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  1. From Plant Extract to a cDNA Encoding a Glucosyltransferase Candidate: Proteomics and Transcriptomics as Tools to Help Elucidate Saponin Biosynthesis in Centella asiatica
    de Costa F, Barber CJ, Reed DW, Covello PS
    Methods Mol Biol, 2016;1405:43-8.
    PMID: 26843164 DOI: 10.1007/978-1-4939-3393-8_5
    Centella asiatica (L.) Urban (Apiaceae), a small annual plant that grows in India, Sri Lanka, Malaysia, and other parts of Asia, is well-known as a medicinal herb with a long history of therapeutic uses. The bioactive compounds present in C. asiatica leaves include ursane-type triterpene sapogenins and saponins-asiatic acid, madecassic acid, asiaticoside, and madecassoside. Various bioactivities have been shown for these compounds, although most of the steps in the biosynthesis of triterpene saponins, including glycosylation, remain uncharacterized at the molecular level. This chapter describes an approach that integrates partial enzyme purification, proteomics methods, and transcriptomics, with the aim of reducing the number of cDNA candidates encoding for a glucosyltransferase involved in saponin biosynthesis and facilitating the elucidation of the pathway in this medicinal plant.
  2. Fulltext Mixed Clinical Pictures of Endogenous Endophthalmitis in a Relapse Leukemic Patient
    Azmi AZ, Patrick S, Isa MIB, Ab Ghani S
    Cureus, 2023 Nov;15(11):e49167.
    PMID: 38130531 DOI: 10.7759/cureus.49167
    Endogenous endophthalmitis is rare but sight-threatening in leukemic patients, which can have devastating sequelae. We report a case of a 15-year-old teenager with acute myeloid leukemia on relapse, presented with a mixed picture of endogenous endophthalmitis. The diagnosis dilemma in this patient proved difficult as Investigations and management can be challenging as young teenagers are usually less cooperative than adults. Endogenous endophthalmitis is not uncommon in this group of patients; however, mixed clinical pictures are almost unheard of, and the final diagnosis can be misleading if not treated accordingly. Viral infections such as cytomegalovirus (CMV), bacterial, and fungal are all considered potential opportunistic infections. Diagnosis of endogenous endophthalmitis is complex and relies heavily on the clinical characteristics of each organism supported by intravitreal tapping and culture samples. However, data from endogenous endophthalmitis in leukemic patients is scarce nowadays across the board. In this case report, we highlight the challenges of managing endogenous endophthalmitis in a young leukemic patient due for bone marrow transplantation. Future studies are needed to investigate the current microorganism trends and treatments available. An algorithm for managing endophthalmitis in immunosuppressed patients should be done to provide a better approach from the get-go.
  3. Fulltext A Multifaceted Presentation of Xerophthalmia in Autistic Patients
    Azmi AZ, Patrick S, Isa MIB, Ab Ghani S
    Cureus, 2023 Nov;15(11):e49172.
    PMID: 38130530 DOI: 10.7759/cureus.49172
    We report the manifestations of vitamin A deficiency (VAD) in three children with underlying autism of different stages. These children were under developmental paediatrician follow-up for autism, and the VAD was not detected until these children presented to Ophthalmology screening for varying stages of signs and symptoms. On further assessment, all of our patients have VAD secondary to poor dietary intake, as autistic patients are associated with having selective eating habits. In our case series, we discuss the spectrum of xerophthalmia presentations, which can be mild and can manifest as punctate epithelial erosions to the more blinding complications at the advanced stage of the disease, mainly irreversible optic neuropathy. The primary management is to address the dietary routine coupled with systemic administration of vitamin A.
  4. Multiple systemic embolisms with septicemia after gastric variceal obliteration with cyanoacrylate
    Tan YM, Goh KL, Kamarulzaman A, Tan PS, Ranjeev P, Salem O, et al.
    Gastrointest Endosc, 2002 Feb;55(2):276-8.
    PMID: 11818941
  5. Fulltext Population Size Estimation of Gay and Bisexual Men and Other Men Who Have Sex With Men Using Social Media-Based Platforms
    Baral S, Turner RM, Lyons CE, Howell S, Honermann B, Garner A, et al.
    JMIR Public Health Surveill, 2018 02 08;4(1):e15.
    PMID: 29422452 DOI: 10.2196/publichealth.9321
    BACKGROUND: Gay, bisexual, and other cisgender men who have sex with men (GBMSM) are disproportionately affected by the HIV pandemic. Traditionally, GBMSM have been deemed less relevant in HIV epidemics in low- and middle-income settings where HIV epidemics are more generalized. This is due (in part) to how important population size estimates regarding the number of individuals who identify as GBMSM are to informing the development and monitoring of HIV prevention, treatment, and care programs and coverage. However, pervasive stigma and criminalization of same-sex practices and relationships provide a challenging environment for population enumeration, and these factors have been associated with implausibly low or absent size estimates of GBMSM, thereby limiting knowledge about the dynamics of HIV transmission and the implementation of programs addressing GBMSM.

    OBJECTIVE: This study leverages estimates of the number of members of a social app geared towards gay men (Hornet) and members of Facebook using self-reported relationship interests in men, men and women, and those with at least one reported same-sex interest. Results were categorized by country of residence to validate official size estimates of GBMSM in 13 countries across five continents.

    METHODS: Data were collected through the Hornet Gay Social Network and by using an a priori determined framework to estimate the numbers of Facebook members with interests associated with GBMSM in South Africa, Ghana, Nigeria, Senegal, Côte d'Ivoire, Mauritania, The Gambia, Lebanon, Thailand, Malaysia, Brazil, Ukraine, and the United States. These estimates were compared with the most recent Joint United Nations Programme on HIV/AIDS (UNAIDS) and national estimates across 143 countries.

    RESULTS: The estimates that leveraged social media apps for the number of GBMSM across countries are consistently far higher than official UNAIDS estimates. Using Facebook, it is also feasible to assess the numbers of GBMSM aged 13-17 years, which demonstrate similar proportions to those of older men. There is greater consistency in Facebook estimates of GBMSM compared to UNAIDS-reported estimates across countries.

    CONCLUSIONS: The ability to use social media for epidemiologic and HIV prevention, treatment, and care needs continues to improve. Here, a method leveraging different categories of same-sex interests on Facebook, combined with a specific gay-oriented app (Hornet), demonstrated significantly higher estimates than those officially reported. While there are biases in this approach, these data reinforce the need for multiple methods to be used to count the number of GBMSM (especially in more stigmatizing settings) to better inform mathematical models and the scale of HIV program coverage. Moreover, these estimates can inform programs for those aged 13-17 years; a group for which HIV incidence is the highest and HIV prevention program coverage, including the availability of pre-exposure prophylaxis (PrEP), is lowest. Taken together, these results highlight the potential for social media to provide comparable estimates of the number of GBMSM across a large range of countries, including some with no reported estimates.

  6. Fulltext Quantification of intracellular payload release from polymersome nanoparticles
    Scarpa E, Bailey JL, Janeczek AA, Stumpf PS, Johnston AH, Oreffo RO, et al.
    Sci Rep, 2016 07 11;6:29460.
    PMID: 27404770 DOI: 10.1038/srep29460
    Polymersome nanoparticles (PMs) are attractive candidates for spatio-temporal controlled delivery of therapeutic agents. Although many studies have addressed cellular uptake of solid nanoparticles, there is very little data available on intracellular release of molecules encapsulated in membranous carriers, such as polymersomes. Here, we addressed this by developing a quantitative assay based on the hydrophilic dye, fluorescein. Fluorescein was encapsulated stably in PMs of mean diameter 85 nm, with minimal leakage after sustained dialysis. No fluorescence was detectable from fluorescein PMs, indicating quenching. Following incubation of L929 cells with fluorescein PMs, there was a gradual increase in intracellular fluorescence, indicating PM disruption and cytosolic release of fluorescein. By combining absorbance measurements with flow cytometry, we quantified the real-time intracellular release of a fluorescein at a single-cell resolution. We found that 173 ± 38 polymersomes released their payload per cell, with significant heterogeneity in uptake, despite controlled synchronisation of cell cycle. This novel method for quantification of the release of compounds from nanoparticles provides fundamental information on cellular uptake of nanoparticle-encapsulated compounds. It also illustrates the stochastic nature of population distribution in homogeneous cell populations, a factor that must be taken into account in clinical use of this technology.
  7. Microstructural white matter changes mediate age-related cognitive decline on the Montreal Cognitive Assessment (MoCA)
    Jolly TA, Cooper PS, Badwi SA, Phillips NA, Rennie JL, Levi CR, et al.
    Psychophysiology, 2016 Feb;53(2):258-67.
    PMID: 26511789 DOI: 10.1111/psyp.12565
    Although the relationship between aging and cognitive decline is well established, there is substantial individual variability in the degree of cognitive decline in older adults. The present study investigates whether variability in cognitive performance in community-dwelling older adults is related to the presence of whole brain or tract-specific changes in white matter microstructure. Specifically, we examine whether age-related decline in performance on the Montreal Cognitive Assessment (MoCA), a cognitive screening tool, is mediated by the white matter microstructural decline. We also examine if this relationship is driven by the presence of cardiovascular risk factors or variability in cerebral arterial pulsatility, an index of cardiovascular risk. Sixty-nine participants (aged 43-87) completed behavioral and MRI testing including T1 structural, T2-weighted FLAIR, and diffusion-weighted imaging (DWI) sequences. Measures of white matter microstructure were calculated using diffusion tensor imaging analyses on the DWI sequence. Multiple linear regression revealed that MoCA scores were predicted by radial diffusivity (RaD) of white matter beyond age or other cerebral measures. While increasing age and arterial pulsatility were associated with increasing RaD, these factors did not mediate the relationship between total white matter RaD and MoCA. Further, the relationship between MoCA and RaD was specific to participants who reported at least one cardiovascular risk factor. These findings highlight the importance of cardiovascular risk factors in the presentation of cognitive decline in old age. Further work is needed to establish whether medical or lifestyle management of these risk factors can prevent or reverse cognitive decline in old age.
  8. Use of recombinant tissue plasminogen activator for treatment of recalcitrant anterior uveitis: A case series
    Patrick S, Hui-Tze C, Wan-Hazabbah WH, Zunaina E, Azhany Y, Liza-Sharmini AT
    J Taibah Univ Med Sci, 2018 Oct;13(5):483-487.
    PMID: 31435366 DOI: 10.1016/j.jtumed.2018.03.005
    Management of inflammation after surgery for recalcitrant anterior uveitis is challenging. Herein, we report successful treatment using intracameral injection of recombinant tissue plasminogen activator (rtPA) in two patients with recalcitrant anterior uveitis, due to infective uveitis and Vogt-Koyanagi-Harada disease, respectively. A 40-year-old woman presented with bilateral redness and vision reduction that had persisted 2 weeks. She also had bilateral anterior uveitis, vasculitis, retinitis, and optic disc swelling. Serology was positive for Bartonella henselae and Toxoplasma gondii. She was treated using long-term systemic corticosteroids and appropriate antibiotics. Our second case; a healthy 30-year-old man with bilateral eye redness and reduced vision without pain, and associated with headache and tinnitus for 1 weeks. He showed bilateral granulomatous inflammation with vitritis, choroiditis, retinitis, and hyperemic optic disc. The patient was diagnosed with Vogt-Koyanagi-Harada disease and treated with systemic corticosteroids. Both patients developed secondary cataracts and glaucoma that necessitated surgical intervention. Persistent chronic inflammation led to the formation of a thick fibrin membrane anterior to the intraocular lens (IOL) after phacoemulsification surgery with IOL implantation. This membrane was removed surgically, and intracameral injection of rtPA (25 μg) was carried out. The persistent inflammation had resolved and visual acuity had significantly improved within 1 week of intracameral rtPA injection. There were no reported ocular or systemic side effects. Intracameral rtPA is beneficial in patients with recalcitrant anterior uveitis who have undergone intraocular surgery. In most cases, surgical intervention improves the patients' vision. Intracameral rtPA should be considered in cases of persistent inflammation of varying etiology.
  9. Non-cirrhotic portal fibrosis/idiopathic portal hypertension: APASL recommendations for diagnosis and management
    Shukla A, Rockey DC, Kamath PS, Kleiner DE, Singh A, Vaidya A, et al.
    Hepatol Int, 2024 Nov 15.
    PMID: 39546143 DOI: 10.1007/s12072-024-10739-6
    Since the Asian Pacific Association for the Study of the Liver (APASL) published guidelines on non-cirrhotic portal fibrosis/idiopathic portal hypertension in 2007, there has been a surge in new information, especially with the introduction of the term porto-sinusoidal vascular disorder (PSVD). Non-cirrhotic intra-hepatic causes of portal hypertension include disorders with a clearly identifiable etiology, such as schistosomiasis, as well as disorders with an unclear etiology such as non-cirrhotic portal fibrosis (NCPF), also termed idiopathic portal hypertension (IPH). This entity is being increasingly recognized as being associated with systemic disease and drug therapy, especially cancer therapy. An international working group with extensive expertise in portal hypertension was assigned with formulating consensus guidelines to clarify the definition, diagnosis, histological features, natural history, and management of NCPF/IPH, especially in the context of PSVD. The guidelines were prepared based on evidence from existing published literature. Whenever there was paucity of evidence, expert opinion was included after detailed deliberation. The goal of this manuscript, therefore, is to enhance the current understanding and help create global consensus on the issues surrounding NCPF/IPH.
  10. Fulltext The Psychological Science Accelerator: Advancing Psychology through a Distributed Collaborative Network
    Moshontz H, Campbell L, Ebersole CR, IJzerman H, Urry HL, Forscher PS, et al.
    Adv Methods Pract Psychol Sci, 2018 Dec;1(4):501-515.
    PMID: 31886452 DOI: 10.1177/2515245918797607
    Concerns have been growing about the veracity of psychological research. Many findings in psychological science are based on studies with insufficient statistical power and nonrepresentative samples, or may otherwise be limited to specific, ungeneralizable settings or populations. Crowdsourced research, a type of large-scale collaboration in which one or more research projects are conducted across multiple lab sites, offers a pragmatic solution to these and other current methodological challenges. The Psychological Science Accelerator (PSA) is a distributed network of laboratories designed to enable and support crowdsourced research projects. These projects can focus on novel research questions, or attempt to replicate prior research, in large, diverse samples. The PSA's mission is to accelerate the accumulation of reliable and generalizable evidence in psychological science. Here, we describe the background, structure, principles, procedures, benefits, and challenges of the PSA. In contrast to other crowdsourced research networks, the PSA is ongoing (as opposed to time-limited), efficient (in terms of re-using structures and principles for different projects), decentralized, diverse (in terms of participants and researchers), and inclusive (of proposals, contributions, and other relevant input from anyone inside or outside of the network). The PSA and other approaches to crowdsourced psychological science will advance our understanding of mental processes and behaviors by enabling rigorous research and systematically examining its generalizability.
  11. Fulltext Circulating bilirubin levels and risk of colorectal cancer: serological and Mendelian randomization analyses
    Seyed Khoei N, Jenab M, Murphy N, Banbury BL, Carreras-Torres R, Viallon V, et al.
    BMC Med, 2020 09 03;18(1):229.
    PMID: 32878631 DOI: 10.1186/s12916-020-01703-w
    BACKGROUND: Bilirubin, a byproduct of hemoglobin breakdown and purported anti-oxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer (CRC). We decided a priori to perform analyses separately in men and women based on suggestive evidence that associations may differ by sex.

    METHODS: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, the main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P 

  12. Fulltext Myocardial injury after noncardiac surgery: a large, international, prospective cohort study establishing diagnostic criteria, characteristics, predictors, and 30-day outcomes
    Botto F, Alonso-Coello P, Chan MT, Villar JC, Xavier D, Srinathan S, et al.
    Anesthesiology, 2014 Mar;120(3):564-78.
    PMID: 24534856 DOI: 10.1097/ALN.0000000000000113
    BACKGROUND: Myocardial injury after noncardiac surgery (MINS) was defined as prognostically relevant myocardial injury due to ischemia that occurs during or within 30 days after noncardiac surgery. The study's four objectives were to determine the diagnostic criteria, characteristics, predictors, and 30-day outcomes of MINS.

    METHODS: In this international, prospective cohort study of 15,065 patients aged 45 yr or older who underwent in-patient noncardiac surgery, troponin T was measured during the first 3 postoperative days. Patients with a troponin T level of 0.04 ng/ml or greater (elevated "abnormal" laboratory threshold) were assessed for ischemic features (i.e., ischemic symptoms and electrocardiography findings). Patients adjudicated as having a nonischemic troponin elevation (e.g., sepsis) were excluded. To establish diagnostic criteria for MINS, the authors used Cox regression analyses in which the dependent variable was 30-day mortality (260 deaths) and independent variables included preoperative variables, perioperative complications, and potential MINS diagnostic criteria.

    RESULTS: An elevated troponin after noncardiac surgery, irrespective of the presence of an ischemic feature, independently predicted 30-day mortality. Therefore, the authors' diagnostic criterion for MINS was a peak troponin T level of 0.03 ng/ml or greater judged due to myocardial ischemia. MINS was an independent predictor of 30-day mortality (adjusted hazard ratio, 3.87; 95% CI, 2.96-5.08) and had the highest population-attributable risk (34.0%, 95% CI, 26.6-41.5) of the perioperative complications. Twelve hundred patients (8.0%) suffered MINS, and 58.2% of these patients would not have fulfilled the universal definition of myocardial infarction. Only 15.8% of patients with MINS experienced an ischemic symptom.

    CONCLUSION: Among adults undergoing noncardiac surgery, MINS is common and associated with substantial mortality.

  13. To which world regions does the valence-dominance model of social perception apply?
    Jones BC, DeBruine LM, Flake JK, Liuzza MT, Antfolk J, Arinze NC, et al.
    Nat Hum Behav, 2021 01;5(1):159-169.
    PMID: 33398150 DOI: 10.1038/s41562-020-01007-2
    Over the past 10 years, Oosterhof and Todorov's valence-dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov's methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov's original analysis strategy, the valence-dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence-dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 5 November 2018. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.7611443.v1 .
  14. The Psychological Science Accelerator's COVID-19 rapid-response dataset
    Buchanan EM, Lewis SC, Paris B, Forscher PS, Pavlacic JM, Beshears JE, et al.
    Sci Data, 2023 Feb 11;10(1):87.
    PMID: 36774440 DOI: 10.1038/s41597-022-01811-7
    In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73,223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, framing, and self-determination across a diverse, global sample obtained at the onset of the COVID-19 pandemic, which can be merged with other time-sampled or geographic data.
  15. Fulltext Author Correction: A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic
    Wang K, Goldenberg A, Dorison CA, Miller JK, Uusberg A, Lerner JS, et al.
    Nat Hum Behav, 2022 Sep;6(9):1318-1319.
    PMID: 36002766 DOI: 10.1038/s41562-022-01441-4
  16. Fulltext A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic
    Wang K, Goldenberg A, Dorison CA, Miller JK, Uusberg A, Lerner JS, et al.
    Nat Hum Behav, 2021 Aug;5(8):1089-1110.
    PMID: 34341554 DOI: 10.1038/s41562-021-01173-x
    The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 12 May 2020. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.c.4878591.v1.
  17. Fulltext In COVID-19 Health Messaging, Loss Framing Increases Anxiety with Little-to-No Concomitant Benefits: Experimental Evidence from 84 Countries
    Dorison CA, Lerner JS, Heller BH, Rothman AJ, Kawachi II, Wang K, et al.
    Affect Sci, 2022 Sep;3(3):577-602.
    PMID: 36185503 DOI: 10.1007/s42761-022-00128-3
    The COVID-19 pandemic (and its aftermath) highlights a critical need to communicate health information effectively to the global public. Given that subtle differences in information framing can have meaningful effects on behavior, behavioral science research highlights a pressing question: Is it more effective to frame COVID-19 health messages in terms of potential losses (e.g., "If you do not practice these steps, you can endanger yourself and others") or potential gains (e.g., "If you practice these steps, you can protect yourself and others")? Collecting data in 48 languages from 15,929 participants in 84 countries, we experimentally tested the effects of message framing on COVID-19-related judgments, intentions, and feelings. Loss- (vs. gain-) framed messages increased self-reported anxiety among participants cross-nationally with little-to-no impact on policy attitudes, behavioral intentions, or information seeking relevant to pandemic risks. These results were consistent across 84 countries, three variations of the message framing wording, and 560 data processing and analytic choices. Thus, results provide an empirical answer to a global communication question and highlight the emotional toll of loss-framed messages. Critically, this work demonstrates the importance of considering unintended affective consequences when evaluating nudge-style interventions.
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