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Xing Wang,1,2 Siew Hoon Teh,1 Xiao-Gang Du,2 Xing-Hua Wang1 1M. Kandiah Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Kajang, SGR, Malaysia; 2Famous TCM Expert Heritage Studio, Xi’an Encephalopathy Hospital Affiliated to Shaanxi University of Chinese Medicine, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Xing-Hua Wang, M. Kandiah Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Kajang, Selangor, Malaysia, Email wangxh@utar.edu.myObjective: Cerebral palsy (CP) is a condition characterized by abnormal pronunciation, posture, and movement, particularly spastic CP, which involves Gross motor dysfunction due to increased muscle tone and stiffness. This monocentric clinical study aims to evaluate the effectiveness of acupuncture and tuina (AT) in improving gross motor function and alleviating associated symptoms in children diagnosed with spastic CP.Methods: A total of 83 eligible patients received AT treatment, while 85 patients received conventional rehabilitation treatment. Both groups underwent a 12-week treatment period following the research protocol. Pre- and post-treatment assessments included the Modified Ashworth Muscle Tension Scale (MAS), Gross Motor Function Measure (GMFM-D and GMFM-E), 6-min walking distance measurement (6MWD), and Modified Children’s Functional Independence Rating Scale (WeeFIM).Results: After 12 weeks of treatment, when compared with baseline, the scores of MAS in both AT group and control group are decreased (p< 0.01, p< 0.01), the scores of GMFM-D, GMFME, 6MWD, WeeFIM in both group are increased (p< 0.01 in all indicators). When compared with control group, AT group had significantly lower MAS scores compared to the control group (p< 0.01), indicating reduced muscle tension. Moreover, AT group showed significantly higher scores in GMFM-D, GMFM-E, 6MWD, and WeeFIM compared to the control group (p< 0.01 in all indicators), indicating improved gross motor function and functional independence. The study also revealed an inverse correlation between the children’s age and treatment efficacy (r= − 0.496, p< 0.01 in AT group, r=− 0.540, p< 0.01 in control group), highlighting the importance of early intervention in the management of CP in children.Conclusion: These findings suggest that AT may effectively enhance gross motor function and alleviate associated symptoms in children diagnosed with spastic CP. Moreover, early initiation of treatment is crucial to maximize therapeutic efficacy in children with spastic CP.Trial Registration: Chinese Clinical Trial Registry, ChiCTR2200059823. Registered on 12 May 2022.Keywords: acupuncture, cerebral palsy, modified Ashworth muscle tension scale, gross motor function, the 6-minute walking distance measurement, children’s functional Independence rating scale

Background and Hypothesis: It is unclear if low birth weight (LBW), preterm birth and small for gestational age (SGA) could synergistically cause chronic kidney disease (CKD) and end-stage kidney disease (ESKD). This cohort study was conducted to examine their individual and combined impacts on the development of CKD and ESKD in childhood., Methods: From the Taiwan Maternal and Child Health Database, we identified 1 477 128 newborns born between January 1, 2009, and December 31, 2016. We used a multivariable Cox regression model to assess the excess risk of CKD and ESKD in children with LBW/preterm/SGA. They were followed from birth until the occurrence of outcomes or until December 31, 2018, with an average follow-up of 5.78 years., Results: This study included 1 361 071 infants with birth weight ≥ 2500 g (92.14%), 104 855 infants with low birth weight (1500 g to < 2500 g) (7.10%), 6 843 infants with very low birth weight (1000 g to < 1500 g) (0.46%), and 4 349 infants with extremely low birth weight (< 1000 g) (0.29%). The multivariable-adjusted model showed that male infants with low birth weight were associated with an increased risk of CKD (aHR 1.20, 95%CI 1.08-1.32) and ESKD (aHR 1.64, 95%CI 1.37-1.97). Female infants with LBW had an increased risk of CKD (aHR 1.18, 95%CI 1.06-1.32) and ESKD (aHR 1.31, 95%CI 1.09-1.58) than those without LBW. In addition to LBW, infants with preterm or SGA condition also had a significantly and synergistically increased risk of CKD and ESKD compared to full-term infants., Conclusion: We found children with LBW, preterm birth, or small for gestational age had a significantly increased risk of CKD and ESKD compared to children without intrauterine growth restriction., (© The Author(s) 2025. Published by Oxford University Press on behalf of the ERA.)

To enhance the performance of entropy algorithms in analyzing complex time series, generalized Gaussian distribution improved permutation entropy (GGDIPE) and its multiscale variant (MGGDIPE) are proposed in this paper. First, the generalized Gaussian distribution cumulative distribution function is employed for data normalization to enhance the algorithm's applicability across time series with diverse distributions. The algorithm further processes the normalized data using improved permutation entropy, which maintains both the absolute magnitude and temporal correlations of the signals, overcoming the equal value issue found in traditional permutation entropy (PE). Simulation results indicate that GGDIPE is less sensitive to parameter variations, exhibits strong noise resistance, accurately reveals the dynamic behavior of chaotic systems, and operates significantly faster than PE. Real-world data analysis shows that MGGDIPE provides markedly better separability for RR interval signals, EEG signals, bearing fault signals, and underwater acoustic signals compared to multiscale PE (MPE) and multiscale dispersion entropy (MDE). Notably, in underwater target recognition tasks, MGGDIPE achieves a classification accuracy of 97.5% across four types of acoustic signals, substantially surpassing the performance of MDE (70.5%) and MPE (62.5%). Thus, the proposed method demonstrates exceptional capability in processing complex time series.

The rise of carbapenem-resistant Klebsiella pneumoniae (CRKP) presents a significant global challenge in clinical and healthcare settings, severely limiting treatment options. This study aimed to utilize a bacteriophage as an alternative therapy against carbapenem-resistant K. pneumoniae . A novel lytic N4-like Klebsiella phage, vB&#95;kpnP&#95;KPYAP-1 (KPYAP-1), was isolated from sewage. It demonstrated efficacy against the K62 serotype polysaccharide capsule of bla OXA-48 -producing K. pneumoniae . KPYAP-1 forms small, clear plaques, has a latent period of 20 min, and reaches a growth plateau at 35 min, with a burst size of 473 plaque-forming units (PFUs) per infected cell. Phylogenetic analysis places KPYAP-1 in the Schitoviridae family, Enquatrovirinae subfamily, and Kaypoctavirus genus. KPYAP-1 employs an N4-like direct terminal repeat mechanism for genome packaging and encodes a large virion-encapsulated RNA polymerase. It lacks integrase or repressor genes, antibiotic resistance genes, bacterial virulence factors, and toxins, ensuring its safety for therapeutic use. Comparative genome analysis revealed that the KPYAP-1 genome is most similar to the KP8 genome, yet differs in tail fiber protein, indicating variations in host recognition. In a zebrafish infection model, KPYAP-1 significantly improved the survival rate of infected fish by 92% at a multiplicity of infection (MOI) of 10, demonstrating its potential for in vivo treatment. These results highlight KPYAP-1 as a promising candidate for developing phage-based therapies targeting carbapenemase-producing K. pneumoniae .

The Academy of Medicine of Malaysia College of Paediatrics acknowledges the role of children in research and this position statement explores the ethical considerations in obtaining assent from minors in the Malaysian context. It highlights the importance in respecting children's agency and navigating cultural complexities. The College proposes flexibility in the minimum age for assent of at least nine years old, while emphasising the need for a tailored assent procedure. Addressing language and cultural diversities and expanding local empirical research on a formal assent process are some building blocks in developing a standardised nationwide process in obtaining assent from children.

Objective: To evaluate the feasibility, safety, and effectiveness of a comprehensive regional program, including the Minimally Invasive Recovery and Empowerment Care (MIREC) pathway, that can significantly reduce hospital stays after laparoscopic gastrectomy without increasing adverse events., Background: Cost-effectiveness and improving patient outcomes are crucial in providing quality gastric cancer care worldwide., Methods: To compare the outcomes of gastric cancer surgery using 2 different models of care within an integrated healthcare system from February 2012 to March 2023. The primary endpoint was the length of hospital stay. The secondary endpoints were the need for intensive care unit care, emergency room (ER) visits, readmission, reoperation, and death within 30 days after surgery., Results: There were 553 patients, 167 in the pre-(February 2012-April 2016) and 386 in the post-MIREC period (May 2016-March 2023). Perioperative chemotherapy utilization increased from 31.7% to 76.4% ( P < 0.0001). Laparoscopic gastrectomy increased from 17.4% to 97.7% ( P < 0.0001). Length of hospitalization decreased from 7 to 2 days ( P < 0.0001), with 32.1% and 88% of patients discharged home on postoperative day 1 and postoperative day 2, respectively. When comparing pre- and post-MIREC, intensive care unit utilization (10.8% vs. 2.9%, P < 0.0001), ER visits (34.7% vs. 19.7%, P = 0.0002), and readmission (18.6% vs. 11.1%, P = 0.019) at 30 days were also considerably lower. In addition, more patients received postoperative adjuvant chemotherapy (31.4% to 63.5%, P < 0.0001), and the time between gastrectomy and starting adjuvant chemotherapy was also less (49-41 days; P = 0.002)., Conclusion: This comprehensive regional program, which encompasses regionalization care, laparoscopic approach, modern oncologic care, surgical subspecialization, and the MIREC pathway, can potentially improve gastric cancer surgery outcomes. These benefits include reduced hospital stays and lower complication rates. As such, this program can revolutionize how gastric cancer surgery is delivered, leading to a higher quality of care and increased value to patients., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Cerebral palsy (CP) is characterized by abnormal pronunciation, posture, and movement. Spastic CP accounts for more than 70% of all CP. To date, there has been no bibliometric analysis to summarize study on spastic CP. Here, we aim to conduct a bibliometric analysis of spastic CP to summarize this field's knowledge structure, research hotspots, and frontiers., Method: Publications about spastic CP were searched utilizing the Web of Science Core Collection (WoSCC) database from 1 January 2000 to 30 November 2022, the WoSCC literature analysis wire, VOSviewer 1.6.18, CiteSpace 6.1.R4 and Online analysis platform for bibliometrics were used to conduct the analysis., Results: A total of 3988 publications, consisting of 3699 articles and 289 reviews, were included in our study. The United States emerged as the most productive country, while Kathleen Univ Leuven was the most productive institution. The leading author was Desloovere K. A total of 238 journals contributed to this field, with Developmental medicine and child neurology being the leading journal. Important keywords and keyword clusters included Spastic cerebral palsy, Reliability, and Gross motor function. Keywords identified through burst detection indicated that hotspots in this field were management, randomized controlled trials, and definition., Conclusion: Based on the analysis of bibliometric on spastic CP over the past 20 years, the trends and the knowledge graph of the countries, institutions, authors, references, and the keywords have been identified, providing accurate and expedited insights into critical information and potentially new directions in the study of spastic CP., (© 2024. The Author(s).)

The global rise of multidrug-resistant Enterobacter cloacae strains, especially those that are resistant to carbapenems and produce metallo-β-lactamases, poses a critical challenge in clinical settings owing to limited treatment options. While bacteriophages show promise in treating these infections, their use is hindered by scarce resources and insufficient genomic data. In this study, we isolated ECLFM1, a novel E. cloacae phage, from sewage water using a carbapenem-resistant clinical strain as the host. ECLFM1 exhibited rapid adsorption and a 15-min latent period, with a burst size of approximately 75 PFU/infected cell. Its genome, spanning 172,036 bp, was characterized and identified as a member of Karamvirus . In therapeutic applications, owing to a high multiplicity of infection, ECLFM1 showed increased survival in zebrafish infected with E. cloacae . This study highlights ECLFM1's potential as a candidate for controlling clinical E. cloacae infections, which would help address challenges in treating multidrug-resistant strains and contribute to the development of alternative treatments.

Multiple drug-resistant (MDR) Pseudomonas aeruginosa commonly causes severe hospital-acquired infections. The gradual emergence of carbapenem-resistant P. aeruginosa has recently gained attention. A wide array of P. aeruginosa-mediated pathogenic mechanisms, including its biofilm-forming ability, limits the use of effective antimicrobial treatments against it. In the present study, we isolated and characterized the phenotypic, biological, and genomic characteristics of a bacteriophage, vB&#95;PaP&#95;phiPA1-3 (phiPA1-3). Biofilm eradication and phage rescue from bacterial infections were assessed to demonstrate the efficacy of the application potential. Host range spectrum analysis revealed that phiPA1-3 is a moderate host range phage that infects 20% of the clinically isolated strains of P. aeruginosa tested, including carbapenem-resistant P. aeruginosa (CRPA). The phage exhibited stability at pH 7.0 and 9.0, with significantly reduced viability below pH 5.0 and beyond pH 9.0. phiPA1-3 is a lytic phage with a burst size of 619 plaque-forming units/infected cell at 37 °C and can effectively lyse bacteria in a multiplicity of infection-dependent manner. The genome size of phiPA1-3 was found to be 73,402 bp, with a G+C content of 54.7%, containing 93 open reading frames, of which 62 were annotated as hypothetical proteins and the remaining 31 had known functions. The phage possesses several proteins similar to those found in N4-like phages, including three types of RNA polymerases. This study concluded that phiPA1-3 belongs to the N4-like Schitoviridae family, can potentially eradicate P. aeruginosa biofilms, and thus, serve as a valuable tool for controlling CRPA infections., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Acinetobacter baumannii is an opportunistic pathogen that significantly causes hospital-acquired infections. Due to its multidrug resistance, treating infections caused by this pathogen is challenging. Recently, phages have gained attention as a potential alternative to antibiotics in treating bacterial infections. While lytic phages are preferred in therapy, the use of temperate phages for this purpose has received less attention. This study characterized a novel temperate phage vB&#95;AbaM&#95;ABMM1 (ABMM1) with antibacterial activity toward A. baumannii. ABMM1 adsorbs quickly, has short latent periods, and is relatively stable at various temperatures and neutral pH. ABMM1 has an icosahedral head and a contractile tail. It has a 75,731 kb circular permuted dsDNA genome containing 86 gene products with 37.3% G + C content and a mosaic arrangement typical of temperate phages. Genomic analysis confirmed that ABMM1 does not have antibiotic-resistance genes or virulence-related factors. The packaging strategy was predicted in silico, suggesting that ABMM1 represents a headful phage. Only truncated ABMM1 prophage was detected and has similarity in the genome of several A. baumannii strains. Despite its ability to integrate into the host chromosome, the high MOI of ABMM1 (MOI 10) effectively killed the host bacterial cells and reduced the fatality rate of bacterial infection in the zebrafish model. These findings indicate that ABMM1 can be an alternative treatment for A. baumannii infection., (© 2023. The Author(s).)

Importance: Same-day home recovery (SHR) is now the standard of care for many major surgical procedures and has the potential to become standard practice for benign foregut procedures (eg, hiatal hernia repair, fundoplication, and Heller myotomy)., Objective: To determine whether SHR for patients undergoing benign foregut surgery is feasible, safe, and effective., Design, Setting, and Participants: This prospective cohort study took place across 19 medical centers within an integrated health care system in northern California from January 2019 through September 2021. Participants included consecutive patients undergoing elective benign foregut surgery., Exposures: Standardized SHR program., Main Outcomes and Measures: The primary end point was the rate of SHR. The secondary end points were 7-day and 30-day rates of postoperative emergency department visits, hospital readmissions, and reoperations., Results: Of 1248 patients who underwent benign foregut surgery from January 2017 through September 2021, 558 were patients before implementation of the SHR program and 690 were patients postimplementation. The mean age of patients was 60 years, and 759 (59%) were female. The preimplementation SHR rate was 64 of 558 patients (11.5%) in 2018 and increased to 82 of 113 patients (72.6%) by 2021 (94/350 [26.9%] in 2019 and 112/227 [49.3%] in 2020; P < .001). There were no statistical differences in the 7-day and 30-day rates of postoperative emergency visits, hospital readmissions, and reoperations or 30-day mortality in the SHR vs non-SHR groups in the postimplementation era., Conclusions and Relevance: In this study, implementation of a regional SHR program among patients undergoing elective benign foregut surgery was feasible, safe, and effective. The changes in perioperative care require comprehensive patient education and full multidisciplinary support. An SHR program for benign foregut procedures has the potential to improve patient care and cost-effectiveness in care delivery.

Multidrug-resistant Acinetobacter baumannii (MDRAB) is a pathogen recognized as antimicrobial-resistant bacteria involved in healthcare-associated infections. Resistance to antibiotics has made alternative therapies necessary. Bacteriophage therapy is considered a potential solution to treat MDRAB. In this study, we isolated and characterized the phage vB&#95;AbaS&#95;TCUP2199 (TCUP2199), which can infect MDRAB. Morphological analysis revealed that TCUP2199 belongs to the Siphoviridae family. TCUP2199 has a wide host range, can adsorb rapidly (68.28% in 2 min), and has a burst size of 196 PFU/cell. At least 16 distinct structural proteins were visualized by SDS polyacrylamide gel electrophoresis. A stability test showed that TCUP2199 was stable at 37 °C and pH 7. Genome analysis of TCUP2199 showed that it consists of a double-stranded DNA genome of 79,572 bp with a G+C content of 40.39%, which contains 98 putative open reading frames, none of which is closely related to the bacteriophage genome sequence that was found in the public database. TCUP2199 shows similarity in genomic organization and putative packaging mechanism with Achromobacter phage JWF and Pseudoalteromonas phage KB12-38 based on protein BLAST and phylogenetic analysis. Because of those unique characteristics, we consider TCUP2199 to be a novel phage that is suitable for inclusion in a phage cocktail to treat A. baumannii infection.

Using bacteriophages (phages) as environmental sanitizers has been recognized as a potential alternative method to remove bacterial contamination in vitro; however, very few studies are available on the application of phages for infection control in hospitals. Here, we performed a 3-year prospective intervention study using aerosolized phage cocktails as biocontrol agents against carbapenem-resistant Acinetobacter baumannii (CRAB) infection in the hospital. When a CRAB-infected patient was identified in an intensive care unit (ICU), their surrounding environment was chosen for phage aerosol decontamination. Before decontamination, 501 clinical specimens from the patients were subjected to antibiotic resistance analysis and phage typing. The optimal phage cocktails were a combination of different phage families or were constructed by next-evolutionary phage typing with the highest score for the host lysis zone to prevent the development of environmental CRAB phage resistance. The phage infection percentage of the antibiotic-resistant A. baumannii strains was 97.1%, whereas the infection percentage in the antibiotic-susceptible strains was 79.3%. During the phage decontamination periods from 2017 to 2019, the percentage of carbapenem-resistant A. baumannii in test ICUs decreased significantly from 65.3% to 55%. The rate of new acquisitions of CRAB infection over the three years was 4.4 per 1000 patient-days, which was significantly lower than that in the control wards (8.9 per 1000 patient-days) where phage decontamination had never been performed. In conclusion, our results support the potential of phage cocktails to decrease CRAB infection rates, and the aerosol generation process may make this approach more comprehensive and time-saving., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: In 2016, Kaiser Permanente Northern California regionalized gastric cancer care, introducing a regional comprehensive multidisciplinary care team, standardizing staging and chemotherapy, and implementing laparoscopic gastrectomy and D2 lymphadenectomy for patients eligible for curative-intent surgery. This study evaluated the effect of regionalization on outcomes., Methods: The retrospective cohort study included gastric cancer cases diagnosed from January 2010 to May 2018. Information was obtained from the electronic medical record, cancer registry, state vital statistics, and chart review. Overall survival was compared in patients with all stages of disease, stage I-III disease, and curative-intent gastrectomy patients using annual inception cohorts. For the latter, the surgical approach and surgical outcomes were also compared., Results: Among 1,429 eligible patients with gastric cancer with all stages of disease, one third were treated after regionalization, 650 had stage I-III disease, and 394 underwent curative-intent surgery. Among surgical patients, neoadjuvant chemotherapy utilization increased from 35% to 66% ( P < .0001), laparoscopic gastrectomy increased from 18% to 92% ( P < .0001), and D2 lymphadenectomy increased from 2% to 80% ( P < .0001). Dissection of ≥ 15 lymph nodes increased from 61% to 95% ( P < .0001). Surgical complication rates did not appear to increase after regionalization. Length of hospitalization decreased from 7 to 3 days ( P < .001). Overall survival at 2 years was as follows: all stages, 32.8% pre and 37.3% post ( P = .20); stage I-III cases with or without surgery, 55.6% and 61.1%, respectively ( P = .25); and among surgery patients, 72.7% and 85.5%, respectively ( P < .03)., Conclusion: Regionalization of gastric cancer care within an integrated system allowed comprehensive multidisciplinary care, conversion to laparoscopic gastrectomy and D2 lymphadenectomy, increased overall survival among surgery patients, and no increase in surgical complications., Competing Interests: Stephen UongEmployment: The Permanente Medical Group IncResearch Funding: The Permanente Medical Group IncTravel, Accommodations, Expenses: The Permanente Medical Group Inc Sharon ShiragaEmployment: Kaiser PermanenteNo other potential conflicts of interest were reported.

Background: We present a novel approach for exiting coronavirus disease 2019 (COVID-19) lockdowns using a 'risk scorecard' to prioritize activities to resume whilst allowing safe reopening., Methods: We modelled cases generated in the community/week, incorporating parameters for social distancing, contact tracing and imported cases. We set thresholds for cases and analysed the effect of varying parameters. An online tool to facilitate country-specific use including the modification of parameters (https://sshsphdemos.shinyapps.io/covid&#95;riskbudget/) enables visualization of effects of parameter changes and trade-offs. Local outbreak investigation data from Singapore illustrate this., Results: Setting a threshold of 0.9 mean number of secondary cases arising from a case to keep R < 1, we showed that opening all activities excluding high-risk ones (e.g. nightclubs) allows cases to remain within threshold; while opening high-risk activities would exceed the threshold and result in escalating cases. An 80% reduction in imported cases per week (141 to 29) reduced steady-state cases by 30% (295 to 205). One-off surges in cases (due to superspreading) had no effect on the steady state if the R remains <1. Increasing the effectiveness of contact tracing (probability of a community case being isolated when infectious) by 33% (0.6 to 0.8) reduced cases by 22% (295 to 231). Cases grew exponentially if the product of the mean number of secondary cases arising from a case and (1-probability of case being isolated) was >1., Conclusions: Countries can utilize a 'risk scorecard' to balance relaxations for travel and domestic activity depending on factors that reduce disease impact, including hospital/ICU capacity, contact tracing, quarantine and vaccination. The tool enabled visualization of the combinations of imported cases and activity levels on the case numbers and the trade-offs required. For vaccination, a reduction factor should be applied both for likelihood of an infected case being present and a close contact getting infected., (© International Society of Travel Medicine 2021. Published by Oxford University Press.)

Wing shape variation has been shown to be useful for delineating forensically important fly species in two Diptera families: Calliphoridae and Sarcophagidae. Compared to DNA-based identification, the cost of geometric morphometric data acquisition and analysis is relatively much lower because the tools required are basic, and stable softwares are available. However, to date, an explicit demonstration of using wing geometric morphometric data for species identity prediction in these two families remains lacking. Here, geometric morphometric data from 19 homologous landmarks on the left wing of males from seven species of Calliphoridae (n = 55), and eight species of Sarcophagidae (n = 40) were obtained and processed using Generalized Procrustes Analysis. Allometric effect was removed by regressing centroid size (in log 10 ) against the Procrustes coordinates. Subsequently, principal component analysis of the allometry-adjusted Procrustes variables was done, with the first 15 principal components used to train a random forests model for species prediction. Using a real test sample consisting of 33 male fly specimens collected around a human corpse at a crime scene, the estimated percentage of concordance between species identities predicted using the random forests model and those inferred using DNA-based identification was about 80.6% (approximate 95% confidence interval = [68.9%, 92.2%]). In contrast, baseline concordance using naive majority class prediction was 36.4%. The results provide proof of concept that geometric morphometric data has good potential to complement morphological and DNA-based identification of blow flies and flesh flies in forensic work., (© 2021 American Academy of Forensic Sciences.)

There are limited studies on the association between systemic autoimmune rheumatic diseases (SARDs) and leptospirosis. Therefore, this study aims to identify the effects of leptospirosis on the risks of developing SARDs with a nationwide retrospective cohort study. Patients with leptospirosis who did not have a diagnosis of SARDs before the index date were enrolled from the Taiwan National Health Insurance Research Database between 2000 and 2010, as the leptospirosis cohort. For each patient with leptospirosis, one control without a history of leptospirosis and SARDs was randomly selected (non-leptospirosis cohort). Cox proportional hazards regression models were used to analyze the risk of SARDs according to sex, age, and comorbidities. Among the 23 million people in the cohort, 3,393 patients with leptospirosis (68.91% men, mean age 52.65 years) and 33,930 controls were followed for 18,778 and 232,999 person-years, respectively. The incidence of SARDs was higher in the leptospirosis cohort than in the non-leptospirosis cohort (1.38 vs 0.33 per 1000 person-years), with a hazard ratio (HR) of 4.42 (95% confidence interval [CI] = 2.82-6.92). The risk of developing SARDs was highest for leptospirosis patients aged ≥65 years (HR = 2.81% CI = 1.07-7.36) compared with patients aged ≤39 years. Patients with leptospirosis have a 4.42-fold higher risk of SARDs than that in the general population. Further research is warranted to investigate the mechanism underlying this association.

Background: Glycogen storage disease type III is an autosomal recessive disorder that is caused by deficiencies of the glycogen debranching enzyme. Mutations within the AGL gene have been found to be heterogeneous, with some common mutations being reported in certain populations. The mutation spectrum of AGL gene in the multi-ethnic Malaysian population is still unknown., Objective: The present study seeks to determine the mutation spectrum of the AGL gene in Malaysian population., Methods: A total of eleven patients (eight Malay, two Chinese and one Bajau) were investigated. Genomic DNA was extracted and subsequently the AGL gene was amplified using specific primers and sequenced. Mutations found were screened in 150 healthy control samples either by restriction enzyme digestion assay or TaqMan ® SNP Genotyping assay., Results: We identified six unreported mutations (c.1423+1G>T, c.2914&#95;2915delAA, c.3814&#95;3815delAG, c.4333T>G, c.4490G>A, c.4531&#95;4534delTGTC) along with three previously reported mutations (c.99C>T, c.1783C>T, c.2681+1G>A). One of the six unreported mutation causes abnormal splicing and results in retention of intron 12 of the mature transcript, while another is a termination read-through. One of the reported mutation c.2681+1G>A was recurrently found in the Malay patients (n = 7 alleles; 31.8%)., Conclusion: The mutation spectrum of the AGL gene in Malaysian patients has shown considerable heterogeneity, and all unreported mutations were absent in all 150 healthy control samples tested.

Background There is a lack of large comprehensive studies in developing countries on paediatric in-patient prescribing errors in different settings. Objectives To determine the characteristics of in-patient prescribing errors among paediatric patients. Setting General paediatric wards, neonatal intensive care units and paediatric intensive care units in government hospitals in Malaysia. Methods This is a cross-sectional multicentre study involving 17 participating hospitals. Drug charts were reviewed in each ward to identify the prescribing errors. All prescribing errors identified were further assessed for their potential clinical consequences, likely causes and contributing factors. Main outcome measures Incidence, types, potential clinical consequences, causes and contributing factors of the prescribing errors. Results The overall prescribing error rate was 9.2% out of 17,889 prescribed medications. There was no significant difference in the prescribing error rates between different types of hospitals or wards. The use of electronic prescribing had a higher prescribing error rate than manual prescribing (16.9 vs 8.2%, p < 0.05). Twenty eight (1.7%) prescribing errors were deemed to have serious potential clinical consequences and 2 (0.1%) were judged to be potentially fatal. Most of the errors were attributed to human factors, i.e. performance or knowledge deficit. The most common contributing factors were due to lack of supervision or of knowledge. Conclusions Although electronic prescribing may potentially improve safety, it may conversely cause prescribing errors due to suboptimal interfaces and cumbersome work processes. Junior doctors need specific training in paediatric prescribing and close supervision to reduce prescribing errors in paediatric in-patients.

Background: Brucea javanica (B. javanica) seeds, also known as "Melada pahit" in Indo-Malay region are traditionally used to treat diabetes. The objective of this study was to determine antidiabetic, antioxidant and anti-inflammatory effects of B. javanica seeds on nicotinamide (NA)-streptozotocin (STZ) induced type 2 diabetic (T2D) rats and to analyze its chemical composition that correlate with their pharmacological activities., Methods: A hydroethanolic extract of B. javanica seeds was fractionated with n-hexane, chloroform and ethyl acetate. An active fraction was selected after screening for its ability to inhibit α-glucosidase and glycogen phosphorylase α (GP-α). Isolation and characterization were carried out by using column chromatography, NMR and LCMS/MS. All isolates were assayed for inhibition of GP-α and α-glucosidase. Antidiabetic effect of active fraction was further evaluated in T2D rat model. Blood glucose and body weight were measured weekly. Serum insulin, lipid profile, renal function, liver glycogen and biomarkers of oxidative stress and inflammation were analyzed after 4-week treatment and compared with standard drug glibenclamide., Results: Ethyl acetate fraction (EAF) exerted good inhibitory potential for α-glucosidase and GP-α compared with other fractions. Chromatographic isolation of the EAF led to the identification of seven compounds: vanillic acid (1), bruceine D (2), bruceine E (3), parahydroxybenzoic acid (4), luteolin (5), protocatechuic acid (6), and gallic acid (7). Among them, Compound (5) was identified as the most potent inhibitor of GP-α and α-glucosidase and its GP-α inhibitory activity (IC 50  = 45.08 μM) was 10-fold higher than that of caffeine (IC 50  = 457.34 μM), and α-glucosidase inhibitory activity (IC 50  = 26.41 μM) was 5.5-fold higher than that of acarbose (IC 50  = 145.83 μM), respectively. Compounds (4), (6), and (7) inhibited GP-α activity in a concentration-dependent manner with IC 50 values of 357.88, 297.37, and 214.38 μM, and their inhibitory effect was higher than that of caffeine. These compounds exhibited weak potency on α-glucosidase compared with acarbose. Compounds (1), (2), and (3) showed no inhibition on both GP-α and α-glucosidase. In vivo study showed that EAF treatment significantly reduced blood glucose level, increased insulin and glycogen contents, decreased markers of oxidative stress and inflammation, and lipid levels in T2D rats compared with untreated group., Conclusions: The EAF has potential therapeutic value for the treatment of T2D via acting as GP-α and α-glucosidase inhibitors by improving hepatic glucose and carbohydrate metabolism, suppressing oxidative stress, and preventing inflammation in T2D rats. According to the results, the efficacy of EAF could be due to the presence of luteolin along with synergistic effect of multiple compounds such as parahydroxybenzoic acid, protocatechuic acid, and gallic acid in B. javanica seeds.

Introduction: Awareness for paediatric palliative care has resulted in the impetus for paediatrician-led palliative care services across Malaysia. However, there is paucity of local data on patients receiving hospital-based paediatric palliative care. We aim to review the clinical spectrum of patients referred to these services., Methods: An observational study of children aged between 0-18 years receiving palliative care at 13 hospitals between 1st January and 31st December 2014 was carried out., Results: There were 315 patients analysed, 90 (28.6%) and 46 (14.6%) were neonates and adolescents respectively. The main ICD-10 diagnostic categories for all patients were identified to be 'Congenital malformations, deformations and chromosomal abnormalities' 117 (37.1%), 'Diseases of nervous system' 76 (24.1%) and 'Neoplasms' 60 (19.0%). At referral 156 (50%) patients had holistic needs assessments. Patients with 'Diseases of nervous system' were assessed to have significantly more physical needs than the other two diagnostic categories. Majority of patients who knew of their diagnosis and prognosis were those with malignancy. Over a fifth of referrals were at their terminal admission. Of 144 who died, 111 (77.1%) had advanced care plans. There was bereavement follow-up in 98 (68.1%) patients., Conclusion: Patients referred for palliative care have varied diagnoses and needs. To ensure all paediatricians are competent to deliver quality care to all children, further education and training initiatives is imperative.

The Clinical Practice Guidelines on Management of Neonatal Jaundice 2003 was updated by a multidisciplinary development group and approved by the Ministry of Health Malaysia in 2014. A systematic review of 13 clinical questions was conducted using evidence retrieved mainly from Medline and Cochrane databases. Critical appraisal was done using the Critical Appraisal Skills Programme checklist. Recommendations were formulated based on the accepted 103 evidences and tailored to local setting as stated below. Neonatal jaundice (NNJ) is a common condition seen in primary care. Multiple risk factors contribute to severe NNJ, which if untreated can lead to adverse neurological outcomes. Visual assessment, transcutaneous bilirubinometer (TcB) and total serum bilirubin (TSB) are the methods used for the detection of NNJ. Phototherapy remains the mainstay of the treatment. Babies with severe NNJ should be followed-up to detect and manage sequelae. Strategies to prevent severe NNJ include health education, identification of risk factors, proper assessment and early referral.

N-carbamylglutamate (NCG) has been used in combination with ammonia scavengers (sodium benzoate, sodium phenylbutyrate) and dialysis to treat hyperammonaemia in methylmalonic aciduria (MMA). The sole use of NCG for acute neonatal hyperammonaemia secondary to MMA is demonstrated in a neonate presenting at day 9 with encephalopathy, severe metabolic acidosis, hyperammonaemia (1,089 μmol/l), ketonuria and urinary methylmalonic acids. Emergency treatment included discontinuing protein feeds, providing high calories, carnitine and hydroxocobalamin. NCG 200 mg given at 0 and 90 min decreased plasma ammonia dramatically from 1,089 to 567 µmol/l at 90 min and further to 236 µmol/l at 6 h. Normalisation of ammonia was achieved at 12 h with two further doses of NCG 100 mg. This allowed for early re-institution of feeds at 14 h, followed by metabolic stabilization and recovery. Due to the effectiveness of NCG in this case, the use of the more invasive conventional ammonia-lowering therapeutic options could be avoided., (© 2016 S. Karger AG, Basel.)

Background: Methicillin-resistant Staphylococcus aureus (MRSA) has been increasingly causing skin and soft tissue infections (SSTIs). Only limited studies have made comparisons between incision and drainage (I&D) alone and I&D with adjunctive antibiotic therapy for treatment effects, and most of the studies were conducted before the emergence of MRSA. This study was to evaluate whether antibiotics provide added benefit to I&D alone for purulent MRSA SSTIs., Methods: This retrospective study collected data on SSTI patients, including patient demographics, treatment strategies, antibiotic susceptibilities of the infecting MRSA isolates, and clinical outcomes over the course of 24 months., Results: Antimicrobial drug susceptibility rate were 100% for vancomycin, teicoplanin, and linezolid. Among the 211 patients, 7.6% were treated solely with I&D (Group A), 62.6% were treated via I&D with adjunctive antibiotic (Group B), and 29.8% patients received only antibiotics (Group C). The cure rate was highest in Group A (93.8%), followed by Group B (90.9%) and Group C (77.8%). Combining Group B and Group C, patients who were treated appropriately demonstrated a higher cute rate (91.3% vs. 75.4%, p = 0.005). Multivariate analysis showed that Group B was more likely to be successfully treated compared to Group C (odds ratio = 2.51, 95% confidence interval = 1.01-6.25, p = 0.047), whereas no difference between Group A and Group B was found (odds ratio = 2.09, 95% confidence interval = 0.20-22.34, p = 0.542, data not shown)., Conclusion: Surgical intervention is the definitive therapy for purulent SSTIs. Adjunctive antibiotic therapy increased the cure rate and appropriateness of prescription is influential., (Copyright © 2014. Published by Elsevier B.V.)

The class IIa histone deacetylases (HDACs) act as transcriptional repressors by altering chromatin structure through histone deacetylation. This family of enzymes regulates muscle development and phenotype, through regulation of muscle-specific genes including myogenin and MyoD (MYOD1). More recently, class IIa HDACs have been implicated in regulation of genes involved in glucose metabolism. However, the effects of HDAC5 on glucose metabolism and insulin action have not been directly assessed. Knockdown of HDAC5 in human primary muscle cells increased glucose uptake and was associated with increased GLUT4 (SLC2A4) expression and promoter activity but was associated with reduced GLUT1 (SLC2A1) expression. There was no change in PGC-1α (PPARGC1A) expression. The effects of HDAC5 knockdown on glucose metabolism were not due to alterations in the initiation of differentiation, as knockdown of HDAC5 after the onset of differentiation also resulted in increased glucose uptake and insulin-stimulated glycogen synthesis. These data show that inhibition of HDAC5 enhances metabolism and insulin action in muscle cells. As these processes in muscle are dysregulated in metabolic disease, HDAC inhibition could be an effective therapeutic strategy to improve muscle metabolism in these diseases. Therefore, we also examined the effects of the pan HDAC inhibitor, Scriptaid, on muscle cell metabolism. In myotubes, Scriptaid increased histone 3 acetylation, GLUT4 expression, glucose uptake and both oxidative and non-oxidative metabolic flux. Together, these data suggest that HDAC5 regulates muscle glucose metabolism and insulin action and that HDAC inhibitors can be used to modulate these parameters in muscle cells.

Adiponectin is one of the most bioactive substances secreted by adipose tissue and is involved in the protection against metabolic syndrome, artherosclerosis and type II diabetes. Research into the use of adiponectin as a promising drug for metabolic syndromes requires production of this hormone in high quantities considering its molecular isoforms. The objective of this study is to produce recombinant human adiponectin by Pichia pastoris (P-ADP) as a cheap and convenient eukaryotic expression system for potential application in pharmaceutical therapy. For comparison, adiponectin was also expressed using the Escherichia coli (E-ADP) expression system. Adiponectin was constructed by overlap-extension PCR, and cloned in standard cloning vector and hosts. Recombinant expression vectors were cloned in the P. pastoris and E. coli host strains, respectively. SDS-PAGE and western blotting were used to detect and analyse expressed recombinant protein in both systems. Adiponectin was purified by affinity chromatography and quantified using the Bradford Assay. The results of this study indicated that P-ADP quantity (0.111 mg/mL) was higher than that of E-ADP (0.04 mg/mL) and both were produced in soluble form. However, P-ADP was able to form high molecular weights of adiponectin molecules, whilst E-ADP was not able to form isoforms higher than trimer. In addition, P-ADP was more active in lowering blood glucose compared with E-ADP. The two types of proteins were equally efficient and significantly decreased blood triglyceride and increased high density lipoprotein. We conclude that P. pastoris is able to produce high quantity of bioactive adiponectin for potential use in treatment of metabolic syndromes.

Background: Primary intestinal lymphoma in the setting of inflammatory bowel disease (IBD) is uncommon and may be associated with immune suppressive therapy. We report clinical features and outcomes in patients with both conditions prior to use of biologic therapy., Methods: All patients with primary intestinal lymphoma and IBD at our institution from 1960-2000 were retrospectively identified. Data reported are frequency (proportion) or median (interquartile range). Kaplan-Meier analysis was performed., Results: Fifteen patients were identified: 14 (93%) were male, 10 (66%) had Crohn's disease. Median age at diagnosis of IBD and lymphoma was 30 (22-51) and 47 (28-68) years, respectively, with bloody diarrhea the most common presenting symptom for each diagnosis. Lymphoma location was colorectal in nine (60%), small bowel in four (27%), and one (6.25%) each: stomach, duodenum, and ileal pouch. Treatments were surgery plus chemotherapy (n = 6), surgery alone (n = 3), chemotherapy alone (n = 2), chemotherapy and radiation (n = 1), surgery and radiation (n = 1); two patients died before treatment. Most patients (n = 11, 73%) were Ann Arbor stages I or II. Large cell B-type histology was most common (n = 9, 60%). Three patients died within 30 days of lymphoma diagnosis. Survival free of death from lymphoma at 1- and 5-years was 78% and 63%, respectively, and was associated with advanced lymphoma stage (P = 0.004)., Conclusions: Diagnosis and treatment of primary intestinal lymphoma in patients with IBD can be challenging and requires a high index of suspicion. Optimal survival requires multimodality therapy., (Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.)