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Addressing the burden of dialysis around the world: A summary of the roundtable discussion on dialysis economics at the First International Congress of Chinese Nephrologists 2015

Li PK, Lui SL, Ng JK, Cai GY, Chan CT, Chen HC, et al.

Nephrology (Carlton), 2017 Dec;22 Suppl 4:3-8.
PMID: 29155495 DOI: 10.1111/nep.13143

To address the issue of heavy dialysis burden due to the rising prevalence of end-stage renal disease around the world, a roundtable discussion on the sustainability of managing dialysis burden around the world was held in Hong Kong during the First International Congress of Chinese Nephrologists in December 2015. The roundtable discussion was attended by experts from Hong Kong, China, Canada, England, Malaysia, Singapore, Taiwan and United States. Potential solutions to cope with the heavy burden on dialysis include the prevention and retardation of the progression of CKD; wider use of home-based dialysis therapy, particularly PD; promotion of kidney transplantation; and the use of renal palliative care service.
Fulltext Psychometric Comparisons of Benevolent and Corrective Humor across 22 Countries: The Virtue Gap in Humor Goes International

Heintz S, Ruch W, Platt T, Pang D, Carretero-Dios H, Dionigi A, et al.

Front Psychol, 2018;9:92.
PMID: 29479326 DOI: 10.3389/fpsyg.2018.00092

Recently, two forms of virtue-related humor, benevolent and corrective, have been introduced. Benevolent humor treats human weaknesses and wrongdoings benevolently, while corrective humor aims at correcting and bettering them. Twelve marker items for benevolent and corrective humor (the BenCor) were developed, and it was demonstrated that they fill the gap between humor as temperament and virtue. The present study investigates responses to the BenCor from 25 samples in 22 countries (overallN= 7,226). The psychometric properties of the BenCor were found to be sufficient in most of the samples, including internal consistency, unidimensionality, and factorial validity. Importantly, benevolent and corrective humor were clearly established as two positively related, yet distinct dimensions of virtue-related humor. Metric measurement invariance was supported across the 25 samples, and scalar invariance was supported across six age groups (from 18 to 50+ years) and across gender. Comparisons of samples within and between four countries (Malaysia, Switzerland, Turkey, and the UK) showed that the item profiles were more similar within than between countries, though some evidence for regional differences was also found. This study thus supported, for the first time, the suitability of the 12 marker items of benevolent and corrective humor in different countries, enabling a cumulative cross-cultural research and eventually applications of humor aiming at the good.
Fulltext Longitudinal effects of common carotid artery stenosis on ocular hemodynamics assessed using laser speckle flowgraphy in a rabbit model

Ismail A, Chen HC, Faye I, Tang TB

Sci Rep, 2020 09 28;10(1):15829.
PMID: 32985560 DOI: 10.1038/s41598-020-72556-9

Real-time impairment of ocular blood flow (OBF) under common carotid artery stenosis (CCAS) has not been ascertained. We aimed to longitudinally assess the impact of CCAS on OBF using a rabbit model. About 75% stenosis was created by tying the common carotid artery with a plastic mandrel using a nylon suture. The plastic mandrel was gently removed, leaving a ligature. Neurological and behavioral assessments were recorded as the clinical indicator of stroke severity. With laser speckle flowgraphy, the pulse waveform parameters namely mean blur rate (MBR), blowout score (BOS), blowout time (BOT), rising rate, S1-area, falling rate (FR), S2-area, flow acceleration index (FAI), acceleration time index, resistive index (RI) and the difference between the maximum and minimum values of MBR (AC) were assessed in overall, vessel, and tissue regions of the optic nerve head (ONH). Longitudinally, BOS significantly increased until day 19 post-surgery, whereas FAI, RI, and AC significantly decreased. Beyond day 19, BOS, BOT, FR, FAI, RI, and AC significantly decreased. We defined two stages representing impaired vessel conditions, namely the vessel resistance phase, where BOS increases and FAI, RI, and AC decrease, and the vessel elasticity phase where BOS, BOT, FR, FAI, RI and AC decrease. These stages provide information about atherosclerosis, assessable non-invasively through the eye.
The evaluation of cartilage differentiations using transforming growth factor beta3 alone and with combination of bone morphogenetic protein-6 on adult stem cells

Ude CC, Chen HC, Norhamdan MY, Azizi BM, Aminuddin BS, Ruszymah BHI

Cell Tissue Bank, 2017 Sep;18(3):355-367.
PMID: 28667462 DOI: 10.1007/s10561-017-9638-1

In our quest to standardize our formula for a clinical trial, transforming growth factor-beta3 (TGF-β3) alone and in combination with bone morphogenetic protein-6 (BMP-6) were evaluated for their effectiveness in cartilage differentiation. Bone Marrow Stem Cells (BMSCs) and Adipose Derived Stem Cells (ADSCs) were induced to chondrogenic lineage using two different media. Native chondrocytes served as positive control. ADSCs and BMSCs proved multipotency by tri-lineage differentiations. ADSC has significantly higher growth kinetics compare to Chondrocyte only p ≤ 0.05. Using TGF-β3 alone, BMSC revealed higher expressions for hyaline cartilage genes compare to ADSCs. Chondrocyte has significantly higher early chondrogenic markers expression to ADSCs and BMSCs, while BMSCs was only higher to ADSC at chondroadherin, p ≤ 0.0001. On mature chondrogenic markers, chondrocytes were significantly higher to ADSCs and BMSCs for aggrecan, collagen IX, sry (sex determining region y)-box9, collagen II and fibromodullin; and only to ADSC for collagen XI. BMSC was higher to ADSC for aggrecan and collagen IX, p ≤ 0.0001. The combination of TGF-β3 + BMP-6 revealed increased gene expressions on both BMSCs and ADSCs for early and mature chondrogenic markers, but no significance difference. For dedifferentiation markers, ADSC was significantly higher to chondrocyte for collagen I. Glycosaminoglycan evaluations with both formulas revealed that chondrocytes were significantly higher to ADSCs and BMSCs, but none was significant to each other, p ≤ 0.0001. Combination of 10 ng TGF-β3 with 10 ng of BMP-6 enhanced chondrogenic potentials of BMSCs and ADSCs compare to TGF-β3 alone. This could be the ideal cocktail for either cell's chondrogenic induction.
Long-term evaluation of osteoarthritis sheep knee, treated with TGF-β3 and BMP-6 induced multipotent stem cells

Ude CC, Shamsul BS, Ng MH, Chen HC, Ohnmar H, Amaramalar SN, et al.

Exp Gerontol, 2018 04;104:43-51.
PMID: 29421350 DOI: 10.1016/j.exger.2018.01.020

BACKGROUND: Hyaline articular cartilage, which protects the bones of diarthrodial joints from forces associated with load bearing, frictions, and impacts has very limited capacities for self-repair. Over the years, the trend of treatments has shifted to regenerations and researchers have been on the quest for a lasting regeneration. We evaluated the treatment of osteoarthritis by chondrogenically induced ADSCs and BMSCs for a long time functional recovery.
METHODS: Osteoarthritis was induced at the right knee of sheep by complete resection of ACL and medial meniscus. Stem cells from sheep were induced to chondrogenic lineage. Test sheep received 5 mls single doses of 2 × 107 autologous PKH26-labelled ADSCs or BMSCs, while controls received basal medium. Functional recovery of the knees was evaluated via electromyography.
RESULTS: Induced ADSCs had 625, 255, 393, 908, 409, 157 and 1062 folds increases of collagen I, collagen II, aggrecan, SOX9, cartilage oligomeric protein, chondroadherin and fibromodullin compare to uninduced cells, while BMSCs had 702, 657, 321, 276, 337, 233 and 1163 respectively; p = .001. Immunocytochemistry was positive for these chondrogenic markers. 12 months post-treatment, controls scored 4 in most regions using ICRS, while the treated had 8; P = .001. Regenerated cartilages were positive to PKH26 and demonstrated the presence of condensing cartilages on haematoxylin and eosin; and Safranin O. OA degenerations caused significant amplitude shift from right to left hind limb. After treatments, controls persisted with significant decreases; while treated samples regained balance.
CONCLUSIONS: Both ADSCs and BMSCs had increased chondrogenic gene expressions using TGF-β3 and BMP-6. The treated knees had improved cartilage scores; PKH26 can provide elongated tracking, while EMG results revealed improved joint recoveries. These could be suitable therapies for osteoarthritis.
Posterolateral spinal fusion with ostegenesis induced BMSC seeded TCP/HA in a sheep model

Shamsul BS, Tan KK, Chen HC, Aminuddin BS, Ruszymah BH

Tissue Cell, 2014 Apr;46(2):152-8.
PMID: 24630213 DOI: 10.1016/j.tice.2014.02.001

Autogenous bone graft is the gold standard for fusion procedure. However, pain at donor site and inconsistent outcome have left a surgeon to venture into some other technique for spinal fusion. The objective of this study was to determine whether osteogenesis induced bone marrow stem cells with the combination of ceramics granules (HA or TCP/HA), and fibrin could serve as an alternative to generate spinal fusion. The sheep's bone marrow mesenchymal stem cells (BMSCs) were aspirated form iliac crest and cultured for several passages until confluence. BMSCs were trypsinized and seeded on hydroxyapatite scaffold (HA) and tricalcium phosphate/hydroxyapatite (TCP/HA) for further osteogenic differentiation in the osteogenic medium one week before implantation. Six adult sheep underwent three-level, bilateral, posterolateral intertransverse process fusions at L1-L6. Three fusion sites in each animal were assigned to three treatments: (a) HA constructs group/L1-L2, (b) TCP/HA constructs group/L2-L3, and (c) autogenous bone graft group/L5-L6. The spinal fusion segments were evaluated using radiography, manual palpation, histological analysis and scanning electron microscopy (SEM) 12 weeks post implantation. The TCP/HA constructs achieved superior lumbar intertransverse fusion compared to HA construct but autogenous bone graft still produced the best fusion among all.
Fulltext The potential of intra-articular injection of chondrogenic-induced bone marrow stem cells to retard the progression of osteoarthritis in a sheep model

Al Faqeh H, Nor Hamdan BM, Chen HC, Aminuddin BS, Ruszymah BH

Exp Gerontol, 2012 Jun;47(6):458-64.
PMID: 22759409 DOI: 10.1016/j.exger.2012.03.018

In recent years, the use of bone marrow mesenchymal stem cell (BMSC) implantation has provided an alternative treatment for osteoarthritis. The objective of this study is to determine whether or not an intra-articular injection of a single dose of autologous chondrogenic induced BMSC could retard the progressive destruction of cartilage in a surgically induced osteoarthritis in sheep. Sheep BMSCs were isolated and divided into two groups. One group was cultured in chondrogenic media containing (Ham's F12:DMEM, 1:1) FD+1% FBS+5 ng/ml TGFβ3+50 ng/ml IGF-1 (CM), and the other group was cultured in the basal media, FD+10% FBS (BM). The procedure for surgically induced osteoarthritis was performed on the donor sheep 6 weeks prior to intra-articular injection into the knee joint of a single dose of BMSC from either group, suspended in 5 ml FD at density of 2 million cells/ml. The control groups were injected with basal media, without cells. Six weeks after injection, gross evidence of retardation of cartilage destruction was seen in the osteoarthritic knee joints treated with CM as well as BM. No significant ICRS (International Cartilage Repair Society) scoring was detected between the two groups with cells. However macroscopically, meniscus repair was observed in the knee joint treated with CM. Severe osteoarthritis and meniscal injury was observed in the control group. Interestingly, histologically the CM group demonstrated good cartilage histoarchitecture, thickness and quality, comparable to normal knee joint cartilage. As a conclusion, intra-articular injection of a single dose of BMSC either chondrogenically induced or not, could retard the progression of osteoarthritis (OA) in a sheep model, but the induced cells indicated better results especially in meniscus regeneration.
Study site: Universiti Kebangsaan Malaysia, Kuala Lumpur
Bone marrow and adipose stem cells can be tracked with PKH26 until post staining passage 6 in in vitro and in vivo

Ude CC, Shamsul BS, Ng MH, Chen HC, Norhamdan MY, Aminuddin BS, et al.

Tissue Cell, 2012 Jun;44(3):156-63.
PMID: 22402173 DOI: 10.1016/j.tice.2012.02.001

Tracking of transplanted cells has become an important procedure in cell therapy. We studied the in vitro dye retention, survival and in vivo tracking of stem cells with PKH26 dye. Sheep BMSCs and ADSCs were labeled with 2, 4 and 8 μmol of PKH26 and monitored for six passages. Labeled BMSCs and ADSCs acquired mean cumulative population doubling of 12.7±0.4 and 14.6±0.5; unlabeled samples had 13.8±0.5 and 15.4±0.6 respectively. Upon staining with 2, 4 and 8 μmol PKH26, BMSCs had retentions of 40.0±5.8, 60.0±2.9 and 95.0±2.9%, while ADSCs had 92.0±1.2, 95.0±1.2 and 98.0±1.2%. ADSCs retentions were significantly higher at 2 and 4 μmol. On dye retention comparison at 8 μmol and 4 μmol for BMSCs and ADSCs; ADSCs were significantly higher at passages 2 and 3. The viability of BMSCs reduced from 94.0±1.2% to 90.0±0.6% and ADSCs from 94.0±1.2% to 52.0±1.2% (p<0.05) after 24h. BMSCs had significant up regulation of the cartilage genes for both the labeled and the unlabeled samples compared to ADSCs (p<0.05). PKH26 fluorescence was detected on the resected portions of the regenerated neo-cartilage. The recommended concentration of PKH26 for ADSCs is 2 μmol and BMSCs is 8 μmol, and they can be tracked up to 49 days.
Autologous implantation of bilayered tissue-engineered respiratory epithelium for tracheal mucosal regenesis in a sheep model

Mohd Heikal MY, Aminuddin BS, Jeevanan J, Chen HC, Sharifah SH, Ruszymah BH

Cells Tissues Organs (Print), 2010;192(5):292-302.
PMID: 20616535 DOI: 10.1159/000318675

The objective of this study was to regenerate the tracheal epithelium using autologous nasal respiratory epithelial cells in a sheep model. Respiratory epithelium and fibroblast cells were harvested from nasal turbinates and cultured for 1 week. After confluence, respiratory epithelium and fibroblast cells were suspended in autologous fibrin polymerized separately to form a tissue-engineered respiratory epithelial construct (TEREC). A 3 × 2 cm² tracheal mucosal defect was created, and implanted with TEREC and titanium mesh as a temporary scaffold. The control groups were divided into 2 groups: polymerized autologous fibrin devoid of cells (group 1), and no construct implanted (group 2). All sheep were euthanized at 4 weeks of implantation. Gross observation of the trachea showed minimal luminal stenosis formation in the experimental group compared to the control groups. Macroscopic evaluation revealed significant mucosal fibrosis in control group 1 (71.8%) as compared to the experimental group (7%). Hematoxylin and eosin staining revealed the presence of minimal overgrowth of fibrous connective tissue covered by respiratory epithelium. A positive red fluorescence staining of PKH26 on engineered tissue 4 weeks after implantation confirmed the presence of cultured nasal respiratory epithelial cells intercalated with native tracheal epithelial cells. Scanning electron microscopy showed the presence of short microvilli representing immature cilia on the surface of the epithelium. Our study showed that TEREC was a good replacement for a tracheal mucosal defect and was able to promote natural regenesis of the tracheal epithelium with minimal fibrosis. This study highlighted a new technique in the treatment of tracheal stenosis.
Measurement of sulphated glycosaminoglycans production after autologous 'chondrocytes-fibrin' constructs implantation in sheep knee joint

Munirah S, Samsudin OC, Chen HC, Salmah SH, Aminuddin BS, Ruszymah BH

Med J Malaysia, 2008 Jul;63 Suppl A:35-6.
PMID: 19024971

Chondrocytes were isolated from articular cartilage biopsy and were cultivated in vitro. Approximately 30 million of cultured chondrocytes per ml were incorporated with autologous plasma-derived fibrin to form three-dimensional construct. Full-thickness punch hole defects were created in lateral and medial femoral condyles. The defects were implanted either with the autologous 'chondrocytes-fibrin' construct (ACFC), autologous chondrocytes (ACI) or fibrin blank (AF). Sheep were euthanized after 12 weeks. The gross morphology of all defects treated with ACFC implantation, ACI and AF exhibited median scores which correspond to a nearly normal appearance according to the International Cartilage Repair Society (ICRS) classification. ACFC significantly enhanced cartilage repair compared to ACI and AF in accordance with the modified O'Driscoll histological scoring scale. The relative sulphated glycosaminoglycans content (%) was significantly higher (p < 0.05) in ACFC when compared to control groups; ACI vs. fibrin only vs. untreated (blank). Results showed that ACFC implantation exhibited superior cartilage-like tissue regeneration compared to ACI. If the result is applicable to the human, it possibly will improve the existing treatment approaches for cartilage restoration in orthopaedic surgery.
A scanning electron microscopic study of in vivo tissue engineered respiratory epithelium in sheep

Heikal MY, Aminuddin BS, Jeevanan J, Chen HC, Sharifah S, Ruszymah BH

Med J Malaysia, 2008 Jul;63 Suppl A:34.
PMID: 19024970

Normal tracheal mucociliary clearance is the key to maintaining the health and defense of respiratory airway. Therefore the present of cilia and mucous blanket are important for tracheal epithelium to function effectively. In the present study, we prepared a tissue engineered respiratory epithelium construct (TEREC) made of autologous respiratory epithelium cells, fibroblast and fibrin from sheep owns blood which replaced a created tracheal mucosal defect. Scanning electron microscopy (SEM) showed encouraging result where immature cilia were present on the surface of TEREC. This result indicates that engineered respiratory epithelium was able to function as normal tissue.
Cell based therapy for osteoarthritis in a sheep model: gross and histological assessment

Alfaqeh H, Norhamdan MY, Chua KH, Chen HC, Aminuddin BS, Ruszymah BH

Med J Malaysia, 2008 Jul;63 Suppl A:37-8.
PMID: 19024972

This study was to determine if autologous bone marrow mesenchymal stem cells (BMSCs) cultured in chondrogenic medium could repair surgically induced osteoarthritis. Sheep BMSCs were cultured in medium containing 5ng/ml TGFbeta3 + 50ng/ml IGF-1 for three weeks. The cultured cells were then suspended at density of 2x10(6) cell/ml and injected intraarticularly into the osteoarthritic knee joint. After six weeks, the distal head of the femur and the proximal tibial plateau were removed and stained with H&E. The results indicated that knee joints treated with autologous BMSCs cultured in chondrogenic medium showed clear evidence of articular cartilage regeneration in comparison with other groups.
Articular cartilage restoration in load-bearing osteochondral defects by implantation of autologous chondrocyte-fibrin constructs: an experimental study in sheep

Munirah S, Samsudin OC, Chen HC, Salmah SH, Aminuddin BS, Ruszymah BH

J Bone Joint Surg Br, 2007 Aug;89(8):1099-109.
PMID: 17785753

Ovine articular chondrocytes were isolated from cartilage biopsy and culture expanded in vitro. Approximately 30 million cells per ml of cultured chondrocytes were incorporated with autologous plasma-derived fibrin to form a three-dimensional construct. Full-thickness punch hole defects were created in the lateral and medial femoral condyles. The defects were implanted with either an autologous 'chondrocyte-fibrin' construct (ACFC), autologous chondrocytes (ACI) or fibrin blanks (AF) as controls. Animals were killed after 12 weeks. The gross appearance of the treated defects was inspected and photographed. The repaired tissues were studied histologically and by scanning electron microscopy analysis. All defects were assessed using the International Cartilage Repair Society (ICRS) classification. Those treated with ACFC, ACI and AF exhibited median scores which correspond to a nearly-normal appearance. On the basis of the modified O'Driscoll histological scoring scale, ACFC implantation significantly enhanced cartilage repair compared to ACI and AF. Using scanning electron microscopy, ACFC and ACI showed characteristic organisation of chondrocytes and matrices, which were relatively similar to the surrounding adjacent cartilage. Implantation of ACFC resulted in superior hyaline-like cartilage regeneration when compared with ACI. If this result is applicable to humans, a better outcome would be obtained than by using conventional ACI.
Fulltext Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Mullins N, Kang J, Campos AI, Coleman JRI, Edwards AC, Galfalvy H, et al.

Biol Psychiatry, 2022 Feb 01;91(3):313-327.
PMID: 34861974 DOI: 10.1016/j.biopsych.2021.05.029

BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.
METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.
RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.
CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
Articular cartilage regeneration with autologous marrow aspirate and hyaluronic Acid: an experimental study in a goat model

Saw KY, Hussin P, Loke SC, Azam M, Chen HC, Tay YG, et al.

Arthroscopy, 2009 Dec;25(12):1391-400.
PMID: 19962065 DOI: 10.1016/j.arthro.2009.07.011

PURPOSE: The purpose of the study was to determine whether postoperative intra-articular injections of autologous marrow aspirate (MA) and hyaluronic acid (HA) after subchondral drilling resulted in better cartilage repair as assessed histologically by Gill scoring.
METHODS: In a goat model we created a 4-mm full-thickness articular cartilage defect in the stifle joint (equivalent to 1.6 cm in the human knee) and conducted subchondral drilling. The animals were divided into 3 groups: group A (control), no injections; group B (HA), weekly injection of 1 mL of sodium hyaluronate for 3 weeks; and group C (HA + MA), similar to group B but with 2 mL of autologous MA in addition to HA. MA was obtained by bone marrow aspiration, centrifuged, and divided into aliquots for cryopreservation. Fifteen animals were equally divided between the groups and sacrificed 24 weeks after surgery, when the joint was harvested, examined macroscopically and histologically.
RESULTS: Of the 15 animals, 2 from group A had died of non-surgery-related complications and 1 from group C was excluded because of a joint infection. In group A the repair constituted mainly scar tissue, whereas in group B there was less scar tissue, with small amounts of proteoglycan and type II collagen at the osteochondral junction. In contrast, repair cartilage from group C animals showed almost complete coverage of the defect with evidence of hyaline cartilage regeneration. Histology assessed by Gill scoring was significantly better in group C with 1-way analysis of variance yielding an F statistic of 10.611 with a P value of .004, which was highly significant.
CONCLUSIONS: Postoperative intra-articular injections of autologous MA in combination with HA after subchondral drilling resulted in better cartilage repair as assessed histologically by Gill scoring in a goat model.
CLINICAL RELEVANCE: After arthroscopic subchondral drilling, this novel technique may result in better articular cartilage regeneration.
Assessment of post-operative pain in cats: a case study on veterinary students of Universiti Putra Malaysia

Lim MY, Chen HC, Omar MA

J Vet Med Educ, 2014;41(2):197-203.
PMID: 24589865 DOI: 10.3138/jvme.0713-099R1

The ability to assess and control pain is listed as one of the desired Day One competencies among veterinary graduates. As such, a study was conducted to examine the current status and effectiveness of a video-based training module on the attitude toward and knowledge of pain assessment in cats among fourth- and final-year veterinary students of Universiti Putra Malaysia (UPM) in January of 2013. A total of 92 students participated in this study, resulting in a response rate of 60.1%. Upon completion of a pre-training survey, the respondents undertook an interactive video-based presentation, followed by a post-training survey. The majority of the students (96.7%) agreed on the importance of pain management. Before the training, many (76.1%) disagreed that they had received adequate training, while 53.3% were not confident in their pain-recognition skills. After training, their knowledge and confidence in pain assessment increased. Responses to the survey were not associated with differences in gender, level of study, or field of interest. Students were found to have mistaken some physiologic parameters as good pain indicators after ovariohysterectomy. Their assessment of three standardized video cases revealed that they could recognize prominent signs of pain but failed to identify changes in behavior that were more subtle. Refinement to the training module is required to address the above deficiencies.
Fulltext Extractable impurities from fluoropolymer-based membrane filters - interference in high-throughput, untargeted analysis

Puah PY, Herng Lee DJ, Mak KH, Ang HJ, Chen HC, Moh PY, et al.

RSC Adv, 2019 Oct 07;9(55):31918-31927.
PMID: 35702663 DOI: 10.1039/c9ra06198c

The removal of particles using fluoropolymer-based membrane filters is usually done so to prolong the life span of an analytical column, prevent hardware damage, and reduce signal suppression. Ironically, these membrane filters tend to leach impurities into the samples as the samples are filtered through them. These impurities have the potential to affect the researcher's interpretation in high-throughput, non-targeted analysis. In this study, extractable impurities from different brands of fluoropolymer-based membrane filters present in the filtrate filtered using the said filters were investigated. The results demonstrated that different brand membrane filters and materials tend to elute vastly different numbers of impurities. There were instances whereby the extractable impurities persisted in both the membrane filter and the filtrate despite the filter being pre-conditioned (up to 3 times). Principle component analysis revealed that filtrates at different purge intervals are distant from the unfiltered samples. Pre-conditioning of the PTFE membrane filters could potentially reduce the number of extractable impurities across the tested brands. PVDF filtrates, however, tend to co-cluster with their respective brands, thus suggesting that dissimilarity persists in brands following conditioning. As such, pre-conditioning of the PTFE membrane filters should be encouraged so as to reduce false positive results, while the use of PVDF membrane filters for mass-spectrometry-based untargeted analysis is not advisable as extractable impurities would still persist after 3 rounds of conditioning. Neither the use of different filter brands, nor the use of different filter materials in a sample batch are encouraged as different membrane materials or brands could potentially elute varying impurities.
Fulltext Streptococcus pneumoniae endophthalmitis: clinical settings, antibiotic susceptibility, and visual outcomes

Chen KJ, Chong YJ, Sun MH, Chen HC, Liu L, Chen YP, et al.

Sci Rep, 2021 03 18;11(1):6195.
PMID: 33737573 DOI: 10.1038/s41598-021-85456-3

Streptococcus pneumoniae endophthalmitis is clinically more severe, more difficult to treat, and carry a higher risk of vision loss, evisceration, or enucleation. This study is to investigate the clinical settings, antibiotic susceptibility, and visual outcomes of S. pneumoniae endophthalmitis at a tertiary referral center in Taiwan. S. pneumoniae endophthalmitis was diagnosed in 38 eyes of 38 patients. The main clinical features were postcataract endophthalmitis (n = 13, 34%) and endophthalmitis associated with corneal ulcer (n = 12, 32%), trauma (n = 6, 16%), endogenous etiology (n = 4, 11%), trabeculectomy (n = 2, 5%), and pterygium excision-related scleral ulcer (n = 1, 3%). Presenting visual acuity ranged from counting fingers to no light perception. Pars plana vitrectomy with intravitreal antibiotics was performed in 17 eyes (39%) in primary or secondary treatments. S. pneumoniae isolates were susceptible to vancomycin (38/38, 100%), penicillin (37/38, 97%), ceftriaxone (37/38, 97%), cefuroxime (12/15, 80%), levofloxacin (13/15 ,87%), and moxifloxacin (15/17, 88%). Final visual acuity was better than 20/400 in 3 of 38 eyes (8%), 5/200 to hand motions in 3 eyes (8%), and light perception to no light perception in 32 eyes (84%). Ten eyes (26%) underwent evisceration or enucleation. Although S. pneumoniae isolates were susceptible to vancomycin, S. pneumoniae endophthalmitis had a very poor visual prognosis.
Dialysis Care and Dialysis Funding in Asia

Tang SCW, Yu X, Chen HC, Kashihara N, Park HC, Liew A, et al.

Am J Kidney Dis, 2020 05;75(5):772-781.
PMID: 31699518 DOI: 10.1053/j.ajkd.2019.08.005

Asia is the largest and most populated continent in the world, with a high burden of kidney failure. In this Policy Forum article, we explore dialysis care and dialysis funding in 17 countries in Asia, describing conditions in both developed and developing nations across the region. In 13 of the 17 countries surveyed, diabetes is the most common cause of kidney failure. Due to great variation in gross domestic product per capita across Asian countries, disparities in the provision of kidney replacement therapy (KRT) exist both within and between countries. A number of Asian nations have satisfactory access to KRT and have comprehensive KRT registries to help inform practices, but some do not, particularly among low- and low-to-middle-income countries. Given these differences, we describe the economic status, burden of kidney failure, and cost of KRT across the different modalities to both governments and patients and how changes in health policy over time affect outcomes. Emerging trends suggest that more affluent nations and those with universal health care or access to insurance have much higher prevalent dialysis and transplantation rates, while in less affluent nations, dialysis access may be limited and when available, provided less frequently than optimal. These trends are also reflected by an association between nephrologist prevalence and individual nations' incomes and a disparity in the number of nephrologists per million population and per thousand KRT patients.
Effects of Sustained-Release Beraprost in Patients With Primary Glomerular Disease or Nephrosclerosis: CASSIOPEIR Study Results

Nakamoto H, Yu XQ, Kim S, Origasa H, Zheng H, Chen J, et al.

Ther Apher Dial, 2020 Feb;24(1):42-55.
PMID: 31119846 DOI: 10.1111/1744-9987.12840

TRK-100STP, a sustained-release preparation of the orally active prostacyclin analogue beraprost sodium, targets renal hypoxia. This study aimed to show the superiority of TRK-100STP over placebos in patients with chronic kidney disease (with either primary glomerular disease or nephrosclerosis) to determine the recommended dose. CASSIOPEIR (Chronic Renal Failure Asian Study with Oral PGI2 Derivative for Evaluating Improvement of Renal Function) was a randomized, double-blind, placebo-controlled study conducted at 160 sites in seven Asia-Pacific countries and regions. Eligible patients (n = 892) were randomized to TRK-100STP 120, 240 μg, or placebo for a treatment period of up to 4 years. The primary efficacy endpoint was time to first occurrence of a renal composite: doubling of serum creatinine or occurrence of end-stage renal disease. No significant differences were observed in composite endpoints between TRK-100STP and placebo (P = 0.5674). Hazard ratios (95% CI) in the TRK-100STP 120 and 240 μg vs. placebo groups were 0.98 (0.78, 1.22) and 0.91 (0.72, 1.14), respectively. The overall incidence of adverse events and adverse drug reactions was comparable between treatment arms.

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