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  1. Fulltext Live virus vaccines based on a yellow fever vaccine backbone: standardized template with key considerations for a risk/benefit assessment
    Monath TP, Seligman SJ, Robertson JS, Guy B, Hayes EB, Condit RC, et al.
    Vaccine, 2015 Jan 01;33(1):62-72.
    PMID: 25446819 DOI: 10.1016/j.vaccine.2014.10.004
    The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viruses inserted into the backbone of another virus (so-called "chimeric virus vaccines"). Many viral vector vaccines are in advanced clinical trials. The first such vaccine to be approved for marketing (to date in Australia, Thailand, Malaysia, and the Philippines) is a vaccine against the flavivirus, Japanese encephalitis (JE), which employs a licensed vaccine (yellow fever 17D) as a vector. In this vaccine, two envelope proteins (prM-E) of YF 17D virus were exchanged for the corresponding genes of JE virus, with additional attenuating mutations incorporated into the JE gene inserts. Similar vaccines have been constructed by inserting prM-E genes of dengue and West Nile into YF 17D virus and are in late stage clinical studies. The dengue vaccine is, however, more complex in that it requires a mixture of four live vectors each expressing one of the four dengue serotypes. This vaccine has been evaluated in multiple clinical trials. No significant safety concerns have been found. The Phase 3 trials met their endpoints in terms of overall reduction of confirmed dengue fever, and, most importantly a significant reduction in severe dengue and hospitalization due to dengue. However, based on results that have been published so far, efficacy in preventing serotype 2 infection is less than that for the other three serotypes. In the development of these chimeric vaccines, an important series of comparative studies of safety and efficacy were made using the parental YF 17D vaccine virus as a benchmark. In this paper, we use a standardized template describing the key characteristics of the novel flavivirus vaccine vectors, in comparison to the parental YF 17D vaccine. The template facilitates scientific discourse among key stakeholders by increasing the transparency and comparability of information. The Brighton Collaboration V3SWG template may also be useful as a guide to the evaluation of other recombinant viral vector vaccines.
  2. Fulltext Liver Function Test Abnormalities in Experimental and Clinical Plasmodium vivax Infection
    Odedra A, Webb L, Marquart L, Britton LJ, Chalon S, Moehrle JJ, et al.
    Am J Trop Med Hyg, 2020 11;103(5):1910-1917.
    PMID: 32815508 DOI: 10.4269/ajtmh.20-0491
    Liver transaminase elevations after treatment in malaria volunteer infection studies (VISs) have raised safety concerns. We investigated transaminase elevations from two human Plasmodium vivax VISs where subjects were treated with chloroquine (n = 24) or artefenomel (n = 8) and compared them with studies in Thailand (n = 41) and Malaysia (n = 76). In the VISs, alanine transaminase (ALT) increased to ≥ 2.5 × upper limit of normal (ULN) in 11/32 (34%) volunteers, peaking 5-8 days post-treatment. Transaminase elevations were asymptomatic, were not associated with elevated bilirubin, and resolved by day 42. The risk of an ALT ≥ 2.5 × ULN increased more than 4-fold (odds ratio [OR] 4.28; 95% CI: 1.26-14.59; P = 0.02) for every log10 increase in the parasite clearance burden (PCB), defined as the log-fold reduction in parasitemia 24 hours post-treatment. Although an elevated ALT ≥ 2.5 × ULN was more common after artefenomel than after chloroquine (5/8 [63%] versus 6/24 [25%]; OR 5.0; 95% CI: 0.91-27.47; P = 0.06), this risk disappeared when corrected for PCB. Peak ALT also correlated with peak C-reactive protein (R = 0.44; P = 0.012). Elevations in ALT (≥ 2.5 × ULN) were less common in malaria-endemic settings, occurring in 1/41 (2.5%) Thai patients treated with artefenomel, and in none of 76 Malaysians treated with chloroquine or artemisinin combination therapy. Post-treatment transaminase elevations are common in experimental P. vivax infection but do not appear to impact on participant safety. Although the mechanism of these changes remains uncertain, host inflammatory response to parasite clearance may be contributory.
  3. Philopatry and reproductive success in Bornean orang-utans (Pongo pygmaeus)
    Goossens B, Setchell JM, James SS, Funk SM, Chikhi L, Abulani A, et al.
    Mol Ecol, 2006 Aug;15(9):2577-88.
    PMID: 16842428
    Behavioural observations suggest that orang-utans are semi-solitary animals with females being philopatric and males roaming more widely in search of receptive partners, leading to the prediction that females are more closely related than males at any given site. In contrast, our study presents evidence for male and female philopatry in the orang-utan. We examined patterns of relatedness and parentage in a wild orang-utan population in Borneo using noninvasively collected DNA samples from animals observed to defecate, and microsatellite markers to assess dispersal and mating strategies. Surprisingly, resident females were equally as related to other resident females (mean r(xy) = 0.303) as resident males were to other resident males (mean r(xy) = 0.305). Moreover, resident females were more related to each other and to the resident males than they were to nonresident females, and resident males were more related to each other (and resident females) than they were to nonresident males. We assigned genetic mothers to 12 individuals in the population, while sires could be identified for eight. Both flanged males and unflanged males achieved paternity, similar to findings reported for Sumatran orang-utans.
  4. Microgeographic evolution of snail shell shape and predator behavior
    Schilthuizen M, van Til A, Salverda M, Liew TS, James SS, bin Elahan B, et al.
    Evolution, 2006 Sep;60(9):1851-8.
    PMID: 17089969
    Genetic divergence in geographically isolated populations is a prerequisite for allopatric speciation, one of the most common modes of speciation. In ecologically equivalent populations existing within a small, environmentally homogeneous area, an important role for environmentally neutral divergence is often found or inferred. We studied a species complex of conspicuously shaped Opisthostoma land snails on scattered limestone outcrops within a small area of lowland rainforest in Borneo. We used shell morphometrics, mitochondrial and nuclear DNA sequences, and marks of predation to study the factors involved in allopatric divergence. We found that a striking geographic divergence exists in shell morphology, which is partly associated with neutral genetic divergence. We also found geographic differentiation in the behavior of the snails' invertebrate predator and evidence of an evolutionary interaction between aspects of shell shape and predator behavior. Our study shows that adaptation to biotic aspects of the environment may play a more important role in allopatric speciation than previously suspected, even on a geographically very small scale.
  5. Fulltext Ultra Brief Psychological Interventions for COVID-19 Pandemic: Introduction of a Locally-Adapted Brief Intervention for Mental Health and Psychosocial Support Service
    Ping NPT, Shoesmith WD, James S, Nor Hadi NM, Yau EKB, Lin LJ
    Malays J Med Sci, 2020 Mar;27(2):51-56.
    PMID: 32788841 MyJurnal DOI: 10.21315/mjms2020.27.2.6
    The ultra-brief psychological interventions (UBPI) was created in 2018 to empower healthcare providers with psychological skills that can be delivered within a short period. Techniques used within UBPI were adopted from a variety of well established psychotherapies and distilled into its core essentials. This enabled practitioners of UBPI to deliver specific psychological skills in the appropriate context to the client within a period of 15-20 min. UBPI was also manualised to standardised training of practitioners. During the novel coronavirus disease of 2019 (COVID-19) pandemic, UBPI was modified to suit the unique psychological demands of the pandemic. This article presents how UBPI was adapted and used with healthcare providers dealing with COVID-19 and also with the public who required psychological first aid (PFA).
  6. Fulltext The Behaviour Changes in Response to COVID-19 Pandemic within Malaysia
    Koh Boon Yau E, Pang Tze Ping N, Shoesmith WD, James S, Nor Hadi NM, Loo JL
    Malays J Med Sci, 2020 Mar;27(2):45-50.
    PMID: 32788840 MyJurnal DOI: 10.21315/mjms2020.27.2.5
    The novel coronavirus infection, COVID-19, is a pandemic that currently affects the whole world. During this period, Malaysians displayed a variety of behaviour changes as a response to COVID-19, including panic buying, mass travelling during movement restriction and even absconding from treatment facilities. This article attempts to explore some of these behaviour changes from a behaviourist perspective in order to get a better understanding of the rationale behind the changes.
  7. Fulltext Loss of complement regulatory proteins on red blood cells in mild malarial anaemia and in Plasmodium falciparum induced blood-stage infection
    Oyong DA, Loughland JR, SheelaNair A, Andrew D, Rivera FDL, Piera KA, et al.
    Malar J, 2019 Sep 18;18(1):312.
    PMID: 31533836 DOI: 10.1186/s12936-019-2962-0
    BACKGROUND: Anaemia is a major consequence of malaria, caused by the removal of both infected and uninfected red blood cells (RBCs) from the circulation. Complement activation and reduced expression of complement regulatory proteins (CRPs) on RBCs are an important pathogenic mechanism in severe malarial anaemia in both Plasmodium falciparum and Plasmodium vivax infection. However, little is known about loss of CRPs on RBCs during mild malarial anaemia and in low-density infection.

    METHODS: The expression of CRP CR1, CD55, CD59, and the phagocytic regulator CD47, on uninfected normocytes and reticulocytes were assessed in individuals from two study populations: (1) P. falciparum and P. vivax-infected patients from a low transmission setting in Sabah, Malaysia; and, (2) malaria-naïve volunteers undergoing P. falciparum induced blood-stage malaria (IBSM). For clinical infections, individuals were categorized into anaemia severity categories based on haemoglobin levels. For IBSM, associations between CRPs and haemoglobin level were investigated.

    RESULTS: CRP expression on RBC was lower in Malaysian individuals with P. falciparum and P. vivax mild malarial anaemia compared to healthy controls. CRP expression was also reduced on RBCs from volunteers during IBSM. Reduction occurred on normocytes and reticulocytes. However, there was no significant association between reduced CRPs and haemoglobin during IBSM.

    CONCLUSIONS: Removal of CRPs occurs on both RBCs and reticulocytes during Plasmodium infection even in mild malarial anaemia and at low levels of parasitaemia.

  8. Fulltext Plasmacytoid dendritic cells appear inactive during sub-microscopic Plasmodium falciparum blood-stage infection, yet retain their ability to respond to TLR stimulation
    Loughland JR, Minigo G, Sarovich DS, Field M, Tipping PE, Montes de Oca M, et al.
    Sci Rep, 2017 06 01;7(1):2596.
    PMID: 28572564 DOI: 10.1038/s41598-017-02096-2
    Plasmacytoid dendritic cells (pDC) are activators of innate and adaptive immune responses that express HLA-DR, toll-like receptor (TLR) 7, TLR9 and produce type I interferons. The role of human pDC in malaria remains poorly characterised. pDC activation and cytokine production were assessed in 59 malaria-naive volunteers during experimental infection with 150 or 1,800 P. falciparum-parasitized red blood cells. Using RNA sequencing, longitudinal changes in pDC gene expression were examined in five adults before and at peak-infection. pDC responsiveness to TLR7 and TLR9 stimulation was assessed in-vitro. Circulating pDC remained transcriptionally stable with gene expression altered for 8 genes (FDR 
  9. Fulltext Persistent Incisional Pain after Noncardiac Surgery: An International Prospective Cohort Study
    Khan JS, Sessler DI, Chan MTV, Wang CY, Garutti I, Szczeklik W, et al.
    Anesthesiology, 2021 10 01;135(4):711-723.
    PMID: 34499129 DOI: 10.1097/ALN.0000000000003951
    BACKGROUND: The purpose of this study was to determine the incidence, characteristics, impact, and risk factors associated with persistent incisional pain. The hypothesis was that patient demographics and perioperative interventions are associated with persistent pain.

    METHODS: This was a secondary analysis of an international prospective cohort study from 2012 to 2014. This study included patients who were 45 yr of age or older who underwent major inpatient noncardiac surgery. Data were collected perioperatively and at 1 yr after surgery to assess for the development of persistent incisional pain (pain present around incision at 1 yr after surgery).

    RESULTS: Among 14,831 patients, 495 (3.3%; 95% CI, 3.1 to 3.6) reported persistent incisional pain at 1 yr, with an average pain intensity of 3.6 ± 2.5 (0 to 10 numeric rating scale), with 35% and 14% reporting moderate and severe pain intensities, respectively. More than half of patients with persistent pain reported needing analgesic medications, and 85% reported interference with daily activities (denominator = 495 in the above proportions). Risk factors for persistent pain included female sex (P = 0.007), Asian ethnicity (P < 0.001), surgery for fracture (P < 0.001), history of chronic pain (P < 0.001), coronary artery disease (P < 0.001), history of tobacco use (P = 0.048), postoperative patient-controlled analgesia (P < 0.001), postoperative continuous nerve block (P = 0.010), insulin initiation within 24 h of surgery (P < 0.001), and withholding nonsteroidal anti-inflammatory medication or cyclooxygenase-2 inhibitors on the day of surgery (P = 0.029 and P < 0.001, respectively). Older age (P < 0.001), endoscopic surgery (P = 0.005), and South Asian (P < 0.001), Native American/Australian (P = 0.004), and Latin/Hispanic ethnicities (P < 0.001) were associated with a lower risk of persistent pain.

    CONCLUSIONS: Persistent incisional pain is a common complication of inpatient noncardiac surgery, occurring in approximately 1 in 30 adults. It results in significant morbidity, interferes with daily living, and is associated with persistent analgesic consumption. Certain demographics, ethnicities, and perioperative practices are associated with increased risk of persistent pain.

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  10. Temporal coexistence mechanisms contribute to the latitudinal gradient in forest diversity
    Usinowicz J, Chang-Yang CH, Chen YY, Clark JS, Fletcher C, Garwood NC, et al.
    Nature, 2017 10 05;550(7674):105-108.
    PMID: 28953870 DOI: 10.1038/nature24038
    The tropical forests of Borneo and Amazonia may each contain more tree species diversity in half a square kilometre than do all the temperate forests of Europe, North America, and Asia combined. Biologists have long been fascinated by this disparity, using it to investigate potential drivers of biodiversity. Latitudinal variation in many of these drivers is expected to create geographic differences in ecological and evolutionary processes, and evidence increasingly shows that tropical ecosystems have higher rates of diversification, clade origination, and clade dispersal. However, there is currently no evidence to link gradients in ecological processes within communities at a local scale directly to the geographic gradient in biodiversity. Here, we show geographic variation in the storage effect, an ecological mechanism that reduces the potential for competitive exclusion more strongly in the tropics than it does in temperate and boreal zones, decreasing the ratio of interspecific-to-intraspecific competition by 0.25% for each degree of latitude that an ecosystem is located closer to the Equator. Additionally, we find evidence that latitudinal variation in climate underpins these differences; longer growing seasons in the tropics reduce constraints on the seasonal timing of reproduction, permitting lower recruitment synchrony between species and thereby enhancing niche partitioning through the storage effect. Our results demonstrate that the strength of the storage effect, and therefore its impact on diversity within communities, varies latitudinally in association with climate. This finding highlights the importance of biotic interactions in shaping geographic diversity patterns, and emphasizes the need to understand the mechanisms underpinning ecological processes in greater detail than has previously been appreciated.
  11. Fulltext Neuroendocrine Cell Hyperplasia of Infancy. Clinical Score and Comorbidities
    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.
  12. Fulltext Longitudinal changes in iron homeostasis in human experimental and clinical malaria
    Woolley SD, Grigg MJ, Marquart L, Gower JSE, Piera K, Nair AS, et al.
    EBioMedicine, 2024 Jul;105:105189.
    PMID: 38851058 DOI: 10.1016/j.ebiom.2024.105189
    BACKGROUND: The interaction between iron status and malaria is incompletely understood. We evaluated longitudinal changes in iron homeostasis in volunteers enrolled in malaria volunteer infection studies (VIS) and in Malaysian patients with falciparum and vivax malaria.

    METHODS: We retrieved data and samples from 55 participants (19 female) enrolled in malaria VIS, and 171 patients (45 female) with malaria and 30 healthy controls (13 female) enrolled in clinical studies in Malaysia. Ferritin, hepcidin, erythropoietin, and soluble transferrin receptor (sTfR) were measured by ELISA.

    FINDINGS: In the VIS, participants' parasitaemia was correlated with baseline mean corpuscular volume (MCV), but not iron status (ferritin, hepcidin or sTfR). Ferritin, hepcidin and sTfR all increased during the VIS. Ferritin and hepcidin normalised by day 28, while sTfR remained elevated. In VIS participants, baseline ferritin was associated with post-treatment increases in liver transaminase levels. In Malaysian patients with malaria, hepcidin and ferritin were elevated on admission compared to healthy controls, while sTfR increased following admission. By day 28, hepcidin had normalised; however, ferritin and sTfR both remained elevated.

    INTERPRETATION: Our findings demonstrate that parasitaemia is associated with an individual's MCV rather than iron status. The persistent elevation in sTfR 4 weeks post-infection in both malaria VIS and clinical malaria may reflect a causal link between malaria and iron deficiency.

    FUNDING: National Health and Medical Research Council (Program Grant 1037304, Project Grants 1045156 and 1156809; Investigator Grants 2016792 to BEB, 2016396 to JCM, 2017436 to MJG); US National Institute of Health (R01-AI116472-03); Malaysian Ministry of Health (BP00500420).

  13. Fulltext Hell's Gate globin I: an acid and thermostable bacterial hemoglobin resembling mammalian neuroglobin
    Teh AH, Saito JA, Baharuddin A, Tuckerman JR, Newhouse JS, Kanbe M, et al.
    FEBS Lett, 2011 Oct 20;585(20):3250-8.
    PMID: 21925500 DOI: 10.1016/j.febslet.2011.09.002
    Hell's Gate globin I (HGbI), a heme-containing protein structurally homologous to mammalian neuroglobins, has been identified from an acidophilic and thermophilic obligate methanotroph, Methylacidiphilum infernorum. HGbI has very high affinity for O(2) and shows barely detectable autoxidation in the pH range of 5.2-8.6 and temperature range of 25-50°C. Examination of the heme pocket by X-ray crystallography and molecular dynamics showed that conformational movements of Tyr29(B10) and Gln50(E7), as well as structural flexibility of the GH loop and H-helix, may play a role in modulating its ligand binding behavior. Bacterial HGbI's unique resistance to the sort of extreme acidity that would extract heme from any other hemoglobin makes it an ideal candidate for comparative structure-function studies of the expanding globin superfamily.
  14. Fulltext Longitudinal changes in iron homeostasis in human experimental and clinical malaria
    Woolley SD, Grigg MJ, Marquart L, Gower J, Piera K, Nair AS, et al.
    medRxiv, 2023 Dec 21.
    PMID: 38196596 DOI: 10.1101/2023.12.19.23300265
    BACKGROUND: The interaction between iron deficiency and malaria is incompletely understood. We evaluated longitudinal changes in iron homeostasis in volunteers enrolled in malaria volunteer infection studies (VIS) and in Malaysian patients with falciparum and vivax malaria.

    METHODS: We retrieved samples and associated data from 55 participants enrolled in malaria VIS, and 171 malaria patients and 30 healthy controls enrolled in clinical studies in Malaysia. Ferritin, hepcidin, erythropoietin, and soluble transferrin receptor (sTfR) were measured by ELISA.

    RESULTS: In the VIS, participants' parasitaemia was correlated with baseline mean corpuscular volume (MCV), but not iron status (ferritin, hepcidin or sTfR). Ferritin, hepcidin and sTfR all increased during the VIS. Ferritin and hepcidin normalised by day 28, while sTfR remained elevated. In VIS participants, baseline iron status (ferritin) was associated with post-treatment increases in liver transaminase levels. In Malaysian malaria patients, hepcidin and ferritin were elevated on admission compared to healthy controls, while sTfR increased following admission. Hepcidin normalised by day 28; however, ferritin and sTfR both remained elevated 4 weeks following admission.

    CONCLUSION: Our findings demonstrate that parasitaemia is associated with an individual's MCV rather than iron status. The persistent elevation in sTfR 4 weeks post-infection in both malaria VIS and clinical malaria may reflect a causal link between malaria and iron deficiency.

  15. Fulltext Relationships between Psychopathology, Psychological Process Variables, and Sociodemographic Variables and Comparison of Quarantined and Non-Quarantined Groups of Malaysian University Students in the COVID-19 Pandemic
    Pang NTP, James S, Giloi N, Rahim SSSA, Omar A, Jeffree MS, et al.
    Int J Environ Res Public Health, 2021 Sep 14;18(18).
    PMID: 34574581 DOI: 10.3390/ijerph18189656
    The COVID-19 pandemic has had considerable psychological health impacts across the globe. This study aimed to establish the psychological process variables underlying psychopathology in Malaysian public university students during the national Movement Control Order (MCO). The aim was to craft structured and sustainable psychological support programs with these students. We conducted a cross-sectional study involving Malaysian university students subjected to the Malaysian MCO. Structured questionnaires measuring sociodemographic factors, measures of depression, anxiety, stress, psychological mindedness, psychological flexibility and state mindfulness were employed. A total of 515 students participated in this study with 12 students (2.3%) being quarantined at the time. Many of them scored 'moderate' or above on the Depression, Anxiety and Stress Scale (DASS) with 20.2%, 25.0% and 14.2%, respectively. Quarantined students had higher depressive symptoms, with female students scoring significantly higher for depression, anxiety, and stress. Multiple regressions suggested gender and quarantine status predicted depression scores. However, only gender significantly predicted anxiety and stress. Psychological flexibility and psychological mindedness (Insight subscale) are significantly correlated with depression, anxiety, and stress, with psychological mindedness predicting all three psychopathologies. This study demonstrates that gender, psychological flexibility, and psychological mindedness are key demographic and psychological factors impacting students. Targeting psychological flexibility and psychological mindedness may enable timely prevention and intervention programs for our students to support their mental and physical health as we move through, and out of, the pandemic.
  16. Opportunities and threats to contact lens practice: A global survey perspective
    Thite N, Desiato A, Shinde L, Wolffsohn JS, Naroo SA, Santodomingo-Rubido J, et al.
    Cont Lens Anterior Eye, 2021 12;44(6):101496.
    PMID: 34426063 DOI: 10.1016/j.clae.2021.101496
    AIM: To understand the views of contact lens (CL) practitioners across the globe regarding what they perceive as opportunities and threats in CL practice.

    METHODS: A self-administered anonymised questionnaire, constructed in English and translated in six more languages, was distributed through reputed international professional bodies and academic institutions worldwide. The questionnaire included items on demographic characteristics, type of practice, and questions designed to explore practitioners' perspective on the future of their CL practice over the next five years.

    RESULTS: A total of 2408 valid responses were analysed. Multifocal CLs for presbyopia, CLs for myopia control, use of daily disposable (DD) CLs for occasional wear, and biocompatible materials to improve comfort were identified as promising areas of opportunities by practitioners (all 8/10). Respondents from North America, and Europe valued DDCLs for occasional wear moderately more favourable (Median: 9/10 for all) as compared to colleagues in Asia (Median: 8/10, p 

  17. Global trends in myopia management attitudes and strategies in clinical practice - 2019 Update
    Wolffsohn JS, Calossi A, Cho P, Gifford K, Jones L, Jones D, et al.
    Cont Lens Anterior Eye, 2020 02;43(1):9-17.
    PMID: 31761738 DOI: 10.1016/j.clae.2019.11.002
    PURPOSE: A survey in 2015 identified a high level of eye care practitioner concern about myopia with a reported moderately high level of activity, but the vast majority still prescribed single vision interventions to young myopes. This research aimed to update these findings 4 years later.

    METHODS: A self-administrated, internet-based questionnaire was distributed in eight languages, through professional bodies to eye care practitioners globally. The questions examined: awareness of increasing myopia prevalence, perceived efficacy of available strategies and adoption levels of such strategies, and reasons for not adopting specific strategies.

    RESULTS: Of the 1336 respondents, concern was highest (9.0 ± 1.6; p 

  18. Current Status of Training and Certification for Congenital Heart Surgery Around the World: Proceedings of the Meetings of the Global Council on Education for Congenital Heart Surgery of the World Society for Pediatric and Congenital Heart Surgery
    Tchervenkov CI, Herbst C, Jacobs JP, Al-Halees Z, Edwin F, Dearani JA, et al.
    World J Pediatr Congenit Heart Surg, 2021 05;12(3):394-405.
    PMID: 33942697 DOI: 10.1177/21501351211003520
    The optimal training of the highly specialized congenital heart surgeon is a long and complex process, which is a significant challenge in most parts of the world. The World Society for Pediatric and Congenital Heart Surgery (WSPCHS) has established the Global Council on Education for Congenital Heart Surgery as a nonprofit organization with the goal of assessing current training and certification and ultimately establishing standardized criteria for the training, evaluation, and certification of congenital heart surgeons around the world. The Global Council and the WSPCHS have reviewed the present status of training and certification for congenital cardiac surgery around the world. There is currently lack of consensus and standardized criteria for training in congenital heart surgery, with significant disparity between continents and countries. This represents significant obstacles to international job mobility of competent congenital heart surgeons and to the efforts to improve the quality of care for patients with Congenital Heart Disease worldwide. The purpose of this article is to summarize and document the present state of training and certification in congenital heart surgery around the world.
  19. Fulltext Genome-wide association analysis provides insights into the molecular etiology of dilated cardiomyopathy
    Zheng SL, Henry A, Cannie D, Lee M, Miller D, McGurk KA, et al.
    Nat Genet, 2024 Dec;56(12):2646-2658.
    PMID: 39572783 DOI: 10.1038/s41588-024-01952-y
    Dilated cardiomyopathy (DCM) is a leading cause of heart failure and cardiac transplantation. We report a genome-wide association study and multi-trait analysis of DCM (14,256 cases) and three left ventricular traits (36,203 UK Biobank participants). We identified 80 genomic risk loci and prioritized 62 putative effector genes, including several with rare variant DCM associations (MAP3K7, NEDD4L and SSPN). Using single-nucleus transcriptomics, we identify cellular states, biological pathways, and intracellular communications that drive pathogenesis. We demonstrate that polygenic scores predict DCM in the general population and modify penetrance in carriers of rare DCM variants. Our findings may inform the design of genetic testing strategies that incorporate polygenic background. They also provide insights into the molecular etiology of DCM that may facilitate the development of targeted therapeutics.
  20. Fulltext Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
    Tobias DK, Merino J, Ahmad A, Aiken C, Benham JL, Bodhini D, et al.
    Nat Med, 2023 Oct;29(10):2438-2457.
    PMID: 37794253 DOI: 10.1038/s41591-023-02502-5
    Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
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