Displaying publications 61 - 80 of 85 in total

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  1. Chang CC, Li C, Webb GI, Tey B, Song J, Ramanan RN
    Sci Rep, 2016;6:21844.
    PMID: 26931649 DOI: 10.1038/srep21844
    Periplasmic expression of soluble proteins in Escherichia coli not only offers a much-simplified downstream purification process, but also enhances the probability of obtaining correctly folded and biologically active proteins. Different combinations of signal peptides and target proteins lead to different soluble protein expression levels, ranging from negligible to several grams per litre. Accurate algorithms for rational selection of promising candidates can serve as a powerful tool to complement with current trial-and-error approaches. Accordingly, proteomics studies can be conducted with greater efficiency and cost-effectiveness. Here, we developed a predictor with a two-stage architecture, to predict the real-valued expression level of target protein in the periplasm. The output of the first-stage support vector machine (SVM) classifier determines which second-stage support vector regression (SVR) classifier to be used. When tested on an independent test dataset, the predictor achieved an overall prediction accuracy of 78% and a Pearson's correlation coefficient (PCC) of 0.77. We further illustrate the relative importance of various features with respect to different models. The results indicate that the occurrence of dipeptide glutamine and aspartic acid is the most important feature for the classification model. Finally, we provide access to the implemented predictor through the Periscope webserver, freely accessible at http://lightning.med.monash.edu/periscope/.
  2. Crystal Thew XE, Lo SC, Ramanan RN, Tey BT, Huy ND, Chien Wei O
    Crit Rev Biotechnol, 2024 May;44(3):477-494.
    PMID: 36788704 DOI: 10.1080/07388551.2023.2170861
    Plastic biodegradation has emerged as a sustainable approach and green alternative in handling the ever-increasing accumulation of plastic wastes in the environment. The complete biodegradation of polyethylene terephthalate is one of the most recent breakthroughs in the field of plastic biodegradation. Despite the success, the effective and complete biodegradation of a wide variety of plastics is still far from the practical implementation, and an on-going effort has been mainly devoted to the exploration of novel microorganisms and enzymes for plastic biodegradation. However, alternative strategies which enhance the existing biodegradation process should not be neglected in the continuous advancement of this field. Thus, this review highlights various strategies which have shown to improve the biodegradation of plastics, which include the pretreatment of plastics using UV irradiation, thermal, or chemical treatments to increase the susceptibility of plastics toward microbial action. Alternative pretreatment strategies are also suggested and compared with the existing techniques. Besides, the effects of additives such as pro-oxidants, natural polymers, and surfactants on plastic biodegradation are discussed. In addition, considerations governing the biodegradation performance, such as the formulation of biodegradation medium, cell-free biocatalysis, and physico-chemical properties of plastics, are addressed. Lastly, the challenges and future prospects for the advancement of plastic biodegradation are also highlighted.
  3. Issitt T, Toe QK, Pedersen SL, Shackshaft T, Ghazaly MM, West L, et al.
    Pulm Circ, 2024 Oct;14(4):e70006.
    PMID: 39697901 DOI: 10.1002/pul2.70006
    Elevated circulating hepcidin levels have been reported in patients with pulmonary artery hypertension (PAH). Hepcidin has been shown to promote proliferation of human pulmonary artery smooth muscle cells (PASMCs) in vitro, suggesting a potential role in PAH pathogenesis. However, the role of human pulmonary artery endothelial cells (PAECs) as either a source of hepcidin, or the effect of hepcidin on PAEC function is not as well described. The objective of this study was to define the role of the hepcidin-ferroportin axis on the phenotype of PAEC and to study potential PAEC-PASMC interactions relevant to the pathogenesis of pulmonary vascular remodeling and PAH. PAECs treated with hepcidin, or interleukin-6 were investigated for both ferroportin and hepcidin release and regulation using immunofluorescence, mRNA levels and cellular release assays. Effects of hepcidin on PASMC and PAEC mitochondrial function was investigated using immunofluorescence and seahorse assay. Migration and proliferation of PASMCs treated with conditioned media from hPAEC treated with hepcidin was investigated using the xCELLigence system and other tools. We demonstrate in this study that PAECs express ferroportin; hepcidin treatment of PAECs resulted in mitochondrial iron accumulation and intracellular hepcidin biosynthesis and release. Conditioned media from hepcidin treated PAECs caused PASMCs to down-regulate ferroportin expression whilst promoting migration and proliferation. Inhibition of hepcidin in PAEC conditioned media limited these responses. PASMC cellular and mitochondrial iron retention are associated with migratory and proliferative responses. This study confirms that the hepcidin ferroportin axis is present and operational in PAECs. Modulation of this axis shows distinct differences in responses seen between PAECS and PASMCs. Stimulation of this axis in PAECs with hepcidin may well institute proliferative and migratory responses in PASMCs of relevance to pathogenesis of PAH offering potential novel therapeutic targets.
  4. van Zonneveld M, Rakha M, Tan SY, Chou YY, Chang CH, Yen JY, et al.
    Sci Rep, 2020 02 07;10(1):2111.
    PMID: 32034221 DOI: 10.1038/s41598-020-58646-8
    This study provides insights in patterns of distribution of abiotic and biotic stress resilience across Vigna gene pools to enhance the use and conservation of these genetic resources for legume breeding. Vigna is a pantropical genus with more than 88 taxa including important crops such as V. radiata (mung bean) and V. unguiculata (cowpea). Our results show that sources of pest and disease resistance occur in at least 75 percent of the Vigna taxa, which were part of screening assessments, while sources of abiotic stress resilience occur in less than 30 percent of screened taxa. This difference in levels of resilience suggests that Vigna taxa co-evolve with pests and diseases while taxa are more conservative to adapt to climatic changes and salinization. Twenty-two Vigna taxa are poorly conserved in genebanks or not at all. This germplasm is not available for legume breeding and requires urgent germplasm collecting before these taxa extirpate on farm and in the wild. Vigna taxa, which tolerate heat and drought stress are rare compared with taxa, which escape these stresses because of short growing seasons or with taxa, which tolerate salinity. We recommend prioritizing these rare Vigna taxa for conservation and screening for combined abiotic and biotic stress resilience resulting from stacked or multifunctional traits. The high presence of salinity tolerance compared with drought stress tolerance, suggests that Vigna taxa are good at developing salt-tolerant traits. Vigna taxa are therefore of high value for legume production in areas that will suffer from salinization under global climate change.
  5. Abbasiliasi S, Tan JS, Ibrahim TA, Ramanan RN, Vakhshiteh F, Mustafa S, et al.
    BMC Microbiol, 2012;12:260.
    PMID: 23153191 DOI: 10.1186/1471-2180-12-260
    Lactic acid bacteria (LAB) can be isolated from traditional milk products. LAB that secrete substances that inhibit pathogenic bacteria and are resistant to acid, bile, and pepsin but not vancomycin may have potential in food applications.
  6. Koh TM, Shanmugam V, Schlipf J, Oesinghaus L, Müller-Buschbaum P, Ramakrishnan N, et al.
    Adv Mater, 2016 May;28(19):3653-61.
    PMID: 26990287 DOI: 10.1002/adma.201506141
    2D perovskites is one of the proposed strategies to enhance the moisture resistance, since the larger organic cations can act as a natural barrier. Nevertheless, 2D perovskites hinder the charge transport in certain directions, reducing the solar cell power conversion efficiency. A nanostructured mixed-dimensionality approach is presented to overcome the charge transport limitation, obtaining power conversion efficiencies over 9%.
  7. Sioson MS, Martindale R, Abayadeera A, Abouchaleh N, Aditianingsih D, Bhurayanontachai R, et al.
    Clin Nutr ESPEN, 2018 04;24:156-164.
    PMID: 29576355 DOI: 10.1016/j.clnesp.2017.11.008
    BACKGROUND & AIMS: Guidance on managing the nutritional requirements of critically ill patients in the intensive care unit (ICU) has been issued by several international bodies. While these guidelines are consulted in ICUs across the Asia-Pacific and Middle East regions, there is little guidance available that is tailored to the unique healthcare environments and demographics across these regions. Furthermore, the lack of consistent data from randomized controlled clinical trials, reliance on expert consensus, and differing recommendations in international guidelines necessitate further expert guidance on regional best practice when providing nutrition therapy for critically ill patients in ICUs in Asia-Pacific and the Middle East.

    METHODS: The Asia-Pacific and Middle East Working Group on Nutrition in the ICU has identified major areas of uncertainty in clinical practice for healthcare professionals providing nutrition therapy in Asia-Pacific and the Middle East and developed a series of consensus statements to guide nutrition therapy in the ICU in these regions.

    RESULTS: Accordingly, consensus statements have been provided on nutrition risk assessment and parenteral and enteral feeding strategies in the ICU, monitoring adequacy of, and tolerance to, nutrition in the ICU and institutional processes for nutrition therapy in the ICU. Furthermore, the Working Group has noted areas requiring additional research, including the most appropriate use of hypocaloric feeding in the ICU.

    CONCLUSIONS: The objective of the Working Group in formulating these statements is to guide healthcare professionals in practicing appropriate clinical nutrition in the ICU, with a focus on improving quality of care, which will translate into improved patient outcomes.

  8. Pek JH, Lim SH, Ho HF, Ramakrishnan TV, Jamaluddin SF, Mesa-Gaerlan FJC, et al.
    Acute medicine & surgery, 2016 04;3(2):65-73.
    PMID: 29123755 DOI: 10.1002/ams2.154
    Aim: We aim to examine the similarities and differences in areas of EM development, workload, workforce, and capabilities and support in the Asia region. Emerging challenges faced by our EM community are also discussed.

    Methods: The National Societies for Emergency Medicine of Hong Kong, India, Japan, Malaysia, Philippines, Singapore, South Korea, Taiwan, Thailand and Turkey participated in the joint Japanese Association of Acute Medicine (JAAM) and Asian Conference of Emergency Medicine (ACEM) Special Symposium held in October 2013 at Tokyo, Japan. The findings are reviewed in this paper.

    Results: Emergency medicine (EM) has over the years evolved into a distinct and recognized medical discipline requiring a unique set of cognitive, administrative and technical skills for managing all types of patients with acute illness or injury. EM has contributed to healthcare by providing effective, safe, efficient and cost-effective patient care. Integrated systems have developed to allow continuity of emergency care from the community into emergency departments. Structured training curriculum for undergraduates, and specialty training programs for postgraduates are in place to equip trainees with the knowledge and skills required for the unique practice of EM.

    Conclusion: The practice of EM still varies among the Asian countries. However, as a region, we strive to continue in our efforts to develop the specialty and improve the delivery of EM.

  9. Quek SC, Lim BK, Domingo E, Soon R, Park JS, Vu TN, et al.
    Int. J. Gynecol. Cancer, 2013 Jan;23(1):148-56.
    PMID: 23221730 DOI: 10.1097/IGC.0b013e31827670fd
    OBJECTIVE: Independent, prospective, multicenter, hospital-based cross-sectional studies were conducted across 5 countries in Asia, namely, Malaysia, Vietnam, Singapore, South Korea, and the Philippines. The objectives of these studies were to evaluate the prevalence of human papillomavirus (HPV) types (high risk and others including coinfections) in women with invasive cervical cancer (ICC) and high-grade precancerous lesions.

    METHODS: Women older than 21 years with a histologic diagnosis of ICC and cervical intraepithelial neoplasia [CIN 2 or 3 and adenocarcinoma in situ (AIS)] were enrolled. Cervical specimens were reviewed by histopathologists to confirm the presence of ICC or CIN 2/3/AIS lesion and tested with short PCR fragment 10-DNA enzyme immunoassay-line probe assay for 14 oncogenic HPV types and 11 non-oncogenic HPV types. The prevalence of HPV 16, HPV 18, and other high-risk HPV types in ICC [including squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma (ADC/ASC)] and CIN 2/3/AIS was estimated.

    RESULTS: In the 5 Asian countries, diagnosis of ICC was confirmed in 500 women [SCC (n = 392) and ADC/ASC (n = 108)], and CIN 2/3/AIS, in 411 women. Human papillomavirus DNA was detected in 93.8% to 97.0% (84.5% for the Philippines) of confirmed ICC cases [94.0%-98.7% of SCC; 87.0%-94.3% (50.0% for the Philippines) of ADC/ASC] and in 93.7% to 100.0% of CIN 2/3/AIS. The most common types observed among ICC cases were HPV 16 (36.8%-61.3%), HPV 18 (12.9%-35.4%), HPV 52 (5.4%-10.3%), and HPV 45 (1.5%-17.2%), whereas among CIN 2/3/AIS cases, HPV 16 (29.7%-46.6%) was the most commonly observed type followed by HPV 52 (17.0%-66.7%) and HPV 58 (8.6%-16.0%).

    CONCLUSIONS: This article presents the data on the HPV prevalence, HPV type distribution, and their role in cervical carcinogenesis in 5 Asian countries. These data are of relevance to public health authorities for evaluating the existing and future cervical cancer prevention strategies including HPV-DNA testing-based screening and HPV vaccination in these Asian populations.

  10. Wang SA, Chang CJ, Do Shin S, Chu SE, Huang CY, Hsu LM, et al.
    J Formos Med Assoc, 2024 Jan;123(1):23-35.
    PMID: 37573159 DOI: 10.1016/j.jfma.2023.07.011
    BACKGROUND/PURPOSE: To develop a prediction model for emergency medical technicians (EMTs) to identify trauma patients at high risk of deterioration to emergency medical service (EMS)-witnessed traumatic cardiac arrest (TCA) on the scene or en route.

    METHODS: We developed a prediction model using the classical cross-validation method from the Pan-Asia Trauma Outcomes Study (PATOS) database from 1 January 2015 to 31 December 2020. Eligible patients aged ≥18 years were transported to the hospital by the EMS. The primary outcome (EMS-witnessed TCA) was defined based on changes in vital signs measured on the scene or en route. We included variables that were immediately measurable as potential predictors when EMTs arrived. An integer point value system was built using multivariable logistic regression. The area under the receiver operating characteristic (AUROC) curve and Hosmer-Lemeshow (HL) test were used to examine discrimination and calibration in the derivation and validation cohorts.

    RESULTS: In total, 74,844 patients were eligible for database review. The model comprised five prehospital predictors: age <40 years, systolic blood pressure <100 mmHg, respiration rate >20/minute, pulse oximetry <94%, and levels of consciousness to pain or unresponsiveness. The AUROC in the derivation and validation cohorts was 0.767 and 0.782, respectively. The HL test revealed good calibration of the model (p = 0.906).

    CONCLUSION: We established a prediction model using variables from the PATOS database and measured them immediately after EMS personnel arrived to predict EMS-witnessed TCA. The model allows prehospital medical personnel to focus on high-risk patients and promptly administer optimal treatment.

  11. Chen JM, Su YC, Cheng CY, Chang CJ, Hsu LM, Shin SD, et al.
    J Neurotrauma, 2024 Dec;41(23-24):2590-2601.
    PMID: 39264870 DOI: 10.1089/neu.2023.0392
    The optimal prehospital blood pressure in patients following traumatic brain injury (TBI) remains controversial. We aimed to assess the association between the systolic blood pressure (SBP) at emergency department triage and patient outcomes following isolated moderate-to-severe TBI. We conducted a cross-national multicenter retrospective cohort study using the Pan-Asia Trauma Outcomes Study database from January 1, 2016, to November 30, 2018. The enrollees were adult patients with isolated moderate-to-severe TBI defined by the International Classification of Diseases code, a Glasgow Coma Scale (GCS) <13 at triage, and a nonhead Abbreviated Injury Scale ≤3. The studied variables were SBPs at triage categorized into different ranges. The primary outcome was 30-day mortality, and the secondary outcome was poor functional status at hospital discharge defined by the modified Rankin Scale ≥4. Multivariable logistic regression was applied to adjust for confounders including country, sex, age, mechanism of injury, prehospital vascular access, respiratory rate, GCS, oxygen saturation, intubation, Injury Severity Score, head surgery, intensive care unit admission, and length of hospital stay. Subgroup analyses were performed on different severity of TBI. A total of 785 patients (median age, 42 years; male patients 77.5%; mean SBP at triage, 136.3 ± 33.1 mmHg) were included in the primary analysis. The lowest 30-day mortality rate existed in patients with SBP of 100-119 mmHg. Taking it as baseline, the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of SBP <100 mmHg, 120-139 mmHg, 140-159 mmHg, and ≥160 mmHg were 7.05 (2.51-19.78), 3.14 (1.14-8.65), 2.91 (1.04-8.17), and 3.28 (1.14-9.42). As for the secondary outcome, the aORs and 95% CIs were 1.36 (0.68-2.68) of <100 mmHg, 0.99 (0.57-1.70) of 120-139 mmHg, 1.23 (0.67-2.25) of 140-159 mmHg, and 1.52 (0.78-2.95) of ≥160 mmHg. Subgroup analyses revealed trends of the best outcomes in both moderate and severe TBI patients with SBP 100-119 mmHg, whereas statistical significance appeared only in patients with severe TBI. SBP of 110-119 mmHg at triage is associated with the lowest 30-day mortality in patients following isolated moderate-to-severe TBI and possibly related to a better functional outcome.
  12. Tee LH, Yang B, Tey BT, Chan ES, Azlan A, Ismail A, et al.
    Food Chem, 2017 Nov 15;235:257-264.
    PMID: 28554634 DOI: 10.1016/j.foodchem.2017.05.021
    Dacryodes rostrata (kembayau) is an important food and oil resource for local communities in Borneo, but it is not commonly known to wider community. The objective of this work is to valorize kembayau fruit by evaluating the characteristics of the oil from the fruit. In this study, the physicochemical characteristics and the lipophilic essential nutrient; the fatty acid composition, vitamin E and beta-carotene content of oils obtained from the peel, pulp and seeds of kembayau fruits were studied. The pulp of the kembayau fruit contained highest proportion of oil, followed by peel and seed. Kembayau fruit contained vitamin E and had trace amount of beta-carotene. Besides, kembayau fruit oils were not toxic to BRL3A cells, provided hepatoprotection and reversed lipid peroxidation in paracetamol-induced toxicity. Our results suggest that kembayau can be a potential source for cooking oil as the physicochemical characteristics are comparable with commercial source such as oil palm.
  13. Ravichandran J, Woon SY, Quek YS, Lim YC, Noor EM, Suresh K, et al.
    Am J Med, 2019 03;132(3):362-366.
    PMID: 30503877 DOI: 10.1016/j.amjmed.2018.11.017
    PURPOSE: The purpose of this study was to examine the association of circulating concentrations of high-sensitivity cardiac troponin I (hs-cTn) in the various trimesters of pregnancy in patients with and without hypertension.

    METHODS: This was a prospective cross-sectional study of pregnant and postnatal women aged between 18-35 years with no coexisting diseases. Serum samples were analysed for hs-TnI.

    RESULTS: A total of 880 women (mean age = 29.1 years [standard deviation = 5.1 years]) were recruited with 129 (14%), 207 (24%), and 416 (47%) patients in the first, second, and third trimesters, respectively. Ninety (10%) participants were recruited in the postnatal period. During pregnancy 28 (3%) patients were classified as having pregnancy-induced hypertension and 10 (1%) as preeclampsia. High-sensitivity cardiac troponin I was measurable in 546 (62%) participants with a median of 1 ng/L (range 0 to 783 ng/L). Troponin concentrations were above the 99th percentile in 19 (2%) individuals. Patients with pregnancy-induced hypertension and preeclampsia had higher concentrations of hs-TnI (median 11 ng/L [interquartile range (IQR) 6 to 22 ng/L] vs 12ng/L [IQR 3 to 98 ng/L] vs 1 ng/L [IQR 0 to 1 ng/L]). In logistic regression modeling hs-cTnI concentration remained an independent predictor of pregnancy-induced hypertension or preeclampsia in both unadjusted and adjusted models (odds ratio 9.3 [95% confidence interval 5.8 to 16.3] and 11.5 [95% confidence interval 6.3 to 24.1], respectively, per doubling of hs-TnI concentrations).

    CONCLUSIONS: Cardiac troponin measured using a high-sensitivity assay is quantifiable in the majority of young pregnant women with 2% of individuals having concentration above the 99th percentile sex-specific threshold. Patients with pregnancy-induced hypertension or preeclampsia had higher cardiac troponin concentrations. Cardiac troponin was a strong independent predictor of pregnancy-induced hypertension or preeclampsia in pregnant and postnatal women.

  14. Tee LH, Yang B, Nagendra KP, Ramanan RN, Sun J, Chan ES, et al.
    Food Chem, 2014 Dec 15;165:247-55.
    PMID: 25038673 DOI: 10.1016/j.foodchem.2014.05.084
    Dacryodes species are evergreen, perennial trees with fleshy fruits and belong to the family Buseraseae. Many Dacryodes species are underutilized but are widely applied in traditional folk medicine to treat malaria, fever and skin diseases. The nutritional compositions, phytochemicals and biological activities of Dacryodes edulis, Dacryodes rostrata, Dacryodes buettneri, Dacryodes klaineana and Dacryodes hexandra are presented. The edible fruits of D. edulis are rich in lipids, proteins, vitamins, fatty acids and amino acids. Its extracts (leaf, fruit and resin) exhibit antioxidant, anti-microbial, anti-carcinogenic and other bioactivities. D. rostrata fruit has significant nutrient content, and is rich in proteins, lipids and minerals. These fruits are also highly rich in polyphenols, anthocyanins and antioxidant activities. This comprehensive review will assist the reader in understanding the nutritional benefits of Dacryodes species and in identifying current research needs.
  15. Liew NC, Chang YH, Choi G, Chu PH, Gao X, Gibbs H, et al.
    Int Angiol, 2012 Dec;31(6):501-16.
    PMID: 23222928
    Venous thromboembolism (VTE) prophylaxis is under-utilized in Asia because of the misconception that its incidence is lower in Asians as compared to the Caucasians. The available data on VTE in Asia is limited due to the lack of well-designed multicenter randomized controlled trials as well as non-standardized research designs, making data comparison difficult. Emerging data indicates that the VTE incidence is not low in Asia, and is comparable to that reported in the Western literature in some instances. There is also a trend towards increasing incidence of VTE, as demonstrated by a number of hospital-based studies in Asia. This could be attributed to lifestyle changes, ageing population, increasing awareness of VTE and wider availability of Duplex ultrasound. The risk of VTE in hospitalized patients remain the same in Asians and Caucasians, even though there may be factors that are inherent to patients in Asia that influence the slight variation in incidence. The utilization rate of VTE prophylaxis remains suboptimal in Asia. The Asian Venous Thrombosis Forum (AVTF) comprises participants from various countries such as China, Hong Kong, India, Indonesia, Korea, Malaysia, Philippines, Singapore, Taiwan, Thailand and experts from Australia and Europe. The forum evaluated the available data on VTE from the Asian region and formulated guidelines tailored to meet the needs of the region. We recommend that serious considerations are given to VTE prophylaxis especially in the at-risk group and a formal hospital policy be established to facilitate the implementation. On admission to the hospital, we recommend assessing the patients for both VTE and bleeding risk. We recommend mechanical prophylaxis for patients at increased risk of bleeding and utilizing it as an adjunctive measure in combination with pharmacological prophylaxis in patients with high risk of VTE. For patients undergoing general or gynecological surgery and with moderate risk for VTE, we recommend prophylaxis with one of the following: low dose unfractionated heparin (LDUH), low molecular weight heparin (LMWH), fondaparinux or intermittent pneumatic compression (IPC). For the same group of patients at high risk of VTE, we recommend pharmacological or combination of pharmacological and mechanical prophylaxis. For patients undergoing major orthopedic surgeries like total hip replacement, total knee replacement and proximal hip fracture surgery, we recommend using one of the following: LMWH, fondaparinux, rivaroxaban, apixaban, edoxaban, dabigatran, warfarin or aspirin with IPC. For patients admitted to the hospital with acute medical illness and has moderate risk of VTE, we recommend prophylaxis with LDUH, LMWH or Fondaparinux. For the same group at high risk of VTE, we recommend combination of pharmacological and mechanical prophylaxis.
  16. Perez-Fernandez D, Shcherbakov D, Matt T, Leong NC, Kudyba I, Duscha S, et al.
    Nat Commun, 2014;5:3112.
    PMID: 24473108 DOI: 10.1038/ncomms4112
    Clinical use of 2-deoxystreptamine aminoglycoside antibiotics, which target the bacterial ribosome, is compromised by adverse effects related to limited drug selectivity. Here we present a series of 4',6'-O-acetal and 4'-O-ether modifications on glucopyranosyl ring I of aminoglycosides. Chemical modifications were guided by measuring interactions between the compounds synthesized and ribosomes harbouring single point mutations in the drug-binding site, resulting in aminoglycosides that interact poorly with the drug-binding pocket of eukaryotic mitochondrial or cytosolic ribosomes. Yet, these compounds largely retain their inhibitory activity for bacterial ribosomes and show antibacterial activity. Our data indicate that 4'-O-substituted aminoglycosides possess increased selectivity towards bacterial ribosomes and little activity for any of the human drug-binding pockets.
  17. Jacob M, Sahu S, Singh YP, Mehta Y, Yang KY, Kuo SW, et al.
    Indian J Crit Care Med, 2020 Nov;24(11):1028-1036.
    PMID: 33384507 DOI: 10.5005/jp-journals-10071-23653
    Introduction: Fluid therapy in critically ill patients, especially timing and fluid choice, is controversial. Previous randomized trials produced conflicting results. This observational study evaluated the effect of colloid use on 90-day mortality and acute kidney injury (RIFLE F) within the Rational Fluid Therapy in Asia (RaFTA) registry in intensive care units.

    Materials and methods: RaFTA is a prospective, observational study in Asian intensive care unit (ICU) patients focusing on fluid therapy and related outcomes. Logistic regression was performed to identify risk factors for increased 90-day mortality and acute kidney injury (AKI).

    Results: Twenty-four study centers joined the RaFTA registry and collected 3,187 patient data sets from November 2011 to September 2012. A follow-up was done 90 days after ICU admission. For 90-day mortality, significant risk factors in the overall population were sepsis at admission (OR 2.185 [1.799; 2.654], p < 0.001), cumulative fluid balance (OR 1.032 [1.018; 1.047], p < 0.001), and the use of vasopressors (OR 3.409 [2.694; 4.312], p < 0.001). The use of colloids was associated with a reduced risk of 90-day mortality (OR 0.655 [0.478; 0.900], p = 0.009). The initial colloid dose was not associated with an increased risk for AKI (OR 1.094 [0.754; 1.588], p = 0.635).

    Conclusion: RaFTA adds the important finding that colloid use was not associated with increased 90-day mortality or AKI after adjustment for baseline patient condition.

    Clinical significance: Early resuscitation with colloids showed potential mortality benefit in the present analysis. Elucidating these findings may be an approach for future research.

    How to cite this article: Jacob M, Sahu S, Singh YP, Mehta Y, Yang K-Y, Kuo S-W, et al. A Prospective Observational Study of Rational Fluid Therapy in Asian Intensive Care Units: Another Puzzle Piece in Fluid Therapy. Indian J Crit Care Med 2020;24(11):1028-1036.

  18. Whitcroft KL, Altundag A, Balungwe P, Boscolo-Rizzo P, Douglas R, Enecilla MLB, et al.
    Rhinology, 2023 Oct 01;61(33):1-108.
    PMID: 37454287 DOI: 10.4193/Rhin22.483
    BACKGROUND: Since publication of the original Position Paper on Olfactory Dysfunction in 2017 (PPOD-17), the personal and societal burden of olfactory disorders has come sharply into focus through the lens of the COVID-19 pandemic. Clinicians, scientists and the public are now more aware of the importance of olfaction, and the impact of its dysfunction on quality of life, nutrition, social relationships and mental health. Accordingly, new basic, translational and clinical research has resulted in significant progress since the PPOD-17. In this updated document, we present and discuss currently available evidence for the diagnosis and management of olfactory dysfunction. Major updates to the current version include, amongst others: new recommendations on olfactory related terminology; new imaging recommendations; new sections on qualitative OD and COVID-19 OD; updated management section. Recommendations were agreed by all co-authors using a modified Delphi process.

    CONCLUSIONS: We have provided an overview of current evidence and expert-agreed recommendations for the definition, investigation, and management of OD. As for our original Position Paper, we hope that this updated document will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency, and generalisability of work in this field.

  19. Trieu HT, Vuong NL, Hung NT, Nguyen Minh T, Nguyen Van VC, Phan TQ, et al.
    BMJ Glob Health, 2025 Mar 11;10(3).
    PMID: 40068930 DOI: 10.1136/bmjgh-2024-017538
    INTRODUCTION: The pathognomonic feature of dengue shock syndrome (DSS) is a transient capillary leak syndrome resulting in profound intravascular volume depletion. WHO management guidelines recommend particular parenteral fluid regimens during the critical leakage phase, including synthetic colloid solutions in certain circumstances. We set out to describe the actual fluid management strategies employed in different settings and to investigate relationships with clinical outcomes.

    METHODS: We performed a retrospective review of paediatric DSS cases managed at seven hospitals across Malaysia, Myanmar and Vietnam. We explored the effects of both initial resuscitation (crystalloid alone or mixed crystalloid/colloid in the first 2 hours) and general management: group 1 (conservative-colloid, crystalloid only), group 2 (intermediate-colloid, colloid for 1-4 hours) or group 3 (liberal-colloid, continuous colloid for more than 4 hours) categorised according to the fluid given over the first 6 hours in clinically stable patients. We incorporated an inverse probability weighting score to adjust for potential differences in baseline severity.

    RESULTS: Among all 691 patients, respiratory compromise (HR 2.08, p=0.022), requirement for nasal continuous positive airway pressure (NCPAP)/ventilation (OR 2.34, p<0.045) and days in hospital after DSS onset (risk ratio, RR 1.33, p=0.032) were significantly worse for mixed crystalloid/colloid versus crystalloid-only initial resuscitation regimens, after adjusting for baseline severity. Among the 547/691 children who stabilised within 2 hours, although a liberal-colloid general management strategy (group 3) was associated with a reduction in recurrent shock episodes (RR 0.13, p=0.043) when compared with a conservative-colloid strategy (group 1), the risks for respiratory compromise (OR 8.84, p<0.001) and requirement for NCPAP/ventilation (OR 8.16, p<0.001) were markedly increased. Additionally, the respective costs for group 3 vs group 1 were significantly higher.

    CONCLUSIONS: The study highlights the potential benefits and risks of using colloid solutions in children with DSS. Formal randomised trials could help determine the most effective and safe parenteral fluid regimens for paediatric DSS. In the meantime, prolonged use of colloid solutions may be inappropriate, especially in settings without access to respiratory support.

  20. Kartsonaki C, Baillie JK, Barrio NG, Baruch J, Beane A, Blumberg L, et al.
    Int J Epidemiol, 2023 Apr 19;52(2):355-376.
    PMID: 36850054 DOI: 10.1093/ije/dyad012
    BACKGROUND: We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, one of the world's largest international, standardized data sets concerning hospitalized patients.

    METHODS: The data set analysed includes COVID-19 patients hospitalized between January 2020 and January 2022 in 52 countries. We investigated how symptoms on admission, co-morbidities, risk factors and treatments varied by age, sex and other characteristics. We used Cox regression models to investigate associations between demographics, symptoms, co-morbidities and other factors with risk of death, admission to an intensive care unit (ICU) and invasive mechanical ventilation (IMV).

    RESULTS: Data were available for 689 572 patients with laboratory-confirmed (91.1%) or clinically diagnosed (8.9%) SARS-CoV-2 infection from 52 countries. Age [adjusted hazard ratio per 10 years 1.49 (95% CI 1.48, 1.49)] and male sex [1.23 (1.21, 1.24)] were associated with a higher risk of death. Rates of admission to an ICU and use of IMV increased with age up to age 60 years then dropped. Symptoms, co-morbidities and treatments varied by age and had varied associations with clinical outcomes. The case-fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients and was on average 21.5%.

    CONCLUSIONS: Age was the strongest determinant of risk of death, with a ∼30-fold difference between the oldest and youngest groups; each of the co-morbidities included was associated with up to an almost 2-fold increase in risk. Smoking and obesity were also associated with a higher risk of death. The size of our international database and the standardized data collection method make this study a comprehensive international description of COVID-19 clinical features. Our findings may inform strategies that involve prioritization of patients hospitalized with COVID-19 who have a higher risk of death.

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