakdown products or other detected contaminants. Water content and heavy metal analysis (n = 11) indicated adherence to regulatory standards and Good Manufacturing Practice. Particle size analysis (n = 20) found two batches with aggregated particles (>400 µm) that were dispersed following sonication. Current batches of BPG were of satisfactory pharmaceutical quality but aggregated particles were found in a modest proportion of samples. Future studies should focus on the physical characteristics of BPG which may contribute to variations in plasma penicillin concentrations an observed needle blockages in clinical practice. Pharmacopeial monographs could be revised to include standards on particle size and crystal morphology of BPG.
Fulltext A pathogenic role for tumor necrosis factor-related apoptosis-inducing ligand in chronic obstructive pulmonary disease

Haw TJ, Starkey MR, Nair PM, Pavlidis S, Liu G, Nguyen DH, et al.

Mucosal Immunol, 2016 Jul;9(4):859-72.
PMID: 26555706 DOI: 10.1038/mi.2015.111

Chronic obstructive pulmonary disease (COPD) is a life-threatening inflammatory respiratory disorder, often induced by cigarette smoke (CS) exposure. The development of effective therapies is impaired by a lack of understanding of the underlining mechanisms. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine with inflammatory and apoptotic properties. We interrogated a mouse model of CS-induced experimental COPD and human tissues to identify a novel role for TRAIL in COPD pathogenesis. CS exposure of wild-type mice increased TRAIL and its receptor messenger RNA (mRNA) expression and protein levels, as well as the number of TRAIL(+)CD11b(+) monocytes in the lung. TRAIL and its receptor mRNA were also increased in human COPD. CS-exposed TRAIL-deficient mice had decreased pulmonary inflammation, pro-inflammatory mediators, emphysema-like alveolar enlargement, and improved lung function. TRAIL-deficient mice also developed spontaneous small airway changes with increased epithelial cell thickness and collagen deposition, independent of CS exposure. Importantly, therapeutic neutralization of TRAIL, after the establishment of early-stage experimental COPD, reduced pulmonary inflammation, emphysema-like alveolar enlargement, and small airway changes. These data provide further evidence for TRAIL being a pivotal inflammatory factor in respiratory diseases, and the first preclinical evidence to suggest that therapeutic agents that target TRAIL may be effective in COPD therapy.
Fulltext The role of plasma microseminoprotein-beta in prostate cancer: an observational nested case-control and Mendelian randomization study in the European prospective investigation into cancer and nutrition

Smith Byrne K, Appleby PN, Key TJ, Holmes MV, Fensom GK, Agudo A, et al.

Ann Oncol, 2019 Jun 01;30(6):983-989.
PMID: 31089709 DOI: 10.1093/annonc/mdz121

BACKGROUND: Microseminoprotein-beta (MSP), a protein secreted by the prostate epithelium, may have a protective role in the development of prostate cancer. The only previous prospective study found a 2% reduced prostate cancer risk per unit increase in MSP. This work investigates the association of MSP with prostate cancer risk using observational and Mendelian randomization (MR) methods.
PATIENTS AND METHODS: A nested case-control study was conducted with the European Prospective Investigation into Cancer and Nutrition (EPIC) with 1871 cases and 1871 matched controls. Conditional logistic regression analysis was used to investigate the association of pre-diagnostic circulating MSP with risk of incident prostate cancer overall and by tumour subtype. EPIC-derived estimates were combined with published data to calculate an MR estimate using two-sample inverse-variance method.
RESULTS: Plasma MSP concentrations were inversely associated with prostate cancer risk after adjusting for total prostate-specific antigen concentration [odds ratio (OR) highest versus lowest fourth of MSP = 0.65, 95% confidence interval (CI) 0.51-0.84, Ptrend = 0.001]. No heterogeneity in this association was observed by tumour stage or histological grade. Plasma MSP concentrations were 66% lower in rs10993994 TT compared with CC homozygotes (per allele difference in MSP: 6.09 ng/ml, 95% CI 5.56-6.61, r2=0.42). MR analyses supported a potentially causal protective association of MSP with prostate cancer risk (OR per 1 ng/ml increase in MSP for MR: 0.96, 95% CI 0.95-0.97 versus EPIC observational: 0.98, 95% CI 0.97-0.99). Limitations include lack of complete tumour subtype information and more complete information on the biological function of MSP.
CONCLUSIONS: In this large prospective European study and using MR analyses, men with high circulating MSP concentration have a lower risk of prostate cancer. MSP may play a causally protective role in prostate cancer.
Fulltext Acute and sub-chronic toxicity of Liberin, an anti-diabetic polyherbal formulation in rats

Suvarna R, Suryakanth VB, Bakthavatchalam P, Kalthur G, Nayak M D, Prabhu MM, et al.

J Ayurveda Integr Med, 2023 Oct 15;14(6):100804.
PMID: 37847964 DOI: 10.1016/j.jaim.2023.100804

BACKGROUND: The polyherbal formulation (PHF) liberin, is known to exert anti-hyperglycemic effects in type 2 diabetes mellitus. Hence, it is important to study the safety profile of PHF in the current study through acute and chronic toxicity evaluation.
OBJECTIVES: This research aims to assess the acute and sub-chronic toxicity of PHF in rats.
MATERIALS AND METHODS: PHF was administered once orally (1000 mg/kg body weight), and the rats (male and female) were monitored for toxicity signs for a 14-day period. For a 28-day chronic toxicity study, rats were daily administered with PHF dose of 500 mg/kg and 1000 mg/kg body weight. Rats were followed up for mortality, weight changes, and other morbidities. Further haematological, biochemical, and histopathological changes were assessed.
RESULTS: No death related to treatment or toxicity signs were recorded in the acute single-dose administration group. The results showed that the PHF was tolerated well up to a dose of 1000 mg/kg body weight. Even at the high dose of 1000 mg/kg body weight, sub-chronic tests did not show any significant difference between the dosed and normal groups. No significant changes were seen in the histopathological analysis of the liver, spleen, and kidney as well as haematological and biochemical parameters in acute, sub-chronic and satellite groups following the administration of PHF.
CONCLUSION: The results confirmed that there was no adverse effect of this PHF at the maximum dose of 1000 mg/kg body weight in Wistar rats. Further, no adverse delayed effects related to PHF were observed in the satellite group. Therefore, this PHF appears safe for therapeutic purposes in the Ayurvedic medicinal system.
Fulltext Fruit and vegetable consumption in relation to hepatocellular carcinoma in a multi-centre, European cohort study

Bamia C, Lagiou P, Jenab M, Aleksandrova K, Fedirko V, Trichopoulos D, et al.

Br. J. Cancer, 2015 Mar 31;112(7):1273-82.
PMID: 25742480 DOI: 10.1038/bjc.2014.654

BACKGROUND: Vegetable and/or fruit intakes in association with hepatocellular carcinoma (HCC) risk have been investigated in case-control studies conducted in specific European countries and cohort studies conducted in Asia, with inconclusive results. No multi-centre European cohort has investigated the indicated associations.

METHODS: In 486,799 men/women from the European Prospective Investigation into Cancer and nutrition, we identified 201 HCC cases after 11 years median follow-up. We calculated adjusted hazard ratios (HRs) for HCC incidence for sex-specific quintiles and per 100 g d(-1) increments of vegetable/fruit intakes.

RESULTS: Higher vegetable intake was associated with a statistically significant, monotonic reduction of HCC risk: HR (100 g d(-1) increment): 0.83; 95% CI: 0.71-0.98. This association was consistent in sensitivity analyses with no apparent heterogeneity across strata of HCC risk factors. Fruit intake was not associated with HCC incidence: HR (100 g d(-1) increment): 1.01; 95% CI: 0.92-1.11.

CONCLUSIONS: Vegetable, but not fruit, intake is associated with lower HCC risk with no evidence for heterogeneity of this association in strata of important HCC risk factors. Mechanistic studies should clarify pathways underlying this association. Given that HCC prognosis is poor and that vegetables are practically universally accessible, our results may be important, especially for those at high risk for the disease.
Fulltext Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with metastatic colorectal cancer

Yoshino T, Cervantes A, Bando H, Martinelli E, Oki E, Xu RH, et al.

ESMO Open, 2023 Jun;8(3):101558.
PMID: 37236086 DOI: 10.1016/j.esmoop.2023.101558

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with metastatic colorectal cancer (mCRC), published in late 2022, were adapted in December 2022, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with mCRC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with mCRC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and the Japanese Society of Medical Oncology (JSMO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian countries. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with mCRC across the different countries of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices, molecular profiling and age and stage at presentation, coupled with a disparity in the drug approvals and reimbursement strategies, between the different countries.
Fulltext Biomarkers of folate and vitamin B12 and breast cancer risk: report from the EPIC cohort

Matejcic M, de Batlle J, Ricci C, Biessy C, Perrier F, Huybrechts I, et al.

Int J Cancer, 2017 Mar 15;140(6):1246-1259.
PMID: 27905104 DOI: 10.1002/ijc.30536

Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vitamin B12 and the risk of BC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Plasma concentrations of folate and vitamin B12 were determined in 2,491 BC cases individually matched to 2,521 controls among women who provided baseline blood samples. Multivariable logistic regression models were used to estimate odds ratios by quartiles of either plasma B vitamin. Subgroup analyses by menopausal status, hormone receptor status of breast tumors (estrogen receptor [ER], progesterone receptor [PR] and human epidermal growth factor receptor 2 [HER2]), alcohol intake and MTHFR polymorphisms (677C > T and 1298A > C) were also performed. Plasma levels of folate and vitamin B12 were not significantly associated with the overall risk of BC or by hormone receptor status. A marginally positive association was found between vitamin B12 status and BC risk in women consuming above the median level of alcohol (ORQ4-Q1 = 1.26; 95% CI 1.00-1.58; Ptrend = 0.05). Vitamin B12 status was also positively associated with BC risk in women with plasma folate levels below the median value (ORQ4-Q1 = 1.29; 95% CI 1.02-1.62; Ptrend = 0.03). Overall, folate and vitamin B12 status was not clearly associated with BC risk in this prospective cohort study. However, potential interactions between vitamin B12 and alcohol or folate on the risk of BC deserve further investigation.
Fulltext Circulating plasma phospholipid fatty acids and risk of pancreatic cancer in a large European cohort

Matejcic M, Lesueur F, Biessy C, Renault AL, Mebirouk N, Yammine S, et al.

Int J Cancer, 2018 Nov 15;143(10):2437-2448.
PMID: 30110135 DOI: 10.1002/ijc.31797

There are both limited and conflicting data on the role of dietary fat and specific fatty acids in the development of pancreatic cancer. In this study, we investigated the association between plasma phospholipid fatty acids and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The fatty acid composition was measured by gas chromatography in plasma samples collected at recruitment from375 incident pancreatic cancer cases and375 matched controls. Associations of specific fatty acids with pancreatic cancer risk were evaluated using multivariable conditional logistic regression models with adjustment for established pancreatic cancer risk factors. Statistically significant inverse associations were found between pancreatic cancer incidence and levels of heptadecanoic acid (ORT3-T1 [odds ratio for highest versus lowest tertile] =0.63; 95%CI[confidence interval] = 0.41-0.98; ptrend = 0.036), n-3 polyunsaturated α-linolenic acid (ORT3-T1 = 0.60; 95%CI = 0.39-0.92; ptrend = 0.02) and docosapentaenoic acid (ORT3-T1 = 0.52; 95%CI = 0.32-0.85; ptrend = 0.008). Industrial trans-fatty acids were positively associated with pancreatic cancer risk among men (ORT3-T1 = 3.00; 95%CI = 1.13-7.99; ptrend = 0.029), while conjugated linoleic acids were inversely related to pancreatic cancer among women only (ORT3-T1 = 0.37; 95%CI = 0.17-0.81; ptrend = 0.008). Among current smokers, the long-chain n-6/n-3 polyunsaturated fatty acids ratio was positively associated with pancreatic cancer risk (ORT3-T1 = 3.40; 95%CI = 1.39-8.34; ptrend = 0.007). Results were robust to a range of sensitivity analyses. Our findings suggest that higher circulating levels of saturated fatty acids with an odd number of carbon atoms and n-3 polyunsaturated fatty acids may be related to lower risk of pancreatic cancer. The influence of some fatty acids on the development of pancreatic cancer may be sex-specific and modulated by smoking.
Fulltext Complete genome and proteome of Acholeplasma laidlawii

Lazarev VN, Levitskii SA, Basovskii YI, Chukin MM, Akopian TA, Vereshchagin VV, et al.

J Bacteriol, 2011 Sep;193(18):4943-53.
PMID: 21784942 DOI: 10.1128/JB.05059-11

We present the complete genome sequence and proteogenomic map for Acholeplasma laidlawii PG-8A (class Mollicutes, order Acholeplasmatales, family Acholeplasmataceae). The genome of A. laidlawii is represented by a single 1,496,992-bp circular chromosome with an average G+C content of 31 mol%. This is the longest genome among the Mollicutes with a known nucleotide sequence. It contains genes of polymerase type I, SOS response, and signal transduction systems, as well as RNA regulatory elements, riboswitches, and T boxes. This demonstrates a significant capability for the regulation of gene expression and mutagenic response to stress. Acholeplasma laidlawii and phytoplasmas are the only Mollicutes known to use the universal genetic code, in which UGA is a stop codon. Within the Mollicutes group, only the sterol-nonrequiring Acholeplasma has the capacity to synthesize saturated fatty acids de novo. Proteomic data were used in the primary annotation of the genome, validating expression of many predicted proteins. We also detected posttranslational modifications of A. laidlawii proteins: phosphorylation and acylation. Seventy-four candidate phosphorylated proteins were found: 16 candidates are proteins unique to A. laidlawii, and 11 of them are surface-anchored or integral membrane proteins, which implies the presence of active signaling pathways. Among 20 acylated proteins, 14 contained palmitic chains, and six contained stearic chains. No residue of linoleic or oleic acid was observed. Acylated proteins were components of mainly sugar and inorganic ion transport systems and were surface-anchored proteins with unknown functions.

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