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  1. Li PK, Lui SL, Ng JK, Cai GY, Chan CT, Chen HC, et al.
    Nephrology (Carlton), 2017 Dec;22 Suppl 4:3-8.
    PMID: 29155495 DOI: 10.1111/nep.13143
    To address the issue of heavy dialysis burden due to the rising prevalence of end-stage renal disease around the world, a roundtable discussion on the sustainability of managing dialysis burden around the world was held in Hong Kong during the First International Congress of Chinese Nephrologists in December 2015. The roundtable discussion was attended by experts from Hong Kong, China, Canada, England, Malaysia, Singapore, Taiwan and United States. Potential solutions to cope with the heavy burden on dialysis include the prevention and retardation of the progression of CKD; wider use of home-based dialysis therapy, particularly PD; promotion of kidney transplantation; and the use of renal palliative care service.
  2. de Carvalho LP, Fong A, Troughton R, Yan BP, Chin CT, Poh SC, et al.
    Thromb. Haemost., 2018 02;118(2):415-426.
    PMID: 29443374 DOI: 10.1160/TH17-08-0564
    Studies on platelet reactivity (PR) testing commonly test PR only after percutaneous coronary intervention (PCI) has been performed. There are few data on pre- and post-PCI testing. Data on simultaneous testing of aspirin and adenosine diphosphate antagonist response are conflicting. We investigated the prognostic value of combined serial assessments of high on-aspirin PR (HASPR) and high on-adenosine diphosphate receptor antagonist PR (HADPR) in patients with acute coronary syndrome (ACS). HASPR and HADPR were assessed in 928 ACS patients before (initial test) and 24 hours after (final test) coronary angiography, with or without revascularization. Patients with HASPR on the initial test, compared with those without, had significantly higher intraprocedural thrombotic events (IPTE) (8.6 vs. 1.2%, p ≤ 0.001) and higher 30-day major adverse cardiovascular and cerebrovascular events (MACCE; 5.2 vs. 2.3%, p = 0.05), but not 12-month MACCE (13.0 vs. 15.1%, p = 0.50). Patients with initial HADPR, compared with those without, had significantly higher IPTE (4.4 vs. 0.9%, p = 0.004), but not 30-day (3.5 vs. 2.3%, p = 0.32) or 12-month MACCE (14.0 vs. 12.5%, p = 0.54). The c-statistic of the Global Registry of Acute Coronary Events (GRACE) score alone, GRACE score + ASPR test and GRACE score + ADPR test for discriminating 30-day MACCE was 0.649, 0.803 and 0.757, respectively. Final ADPR was associated with 30-day MACCE among patients with intermediate-to-high GRACE score (adjusted odds ratio [OR]: 4.50, 95% confidence interval [CI]: 1.14-17.66), but not low GRACE score (adjusted OR: 1.19, 95% CI: 0.13-10.79). In conclusion, both HASPR and HADPR predict ischaemic events in ACS. This predictive utility is time-dependent and risk-dependent.
  3. Yew CW, Hoque MZ, Pugh-Kitingan J, Minsong A, Voo CLY, Ransangan J, et al.
    Ann. Hum. Genet., 2018 07;82(4):216-226.
    PMID: 29521412 DOI: 10.1111/ahg.12246
    The region of northern Borneo is home to the current state of Sabah, Malaysia. It is located closest to the southern Philippine islands and may have served as a viaduct for ancient human migration onto or off of Borneo Island. In this study, five indigenous ethnic groups from Sabah were subjected to genome-wide SNP genotyping. These individuals represent the "North Borneo"-speaking group of the great Austronesian family. They have traditionally resided in the inland region of Sabah. The dataset was merged with public datasets, and the genetic relatedness of these groups to neighboring populations from the islands of Southeast Asia, mainland Southeast Asia and southern China was inferred. Genetic structure analysis revealed that these groups formed a genetic cluster that was independent of the clusters of neighboring populations. Additionally, these groups exhibited near-absolute proportions of a genetic component that is also common among Austronesians from Taiwan and the Philippines. They showed no genetic admixture with Austro-Melanesian populations. Furthermore, phylogenetic analysis showed that they are closely related to non-Austro-Melansian Filipinos as well as to Taiwan natives but are distantly related to populations from mainland Southeast Asia. Relatively lower heterozygosity and higher pairwise genetic differentiation index (FST ) values than those of nearby populations indicate that these groups might have experienced genetic drift in the past, resulting in their differentiation from other Austronesians. Subsequent formal testing suggested that these populations have received no gene flow from neighboring populations. Taken together, these results imply that the indigenous ethnic groups of northern Borneo shared a common ancestor with Taiwan natives and non-Austro-Melanesian Filipinos and then isolated themselves on the inland of Sabah. This isolation presumably led to no admixture with other populations, and these individuals therefore underwent strong genetic differentiation. This report contributes to addressing the paucity of genetic data on representatives from this strategic region of ancient human migration event(s).
  4. Bo ZM, Tan WK, Chong CSC, Lye MS, Parmasivam S, Pang ST, et al.
    PLoS One, 2022;17(11):e0277802.
    PMID: 36395327 DOI: 10.1371/journal.pone.0277802
    Acute pharyngitis (AP) is a common reason for private primary care consultations, thus providing an avenue for widespread antibiotic intake among the community. However, there is limited data on the antibiotic prescription appropriateness and resistance information in the Malaysian private primary care setting, therefore, this study aimed to investigate the prevalence of isolated viruses and bacteria, antibiotic resistance patterns, antibiotic prescription patterns and appropriateness by general practitioners (GPs) and factors affecting antibiotic resistance and antibiotic prescription patterns. To investigate, a cross-sectional study was conducted among 205 patients presenting with AP symptoms at private primary care clinics in central Malaysia from 3rd January 2016 to 30th November 2016. Throat swabs were collected from 205 AP patients for two purposes: (i) the detection of four common respiratory viruses associated with AP via reverse-transcription real-time PCR (qRT-PCR); and (ii) bacterial identification using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS). Bacterial isolates were then subjected to antibiotic susceptibility screening and McIsaac scoring was calculated post-prescription based on GP selection of criteria. Generalized estimating equations analysis with multiple logistic regression was conducted to identify factors associated with presence of virus and antibiotic prescription. The results showed that 95.1% (195/205) of patients had at least one of the four viruses, with rhinovirus (88.5%) being the most prevalent, followed by adenovirus (74.9%), influenza A virus (4.6%) and enterovirus (2.1%). A total of 862 non-repetitive colonies were isolated from the culture of throat swabs from 205 patients who were positive for bacteria. From a total of 22 genera, Streptococcus constitutes the most prevalent bacteria genus (40.9%), followed by Neisseria (20%), Rothia (13.0%), Staphylococcus (11%) and Klebsiella (4.9%). Only 5 patients carried group A beta-hemolytic streptococci (GABHS). We also report the presence of vancomycin-resistant S. aureus or VRSA (n = 9, 10.1%) among which one isolate is a multidrug-resistant methicillin-resistant S. aureus (MDR-MRSA), while 54.1% (n = 111) were found to carry at least one antibiotic-resistant bacteria species. Application of the McIsaac scoring system indicated that 87.8% (n = 180) of patients should not be prescribed antibiotics as the majority of AP patients in this study had viral pharyngitis. The antibiotic prescription appropriateness by applying post-prescription McIsaac scoring was able to rule out GABHS pharyngitis in this sample with a GABHS culture-positive sensitivity of 40% (n = 2/5) and specificity of 90% (180/200). In conclusion, antibiotic-resistant throat isolates and over-prescription of antibiotics were observed and McIsaac scoring system is effective in guiding GPs to determine occurrences of viral pharyngitis to reduce unnecessary antibiotic prescription.
  5. Kiyooka T, Ohanyan V, Yin L, Pung YF, Chen YR, Chen CL, et al.
    Basic Res Cardiol, 2022 Jan 17;117(1):3.
    PMID: 35039940 DOI: 10.1007/s00395-021-00908-1
    Endothelial dysfunction in diabetes is generally attributed to oxidative stress, but this view is challenged by observations showing antioxidants do not eliminate diabetic vasculopathy. As an alternative to oxidative stress-induced dysfunction, we interrogated if impaired mitochondrial function in endothelial cells is central to endothelial dysfunction in the metabolic syndrome. We observed reduced coronary arteriolar vasodilation to the endothelium-dependent dilator, acetylcholine (Ach), in Zucker Obese Fatty rats (ZOF, 34 ± 15% [mean ± standard deviation] 10-3 M) compared to Zucker Lean rats (ZLN, 98 ± 11%). This reduction in dilation occurred concomitantly with mitochondrial DNA (mtDNA) strand lesions and reduced mitochondrial complex activities in the endothelium of ZOF versus ZLN. To demonstrate endothelial dysfunction is linked to impaired mitochondrial function, administration of a cell-permeable, mitochondria-directed endonuclease (mt-tat-EndoIII), to repair oxidatively modified DNA in ZOF, restored mitochondrial function and vasodilation to Ach (94 ± 13%). Conversely, administration of a cell-permeable, mitochondria-directed exonuclease (mt-tat-ExoIII) produced mtDNA strand breaks in ZLN, reduced mitochondrial complex activities and vasodilation to Ach in ZLN (42 ± 16%). To demonstrate that mitochondrial function is central to endothelium-dependent vasodilation, we introduced (via electroporation) liver mitochondria (from ZLN) into the endothelium of a mesenteric vessel from ZOF and restored endothelium-dependent dilation to vasoactive intestinal peptide (VIP at 10-5 M, 4 ± 3% vasodilation before mitochondrial transfer and 48 ± 36% after transfer). Finally, to demonstrate mitochondrial function is key to endothelium-dependent dilation, we administered oligomycin (mitochondrial ATP synthase inhibitor) and observed a reduction in endothelium-dependent dilation. We conclude that mitochondrial function is critical for endothelium-dependent vasodilation.
  6. Gephart JA, Henriksson PJG, Parker RWR, Shepon A, Gorospe KD, Bergman K, et al.
    Nature, 2021 Sep;597(7876):360-365.
    PMID: 34526707 DOI: 10.1038/s41586-021-03889-2
    Fish and other aquatic foods (blue foods) present an opportunity for more sustainable diets1,2. Yet comprehensive comparison has been limited due to sparse inclusion of blue foods in environmental impact studies3,4 relative to the vast diversity of production5. Here we provide standardized estimates of greenhouse gas, nitrogen, phosphorus, freshwater and land stressors for species groups covering nearly three quarters of global production. We find that across all blue foods, farmed bivalves and seaweeds generate the lowest stressors. Capture fisheries predominantly generate greenhouse gas emissions, with small pelagic fishes generating lower emissions than all fed aquaculture, but flatfish and crustaceans generating the highest. Among farmed finfish and crustaceans, silver and bighead carps have the lowest greenhouse gas, nitrogen and phosphorus emissions, but highest water use, while farmed salmon and trout use the least land and water. Finally, we model intervention scenarios and find improving feed conversion ratios reduces stressors across all fed groups, increasing fish yield reduces land and water use by up to half, and optimizing gears reduces capture fishery emissions by more than half for some groups. Collectively, our analysis identifies high-performing blue foods, highlights opportunities to improve environmental performance, advances data-poor environmental assessments, and informs sustainable diets.
  7. Chen K, Wong TH, Tan YG, Tay KJ, Tan WC, Chan J, et al.
    Front Oncol, 2024;14:1386597.
    PMID: 38947889 DOI: 10.3389/fonc.2024.1386597
    Treatment intensification with androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPi) have led to improved survival in advanced prostate cancer. However, ADT is linked to significant cardiovascular toxicity, and ARPi also negatively impacts cardiovascular health. Together with a higher prevalence of baseline cardiovascular risk factors reported among prostate cancer survivors at diagnosis, there is a pressing need to prioritise and optimise cardiovascular health in this population. Firstly, While no dedicated cardiovascular toxicity risk calculators are available, other tools such as SCORE2 can be used for baseline cardiovascular risk assessment. Next, selected patients on combination therapy may benefit from de-escalation of ADT to minimise its toxicities while maintaining cancer control. These patients can be characterised by an exceptional PSA response to hormonal treatment, favourable disease characteristics and competing comorbidities that warrant a less aggressive treatment regime. In addition, emerging molecular and genomic biomarkers hold the potential to identify patients who are suited for a de-escalated treatment approach either with ADT or with ARPi. One such biomarker is AR-V7 splice variant that predicts resistance to ARPi. Lastly, optimization of modifiable cardiovascular risk factors for patients through a coherent framework (ABCDE) and exercise therapy is equally important. This article aims to comprehensively review the cardiovascular impact of hormonal manipulation in metastatic hormone-sensitive prostate cancer, propose overarching strategies to mitigate cardiovascular toxicity associated with hormonal treatment, and, most importantly, raise awareness about the detrimental cardiovascular effects inherent in our current management strategies involving hormonal agents.
  8. Ng ML, Majid AMSA, Yee SM, Natesan V, Basheer MKA, Gnanasekaran A, et al.
    Support Care Cancer, 2024 May 06;32(6):331.
    PMID: 38710920 DOI: 10.1007/s00520-024-08536-w
    AIM: We evaluated the efficacy and safety of Nuvastatic™ (C5OSEW5050ESA) in improving cancer-related fatigue (CRF) among cancer patients.

    METHODS: This multicenter randomized double-blind placebo-controlled phase 2 trial included 110 solid malignant tumor patients (stage II-IV) undergoing chemotherapy. They were randomly selected and provided oral Nuvastatic™ 1000 mg (N = 56) or placebo (N = 54) thrice daily for 9 weeks. The primary outcomes were fatigue (Brief Fatigue Inventory (BFI)) and Visual Analog Scale for Fatigue (VAS-F)) scores measured before and after intervention at baseline and weeks 3, 6, and 9. The secondary outcomes were mean group difference in the vitality subscale of the Medical Outcome Scale Short Form-36 (SF-36) and urinary F2-isoprostane concentration (an oxidative stress biomarker), Eastern Cooperative Oncology Group scores, adverse events, and biochemical and hematologic parameters. Analysis was performed by intention-to-treat (ITT). Primary and secondary outcomes were assessed by two-way repeated-measures analysis of variance (mixed ANOVA).

    RESULTS: The Nuvastatic™ group exhibited an overall decreased fatigue score compared with the placebo group. Compared with the placebo group, the Nuvastatic™ group significantly reduced BFI-fatigue (BFI fatigue score, F (1.4, 147) = 16.554, p 

  9. McLeod M, Torode J, Leung K, Bhoo-Pathy N, Booth C, Chakowa J, et al.
    Lancet Oncol, 2024 Feb;25(2):e63-e72.
    PMID: 38301704 DOI: 10.1016/S1470-2045(23)00568-5
    This Policy Review sourced opinions from experts in cancer care across low-income and middle-income countries (LMICs) to build consensus around high-priority measures of care quality. A comprehensive list of quality indicators in medical, radiation, and surgical oncology was identified from systematic literature reviews. A modified Delphi study consisting of three 90-min workshops and two international electronic surveys integrating a global range of key clinical, policy, and research leaders was used to derive consensus on cancer quality indicators that would be both feasible to collect and were high priority for cancer care systems in LMICs. Workshop participants narrowed the list of 216 quality indicators from the literature review to 34 for inclusion in the subsequent surveys. Experts' responses to the surveys showed consensus around nine high-priority quality indicators for measuring the quality of hospital-based cancer care in LMICs. These quality indicators focus on important processes of care delivery from accurate diagnosis (eg, histologic diagnosis via biopsy and TNM staging) to adequate, timely, and appropriate treatment (eg, completion of radiotherapy and appropriate surgical intervention). The core indicators selected could be used to implement systems of feedback and quality improvement.
  10. Luo N, Teng TK, Tay WT, Anand IS, Kraus WE, Liew HB, et al.
    Am Heart J, 2017 Sep;191:75-81.
    PMID: 28888273 DOI: 10.1016/j.ahj.2017.06.016
    BACKGROUND: Assessing health-related quality of life (HRQoL) in patients with heart failure (HF) is an important goal of clinical care and HF research. We sought to investigate ethnic differences in perceived HRQoL and its association with mortality among patients with HF and left ventricular ejection fraction ≤35%, controlling for demographic characteristics and HF severity.

    METHODS AND RESULTS: We compared 5697 chronic HF patients of Indian (26%), white (23%), Chinese (17%), Japanese/Koreans (12%), black (12%), and Malay (10%) ethnicities from the HF-ACTION and ASIAN-HF multinational studies using the Kansas City Cardiomyopathy Questionnaire (KCCQ; range 0-100; higher scores reflect better health status). KCCQ scores were lowest in Malay (58±22) and Chinese (60±23), intermediate in black (64±21) and Indian (65±23), and highest in white (67±20) and Japanese or Korean patients (67±22) after adjusting for age, sex, educational status, HF severity, and risk factors. Self-efficacy, which measures confidence in the ability to manage symptoms, was lower in all Asian ethnicities (especially Japanese/Koreans [60±26], Malay [66±23], and Chinese [64±28]) compared to black (80±21) and white (82±19) patients, even after multivariable adjustment (P

  11. Welch V, Tanjong Ghogomu E, Dowling S, Choo WY, Yunus RM, Mohd TAMT, et al.
    Campbell Syst Rev, 2023 Sep;19(3):e1340.
    PMID: 37361556 DOI: 10.1002/cl2.1340
    This is the protocol for an evidence and gap map. The objectives are as follows: This EGM aims to map available evidence on the effects of in-person interventions to reduce social isolation and/or loneliness across all age groups in all settings.
  12. Lai WX, Chan AW, Matchar DB, Ansah JP, Lien CTC, Ismail NH, et al.
    BMC Geriatr, 2023 Sep 22;23(1):586.
    PMID: 37740182 DOI: 10.1186/s12877-023-04294-2
    BACKGROUND: Falls in older adults are the result of a complex web of interacting causes, that further results in other physical, emotional, and psychological sequelae. A conceptual framework that represents the reciprocal dynamics of these causal factors can enable clinicians, researchers, and policymakers to clarify goals in falls intervention in older adults.

    METHODS: A Group Model Building (GMB) exercise was conducted with researchers and clinicians from academic units and public healthcare institutes in Singapore. The aim of the exercise was to produce a shared visual representation of the causal structure for falls and engage in discussions on how current and future falls intervention programmes can address falls in the older adults, especially in the Asian context. It was conducted in four steps: 1) Outlining and prioritising desirable patient outcomes, 2) Conceptual model building, 3) Identifying key intervention elements of effective falls intervention programmes, 4) Mapping of interventions to outcomes. This causal loop diagram (CLD) was then used to generate insights into the current understanding of falls causal relationships, current efforts in falls intervention in Singapore, and used to identify gaps in falls research that could be further advanced in future intervention studies.

    RESULTS: Four patient outcomes were identified by the group as key in falls intervention: 1) Falls, 2) Injurious falls, 3) Fear of falling, and 4) Restricted mobility and life space. A CLD of the reciprocal relationships between risk factors and these outcomes are represented in four sub-models: 1) Fear of falling, 2) Injuries associated with falls, 3) Caregiver overprotectiveness, 4) Post-traumatic stress disorder and psychological resilience. Through this GMB exercise, the group gained the following insights: (1) Psychological sequelae of falls is an important falls intervention outcome. (2) The effects of family overprotectiveness, psychological resilience, and PTSD in exacerbating the consequences of falls are not well understood. (3) There is a need to develop multi-component falls interventions to address the multitude of falls and falls related sequelae.

    CONCLUSION: This work illustrates the potential of GMB to promote shared understanding of complex healthcare problems and to provide a roadmap for the development of more effective preventive actions.

  13. Gan CC, Tan RY, Delaney CL, Puckridge PJ, Pang SC, Tng ARK, et al.
    J Vasc Access, 2022 Nov 03.
    PMID: 36330556 DOI: 10.1177/11297298221130897
    BACKGROUND: Treatment of cephalic arch stenosis (CAS) is associated with high risk of failure and complications. Although stent-graft (SG) placement has improved patency rates, stent edge restenosis has been raised as a potential limiting factor for SG usage in CAS. This study aims to evaluate the safety and efficacy of combining stent graft placement with paclitaxel-coated balloon (PCB) angioplasty versus PCB alone in the treatment of CAS.

    METHODS: This is an investigator-initiated, prospective, international, multicenter, open-label, randomized control clinical trial that plans to recruit 80 patients, who require fistuloplasty from dysfunctional arteriovenous fistula (AVF) from CAS. Eligible participants are randomly assigned to receive treatment with SG and PCB or PCB alone in a 1:1 ratio post-angioplasty (n = 40 in each arm). Randomization is stratified by de novo or recurrent lesion, and the participants are followed up for 1 year. The primary endpoints of the study are target lesion primary patency (TLPP) and access circuit primary patency (ACPP) rates at 6-months. The secondary endpoints are TLPP and ACPP at 3- and 12-month; target lesion and access circuit assisted primary and secondary patency rates at 3, 6, and 12-months and the total number of interventions; complication rate; and cost-effectiveness.

    DISCUSSION: This study will evaluate the clinical efficacy and safety of combination SG and PCB implantation compared to PCB alone in the treatment of CAS for hemodialysis patients.

  14. Ye Z, Nguyen TL, Dite GS, MacInnis RJ, Schmidt DF, Makalic E, et al.
    Breast Cancer Res, 2023 Oct 25;25(1):127.
    PMID: 37880807 DOI: 10.1186/s13058-023-01733-1
    BACKGROUND: Mammogram risk scores based on texture and density defined by different brightness thresholds are associated with breast cancer risk differently and could reveal distinct information about breast cancer risk. We aimed to investigate causal relationships between these intercorrelated mammogram risk scores to determine their relevance to breast cancer aetiology.

    METHODS: We used digitised mammograms for 371 monozygotic twin pairs, aged 40-70 years without a prior diagnosis of breast cancer at the time of mammography, from the Australian Mammographic Density Twins and Sisters Study. We generated normalised, age-adjusted, and standardised risk scores based on textures using the Cirrus algorithm and on three spatially independent dense areas defined by increasing brightness threshold: light areas, bright areas, and brightest areas. Causal inference was made using the Inference about Causation from Examination of FAmilial CONfounding (ICE FALCON) method.

    RESULTS: The mammogram risk scores were correlated within twin pairs and with each other (r = 0.22-0.81; all P 

  15. Smedley CJ, Stanley PA, Qazzaz ME, Prota AE, Olieric N, Collins H, et al.
    Sci Rep, 2018 Jul 13;8(1):10617.
    PMID: 30006510 DOI: 10.1038/s41598-018-28880-2
    The jerantinine family of Aspidosperma indole alkaloids from Tabernaemontana corymbosa are potent microtubule-targeting agents with broad spectrum anticancer activity. The natural supply of these precious metabolites has been significantly disrupted due to the inclusion of T. corymbosa on the endangered list of threatened species by the International Union for Conservation of Nature. This report describes the asymmetric syntheses of (-)-jerantinines A and E from sustainably sourced (-)-tabersonine, using a straight-forward and robust biomimetic approach. Biological investigations of synthetic (-)-jerantinine A, along with molecular modelling and X-ray crystallography studies of the tubulin-(-)-jerantinine B acetate complex, advocate an anticancer mode of action of the jerantinines operating via microtubule disruption resulting from binding at the colchicine site. This work lays the foundation for accessing useful quantities of enantiomerically pure jerantinine alkaloids for future development.
  16. Tuck SL, O'Brien MJ, Philipson CD, Saner P, Tanadini M, Dzulkifli D, et al.
    Proc Biol Sci, 2016 Dec 14;283(1844).
    PMID: 27928046
    One of the main environmental threats in the tropics is selective logging, which has degraded large areas of forest. In southeast Asia, enrichment planting with seedlings of the dominant group of dipterocarp tree species aims to accelerate restoration of forest structure and functioning. The role of tree diversity in forest restoration is still unclear, but the 'insurance hypothesis' predicts that in temporally and spatially varying environments planting mixtures may stabilize functioning owing to differences in species traits and ecologies. To test for potential insurance effects, we analyse the patterns of seedling mortality and growth in monoculture and mixture plots over the first decade of the Sabah biodiversity experiment. Our results reveal the species differences required for potential insurance effects including a trade-off in which species with denser wood have lower growth rates but higher survival. This trade-off was consistent over time during the first decade, but growth and mortality varied spatially across our 500 ha experiment with species responding to changing conditions in different ways. Overall, average survival rates were extreme in monocultures than mixtures consistent with a potential insurance effect in which monocultures of poorly surviving species risk recruitment failure, whereas monocultures of species with high survival have rates of self-thinning that are potentially wasteful when seedling stocks are limited. Longer-term monitoring as species interactions strengthen will be needed to more comprehensively test to what degree mixtures of species spread risk and use limited seedling stocks more efficiently to increase diversity and restore ecosystem structure and functioning.
  17. Abir T, Kalimullah NA, Osuagwu UL, Nur-A Yazdani DM, Husain T, Goson PC, et al.
    Ann Glob Health, 2021 04 26;87(1):43.
    PMID: 33981590 DOI: 10.5334/aogh.3269
    Background: Feelings of isolation, insecurity, and instability triggered by COVID-19 could have a long-term impact on the mental health status of individuals.

    Objectives: The aim of this study was to examine the prevalence of mental health symptoms (anxiety, depression, and stress) in Bangladesh and the factors associated with these symptoms during the COVID-19 pandemic.

    Methods: From 1 to 30 April 2020, we used a validated self-administered questionnaire to conduct a cross-sectional study on 10,609 participants through an online survey platform. We assessed mental health status using the Depression, Anxiety, and Stress Scale (DASS-21). The total depression, anxiety, and stress subscale scores were divided into normal, mild, moderate, severe, and multinomial logistic regression was used to examine associated factors.

    Findings: The prevalence of depressive symptoms was 15%, 34%, and 15% for mild, moderate, and severe depressive symptoms, respectively. The prevalence of anxiety symptoms was 59% for severe anxiety symptoms, 14% for moderate anxiety symptoms, and 14% for mild anxiety symptoms, while the prevalence for stress levels were 16% for severe stress level, 22% for moderate stress level, and 13% for mild stress level. Multivariate analyses revealed that the most consistent factors associated with mild, moderate, and severe of the three mental health subscales (depression, anxiety, and stress) were respondents who lived in Dhaka and Rangpur division, females, those who self-quarantined in the previous seven days before the survey, and those respondents who experienced chills, breathing difficulty, dizziness, and sore throat.

    Conclusion: Our results showed that about 64%, 87%, and 61% of the respondents in Bangladesh reported high levels of depression, anxiety, and stress, respectively. There is a need for mental health support targeting women and those who self-quarantined or lived in Dhaka and Rangpur during the pandemic.

  18. Liptzin DR, Pickett K, Brinton JT, Agarwal A, Fishman MP, Casey A, et al.
    Ann Am Thorac Soc, 2020 Jun;17(6):724-728.
    PMID: 32109152 DOI: 10.1513/AnnalsATS.201908-617OC
    Rationale: Neuroendocrine cell hyperplasia of infancy (NEHI) is an important form of children's interstitial and diffuse lung disease for which the diagnostic strategy has evolved. The prevalence of comorbidities in NEHI that may influence treatment has not been previously assessed.Objectives: To evaluate a previously unpublished NEHI clinical score for assistance in diagnosis of NEHI and to assess comorbidities in NEHI.Methods: We performed a retrospective chart review of 199 deidentified patients with NEHI from 11 centers. Data were collected in a centralized Research Electronic Data Capture registry and we performed descriptive statistics.Results: The majority of patients with NEHI were male (66%). The sensitivity of the NEHI Clinical Score was 87% (95% confidence interval [CI], 0.82-0.91) for all patients from included centers and 93% (95% CI, 0.86-0.97) for those with complete scores (e.g., no missing data). Findings were similar when we limited the population to the 75 patients diagnosed by lung biopsy (87%; 95% CI, 0.77-0.93). Of those patients evaluated for comorbidities, 51% had gastroesophageal reflux, 35% had aspiration or were at risk for aspiration, and 17% had evidence of immune system abnormalities.Conclusions: The NEHI Clinical Score is a sensitive tool for clinically evaluating NEHI; however, its specificity has not yet been addressed. Clinicians should consider evaluating patients with NEHI for comorbidities, including gastroesophageal reflux, aspiration, and immune system abnormalities, because these can contribute to the child's clinical picture and may influence clinical course and treatment.
  19. Bannister ML, Alvarez-Laviada A, Thomas NL, Mason SA, Coleman S, du Plessis CL, et al.
    Br J Pharmacol, 2016 08;173(15):2446-59.
    PMID: 27237957 DOI: 10.1111/bph.13521
    BACKGROUND AND PURPOSE: Flecainide is a use-dependent blocker of cardiac Na(+) channels. Mechanistic analysis of this block showed that the cationic form of flecainide enters the cytosolic vestibule of the open Na(+) channel. Flecainide is also effective in the treatment of catecholaminergic polymorphic ventricular tachycardia but, in this condition, its mechanism of action is contentious. We investigated how flecainide derivatives influence Ca(2) (+) -release from the sarcoplasmic reticulum through the ryanodine receptor channel (RyR2) and whether this correlates with their effectiveness as blockers of Na(+) and/or RyR2 channels.

    EXPERIMENTAL APPROACH: We compared the ability of fully charged (QX-FL) and neutral (NU-FL) derivatives of flecainide to block individual recombinant human RyR2 channels incorporated into planar phospholipid bilayers, and their effects on the properties of Ca(2) (+) sparks in intact adult rat cardiac myocytes.

    KEY RESULTS: Both QX-FL and NU-FL were partial blockers of the non-physiological cytosolic to luminal flux of cations through RyR2 channels but were significantly less effective than flecainide. None of the compounds influenced the physiologically relevant luminal to cytosol cation flux through RyR2 channels. Intracellular flecainide or QX-FL, but not NU-FL, reduced Ca(2) (+) spark frequency.

    CONCLUSIONS AND IMPLICATIONS: Given its inability to block physiologically relevant cation flux through RyR2 channels, and its lack of efficacy in blocking the cytosolic-to-luminal current, the effect of QX-FL on Ca(2) (+) sparks is likely, by analogy with flecainide, to result from Na(+) channel block. Our data reveal important differences in the interaction of flecainide with sites in the cytosolic vestibules of Na(+) and RyR2 channels.

  20. Battlay P, Wilson J, Bieker VC, Lee C, Prapas D, Petersen B, et al.
    Nat Commun, 2023 Mar 27;14(1):1717.
    PMID: 36973251 DOI: 10.1038/s41467-023-37303-4
    Adaptation is the central feature and leading explanation for the evolutionary diversification of life. Adaptation is also notoriously difficult to study in nature, owing to its complexity and logistically prohibitive timescale. Here, we leverage extensive contemporary and historical collections of Ambrosia artemisiifolia-an aggressively invasive weed and primary cause of pollen-induced hayfever-to track the phenotypic and genetic causes of recent local adaptation across its native and invasive ranges in North America and Europe, respectively. Large haploblocks-indicative of chromosomal inversions-contain a disproportionate share (26%) of genomic regions conferring parallel adaptation to local climates between ranges, are associated with rapidly adapting traits, and exhibit dramatic frequency shifts over space and time. These results highlight the importance of large-effect standing variants in rapid adaptation, which have been critical to A. artemisiifolia's global spread across vast climatic gradients.
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