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Nasal allergies in the Asian-Pacific population: results from the Allergies in Asia-Pacific Survey

Katelaris CH, Lai CK, Rhee CS, Lee SH, Yun WD, Lim-Varona L, et al.

Am J Rhinol Allergy, 2011 Sep-Oct;25 Suppl 1:S3-15.
PMID: 22185687 DOI: 10.2500/ajra.2011.25.3674

The Allergies in Asia-Pacific Survey describes the symptoms, impact, and treatment of allergic rhinitis (AR) across Australia, China, Hong Kong, Malaysia, Singapore, Taiwan, Vietnam, and the Philippines. The Allergies in Asia-Pacific Survey was undertaken to further clarify the prevalence of physician-diagnosed nasal allergies (NAs), impact on quality-of-life (QOL), existing treatment paradigms and gaps, and NA medications currently used in treatment.
Fulltext In depth analysis of the Sox4 gene locus that consists of sense and natural antisense transcripts

Ling KH, Brautigan PJ, Moore S, Fraser R, Leong MP, Leong JW, et al.

Data Brief, 2016 Jun;7:282-90.
PMID: 26958646 DOI: 10.1016/j.dib.2016.01.045

SRY (Sex Determining Region Y)-Box 4 or Sox4 is an important regulator of the pan-neuronal gene expression during post-mitotic cell differentiation within the mammalian brain. Sox4 gene locus has been previously characterized with multiple sense and overlapping natural antisense transcripts [1], [2]. Here we provide accompanying data on various analyses performed and described in Ling et al. [2]. The data include a detail description of various features found at Sox4 gene locus, additional experimental data derived from RNA-Fluorescence in situ Hybridization (RNA-FISH), Western blotting, strand-specific reverse-transcription quantitative polymerase chain reaction (RT-qPCR), gain-of-function and in situ hybridization (ISH) experiments. All the additional data provided here support the existence of an endogenous small interfering- or PIWI interacting-like small RNA known as Sox4_sir3, which origin was found within the overlapping region consisting of a sense and a natural antisense transcript known as Sox4ot1.
Fulltext Dihydrofolate-Reductase Mutations in Plasmodium knowlesi Appear Unrelated to Selective Drug Pressure from Putative Human-To-Human Transmission in Sabah, Malaysia

Grigg MJ, Barber BE, Marfurt J, Imwong M, William T, Bird E, et al.

PLoS One, 2016;11(3):e0149519.
PMID: 26930493 DOI: 10.1371/journal.pone.0149519

BACKGROUND: Malaria caused by zoonotic Plasmodium knowlesi is an emerging threat in Eastern Malaysia. Despite demonstrated vector competency, it is unknown whether human-to-human (H-H) transmission is occurring naturally. We sought evidence of drug selection pressure from the antimalarial sulfadoxine-pyrimethamine (SP) as a potential marker of H-H transmission.
METHODS: The P. knowlesi dihdyrofolate-reductase (pkdhfr) gene was sequenced from 449 P. knowlesi malaria cases from Sabah (Malaysian Borneo) and genotypes evaluated for association with clinical and epidemiological factors. Homology modelling using the pvdhfr template was used to assess the effect of pkdhfr mutations on the pyrimethamine binding pocket.
RESULTS: Fourteen non-synonymous mutations were detected, with the most common being at codon T91P (10.2%) and R34L (10.0%), resulting in 21 different genotypes, including the wild-type, 14 single mutants, and six double mutants. One third of the P. knowlesi infections were with pkdhfr mutants; 145 (32%) patients had single mutants and 14 (3%) had double-mutants. In contrast, among the 47 P. falciparum isolates sequenced, three pfdhfr genotypes were found, with the double mutant 108N+59R being fixed and the triple mutants 108N+59R+51I and 108N+59R+164L occurring with frequencies of 4% and 8%, respectively. Two non-random spatio-temporal clusters were identified with pkdhfr genotypes. There was no association between pkdhfr mutations and hyperparasitaemia or malaria severity, both hypothesized to be indicators of H-H transmission. The orthologous loci associated with resistance in P. falciparum were not mutated in pkdhfr. Subsequent homology modelling of pkdhfr revealed gene loci 13, 53, 120, and 173 as being critical for pyrimethamine binding, however, there were no mutations at these sites among the 449 P. knowlesi isolates.
CONCLUSION: Although moderate diversity was observed in pkdhfr in Sabah, there was no evidence this reflected selective antifolate drug pressure in humans.
Fulltext Derivation of an endogenous small RNA from double-stranded Sox4 sense and natural antisense transcripts in the mouse brain

Ling KH, Brautigan PJ, Moore S, Fraser R, Cheah PS, Raison JM, et al.

Genomics, 2016 Mar;107(2-3):88-99.
PMID: 26802803 DOI: 10.1016/j.ygeno.2016.01.006

Natural antisense transcripts (NATs) are involved in cellular development and regulatory processes. Multiple NATs at the Sox4 gene locus are spatiotemporally regulated throughout murine cerebral corticogenesis. In the study, we evaluated the potential functional role of Sox4 NATs at Sox4 gene locus. We demonstrated Sox4 sense and NATs formed dsRNA aggregates in the cytoplasm of brain cells. Over expression of Sox4 NATs in NIH/3T3 cells generally did not alter the level of Sox4 mRNA expression or protein translation. Upregulation of a Sox4 NAT known as Sox4ot1 led to the production of a novel small RNA, Sox4_sir3. Its biogenesis is Dicer1-dependent and has characteristics resemble piRNA. Expression of Sox4_sir3 was observed in the marginal and germinative zones of the developing and postnatal brains suggesting a potential role in regulating neurogenesis. We proposed that Sox4 sense-NATs serve as Dicer1-dependent templates to produce a novel endo-siRNA- or piRNA-like Sox4_sir3.
Double-blind randomised controlled trial of vitamin D3 supplementation for the prevention of acute respiratory infection in older adults and their carers (ViDiFlu)

Martineau AR, Hanifa Y, Witt KD, Barnes NC, Hooper RL, Patel M, et al.

Thorax, 2015 Oct;70(10):953-60.
PMID: 26063508 DOI: 10.1136/thoraxjnl-2015-206996

RATIONALE: Low-dose vitamin D supplementation is already recommended in older adults for prevention of fractures and falls, but clinical trials investigating whether higher doses could provide additional protection against acute respiratory infection (ARI) are lacking.
OBJECTIVE: To conduct a clinical trial of high-dose versus low-dose vitamin D3 supplementation for ARI prevention in residents of sheltered-accommodation housing blocks ('schemes') and their carers in London, UK.
MEASUREMENTS AND METHODS: Fifty-four schemes (137 individual participants) were allocated to the active intervention (vitamin D3 2.4 mg once every 2 months +10 μg daily for residents, 3 mg once every 2 months for carers), and 54 schemes with 103 participants were allocated to control (placebo once every 2 months +vitamin D3 10 μg daily for residents, placebo once every 2 months for carers) for 1 year. Primary outcome was time to first ARI; secondary outcomes included time to first upper/lower respiratory infection (URI/LRI, analysed separately), and symptom duration.
MAIN RESULTS: Inadequate vitamin D status was common at baseline: 220/240 (92%) participants had serum 25(OH)D concentration <75 nmol/L. The active intervention did not influence time to first ARI (adjusted HR (aHR) 1.18, 95% CI 0.80 to 1.74, p=0.42). When URI and LRI were analysed separately, allocation to the active intervention was associated with increased risk of URI (aHR 1.48, 95% CI 1.02 to 2.16, p=0.039) and increased duration of URI symptoms (median 7.0 vs 5.0 days for active vs control, adjusted ratio of geometric means 1.34, 95% CI 1.09 to 1.65, p=0.005), but not with altered risk or duration of LRI.
CONCLUSIONS: Addition of intermittent bolus-dose vitamin D3 supplementation to a daily low-dose regimen did not influence risk of ARI in older adults and their carers, but was associated with increased risk and duration of URI.
TRIAL REGISTRATION NUMBER: clinicaltrials.gov NCT01069874.
Fulltext Treatment of dementia and mild cognitive impairment with or without cerebrovascular disease: Expert consensus on the use of Ginkgo biloba extract, EGb 761®

Kandiah N, Ong PA, Yuda T, Ng LL, Mamun K, Merchant RA, et al.

CNS Neurosci Ther, 2019 02;25(2):288-298.
PMID: 30648358 DOI: 10.1111/cns.13095

BACKGROUND: The Ginkgo biloba special extract, EGb 761® has been widely used in the treatment of neuropsychiatric disorders, including Alzheimer's disease (AD).
METHODS: To guide clinical practice in the Asian region, the Asian Clinical Expert Group on Neurocognitive Disorders compiled evidence-based consensus recommendations regarding the use of EGb 761® in neurocognitive disorders with/without cerebrovascular disease.
RESULTS: Key randomized trials and robust meta-analyses have demonstrated significant improvement in cognitive function, neuropsychiatric symptoms, activities of daily living (ADL) and quality of life with EGb 761® versus placebo in patients with mild-to-moderate dementia. In those with mild cognitive impairment (MCI), EGb 761® has also demonstrated significant symptomatic improvement versus placebo. World Federation of Societies of Biological Psychiatry guidelines list EGb 761® with the same strength of evidence as acetylcholinesterase inhibitors and N-methyl-D-aspartate (NMDA) antagonists e.g. memantine (Grade 3 recommendation; Level B evidence). Only EGb 761® had Level B evidence in improving cognition, behaviour, and ADL in both AD and vascular dementia patients. Safety analyses show EGb 761® to have a positive risk-benefit profile. While concerns have been raised regarding a possible increased bleeding risk, several randomized trials and two meta-analyses have not supported this association.
CONCLUSIONS: The Expert Group foresee an important role for EGb 761® , used alone or as an add-on therapy, in the treatment of MCI and dementias, particularly when patients do not derive benefit from acetylcholinesterase inhibitors or NMDA antagonists. EGb 761® should be used in alignment with local clinical practice guidelines.
Fulltext Burnout and work-related stressors in gastroenterology: a protocol for a multinational observational study in the ASEAN region

Ong J, Ong AML, Ong S, Xin X, Lee YY, Pausawasdi N, et al.

BMJ Open Gastroenterol, 2020 11;7(1).
PMID: 33148790 DOI: 10.1136/bmjgast-2020-000534

BACKGROUND: Clinician burnout is an important occupational hazard that may be exacerbated by the novel COVID-19 pandemic. Within Southeast Asia, burnout in gastroenterology is understudied. The primary objective of this study is to estimate the prevalence of burnout symptoms within gastroenterology, in member states of the Associations of Southeast Asian Nations (ASEAN), during and after the COVID-19 pandemic. The secondary objective is to identify work-related stressors that contribute to burnout in ASEAN gastroenterologists.
METHODS AND ANALYSIS: This is an observational study that will use anonymised online surveys to estimate the prevalence of burnout symptoms at two time points: during the COVID-19 pandemic in 2020 and in 2022 (assumed to be after the pandemic). Gastroenterologists from Singapore, Malaysia, Thailand, Indonesia, Philippines and Brunei will be invited to participate in the online survey through their national gastroenterology and endoscopy societies. Burnout will be assessed using the Maslach Burnout Inventory-Human Services Survey tool. Supplementary questions will collect demographic and qualitative data. Associations between demographic characteristics and burnout will be tested by multiple regression.
RESULTS: The prevalence of burnout symptoms in gastroenterology during the COVID-19 pandemic, and the baseline prevalence after COVID-19, will be established in the above-mentioned countries. Work-related stressors commonly associated with burnout will be identified, allowing the introduction of preventative measures to reduce burnout in the future.
ETHICS AND DISSEMINATION: Ethical approval was granted by the Singhealth Centralised Institutional Review Board (2020/2709). Results will be submitted for publication.
Fulltext The chromosome-scale reference genome of black pepper provides insight into piperine biosynthesis

Hu L, Xu Z, Wang M, Fan R, Yuan D, Wu B, et al.

Nat Commun, 2019 10 16;10(1):4702.
PMID: 31619678 DOI: 10.1038/s41467-019-12607-6

Black pepper (Piper nigrum), dubbed the 'King of Spices' and 'Black Gold', is one of the most widely used spices. Here, we present its reference genome assembly by integrating PacBio, 10x Chromium, BioNano DLS optical mapping, and Hi-C mapping technologies. The 761.2 Mb sequences (45 scaffolds with an N50 of 29.8 Mb) are assembled into 26 pseudochromosomes. A phylogenomic analysis of representative plant genomes places magnoliids as sister to the monocots-eudicots clade and indicates that black pepper has diverged from the shared Laurales-Magnoliales lineage approximately 180 million years ago. Comparative genomic analyses reveal specific gene expansions in the glycosyltransferase, cytochrome P450, shikimate hydroxycinnamoyl transferase, lysine decarboxylase, and acyltransferase gene families. Comparative transcriptomic analyses disclose berry-specific upregulated expression in representative genes in each of these gene families. These data provide an evolutionary perspective and shed light on the metabolic processes relevant to the molecular basis of species-specific piperine biosynthesis.
Fulltext Overview of Urethral Reconstruction by Tissue Engineering: Current Strategies, Clinical Status and Future Direction

Rashidbenam Z, Jasman MH, Hafez P, Tan GH, Goh EH, Fam XI, et al.

Tissue Eng Regen Med, 2019 08;16(4):365-384.
PMID: 31413941 DOI: 10.1007/s13770-019-00193-z

BACKGROUND: Urinary tract is subjected to a variety of disorders such as urethral stricture, which often develops as a result of scarring process. Urethral stricture can be treated by urethral dilation and urethrotomy; but in cases of long urethral strictures, substitution urethroplasty with genital skin and buccal mucosa grafts is the only option. However a number of complications such as infection as a result of hair growth in neo-urethra, and stone formation restrict the application of those grafts. Therefore, tissue engineering techniques recently emerged as an alternative approach, aiming to overcome those restrictions. The aim of this review is to provide a comprehensive coverage on the strategies employed and the translational status of urethral tissue engineering over the past years and to propose a combinatory strategy for the future of urethral tissue engineering.
METHODs: Data collection was based on the key articles published in English language in years between 2006 and 2018 using the searching terms of urethral stricture and tissue engineering on PubMed database.
RESULTS: Differentiation of mesenchymal stem cells into urothelial and smooth muscle cells to be used for urologic application does not offer any advantage over autologous urothelial and smooth muscle cells. Among studied scaffolds, synthetic scaffolds with proper porosity and mechanical strength is the best option to be used for urethral tissue engineering.
CONCLUSION: Hypoxia-preconditioned mesenchymal stem cells in combination with autologous cells seeded on a pre-vascularized synthetic and biodegradable scaffold can be said to be the best combinatory strategy in engineering of human urethra.
Genomic structure of the native inhabitants of Peninsular Malaysia and North Borneo suggests complex human population history in Southeast Asia

Yew CW, Lu D, Deng L, Wong LP, Ong RT, Lu Y, et al.

Hum Genet, 2018 Feb;137(2):161-173.
PMID: 29383489 DOI: 10.1007/s00439-018-1869-0

Southeast Asia (SEA) is enriched with a complex history of peopling. Malaysia, which is located at the crossroads of SEA, has been recognized as one of the hubs for early human migration. To unravel the genomic complexity of the native inhabitants of Malaysia, we sequenced 12 samples from 3 indigenous populations from Peninsular Malaysia and 4 native populations from North Borneo to a high coverage of 28-37×. We showed that the Negritos from Peninsular Malaysia shared a common ancestor with the East Asians, but exhibited some level of gene flow from South Asia, while the North Borneo populations exhibited closer genetic affinity towards East Asians than the Malays. The analysis of time of divergence suggested that ancestors of Negrito were the earliest settlers in the Malay Peninsula, whom first separated from the Papuans ~ 50-33 thousand years ago (kya), followed by East Asian (~ 40-15 kya), while the divergence time frame between North Borneo and East Asia populations predates the Austronesian expansion period implies a possible pre-Neolithic colonization. Substantial Neanderthal ancestry was confirmed in our genomes, as was observed in other East Asians. However, no significant difference was observed, in terms of the proportion of Denisovan gene flow into these native inhabitants from Malaysia. Judging from the similar amount of introgression in the Southeast Asians and East Asians, our findings suggest that the Denisovan gene flow may have occurred before the divergence of these populations and that the shared similarities are likely an ancestral component.
Fulltext Unintended Consequences: Fluid Resuscitation Worsens Shock in an Ovine Model of Endotoxemia

Byrne L, Obonyo NG, Diab SD, Dunster KR, Passmore MR, Boon AC, et al.

Am J Respir Crit Care Med, 2018 10 15;198(8):1043-1054.
PMID: 29882682 DOI: 10.1164/rccm.201801-0064OC

RATIONALE: Fluid resuscitation is widely considered a life-saving intervention in septic shock; however, recent evidence has brought both its safety and efficacy in sepsis into question.
OBJECTIVES: In this study, we sought to compare fluid resuscitation with vasopressors with the use of vasopressors alone in a hyperdynamic model of ovine endotoxemia.
METHODS: Endotoxemic shock was induced in 16 sheep, after which they received fluid resuscitation with 40 ml/kg of 0.9% saline or commenced hemodynamic support with protocolized noradrenaline and vasopressin. Microdialysis catheters were inserted into the arterial circulation, heart, brain, kidney, and liver to monitor local metabolism. Blood samples were recovered to measure serum inflammatory cytokines, creatinine, troponin, atrial natriuretic peptide, brain natriuretic peptide, and hyaluronan. All animals were monitored and supported for 12 hours after fluid resuscitation.
MEASUREMENTS AND MAIN RESULTS: After resuscitation, animals that received fluid resuscitation required significantly more noradrenaline to maintain the same mean arterial pressure in the subsequent 12 hours (68.9 mg vs. 39.6 mg; P = 0.04). Serum cytokines were similar between groups. Atrial natriuretic peptide increased significantly after fluid resuscitation compared with that observed in animals managed without fluid resuscitation (335 ng/ml [256-382] vs. 233 ng/ml [144-292]; P = 0.04). Cross-sectional time-series analysis showed that the rate of increase of the glycocalyx glycosaminoglycan hyaluronan was greater in the fluid-resuscitated group over the course of the study (P = 0.02).
CONCLUSIONS: Fluid resuscitation resulted in a paradoxical increase in vasopressor requirement. Additionally, it did not result in improvements in any of the measured microcirculatory- or organ-specific markers measured. The increase in vasopressor requirement may have been due to endothelial/glycocalyx damage secondary to atrial natriuretic peptide-mediated glycocalyx shedding.
Fulltext Activating CARD14 Mutations Are Associated with Generalized Pustular Psoriasis but Rarely Account for Familial Recurrence in Psoriasis Vulgaris

Berki DM, Liu L, Choon SE, David Burden A, Griffiths CEM, Navarini AA, et al.

J Invest Dermatol, 2015 Dec;135(12):2964-2970.
PMID: 26203641 DOI: 10.1038/jid.2015.288

Caspase recruitment family member 14 (CARD14, also known as CARMA2), is a scaffold protein that mediates NF-κB signal transduction in skin keratinocytes. Gain-of-function CARD14 mutations have been documented in familial forms of psoriasis vulgaris (PV) and pityriasis rubra pilaris (PRP). More recent investigations have also implicated CARD14 in the pathogenesis of pustular psoriasis. Follow-up studies, however, have been limited, so that it is not clear to what extent CARD14 alleles account for the above conditions. Here, we sought to address this question by carrying out a systematic CARD14 analysis in an extended patient cohort (n=416). We observed no disease alleles in subjects with familial PV (n=159), erythrodermic psoriasis (n=23), acral pustular psoriasis (n=100), or sporadic PRP (n=29). Conversely, our analysis of 105 individuals with generalized pustular psoriasis (GPP) identified a low-frequency variant (p.Asp176His) that causes constitutive CARD14 oligomerization and shows a significant association with GPP in Asian populations (P=8.4×10(-5); odds ratio=6.4). These data indicate that the analysis of CARD14 mutations could help stratify pustular psoriasis cohorts but would be mostly uninformative in the context of psoriasis and sporadic PRP.
Fulltext Fabrication of Adipose-Derived Stem Cell-Based Self-Assembled Scaffold under Hypoxia and Mechanical Stimulation for Urethral Tissue Engineering

Rashidbenam Z, Jasman MH, Tan GH, Goh EH, Fam XI, Ho CCK, et al.

Int J Mol Sci, 2021 Mar 25;22(7).
PMID: 33805910 DOI: 10.3390/ijms22073350

Long urethral strictures are often treated with autologous genital skin and buccal mucosa grafts; however, risk of hair ingrowth and donor site morbidity, restrict their application. To overcome this, we introduced a tissue-engineered human urethra comprising adipose-derived stem cell (ASC)-based self-assembled scaffold, human urothelial cells (UCs) and smooth muscle cells (SMCs). ASCs were cultured with ascorbic acid to stimulate extracellular matrix (ECM) production. The scaffold (ECM) was stained with collagen type-I antibody and the thickness was measured under a confocal microscope. Results showed that the thickest scaffold (28.06 ± 0.59 μm) was achieved with 3 × 104 cells/cm2 seeding density, 100 μg/mL ascorbic acid concentration under hypoxic and dynamic culture condition. The biocompatibility assessment showed that UCs and SMCs seeded on the scaffold could proliferate and maintain the expression of their markers (CK7, CK20, UPIa, and UPII) and (α-SMA, MHC and Smootheline), respectively, after 14 days of in vitro culture. ECM gene expression analysis showed that the ASC and dermal fibroblast-based scaffolds (control) were comparable. The ASC-based scaffold can be handled and removed from the plate. This suggests that multiple layers of scaffold can be stacked to form the urothelium (seeded with UCs), submucosal layer (ASCs only), and smooth muscle layer (seeded with SMCs) and has the potential to be developed into a fully functional human urethra for urethral reconstructive surgeries.
Current and Future Potential Impact of COVID-19 on Kratom (Mitragyna speciosa Korth.) Supply and Use

Singh D, Brown PN, Cinosi E, Corazza O, Henningfield JE, Garcia-Romeu A, et al.

Front Psychiatry, 2020;11:574483.
PMID: 33324252 DOI: 10.3389/fpsyt.2020.574483

Kratom (Mitragyna speciosa Korth., Rubiaceae) is native to and has traditional use in Southeast Asia. The number of kratom users outside of Southeast Asia has increased significantly in recent decades with use spreading to the Unites States (US) and Europe. Because of its reputed opioid-like psychoactive effects at higher doses, kratom has been regulated in several countries and is subject to an import ban by the US Food and Drug Administration. Nonetheless, in the US it is estimated that 10-15 million people consume kratom primarily for the self-treatment of pain, psychiatric disorders, to mitigate withdrawal from or dependence on opioids, and to self-treat opioid use disorder or other substance use disorders (SUDs). Due to the global COVID-19 pandemic, a shortage in the supply of kratom products may place unexpected burdens on kratom users, potentially influencing some who use kratom for SUD self-treatment to regress to harmful drug use, hence increasing the likelihood of adverse outcomes, including overdose. Inadequate treatment, treatment barriers, and increases in the sales of adulterated kratom products on the internet or in convenience stores could exacerbate circumstances further. Although there are currently no verified indications of kratom scarcity, researchers and clinicians should be aware of and remain vigilant to this unanticipated possibility.
Fulltext Comprehensive genomic and immunological characterization of Chinese non-small cell lung cancer patients

Zhang XC, Wang J, Shao GG, Wang Q, Qu X, Wang B, et al.

Nat Commun, 2019 04 16;10(1):1772.
PMID: 30992440 DOI: 10.1038/s41467-019-09762-1

Deep understanding of the genomic and immunological differences between Chinese and Western lung cancer patients is of great importance for target therapy selection and development for Chinese patients. Here we report an extensive molecular and immune profiling study of 245 Chinese patients with non-small cell lung cancer. Tumor-infiltrating lymphocyte estimated using immune cell signatures is found to be significantly higher in adenocarcinoma (ADC, 72.5%) compared with squamous cell carcinoma (SQCC, 54.4%). The correlation of genomic alterations with immune signatures reveals that low immune infiltration was associated with EGFR mutations in ADC samples, PI3K and/or WNT pathway activation in SQCC. While KRAS mutations are found to be significantly associated with T cell infiltration in ADC samples. The SQCC patients with high antigen presentation machinery and cytotoxic T cell signature scores are found to have a prolonged overall survival time.
Priorities for the global advancement of care for older adults with cancer: an update of the International Society of Geriatric Oncology Priorities Initiative

Extermann M, Brain E, Canin B, Cherian MN, Cheung KL, de Glas N, et al.

Lancet Oncol, 2021 01;22(1):e29-e36.
PMID: 33387502 DOI: 10.1016/S1470-2045(20)30473-3

In 2011, the International Society of Geriatric Oncology (SIOG) published the SIOG 10 Priorities Initiative, which defined top priorities for the improvement of the care of older adults with cancer worldwide.1 Substantial scientific, clinical, and educational progress has been made in line with these priorities and international health policy developments have occurred, such as the shift of emphasis by WHO from communicable to non-communicable diseases and the adoption by the UN of its Sustainable Development Goals 2030. Therefore, SIOG has updated its priority list. The present document addresses four priority domains: education, clinical practice, research, and strengthening collaborations and partnerships. In this Policy Review, we reflect on how these priorities would apply in different economic settings, namely in high-income countries versus low-income and middle-income countries. SIOG hopes that it will offer guidance for international and national endeavours to provide adequate universal health coverage for older adults with cancer, who represent a major and rapidly growing group in global epidemiology.
Fulltext Cancer and COVID-19 vaccines: a complex global picture

Yusuf A, Sarfati D, Booth CM, Pramesh CS, Lombe D, Aggarwal A, et al.

Lancet Oncol, 2021 06;22(6):749-751.
PMID: 33930324 DOI: 10.1016/S1470-2045(21)00244-8
Induction of Apoptosis and Autophagy by Ternary Copper Complex Towards Breast Cancer Cells

Lee ZY, Leong CH, Lim KUL, Wong CCS, Pongtheerawan P, Arikrishnan SA, et al.

Anticancer Agents Med Chem, 2021 Jul 26.
PMID: 34315396 DOI: 10.2174/1871520621666210726132543

BACKGROUND: Copper complex has been gaining much attention in anticancer research as targeted agent since cancer cells uptake more copper than non-cancerous cells. Our group has synthesised a ternary copper complex which is composed of 1,10-phenanthroline and tyrosine [Cu(phen)(L-tyr)Cl].3H20. These two payloads are designed to cleave DNA and inhibit protein degradation system (proteasome) concurrently in cancer cells, making this copper complex a dual-target compound.
OBJECTIVE: Current study was carried out to investigate the mode of cell death and role of autophagy induced by [Cu(phen)(L-tyr)Cl].3H20 in MCF-7 and MDA-MB-231 breast cancer cells.
METHODS: Growth inhibition of [Cu(phen)(L-tyr)Cl].3H20 towards MDA-MB-231 and human non-cancerous MCF10A breast cells was determined by MTT assay. Annexin-V-FITC/PI and cell cycle analysis were evaluated by flow cytometry. The expression of p53, Bax, caspase-9, caspase-7, caspase-3 and LC3 were determined using western blot analysis. The cells were then co-treated with hydroxychloroquine to ascertain the role of autophagy induced by [Cu(phen)(L-tyr)Cl].3H20.
RESULTS: [Cu(phen)(L-tyr)Cl].3H20 inhibited the growth of cancer cells dose-dependently with less toxicity towards MCF10A cells. Additionally, [Cu(phen)(L-tyr)Cl].3H20 induced apoptosis and cell cycle arrest towards MCF-7 and MDA-MB-231 breast cancer cells possibly via regulation of p53, Bax, caspase-9, caspase-3 and capase-7. The expression of LC3II was upregulated in both cancer cell lines upon treatment with [Cu(phen)(L-tyr) Cl].3H20, indicating the induction of autophagy. Co-treatment with autophagy inhibitor hydroxychloroquine significantly enhanced growth inhibition of both cell lines, suggesting that the autophagy induced by [Cu(phen)(L-tyr) Cl].3H20 in both breast cancer cells was promoting cell survival.
CONCLUSION: [Cu(phen)(L-tyr)Cl].3H20 holds great potential to be developed for breast cancer treatment.
The importance of Indigenous Peoples' lands for the conservation of terrestrial mammals

O'Bryan CJ, Garnett ST, Fa JE, Leiper I, Rehbein JA, Fernández-Llamazares Á, et al.

Conserv Biol, 2021 06;35(3):1002-1008.
PMID: 32852067 DOI: 10.1111/cobi.13620

Indigenous Peoples' lands cover over one-quarter of Earth's surface, a significant proportion of which is still free from industrial-level human impacts. As a result, Indigenous Peoples and their lands are crucial for the long-term persistence of Earth's biodiversity and ecosystem services. Yet, information on species composition on these lands globally remains largely unknown. We conducted the first comprehensive analysis of terrestrial mammal composition across mapped Indigenous lands based on data on area of habitat (AOH) for 4460 mammal species assessed by the International Union for Conservation of Nature. We overlaid each species' AOH on a current map of Indigenous lands and found that 2695 species (60% of assessed mammals) had ≥10% of their ranges on Indigenous Peoples' lands and 1009 species (23%) had >50% of their ranges on these lands. For threatened species, 473 (47%) occurred on Indigenous lands with 26% having >50% of their habitat on these lands. We also found that 935 mammal species (131 categorized as threatened) had ≥ 10% of their range on Indigenous Peoples' lands that had low human pressure. Our results show how important Indigenous Peoples' lands are to the successful implementation of conservation and sustainable development agendas worldwide.
Fulltext Insights from CREDENCE trial indicate an acute drop in estimated glomerular filtration rate during treatment with canagliflozin with implications for clinical practice

Oshima M, Jardine MJ, Agarwal R, Bakris G, Cannon CP, Charytan DM, et al.

Kidney Int, 2021 04;99(4):999-1009.
PMID: 33316282 DOI: 10.1016/j.kint.2020.10.042

Canagliflozin slows the progression of chronic kidney disease in patients with type 2 diabetes and induces a reversible acute drop in estimated glomerular filtration rate (eGFR), believed to be a hemodynamic effect. Predictors of the initial drop and its association with long-term eGFR trajectories and safety outcomes are unknown. To assess this, we performed a post-hoc analysis of 4289 participants in the CREDENCE trial with type 2 diabetes and chronic kidney disease equally split into treatment and placebo groups who had eGFR measured at both baseline and week three. The eGFR was categorized at week three as greater than a 10% decline; between 0 and 10% decline; and no decline. Long-term eGFR trajectories and safety outcomes were estimated in each category of acute eGFR change by linear mixed effects models and Cox regression after adjustment for baseline characteristics and medications use. Significantly more participants in the canagliflozin (45%) compared to the placebo (21%) group experienced an acute drop in eGFR over 10%. An over 30% drop occurred infrequently (4% of participants with canagliflozin and 2% with placebo). The odds ratio for a drop in eGFR over 10% with canagliflozin compared to placebo was significant at 3.03 (95% confidence interval 2.65, 3.47). Following the initial drop in eGFR, multivariable adjusted long-term eGFR trajectories, as well as overall and kidney safety profiles, in those treated with canagliflozin were similar across eGFR decline categories. Thus, although acute drops in eGFR over 10% occurred in nearly half of all participants following initiation of canagliflozin, the clinical benefit of canagliflozin was observed regardless. Additionally, safety outcomes were similar among subgroups of acute eGFR drop.

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