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Fulltext Early Nutrition eAcademy Southeast Asia e-Learning for Enhancing Knowledge on Nutrition during the First 1000 Days of Life

Brands B, Chomtho S, Suthutvoravut U, Chiong Meng Boey C, Tang SF, Godfrey KM, et al.

Nutrients, 2020 Jun 18;12(6).
PMID: 32570814 DOI: 10.3390/nu12061817

BACKGROUND: The double burden of both under- and overnutrition during the first 1000 days is highly prevalent in Southeast Asia (SEA), with major implications for lifelong health. Tackling this burden requires healthcare professionals (HCPs) to acquire evidence-based current knowledge and counselling skills. We assessed the needs of HCPs in SEA and developed a continuing medical education/professional development (CME/CPD) program using an e-learning platform to reduce existing gaps.
METHODS: European, Thai and Malaysian universities collaborated with SEA national nutrition associations in the Early Nutrition eAcademy Southeast Asia (ENeA SEA) project. We assessed HCPs' needs using questionnaires and mapped CME/CPD programmes and regulations through stakeholder questionnaires. Using a co-creation approach, we established an e-learning platform. Evaluation in users was undertaken using questionnaires.
RESULTS: HCPs in SEA reported major training gaps relating to the first 1000 days of nutrition and limited impact of existing face-to-face training. Existing pre/postgraduate, residency and CME/CPD programmes did not adequately address the topic. To address these gaps, we produced a targeted e-learning platform with six modules and CME-tests. National ministries, Thai and Malaysian universities, and professional associations endorsed the training platform. To date, over 2600 HCPs have registered. Evaluation shows high acceptance and a very positive assessment.
CONCLUSIONS: Dedicated e-learning can reduce major gaps in HCP training in SEA regarding nutrition during the first 1000 days of life at scale and is highly valued by both users and key stakeholders.
Fulltext Reduced cardiomyocyte Na+ current in the age-dependent murine Pgc-1β-/- model of ventricular arrhythmia

Ahmad S, Valli H, Smyth R, Jiang AY, Jeevaratnam K, Matthews HR, et al.

J Cell Physiol, 2019 Apr;234(4):3921-3932.
PMID: 30146680 DOI: 10.1002/jcp.27183

Peroxisome proliferator-activated receptor-γ coactivator-1 deficient (Pgc-1β-/- ) murine hearts model the increased, age-dependent, ventricular arrhythmic risks attributed to clinical conditions associated with mitochondrial energetic dysfunction. These were accompanied by compromised action potential (AP) upstroke rates and impaired conduction velocities potentially producing arrhythmic substrate. We tested a hypothesis implicating compromised Na+ current in these electrophysiological phenotypes by applying loose patch-clamp techniques in intact young and aged, wild-type (WT) and Pgc-1β-/- , ventricular cardiomyocyte preparations for the first time. This allowed conservation of their in vivo extracellular and intracellular conditions. Depolarising steps elicited typical voltage-dependent activating and inactivating inward Na+ currents with peak amplitudes increasing or decreasing with their respective activating or preceding inactivating voltage steps. Two-way analysis of variance associated Pgc-1β-/- genotype with independent reductions in maximum peak ventricular Na+ currents from -36.63 ± 2.14 (n = 20) and -35.43 ± 1.96 (n = 18; young and aged WT, respectively), to -29.06 ± 1.65 (n = 23) and -27.93 ± 1.63 (n = 20; young and aged Pgc-1β-/- , respectively) pA/μm2 (p
Fulltext Ventricular pro-arrhythmic phenotype, arrhythmic substrate, ageing and mitochondrial dysfunction in peroxisome proliferator activated receptor-γ coactivator-1β deficient (Pgc-1β-/-) murine hearts

Ahmad S, Valli H, Chadda KR, Cranley J, Jeevaratnam K, Huang CL

Mech Ageing Dev, 2018 Jul;173:92-103.
PMID: 29763629 DOI: 10.1016/j.mad.2018.05.004

INTRODUCTION: Ageing and age-related bioenergetic conditions including obesity, diabetes mellitus and heart failure constitute clinical ventricular arrhythmic risk factors.
MATERIALS AND METHODS: Pro-arrhythmic properties in electrocardiographic and intracellular recordings were compared in young and aged, peroxisome proliferator-activated receptor-γ coactivator-1β knockout (Pgc-1β-/-) and wild type (WT), Langendorff-perfused murine hearts, during regular and programmed stimulation (PES), comparing results by two-way ANOVA.
RESULTS AND DISCUSSION: Young and aged Pgc-1β-/- showed higher frequencies and durations of arrhythmic episodes through wider PES coupling-interval ranges than WT. Both young and old, regularly-paced, Pgc-1β-/- hearts showed slowed maximum action potential (AP) upstrokes, (dV/dt)max (∼157 vs. 120-130 V s-1), prolonged AP latencies (by ∼20%) and shortened refractory periods (∼58 vs. 51 ms) but similar AP durations (∼50 ms at 90% recovery) compared to WT. However, Pgc-1β-/- genotype and age each influenced extrasystolic AP latencies during PES. Young and aged WT ventricles displayed distinct, but Pgc-1β-/- ventricles displayed similar dependences of AP latency upon (dV/dt)max resembling aged WT. They also independently increased myocardial fibrosis. AP wavelengths combining activation and recovery terms paralleled contrasting arrhythmic incidences in Pgc-1β-/- and WT hearts. Mitochondrial dysfunction thus causes pro-arrhythmic Pgc-1β-/- phenotypes by altering AP conduction through reducing (dV/dt)max and causing age-dependent fibrotic change.
Financial toxicity associated with a cancer diagnosis in publicly funded healthcare countries: a systematic review

Longo CJ, Fitch MI, Banfield L, Hanly P, Yabroff KR, Sharp L

Support Care Cancer, 2020 Oct;28(10):4645-4665.
PMID: 32653957 DOI: 10.1007/s00520-020-05620-9

PURPOSE: Financial toxicity related to cancer diagnosis and treatment is a common issue in developed countries. We seek to systematically summarize the extent of the issue in very high development index countries with publicly funded healthcare.
METHODS: We identified articles published Jan 1, 2005, to March 7, 2019, describing financial burden/toxicity experienced by cancer patients and/or informal caregivers using OVID Medline Embase and PsychInfo, CINAHL, Business Source Complete, and EconLit databases. Only English language peer-reviewed full papers describing studies conducted in very high development index countries with predominantly publicly funded healthcare were eligible (excluded the USA). All stages of the review were evaluated in teams of two researchers excepting the final data extraction (CJL only).
RESULTS: The searches identified 7117 unique articles, 32 of which were eligible. Studies were undertaken in Canada, Australia, Ireland, UK, Germany, Denmark, Malaysia, Finland, France, South Korea, and the Netherlands. Eighteen studies reported patient/caregiver out-of-pocket costs (range US$17-US$506/month), 18 studies reported patient/caregiver lost income (range 17.6-67.3%), 14 studies reported patient/caregiver travel and accommodation costs (range US$8-US$393/month), and 6 studies reported financial stress (range 41-48%), strain (range 7-39%), or financial burden/distress/toxicity among patients/caregivers (range 22-27%). The majority of studies focused on patients, with some including caregivers. Financial toxicity was greater in those with early disease and/or more severe cancers.
CONCLUSIONS: Despite government-funded universal public healthcare, financial toxicity is an issue for cancer patients and their families. Although levels of toxicity vary between countries, the findings suggest financial protection appears to be inadequate in many countries.
Fulltext Characterization of the highly active polyhydroxyalkanoate synthase of Chromobacterium sp. strain USM2

Bhubalan K, Chuah JA, Shozui F, Brigham CJ, Taguchi S, Sinskey AJ, et al.

Appl Environ Microbiol, 2011 May;77(9):2926-33.
PMID: 21398494 DOI: 10.1128/AEM.01997-10

The synthesis of bacterial polyhydroxyalkanoates (PHA) is very much dependent on the expression and activity of a key enzyme, PHA synthase (PhaC). Many efforts are being pursued to enhance the activity and broaden the substrate specificity of PhaC. Here, we report the identification of a highly active wild-type PhaC belonging to the recently isolated Chromobacterium sp. USM2 (PhaC(Cs)). PhaC(Cs) showed the ability to utilize 3-hydroxybutyrate (3HB), 3-hydroxyvalerate (3HV), and 3-hydroxyhexanoate (3HHx) monomers in PHA biosynthesis. An in vitro assay of recombinant PhaC(Cs) expressed in Escherichia coli showed that its polymerization of 3-hydroxybutyryl-coenzyme A activity was nearly 8-fold higher (2,462 ± 80 U/g) than that of the synthase from the model strain C. necator (307 ± 24 U/g). Specific activity using a Strep2-tagged, purified PhaC(Cs) was 238 ± 98 U/mg, almost 5-fold higher than findings of previous studies using purified PhaC from C. necator. Efficient poly(3-hydroxybutyrate) [P(3HB)] accumulation in Escherichia coli expressing PhaC(Cs) of up to 76 ± 2 weight percent was observed within 24 h of cultivation. To date, this is the highest activity reported for a purified PHA synthase. PhaC(Cs) is a naturally occurring, highly active PHA synthase with superior polymerizing ability.
Fulltext Making seafood accessible to low-income and nutritionally vulnerable populations on the U.S. West Coast

Koehn JZ, Quinn EL, Otten JJ, Allison EH, Anderson CM

J Agric Food Syst Community Dev, 2020;10(1):171-189.
PMID: 33996191 DOI: 10.5304/jafscd.2020.101.027

Along the U.S. West Coast, sustainable management has rebuilt fish stocks, providing an opportunity to supply nutrient-rich food to adjacent coastal communities where food insecurity and diet-based diseases are common. However, the market has not successfully supplied locally sourced seafood to nutritionally vulnerable people. Rather, a few organizations make this connection on a limited scale. We used a "positive deviant" approach to learn how these organizations' efforts developed, how they overcame challenges, and what conditions enabled their interventions. We found that organizations in these positive deviant cases provided fish from a wide variety of species and sources, and distributed them through different channels to a diversity of end consumers. A key factor facilitating success was the ability to negotiate a price point that was both profitable and reasonable for organizations supplying nutritionally vulnerable or low-income consumers. Further-more, securing access to grants overcame initial costs of establishing new supply channels. All cases highlighted the importance of individual champions who encouraged development and cultural connections between the initiative and the nearby community. Organizations overcame key challenges by establishing regulations governing these new channels and either using partnerships or vertically integrating to reduce costs associated with processing and transport. Oftentimes training and education were also critical to instruct workers on how to process unfamiliar fish and to increase consumer awareness of local fish and how to prepare them. These lessons illuminate pathways to improve the contribution of local seafood to the healthy food system.
Fulltext Poor Sleep Quality, Depression and Social Support Are Determinants of Serum Phosphate Level among Hemodialysis Patients in Malaysia

Ng ESY, Wong PY, Kamaruddin ATH, Lim CTS, Chan YM

Int J Environ Res Public Health, 2020 Jul 16;17(14).
PMID: 32708766 DOI: 10.3390/ijerph17145144

Despite optimal control of serum phosphate level being imperative to avoid undesirable health outcomes, hyperphosphataemia is a highly prevalent mineral abnormality among the dialysis population. This study aimed to determine factors associated with hyperphosphatemia among hemodialysis patients in Malaysia. Multiple linear regression analysis was used to ascertain the possible factors that influence serum phosphate levels. A total of 217 hemodialysis patients were recruited. Hyperphosphatemia was prevalent. Only approximately 25% of the patients were aware that optimal control of hyperphosphatemia requires the combined effort of phosphate binder medication therapy, dietary restriction, and dialysis prescription. The presence of diabetes mellitus may affect serum phosphate levels, complicating dietary phosphorus management. Patients who were less depressive portrayed higher serum phosphate levels, implying intentional non-compliance. Better compliance on phosphate binder, longer sleep duration, and higher social support was associated with a lower level of serum phosphate. Despite sleep disturbance being one of the most prevalent and intense symptom burdens identified by hemodialysis patients, relatively few studies have addressed this issue. It is time to formulate sleep therapeutic interventions besides the encouragement of strong social support, hoping which many clinical outcomes including hyperphosphatemia can be better controlled among hemodialysis patients.
Fulltext Multiple targets for flecainide action: implications for cardiac arrhythmogenesis

Salvage SC, Chandrasekharan KH, Jeevaratnam K, Dulhunty AF, Thompson AJ, Jackson AP, et al.

Br J Pharmacol, 2018 Apr;175(8):1260-1278.
PMID: 28369767 DOI: 10.1111/bph.13807

Flecainide suppresses cardiac tachyarrhythmias including paroxysmal atrial fibrillation, supraventricular tachycardia and arrhythmic long QT syndromes (LQTS), as well as the Ca2+ -mediated, catecholaminergic polymorphic ventricular tachycardia (CPVT). However, flecainide can also exert pro-arrhythmic effects most notably following myocardial infarction and when used to diagnose Brugada syndrome (BrS). These divergent actions result from its physiological and pharmacological actions at multiple, interacting levels of cellular organization. These were studied in murine genetic models with modified Nav channel or intracellular ryanodine receptor (RyR2)-Ca2+ channel function. Flecainide accesses its transmembrane Nav 1.5 channel binding site during activated, open, states producing a use-dependent antagonism. Closing either activation or inactivation gates traps flecainide within the pore. An early peak INa related to activation of Nav channels followed by rapid de-activation, drives action potential (AP) upstrokes and their propagation. This is diminished in pro-arrhythmic conditions reflecting loss of function of Nav 1.5 channels, such as BrS, accordingly exacerbated by flecainide challenge. Contrastingly, pro-arrhythmic effects attributed to prolonged AP recovery by abnormal late INaL following gain-of-function modifications of Nav 1.5 channels in LQTS3 are reduced by flecainide. Anti-arrhythmic effects of flecainide that reduce triggering in CPVT models mediated by sarcoplasmic reticular Ca2+ release could arise from its primary actions on Nav channels indirectly decreasing [Ca2+ ]i through a reduced [Na+ ]i and/or direct open-state RyR2-Ca2+ channel antagonism. The consequent [Ca2+ ]i alterations could also modify AP propagation velocity and therefore arrhythmic substrate through its actions on Nav 1.5 channel function. This is consistent with the paradoxical differences between flecainide actions upon Na+ currents, AP conduction and arrhythmogenesis under circumstances of normal and increased RyR2 function.
LINKED ARTICLES: This article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc.
Fulltext Wealthy countries dominate industrial fishing

McCauley DJ, Jablonicky C, Allison EH, Golden CD, Joyce FH, Mayorga J, et al.

Sci Adv, 2018 Aug;4(8):eaau2161.
PMID: 30083613 DOI: 10.1126/sciadv.aau2161

The patterns by which different nations share global fisheries influence outcomes for food security, trajectories of economic development, and competition between industrial and small-scale fishing. We report patterns of industrial fishing effort for vessels flagged to higher- and lower-income nations, in marine areas within and beyond national jurisdiction, using analyses of high-resolution fishing vessel activity data. These analyses reveal global dominance of industrial fishing by wealthy nations. Vessels flagged to higher-income nations, for example, are responsible for 97% of the trackable industrial fishing on the high seas and 78% of such effort within the national waters of lower-income countries. These publicly accessible vessel tracking data have important limitations. However, insights from these new analyses can begin to strategically inform important international- and national-level efforts underway now to ensure equitable and sustainable sharing of fisheries.
Adolescents and young adults with cancer: Considerations from the Southeast Asian perspective

Dee EC, Eala MAB, Chua MLK, Bray F, Bhoo-Pathy N

Pediatr Blood Cancer, 2022 Jul;69(7):e29593.
PMID: 35129873 DOI: 10.1002/pbc.29593
Fulltext Proximate Analysis and Safety Profile of Farmed Edible Bird's Nest in Malaysia and Its Effect on Cancer Cells

Tan SN, Sani D, Lim CW, Ideris A, Stanslas J, Lim CTS

Evid Based Complement Alternat Med, 2020;2020:8068797.
PMID: 32051689 DOI: 10.1155/2020/8068797

Edible bird's nest (EBN) which is solidified swiftlet's saliva contains high nutritional value. It is widely consumed in countries like Malaysia, Indonesia, and Thailand. However, previous proximate analysis of Malaysia EBN was not representative of all the regions in Malaysia. In recent years, safety issues such as high nitrate and nitrite contents, presence of heavy metal, adulteration, fungal infection, and cancer cell stimulation were associated with EBN. Hence, this study aimed to determine the proximate analysis, safety profile during normal weather and hazy periods, and its effect on cancer cells stimulation in Malaysia-farmed EBN. Seven raw cleaned EBN samples were sourced from 6 different regions in Malaysia. Proximate analysis and safety profile were performed using official AOCA methods and Malaysian Standard. High protein (53.03-56.37%) and carbohydrate content (27.97-31.68%) with an acceptable level of moisture (10.8-14.04%) and ash (2.22-3.38%) were reported. A good safety profile was obtained with low nitrite and nitrate levels, with undetectable heavy metals and no significant growth of pathogenic microorganism except mould. Epidermal growth factor was detected but below the quantification level with the chicken EGF ELISA kit. The microculture tetrazolium (MTT) assay was performed for growth stimulation assessment comparing human EGF and EBN. There was no significant cell growth observed in cancer cells after EBN treatment. In conclusion, EBN Malaysia has a good nutritional profile, free of heavy metals, and an acceptable level of nitrate, nitrite, and microorganism profile except for mould contents. Furthermore, the in vitro study indicated that EBN was not associated with cancer cell growth.
Fulltext Digging deeper: new gene order rearrangements and distinct patterns of codons usage in mitochondrial genomes among shrimps from the Axiidea, Gebiidea and Caridea (Crustacea: Decapoda)

Tan MH, Gan HM, Lee YP, Poore GC, Austin CM

PeerJ, 2017;5:e2982.
PMID: 28265498 DOI: 10.7717/peerj.2982

BACKGROUND: Whole mitochondrial DNA is being increasingly utilized for comparative genomic and phylogenetic studies at deep and shallow evolutionary levels for a range of taxonomic groups. Although mitogenome sequences are deposited at an increasing rate into public databases, their taxonomic representation is unequal across major taxonomic groups. In the case of decapod crustaceans, several infraorders, including Axiidea (ghost shrimps, sponge shrimps, and mud lobsters) and Caridea (true shrimps) are still under-represented, limiting comprehensive phylogenetic studies that utilize mitogenomic information.
METHODS: Sequence reads from partial genome scans were generated using the Illumina MiSeq platform and mitogenome sequences were assembled from these low coverage reads. In addition to examining phylogenetic relationships within the three infraorders, Axiidea, Gebiidea, and Caridea, we also investigated the diversity and frequency of codon usage bias and mitogenome gene order rearrangements.
RESULTS: We present new mitogenome sequences for five shrimp species from Australia that includes two ghost shrimps, Callianassa ceramica and Trypaea australiensis, along with three caridean shrimps, Macrobrachium bullatum, Alpheus lobidens, and Caridina cf. nilotica. Strong differences in codon usage were discovered among the three infraorders and significant gene order rearrangements were observed. While the gene order rearrangements are congruent with the inferred phylogenetic relationships and consistent with taxonomic classification, they are unevenly distributed within and among the three infraorders.
DISCUSSION: Our findings suggest potential for mitogenome rearrangements to be useful phylogenetic markers for decapod crustaceans and at the same time raise important questions concerning the drivers of mitogenome evolution in different decapod crustacean lineages.
Fulltext Evaluation of the I-PLAN Intervention to Promote Hearing Aid Use in New Adult Users: a Randomized Controlled Trial

Ismail AH, Armitage CJ, Munro KJ, Marsden A, Dawes PD

Ear Hear, 2022 01 06;43(4):1103-1113.
PMID: 34999593 DOI: 10.1097/AUD.0000000000001195

OBJECTIVE: Provision of information is already part of standard care and may not be sufficient to promote hearing aid use. The I-PLAN is a behavior change intervention that is designed to promote hearing aid use in adults. It consists of a prompt, an action plan and provision of information. The objective was to test the effectiveness of the I-PLAN prompt and plan components in promoting hearing aid use and benefit. Hypotheses were: there would be greater hearing aid use, benefit, self-regulation, and hearing aid use habit among participants who received the prompt or plan component, compared with no prompt or no plan component, and the effect would be the greatest in participants who received both prompt and plan; and self-regulation and habit would mediate the effect of prompt and/or plan components on hearing aid use and benefit.
DESIGN: A 2 x 2 factorial randomized controlled trial design. Two hundred forty new adult patients (60 in each group) were randomized to: information (info) only; info + prompt; info + plan; or info + prompt + plan. All participants received treatment as usual in addition to I-PLAN components, which were provided in a sealed envelope at the end of the hearing aid fitting consultation. Participants in the prompt group were instructed to use their hearing aid box as a physical prompt to remind them to use the device. Participants in the plan group were instructed to write an action plan to encourage them to turn their intentions into action. Participants, audiologists, and researchers were blinded to group allocation. The primary outcome was self-reported proportion of time hearing aids were used in situations where they had listening difficulties. Secondary outcomes were hearing aid use derived from data logging, self-reported hearing aid benefit, self-reported self-regulation, and habit. Outcomes were measured at 6-week post-fitting.
RESULTS: Contrary to predictions, participants who received the prompt component reported using their hearing aid less than participants without the prompt (p = 0.03; d = 0.24). The mean proportion of time hearing aid were used was 73.4% of the time in the prompt group compared with 79.9% of the time in the no prompt group. Participants who received the plan component reported using their hearing aids more frequently than those who did not receive the plan (Meanplan = 81.0% vs Meannoplan = 71.8% of the time; p = 0.01; d = 0.34). Receiving both prompt and plan components did not change self-reported proportion of time hearing aids were used but data-logging use was significantly reduced. The prompt reduced self-regulation of hearing aid use compared with the no prompt (p = 0.04; d = 0.28), while the plan promoted stronger hearing aid use habits than the no plan group (p = 0.02; d = 0.30).
CONCLUSIONS: Audiologists should consider using action plans to promote hearing aid use. Despite the decrease in hearing aid use when using the hearing aid box as a physical prompt, hearing aid use was still high (≈70% of the time). The hearing aid box may have slightly reduced hearing aid use by undermining self-regulation. Participants may have delegated responsibility for hearing aid use to the prompt. Subsequent studies should evaluate different prompts and test the long-term benefit of the plan on hearing aid use via habit formation.
Fulltext Protein Profiling in Human Papillomavirus-Associated Cervical Carcinogenesis: Cornulin as a Biomarker for Disease Progression

Kumarasamy G, Ismail MN, Tuan Sharif SE, Desire C, Mittal P, Hoffmann P, et al.

Curr Issues Mol Biol, 2023 Apr 20;45(4):3603-3627.
PMID: 37185759 DOI: 10.3390/cimb45040235

Nearly 90% of cervical cancers are linked to human papillomavirus (HPV). Uncovering the protein signatures in each histological phase of cervical oncogenesis provides a path to biomarker discovery. The proteomes extracted from formalin-fixed paraffin-embedded tissues of the normal cervix, HPV16/18-associated squamous intraepithelial lesion (SIL), and squamous cell carcinoma (SCC) were compared using liquid chromatography-mass spectrometry (LC-MS). A total of 3597 proteins were identified, with 589, 550, and 1570 proteins unique to the normal cervix, SIL, and SCC groups, respectively, while 332 proteins overlapped between the three groups. In the transition from normal cervix to SIL, all 39 differentially expressed proteins were downregulated, while all 51 proteins discovered were upregulated in SIL to SCC. The binding process was the top molecular function, while chromatin silencing in the SIL vs. normal group, and nucleosome assembly in SCC vs. SIL groups was the top biological process. The PI3 kinase pathway appears crucial in initiating neoplastic transformation, while viral carcinogenesis and necroptosis are important for cell proliferation, migration, and metastasis in cervical cancer development. Annexin A2 and cornulin were selected for validation based on LC-MS results. The former was downregulated in the SIL vs. normal cervix and upregulated in the progression from SIL to SCC. In contrast, cornulin exhibited the highest expression in the normal cervix and lowest in SCC. Although other proteins, such as histones, collagen, and vimentin, were differentially expressed, their ubiquitous expression in most cells precluded further analysis. Immunohistochemical analysis of tissue microarrays found no significant difference in Annexin A2 expression between the groups. Conversely, cornulin exhibited the strongest expression in the normal cervix and lowest in SCC, supporting its role as a tumor suppressor and potential biomarker for disease progression.
Physiological characteristics and performance of a world-record breaking tower runner

Loh TC, Tee CCL, Pok C, Girard O, Brickley G, James C

J Sports Sci, 2023 Mar;41(5):451-455.
PMID: 37286473 DOI: 10.1080/02640414.2023.2221957

This study reports the physiological and performance profiles of a world-class tower runner during a 6-week period surrounding a successful Guinness World Record (WR) attempt, and discusses the efficacy of a tower running specific field test. The world-ranked number 2 tower runner completed four exercise tests [laboratory treadmill assessment (3 weeks before the WR attempt), familiarisation to a specific incremental tower running field test (1 week before), tower running field test (1 week after), and tower running time trial (TT) (3 weeks after)] and the WR attempt within 6-week period. Peak oxygen consumption (VO2peak) during the laboratory test, field test, and TT were 73.3, 75.5 and 78.3 mL·kg-1·min-1, respectively. The VO2 corresponding to the second ventilatory threshold was 67.3 mL·kg-1·min-1 (89.1% of VO2peak), identified at stage 4 (tempo; 100 b·min-1), during the field test. The duration of the TT was 10 min 50 s, with an average VO2 of 71.7 mL·kg-1·min-1 (91.6% of VO2peak), HR of 171 b·min-1 (92% of peak HR), vertical speed of 0.47 m·s-1, and cadence was 117 steps·min-1. A world-class tower runner possesses a well-developed aerobic capacity. A specific, field-based test revealed greater VO2peak than a laboratory test, indicating a need for sport-specific testing procedures.
Fulltext The association between subcortical and cortical fMRI and lifetime noise exposure in listeners with normal hearing thresholds

Dewey RS, Francis ST, Guest H, Prendergast G, Millman RE, Plack CJ, et al.

Neuroimage, 2020 Jan 01;204:116239.
PMID: 31586673 DOI: 10.1016/j.neuroimage.2019.116239

In animal models, exposure to high noise levels can cause permanent damage to hair-cell synapses (cochlear synaptopathy) for high-threshold auditory nerve fibers without affecting sensitivity to quiet sounds. This has been confirmed in several mammalian species, but the hypothesis that lifetime noise exposure affects auditory function in humans with normal audiometric thresholds remains unconfirmed and current evidence from human electrophysiology is contradictory. Here we report the auditory brainstem response (ABR), and both transient (stimulus onset and offset) and sustained functional magnetic resonance imaging (fMRI) responses throughout the human central auditory pathway across lifetime noise exposure. Healthy young individuals aged 25-40 years were recruited into high (n = 32) and low (n = 30) lifetime noise exposure groups, stratified for age, and balanced for audiometric threshold up to 16 kHz fMRI demonstrated robust broadband noise-related activity throughout the auditory pathway (cochlear nucleus, superior olivary complex, nucleus of the lateral lemniscus, inferior colliculus, medial geniculate body and auditory cortex). fMRI responses in the auditory pathway to broadband noise onset were significantly enhanced in the high noise exposure group relative to the low exposure group, differences in sustained fMRI responses did not reach significance, and no significant group differences were found in the click-evoked ABR. Exploratory analyses found no significant relationships between the neural responses and self-reported tinnitus or reduced sound-level tolerance (symptoms associated with synaptopathy). In summary, although a small effect, these fMRI results suggest that lifetime noise exposure may be associated with central hyperactivity in young adults with normal hearing thresholds.
Neutron-activated theranostic radionuclides for nuclear medicine

Tan HY, Yeong CH, Wong YH, McKenzie M, Kasbollah A, Md Shah MN, et al.

Nucl Med Biol, 2020;90-91:55-68.
PMID: 33039974 DOI: 10.1016/j.nucmedbio.2020.09.005

Theranostics in nuclear medicine refers to personalized patient management that involves targeted therapy and diagnostic imaging using a single or combination of radionuclide (s). The radionuclides emit both alpha (α) or beta (β-) particles and gamma (γ) rays which possess therapeutic and diagnostic capabilities, respectively. However, the production of these radionuclides often faces difficulties due to high cost, complexity of preparation methods and that the products are often sourced far from the healthcare facilities, hence losing activity due to radioactive decay during transportation. Subject to the availability of a nuclear reactor within an accessible distance from healthcare facilities, neutron activation is the most practical and cost-effective route to produce radionuclides suitable for theranostic purposes. Holmium-166 (166Ho), Lutetium-177 (177Lu), Rhenium-186 (186Re), Rhenium-188 (188Re) and Samarium-153 (153Sm) are some of the most promising neutron-activated radionuclides that are currently in clinical practice and undergoing clinical research for theranostic applications. The aim of this paper is to review the physical characteristics, current clinical applications and future prospects of these neutron activated radionuclides in theranostics. The production, physical properties, validated clinical applications and clinical studies for each neutron-activated radionuclide suitable for theranostic use in nuclear medicine are reviewed in this paper.
Fulltext Three-Component Access to Functionalized Spiropyrrolidine Heterocyclic Scaffolds and Their Cholinesterase Inhibitory Activity

Boudriga S, Haddad S, Murugaiyah V, Askri M, Knorr M, Strohmann C, et al.

Molecules, 2020 Apr 23;25(8).
PMID: 32340203 DOI: 10.3390/molecules25081963

A novel one-pot [3+2]-cycloaddition reaction of (E)-3-arylidene-1-phenyl-succinimides, cyclic 1,2-diketones (isatin, 5-chloro-isatin and acenaphtenequinone), and diverse α-aminoacids such as 2-phenylglycine or sarcosine is reported. The reaction provides succinimide-substituted dispiropyrrolidine derivatives with high regio- and diastereoselectivities under mild reaction conditions. The stereochemistry of these N-heterocycles has been confirmed by four X-ray diffraction studies. Several synthetized compounds show higher inhibition on acetylcholinesterase (AChE) than butyrylcholinesterase (BChE). Of the 17 synthesized compounds tested, five exhibit good AChE inhibition with IC50 of 11.42 to 22.21 µM. A molecular docking study has also been undertaken for compound 4n possessing the most potent AChE inhibitory activity, disclosing its binding to the peripheral anionic site of AChE enzymes.
Fulltext Effects of ageing on pro-arrhythmic ventricular phenotypes in incrementally paced murine Pgc-1β -/- hearts

Ahmad S, Valli H, Edling CE, Grace AA, Jeevaratnam K, Huang CL

Pflugers Arch, 2017 Dec;469(12):1579-1590.
PMID: 28821956 DOI: 10.1007/s00424-017-2054-3

A range of chronic clinical conditions accompany cardiomyocyte energetic dysfunction and constitute independent risk factors for cardiac arrhythmia. We investigated pro-arrhythmic and arrhythmic phenotypes in energetically deficient C57BL mice with genetic ablation of the mitochondrial promoter peroxisome proliferator-activated receptor-γ coactivator-1β (Pgc-1β), a known model of ventricular arrhythmia. Pro-arrhythmic and cellular action potential (AP) characteristics were compared in intact Langendorff-perfused hearts from young (12-16 week) and aged (> 52 week), wild-type (WT) and Pgc-1β -/- mice. Simultaneous electrocardiographic and intracellular microelectrode recordings were made through successive trains of 100 regular stimuli at progressively incremented heart rates. Aged Pgc-1β -/- hearts displayed an increased incidence of arrhythmia compared to other groups. Young and aged Pgc-1β -/- hearts showed higher incidences of alternans in both AP activation (maximum AP upshoot velocity (dV/dt)max and latency), recovery (action potential duration (APD90) and resting membrane potential (RMP) characteristics compared to WT hearts. This was particularly apparent at lower pacing frequencies. These findings accompanied reduced (dV/dt)max and increased AP latency values in the Pgc-1β -/- hearts. APs observed prior to termination of the protocol showed lower (dV/dt)max and longer AP latencies, but indistinguishable APD90 and RMPs in arrhythmic compared to those in non-arrhythmic hearts. APD restitution analysis showed that Pgc-1β -/- and WT hearts showed similar limiting gradients. However, Pgc-1β -/- hearts had shortened plateau AP wavelengths, particularly in aged Pgc-1β -/- hearts. Pgc-1β -/- hearts therefore show pro-arrhythmic instabilities attributable to altered AP conduction and activation rather than recovery characteristics.
Fulltext Determination of the Most Efficient Household Technique for the Reduction of Pesticide Residues from Raw Fish Muscles

Islam MA, Amin SMN, Brown CL, Juraimi AS, Uddin MK, Arshad A

Foods, 2022 Apr 27;11(9).
PMID: 35563977 DOI: 10.3390/foods11091254

Substantial quantities of pesticides are routinely applied to enhance agricultural crop production. Pesticides used in this way continuously accumulate in the environment and in foods. Harvested crops contain pesticide residues at various concentrations, with potential harmful impacts on human health. Hence, it is of value to identify techniques for the effective decontamination of tainted foods. However, cleaning with water or household agents, e.g., acetic acid and sodium bicarbonate, are recognized treatments for the efficient degradation of pesticides from vegetables and fruits. There is an apparent void of information about the decontamination treatments for raw fishes using household agents that are affordable for all classes of consumers. Hence, the present study was performed to determine the most efficient household technique for reducing pesticide residue levels from precooked raw fish to ensure the utmost food safety. Fish muscles of four species of fishes, viz., Clarias gariepinus, Channa striatus, Anabas testudineus and Trichogaster trichopterus, were treated with six treatments: washing with running tap water (T1), dipping in normal water (T2), dipping in 2% salt solution (T3), dipping in 2% vinegar (T4), dipping in 0.1% sodium bicarbonate solution (T5) as well as dipping in 0.1% sodium bicarbonate solution + 2% vinegar + 2% salt solution + lemon juice (T6), as fish muscle is the major consumable portion of fish. The current study demonstrated that the removal percentage of lindane, heptachlor, aldrin, endosulfan, dieldrin, endrin, DDT, methoxychlor and cypermethrin residues against the treated household treatments, in downward order, were soaking in 0.1% sodium bicarbonate solution + 2% vinegar + 2% salt solution + lemon juice solution (T6) > soaking in 2% vinegar (T4) solution > soaking in 0.1% sodium bicarbonate (T5) solution > soaking in 2% salt (T3) solution > washing with running tap water (T1) > soaking in stable normal water (T2). The treatment of raw fish muscle samples by soaking them in 0.1% sodium bicarbonate solution + 2% vinegar + 2% salt solution + lemon juice was found to be the most efficient household treatment, performing significant reductions (%) in pesticide concentration: 72−80% (p < 0.05) in Channa striata, 71−79% (p < 0.05) in Clarias gariepinus, 74−80% (p < 0.05) in Anabas testudineus as well as 78−81% (p < 0.05) in Trichogaster trichopterus before cooking.

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