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  1. Schaefer B, Bartosova M, Macher-Goeppinger S, Sallay P, Vörös P, Ranchin B, et al.
    Kidney Int, 2018 08;94(2):419-429.
    PMID: 29776755 DOI: 10.1016/j.kint.2018.02.022
    The effect of peritoneal dialysates with low-glucose degradation products on peritoneal membrane morphology is largely unknown, with functional relevancy predominantly derived from experimental studies. To investigate this, we performed automated quantitative histomorphometry and molecular analyses on 256 standardized peritoneal and 172 omental specimens from 56 children with normal renal function, 90 children with end-stage kidney disease at time of catheter insertion, and 82 children undergoing peritoneal dialysis using dialysates with low-glucose degradation products. Follow-up biopsies were obtained from 24 children after a median peritoneal dialysis of 13 months. Prior to dialysis, mild parietal peritoneal inflammation, epithelial-mesenchymal transition and vasculopathy were present. After up to six and 12 months of peritoneal dialysis, blood microvessel density was 110 and 93% higher, endothelial surface area per peritoneal volume 137 and 95% greater, and submesothelial thickness 23 and 58% greater, respectively. Subsequent peritoneal changes were less pronounced. Mesothelial cell coverage was lower and vasculopathy advanced, whereas lymphatic vessel density was unchanged. Morphological changes were accompanied by early fibroblast activation, leukocyte and macrophage infiltration, diffuse podoplanin presence, epithelial mesenchymal transdifferentiation, and by increased proangiogenic and profibrotic cytokine abundance. These transformative changes were confirmed by intraindividual comparisons. Peritoneal microvascular density correlated with peritoneal small-molecular transport function by uni- and multivariate analysis. Thus, in children on peritoneal dialysis neutral pH dialysates containing low-glucose degradation products induce early peritoneal inflammation, fibroblast activation, epithelial-mesenchymal transition and marked angiogenesis, which determines the PD membrane transport function.
    Matched MeSH terms: Child, Preschool
  2. Chin MC, Sivasampu S, Khoo EM
    PLoS One, 2017;12(6):e0180443.
    PMID: 28662193 DOI: 10.1371/journal.pone.0180443
    OBJECTIVE: Use of oral short-acting beta 2-agonist (SABA) persists in non-resource poor countries despite concerns for its lower efficacy and safety. Utilisation and reasons for such use is needed to support the effort to discourage the use of oral SABA in asthma. This study examined the frequency of oral short-acting Beta 2-agonist (SABA) usage in the management of asthma in primary care and determined correlates of its usage.
    METHODS: Data used were from the 2014 National Medical Care Survey in Malaysia, a nationally representative survey of primary care encounters (weighted n = 325818). Using methods of analysis of data for complex surveys, we determined the frequency of asthma diagnosis in primary care and the rate of asthma medication prescription, which includes oral SABA. Multivariate logistic regression models were built to assess associations with the prescription of oral SABA.
    RESULTS: A weighted estimate of 9241 encounters presented to primary care with asthma in 2014. The mean age of the patients was 39.1 years. The rate of oral SABA, oral steroids, inhaled SABA and inhaled corticosteroids prescriptions were 33, 33, 50 and 23 per 100 asthma encounters, respectively. It was most commonly used in patients with the age ranged between 20 to less than 40 years. Logistic regression models showed that there was a higher odds of oral SABA usage in the presence of respiratory infection, prescription of oral corticosteroids and in the private sector.
    CONCLUSION: Oral SABA use in asthma is found to be common in a non- resource poor setting and its use could be attributed to a preference for oral medicines along undesirable clinical practices within a fragmented health system.
    Matched MeSH terms: Child, Preschool
  3. Väisänen E, Paloniemi M, Kuisma I, Lithovius V, Kumar A, Franssila R, et al.
    Sci Rep, 2016 12 14;6:39267.
    PMID: 27966636 DOI: 10.1038/srep39267
    Two human parvoviruses were recently discovered by metagenomics in Africa, bufavirus (BuV) in 2012 and tusavirus (TuV) in 2014. These viruses have been studied exclusively by PCR in stool and detected only in patients with diarrhoea, although at low prevalence. Three genotypes of BuV have been identified. We detected, by in-house EIA, BuV1-3 IgG antibodies in 7/228 children (3.1%) and 10/180 adults (5.6%), whereas TuV IgG was found in one child (0.4%). All children and 91% of the adults were Finnish, yet interestingly 3/6 adults of Indian origin were BuV-IgG positive. By competition EIA, no cross-reactivity between the BuVs was detected, indicating that the BuV genotypes represent distinct serotypes. Furthermore, we analysed by BuV qPCR stool and nasal swab samples from 955 children with gastroenteritis, respiratory illness, or both, and found BuV DNA in three stools (0.3%) and for the first time in a nasal swab (0.1%). This is the first study documenting the presence of BuV and TuV antibodies in humans. Although the seroprevalences of both viruses were low in Finland, our results indicate that BuV infections might be widespread in Asia. The BuV-specific humoral immune responses appeared to be strong and long-lasting, pointing to systemic infection in humans.
    Matched MeSH terms: Child, Preschool
  4. Gan CS, Wong JJ, Samransamruajkit R, Chuah SL, Chor YK, Qian S, et al.
    Pediatr Crit Care Med, 2018 10;19(10):e504-e513.
    PMID: 30036234 DOI: 10.1097/PCC.0000000000001667
    OBJECTIVES: Extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome are poorly described in the literature. We aimed to describe and compare the epidemiology, risk factors for mortality, and outcomes in extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome.

    DESIGN: This is a secondary analysis of a multicenter, retrospective, cohort study. Data on epidemiology, ventilation, therapies, and outcomes were collected and analyzed. Patients were classified into two mutually exclusive groups (extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome) based on etiologies. Primary outcome was PICU mortality. Cox proportional hazard regression was used to identify risk factors for mortality.

    SETTING: Ten multidisciplinary PICUs in Asia.

    PATIENTS: Mechanically ventilated children meeting the Pediatric Acute Lung Injury Consensus Conference criteria for pediatric acute respiratory distress syndrome between 2009 and 2015.

    INTERVENTIONS: None.

    MEASUREMENTS AND MAIN RESULTS: Forty-one of 307 patients (13.4%) and 266 of 307 patients (86.6%) were classified into extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome groups, respectively. The most common causes for extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome were sepsis (82.9%) and pneumonia (91.7%), respectively. Children with extrapulmonary pediatric acute respiratory distress syndrome were older, had higher admission severity scores, and had a greater proportion of organ dysfunction compared with pulmonary pediatric acute respiratory distress syndrome group. Patients in the extrapulmonary pediatric acute respiratory distress syndrome group had higher mortality (48.8% vs 24.8%; p = 0.002) and reduced ventilator-free days (median 2.0 d [interquartile range 0.0-18.0 d] vs 19.0 d [0.5-24.0 d]; p = 0.001) compared with the pulmonary pediatric acute respiratory distress syndrome group. After adjusting for site, severity of illness, comorbidities, multiple organ dysfunction, and severity of acute respiratory distress syndrome, extrapulmonary pediatric acute respiratory distress syndrome etiology was not associated with mortality (adjusted hazard ratio, 1.56 [95% CI, 0.90-2.71]).

    CONCLUSIONS: Patients with extrapulmonary pediatric acute respiratory distress syndrome were sicker and had poorer clinical outcomes. However, after adjusting for confounders, it was not an independent risk factor for mortality.

    Matched MeSH terms: Child, Preschool
  5. Ashikin A, Al-Mekhlafi HM, Moktar N, Anuar TS
    Parasitol Int, 2017 Apr;66(2):163-165.
    PMID: 28115231 DOI: 10.1016/j.parint.2017.01.013
    Most studies of opportunistic infections focus on immunocompromised patients. However, there is a lack of information on microsporidiosis in healthy people (immunocompetent) worldwide. This study aimed to detect and identify microsporidia species in immunocompetent Orang Asli living in Pahang, Malaysia. Orang Asli is a collective term for a group of indigenous people that usually reside in the interior regions of Peninsular Malaysia. They comprise about 0.7% of the total population in Malaysia and 76% of them lived below the poverty line i.e., poor housing conditions with the lack of access to safe drinking water and adequate sanitation, contaminated environment, high illiteracy rate and unhygienic practices by these people. Stool samples were collected from 209 Orang Asli and analyzed for detecting the presence of Enterocytozoon bieneusi and Encephalitozoon intestinalis by polymerase chain reaction assay targeting small subunit ribosomal RNA gene. E. bieneusi was detected in 8 individuals (3.83%). This infection was commonly found in males than females (5.2% vs. 2.7%). All infected Orang Asli were adults, with a mean age of 44years. Diarrhea and other gastrointestinal symptoms were reported in one case (12.5%) among individuals infected with this species. These findings clearly show that exposure to E. bieneusi may actually be common than reported. The accurate detection and identification of microsporidian species by molecular technique will improve therapy, clinical manifestations and prognosis of this infection, as no antiparasitic therapy has been approved for E. bieneusi. It is hoped that these findings will allow the formulation of better health management and disease prevention advisories, and improvement in the standards of health in similar communities.
    Matched MeSH terms: Child, Preschool
  6. Rajoo Y, Ambu S, Lim YA, Rajoo K, Tey SC, Lu CW, et al.
    PLoS One, 2017;12(1):e0170174.
    PMID: 28095446 DOI: 10.1371/journal.pone.0170174
    Intestinal parasitic infections (IPIs) have been recognized as one of the most significant causes of illness among disadvantaged communities. Many studies have been conducted on the prevalence of IPIs in Malaysia. However, these studies mostly focused on the indigenous groups in Peninsular Malaysia. The present study was conducted to provide the current baseline data on prevalence of IPIs, anaemia, malnutrition and associated risk factors among the indigenous communities in Sarawak, situation at northwest Borneo island of Malaysia. A cross sectional study was conducted among the longhouses communities. Stool samples were obtained and examined for the presence of IPIs using microscopy technique. Haemoglobin measurement was done using a portable haemoglobin analyzer. Malnutrition (i.e., stunting, underweight and wasting) was assessed using the WHO Anthro software. Statistical analysis was carried out using SPSS software. A total of 341participants took part in this study. The overall prevalence of IPIs was 57.5%. Multivariate analysis indicated that the absence of toilets (OR = 1.6; 95% CI = 1.1-2.7; p = 0.002) and close contact with animals (OR = 1.8; 95% CI = 1.3-2.9; p = 0.027) as significant predictors for IPIs. The incidence of anaemia was 36.4%. The incidence of underweight, wasting and stunting were 22.2%, 5.6% and 35.4%, respectively. Multivariate analysis demonstrated that low level of parental education attainment (OR = 1.9; 95% CI = 1.2-3.0; p = 0.006) was identified as significant predictor for anaemia. The incidence of wasting was significantly associated with mild anaemia (OR = 1.2; 95% CI = 0.9-1.7; p = 0.024). Low household income was identified as significant predictor for stunting (OR = 2.1; 95% CI = 9.8-22.2; p = 0.001) and underweight (OR = 1.9; 95% CI = 5.6-18.7; p = 0.037), respectively. Essentially, the present study highlighted that intestinal parasitic infections, anaemia and malnutrition are still prevalent among rural indigenous community in Sarawak. Improvement of socioeconomic status, periodic mass deworming, iron supplementation and health education program should be included in the control and prevention of public health strategies.
    Matched MeSH terms: Child, Preschool
  7. Mohtar S, Hui TWC, Irwin MG
    Paediatr Anaesth, 2018 11;28(11):1035-1042.
    PMID: 30281181 DOI: 10.1111/pan.13502
    BACKGROUND: Video-assisted thoracoscopic surgery has dramatically increased over the last decade because of both medical and cosmetic benefits. Anesthesia for video-assisted thoracoscopic surgery in small children is more challenging compared to adults due to the considerable problems posed by small airway dimensions and ventilation. The optimal technique for one-lung ventilation has yet to be established and the use of remifentanil infusion in this setting is not well described.

    AIMS: This study investigated the use of extraluminal bronchial blocker placement for one-lung ventilation and the effect of infusion of remifentanil in infants and small children undergoing video-assisted thoracoscopic surgery.

    METHODS: We retrospectively reviewed the technique of one-lung ventilation and the hemodynamic effects of remifentanil infusion in 31 small children during elective video-assisted thoracoscopic surgery for congenital lung lesions under anesthesia with sevoflurane or isoflurane, oxygen, and air. Patients' heart rate, blood pressure, and endtidal carbon dioxide at baseline (after induction of anesthesia), immediately after one-lung ventilation, during carbon dioxide insufflation, and at the end of one-lung ventilation were extracted from the database and analyzed. The use of vasopressors or dexmedetomidine was also recorded and analyzed.

    RESULTS: Extraluminal placement of a bronchial blocker alongside the tracheal tube was successfully performed in 90.3% of cases (28 patients) without any serious complications or arterial oxygen desaturation. There was no significant rise in blood pressure or heart rate even with the rise of endtidal carbon dioxide concentration during video-assisted thoracoscopic surgery. In 58% of patients (18 patients), phenylephrine was administered to maintain the blood pressure within 20% of the baseline value. There was no significant change in the heart rate of all patients at each time point.

    CONCLUSION: One-lung ventilation with an extraluminal parallel blocker was used effectively in this series of young children undergoing thoracoscopic excision of congenital pulmonary lesions. Remifentanil infusion attenuated surgical stress effectively in infants and small children undergoing video-assisted thoracoscopic surgery.

    Matched MeSH terms: Child, Preschool
  8. Fieldhouse JK, Toh TH, Lim WH, Ting J, Ha SJ, Hii KC, et al.
    PLoS One, 2018;13(8):e0202147.
    PMID: 30110367 DOI: 10.1371/journal.pone.0202147
    BACKGROUND: Respiratory syncytial virus (RSV) and parainfluenza virus (PIV) are frequent causes of pneumonia and death among children at Sibu and Kapit Hospitals in Sarawak, Malaysia.

    OBJECTIVES: To determine the prevalence and risk factors for RSV subtypes A and B and PIV types 1-4 among patients hospitalized with pneumonia.

    METHODS: In a cross-sectional, pilot study nasopharyngeal swabs were studied with real-time reverse transcription polymerase chain reaction assays. Concurrently, we helped Sibu and Kapit Hospitals adapt their first molecular diagnostics for RSV and PIV.

    RESULTS: Of 129 specimens collected (June to July 2017), 39 tested positive for RSV-A (30.2%), two were positive for RSV B (1.6%), one was positive for PIV-3 (0.8%) and one was positive for PIV-4 (0.8%). No samples were positive for PIV-1 or PIV-2. Of the 39 RSV-A positive specimens, 46.2% were collected from children under one year of age and only 5.1% were from patients over the age of 18. A multivariable analysis found the odds of children <1 year of age testing positive for RSV-A were 32.7 (95% CI: 3.9, 276.2) times larger than >18 years of age, and the odds of patients hospitalized at Kapit Hospital testing positive for RSV-A were 3.2 (95% CI: 1.3, 7.8) times larger than patients hospitalized at Sibu Hospital.

    CONCLUSION: This study found an unusually high prevalence of RSV-A among pneumonia patients admitted to the two hospitals. Subsequently, Sibu Hospital adapted the molecular assays with the goal of providing more directed care for such pneumonia patients.

    Matched MeSH terms: Child, Preschool
  9. Harun SN, Wainwright CE, Grimwood K, Hennig S, Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) study group
    Thorax, 2019 02;74(2):125-131.
    PMID: 30275132 DOI: 10.1136/thoraxjnl-2018-211550
    BACKGROUND: The impact of Aspergillus on lung disease in young children with cystic fibrosis is uncertain.
    AIMS: To determine if positive respiratory cultures of Aspergillus species are associated with: (1) increased structural lung injury at age 5 years; (2) accelerated lung function decline between ages 5 years and 14 years and (3) to identify explanatory variables.
    METHODS: A cross-sectional analysis of association between Aspergillus positive bronchoalveolar lavage (BAL) cultures and chest high-resolution CT (HRCT) scan findings at age 5 years in subjects from the Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) study was performed. A non-linear mixed-effects disease progression model was developed using FEV1% predicted measurements at age 5 years from the ACFBAL study and at ages 6-14 years for these subjects from the Australian Cystic Fibrosis Data Registry.
    RESULTS: Positive Aspergillus BAL cultures at age 5 years were significantly associated with increased HRCT scores for air trapping (OR 5.53, 95% CI 2.35 to 10.82). However, positive Aspergillus cultures were not associated with either FEV1% predicted at age 5 years or FEV1% predicted by age following adjustment for body mass index z-score and hospitalisation secondary to pulmonary exacerbations. Lung function demonstrated a non-linear decline in this population.
    CONCLUSION: In children with cystic fibrosis, positive Aspergillus BAL cultures at age 5 years were associated contemporaneously with air trapping but not bronchiectasis. However, no association was observed between positive Aspergillus BAL cultures on FEV1% predicted at age 5 years or with lung function decline between ages 5 years and 14 years.
    Matched MeSH terms: Child, Preschool
  10. Tomashek KM, Wills B, See Lum LC, Thomas L, Durbin A, Leo YS, et al.
    PLoS Negl Trop Dis, 2018 10;12(10):e0006497.
    PMID: 30286085 DOI: 10.1371/journal.pntd.0006497
    Dengue is a major public health problem worldwide. Although several drug candidates have been evaluated in randomized controlled trials, none has been effective and at present, early recognition of severe dengue and timely supportive care are used to reduce mortality. While the first dengue vaccine was recently licensed, and several other candidates are in late stage clinical trials, future decisions regarding widespread deployment of vaccines and/or therapeutics will require evidence of product safety, efficacy and effectiveness. Standard, quantifiable clinical endpoints are needed to ensure reproducibility and comparability of research findings. To address this need, we established a working group of dengue researchers and public health specialists to develop standardized endpoints and work towards consensus opinion on those endpoints. After discussion at two working group meetings and presentations at international conferences, a Delphi methodology-based query was used to finalize and operationalize the clinical endpoints. Participants were asked to select the best endpoints from proposed definitions or offer revised/new definitions, and to indicate whether contributing items should be designated as optional or required. After the third round of inquiry, 70% or greater agreement was reached on moderate and severe plasma leakage, moderate and severe bleeding, acute hepatitis and acute liver failure, and moderate and severe neurologic disease. There was less agreement regarding moderate and severe thrombocytopenia and moderate and severe myocarditis. Notably, 68% of participants agreed that a 50,000 to 20,000 mm3 platelet range be used to define moderate thrombocytopenia; however, they remained divided on whether a rapid decreasing trend or one platelet count should be case defining. While at least 70% agreement was reached on most endpoints, the process identified areas for further evaluation and standardization within the context of ongoing clinical studies. These endpoints can be used to harmonize data collection and improve comparability between dengue clinical trials.
    Matched MeSH terms: Child, Preschool
  11. Sultan S, Irfan SM, Zaidi SM
    Med J Malaysia, 2018 08;73(4):185-189.
    PMID: 30121679
    BACKGROUND: It is being increasingly recognised that thalassemia major patients, like intermedia, have increased propensity for thromboembolism. Deficiency of natural anticoagulants is more recently defined finding contributing to the hypercoagulable state. The aim this study is to determine natural anticoagulants levels and their correlation with maternal characteristics, haematological and biochemical markers.

    METHODS: This is a prospective case-control study. We registered 80 patients and 60 healthy controls from Jan 2009 to Dec 2013. Complete blood counts, prothrombin time, activated partial thromboplastin time, protein C, protein S, antithrombin, serum ferritin, liver enzymes; HbsAg and Anti- HCV were evaluated.

    RESULT: There were 42 males and 38 females with mean age of 12.30±5.50 years. The mean protein C, protein S and antithrombin in patients and control were 58.25±22.5 versus 110.67±22.60, 67.90±19.58 versus 98.70±21.54 and 89.73±18.09 versus 104.0±10.98 (p<0.001) respectively. Protein C was predominantly deficient in 65% followed by protein S and antithrombin in 35% and 20% respectively. Protein C deficiency divulged positive correlation with protein S deficiency (p = 0.035) and antithrombin deficiency with hemoglobin of ≤8gm% (p<0.0025). No significant correlation of prothrombotic markers was established with maternal characteristics, hepatic dysfunction, hepatitis and serum ferritin.

    CONCLUSION: Substantial decrement in prothrombotic markers, primarily protein C, may be implicated in elevated thrombosis; however follow-up data is required to establish definitive thromboembolic events.

    Matched MeSH terms: Child, Preschool
  12. Xi B, Zong X, Kelishadi R, Litwin M, Hong YM, Poh BK, et al.
    J Clin Endocrinol Metab, 2020 04 01;105(4).
    PMID: 31723976 DOI: 10.1210/clinem/dgz195
    CONTEXT: No universal waist circumference (WC) percentile cutoffs used have been proposed for screening central obesity in children and adolescents.

    OBJECTIVE: To develop international WC percentile cutoffs for children and adolescents with normal weight based on data from 8 countries in different global regions and to examine the relation with cardiovascular risk.

    DESIGN AND SETTING: We used pooled data on WC in 113,453 children and adolescents (males 50.2%) aged 4 to 20 years from 8 countries in different regions (Bulgaria, China, Iran, Korea, Malaysia, Poland, Seychelles, and Switzerland). We calculated WC percentile cutoffs in samples including or excluding children with obesity, overweight, or underweight. WC percentiles were generated using the general additive model for location, scale, and shape (GAMLSS). We also estimated the predictive power of the WC 90th percentile cutoffs to predict cardiovascular risk using receiver operator characteristics curve analysis based on data from 3 countries that had available data (China, Iran, and Korea). We also examined which WC percentiles linked with WC cutoffs for central obesity in adults (at age of 18 years).

    MAIN OUTCOME MEASURE: WC measured based on recommendation by the World Health Organization.

    RESULTS: We validated the performance of the age- and sex-specific 90th percentile WC cutoffs calculated in children and adolescents (6-18 years of age) with normal weight (excluding youth with obesity, overweight, or underweight) by linking the percentile with cardiovascular risk (area under the curve [AUC]: 0.69 for boys; 0.63 for girls). In addition, WC percentile among normal weight children linked relatively well with established WC cutoffs for central obesity in adults (eg, AUC in US adolescents: 0.71 for boys; 0.68 for girls).

    CONCLUSION: The international WC cutoffs developed in this study could be useful to screen central obesity in children and adolescents aged 6 to 18 years and allow direct comparison of WC distributions between populations and over time.

    Matched MeSH terms: Child, Preschool
  13. Gil Cuesta J, van Loenhout JAF, de Lara Banquesio ML, Mustaffa M, Guha-Sapir D
    Disaster Med Public Health Prep, 2020 02;14(1):34-38.
    PMID: 31679549 DOI: 10.1017/dmp.2019.99
    INTRODUCTION AND OBJECTIVES: Typhoon Haiyan partially destroyed the Ormoc District Hospital in the Philippines. A field hospital was established to replace its outpatient department for 5 weeks. We investigated the reasons for medical consultation in the field hospital.

    METHODS: We described the consultations by sex, age, week, and diagnosis according to the Surveillance in Post-Extreme Emergencies and Disasters system. We compared the number and proportion of upper respiratory tract infections (URTIs) with a control season in 2014.

    RESULTS: We included 6785 consultations, 55.9% from women. The majority of consultations were communicable diseases (88.2%) followed by noncommunicable (7.1%) and injuries (5.6%). Males suffered more often from injuries than women (66.0% vs 34.0%). Consultations due to injuries decreased from 10.0% in the first to 2.9% in the last week. The most frequent diagnosis over the study period was acute respiratory infections (ARIs) (73.1%), of which 83.0% were children. The number of daily URTIs was higher than in a similar 2014 period.

    CONCLUSIONS: ARI was the most prevalent diagnosis. We recommend ARI treatments being fully accessible after such a disaster. During the first week, injury prevention should focus on adult men. Studies after natural disasters should include control periods to better understand disease distribution, ultimately improving the prioritization in disasters.

    Matched MeSH terms: Child, Preschool
  14. Haque N, Khan IM, Abu Kasim NH
    Cytokine, 2019 08;120:144-154.
    PMID: 31071675 DOI: 10.1016/j.cyto.2019.04.018
    The immunomodulatory properties of mesenchymal stem cells (MSCs) from autologous and allogeneic sources are useful in stimulating tissue regeneration and repair. To obtain a high number of MSCs for transplantation requires extensive in vitro expansion with culture media supplements that can cause xeno-contamination of cells potentially compromising function and clinical outcomes. In this study stem cells from human extracted deciduous teeth (SHED) were cultured in Knockout™ DMEM supplemented with either pooled human serum (pHS) or foetal bovine serum (FBS) to compare their suitability in maintaining immunomodulatory properties of cells during in vitro expansion. No significant difference in cell survival of SHED grown in pHS (pHS-SHED) or FBS (FBS-SHED) was observed when co-cultured with complement, monocytes or lymphocytes. However, significant changes in the expression of sixteen paracrine factors involved in immunomodulation were observed in the supernatants of FBS-SHED co-cultures with monocytes or lymphocytes compared to that in pHS-SHEDs after both 24 and 120 h of incubation. Further analysis of changing protein levels of paracrine factors in co-cultures using biological pathway analysis software predicted upregulation of functions associated with immunogenicity in FBS-SHED and lymphocyte co-cultures compared to pHS-SHED co-cultures. Pathway analysis also predicted significant stimulation of HMGB1 and TREM1 signalling pathways in FBS-SHED co-cultures indicating activation of immune cells and inflammation. Though FBS supplementation does not impact survival of SHED, our combinatorial biological pathway analysis supports the idea that in vitro expansion of SHEDs in pHS provides optimal conditions to minimise xeno-contamination and inflammation and maintain their immunomodulatory properties.
    Matched MeSH terms: Child, Preschool
  15. Cohen C, Moreira ED, Nañez H, Nachiappan JP, Arvinder-Singh HS, Huoi C, et al.
    Vaccine, 2019 03 22;37(13):1868-1875.
    PMID: 30826144 DOI: 10.1016/j.vaccine.2019.01.087
    BACKGROUND: The background incidence of viscerotropic- (VLD) and neurotropic-like disease (NLD) unrelated to immunization in dengue-endemic countries is currently unknown.

    METHODS: This retrospective population-based analysis estimated crude and standardized incidences of VLD and NLD in twelve hospitals in Brazil (n = 3), Mexico (n = 3), and Malaysia (n = 6) over a 1-year period before the introduction of the tetravalent dengue vaccine. Catchment areas were estimated using publicly available population census information and administrative data. The denominator population for incidence rates was calculated, and sensitivity analyses assessed the impact of important assumptions.

    RESULTS: Total cases adjudicated as definite VLD were 5, 57, and 56 in Brazil, Mexico, and Malaysia, respectively. Total cases adjudicated as definite NLD were 103, 29, and 26 in Brazil, Mexico, and Malaysia, respectively. Crude incidence rates of cases adjudicated as definite VLD in Brazil, Mexico, and Malaysia were 1.17, 2.60, and 1.48 per 100,000 person-years, respectively. Crude incidence rates of cases adjudicated as definite NLD in Brazil, Mexico, and Malaysia were 4.45, 1.32, and 0.69 per 100,000 person-years, respectively.

    CONCLUSIONS: Background incidence estimates of VLD and NLD obtained in Mexico, Brazil, and Malaysia could provide context for cases occurring after the introduction of the tetravalent dengue vaccine.

    Matched MeSH terms: Child, Preschool
  16. Maran S, Ee R, Faten SA, Sy Bing C, Khaw KY, Erin Lim SH, et al.
    PLoS One, 2020;15(4):e0230982.
    PMID: 32315303 DOI: 10.1371/journal.pone.0230982
    Atrial septal defect (ASD) is one of the most common congenital heart defects diagnosed in children. Sarcomeric genes has been attributed to ASD and knockdown of MYH3 functionally homologues gene in chick models indicated abnormal atrial septal development. Here, we report for the first time, a case-control study investigating the role of MYH3 among non-syndromic ASD patients in contributing to septal development. Four amplicons which will amplifies the 40 kb MYH3 were designed and amplified using long range-PCR. The amplicons were then sequenced using indexed paired-end libraries on the MiSeq platform. The STREGA guidelines were applied for planning and reporting. The non-synonymous c. 3574G>A (p.Ala1192Thr) [p = 0.001, OR = 2.30 (1.36-3.87)] located within the tail domain indicated a highly conserved protein region. The mutant model of c. 3574G>A (p.Ala1192Thr) showed high root mean square deviation (RMSD) values compared to the wild model. To our knowledge, this is the first study to provide compelling evidence on the pathogenesis of MYH3 variants towards ASD hence, suggesting the crucial role of non-synonymous variants in the tail domain of MYH3 towards atrial septal development. It is hoped that this gene can be used as panel for diagnosis of ASD in future.
    Matched MeSH terms: Child, Preschool
  17. GBD 2016 Causes of Death Collaborators
    Lancet, 2017 Sep 16;390(10100):1151-1210.
    PMID: 28919116 DOI: 10.1016/S0140-6736(17)32152-9
    BACKGROUND: Monitoring levels and trends in premature mortality is crucial to understanding how societies can address prominent sources of early death. The Global Burden of Disease 2016 Study (GBD 2016) provides a comprehensive assessment of cause-specific mortality for 264 causes in 195 locations from 1980 to 2016. This assessment includes evaluation of the expected epidemiological transition with changes in development and where local patterns deviate from these trends.
    METHODS: We estimated cause-specific deaths and years of life lost (YLLs) by age, sex, geography, and year. YLLs were calculated from the sum of each death multiplied by the standard life expectancy at each age. We used the GBD cause of death database composed of: vital registration (VR) data corrected for under-registration and garbage coding; national and subnational verbal autopsy (VA) studies corrected for garbage coding; and other sources including surveys and surveillance systems for specific causes such as maternal mortality. To facilitate assessment of quality, we reported on the fraction of deaths assigned to GBD Level 1 or Level 2 causes that cannot be underlying causes of death (major garbage codes) by location and year. Based on completeness, garbage coding, cause list detail, and time periods covered, we provided an overall data quality rating for each location with scores ranging from 0 stars (worst) to 5 stars (best). We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to generate estimates for each location, year, age, and sex. We assessed observed and expected levels and trends of cause-specific deaths in relation to the Socio-demographic Index (SDI), a summary indicator derived from measures of average income per capita, educational attainment, and total fertility, with locations grouped into quintiles by SDI. Relative to GBD 2015, we expanded the GBD cause hierarchy by 18 causes of death for GBD 2016.
    FINDINGS: The quality of available data varied by location. Data quality in 25 countries rated in the highest category (5 stars), while 48, 30, 21, and 44 countries were rated at each of the succeeding data quality levels. Vital registration or verbal autopsy data were not available in 27 countries, resulting in the assignment of a zero value for data quality. Deaths from non-communicable diseases (NCDs) represented 72·3% (95% uncertainty interval [UI] 71·2-73·2) of deaths in 2016 with 19·3% (18·5-20·4) of deaths in that year occurring from communicable, maternal, neonatal, and nutritional (CMNN) diseases and a further 8·43% (8·00-8·67) from injuries. Although age-standardised rates of death from NCDs decreased globally between 2006 and 2016, total numbers of these deaths increased; both numbers and age-standardised rates of death from CMNN causes decreased in the decade 2006-16-age-standardised rates of deaths from injuries decreased but total numbers varied little. In 2016, the three leading global causes of death in children under-5 were lower respiratory infections, neonatal preterm birth complications, and neonatal encephalopathy due to birth asphyxia and trauma, combined resulting in 1·80 million deaths (95% UI 1·59 million to 1·89 million). Between 1990 and 2016, a profound shift toward deaths at older ages occurred with a 178% (95% UI 176-181) increase in deaths in ages 90-94 years and a 210% (208-212) increase in deaths older than age 95 years. The ten leading causes by rates of age-standardised YLL significantly decreased from 2006 to 2016 (median annualised rate of change was a decrease of 2·89%); the median annualised rate of change for all other causes was lower (a decrease of 1·59%) during the same interval. Globally, the five leading causes of total YLLs in 2016 were cardiovascular diseases; diarrhoea, lower respiratory infections, and other common infectious diseases; neoplasms; neonatal disorders; and HIV/AIDS and tuberculosis. At a finer level of disaggregation within cause groupings, the ten leading causes of total YLLs in 2016 were ischaemic heart disease, cerebrovascular disease, lower respiratory infections, diarrhoeal diseases, road injuries, malaria, neonatal preterm birth complications, HIV/AIDS, chronic obstructive pulmonary disease, and neonatal encephalopathy due to birth asphyxia and trauma. Ischaemic heart disease was the leading cause of total YLLs in 113 countries for men and 97 countries for women. Comparisons of observed levels of YLLs by countries, relative to the level of YLLs expected on the basis of SDI alone, highlighted distinct regional patterns including the greater than expected level of YLLs from malaria and from HIV/AIDS across sub-Saharan Africa; diabetes mellitus, especially in Oceania; interpersonal violence, notably within Latin America and the Caribbean; and cardiomyopathy and myocarditis, particularly in eastern and central Europe. The level of YLLs from ischaemic heart disease was less than expected in 117 of 195 locations. Other leading causes of YLLs for which YLLs were notably lower than expected included neonatal preterm birth complications in many locations in both south Asia and southeast Asia, and cerebrovascular disease in western Europe.
    INTERPRETATION: The past 37 years have featured declining rates of communicable, maternal, neonatal, and nutritional diseases across all quintiles of SDI, with faster than expected gains for many locations relative to their SDI. A global shift towards deaths at older ages suggests success in reducing many causes of early death. YLLs have increased globally for causes such as diabetes mellitus or some neoplasms, and in some locations for causes such as drug use disorders, and conflict and terrorism. Increasing levels of YLLs might reflect outcomes from conditions that required high levels of care but for which effective treatments remain elusive, potentially increasing costs to health systems.
    FUNDING: Bill & Melinda Gates Foundation.
    Malaysian collaborators: School of Medicine, Xiamen University Malaysia Campus, Sepang, Malaysia (Y J Kim PhD); School of Medical Sciences, University of Science Malaysia, Kubang Kerian, Malaysia (K I Musa MD); Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia (R Sahathevan PhD); Department of Community Medicine, International Medical University, Kuala Lumpur, Malaysia (C T Sreeramareddy MD)
    Matched MeSH terms: Child, Preschool
  18. GBD 2016 Disease and Injury Incidence and Prevalence Collaborators
    Lancet, 2017 Sep 16;390(10100):1211-1259.
    PMID: 28919117 DOI: 10.1016/S0140-6736(17)32154-2
    BACKGROUND: As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016.
    METHODS: We estimated prevalence and incidence for 328 diseases and injuries and 2982 sequelae, their non-fatal consequences. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between incidence, prevalence, remission, and cause of death rates for each condition. For some causes, we used alternative modelling strategies if incidence or prevalence needed to be derived from other data. YLDs were estimated as the product of prevalence and a disability weight for all mutually exclusive sequelae, corrected for comorbidity and aggregated to cause level. We updated the Socio-demographic Index (SDI), a summary indicator of income per capita, years of schooling, and total fertility rate. GBD 2016 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).
    FINDINGS: Globally, low back pain, migraine, age-related and other hearing loss, iron-deficiency anaemia, and major depressive disorder were the five leading causes of YLDs in 2016, contributing 57·6 million (95% uncertainty interval [UI] 40·8-75·9 million [7·2%, 6·0-8·3]), 45·1 million (29·0-62·8 million [5·6%, 4·0-7·2]), 36·3 million (25·3-50·9 million [4·5%, 3·8-5·3]), 34·7 million (23·0-49·6 million [4·3%, 3·5-5·2]), and 34·1 million (23·5-46·0 million [4·2%, 3·2-5·3]) of total YLDs, respectively. Age-standardised rates of YLDs for all causes combined decreased between 1990 and 2016 by 2·7% (95% UI 2·3-3·1). Despite mostly stagnant age-standardised rates, the absolute number of YLDs from non-communicable diseases has been growing rapidly across all SDI quintiles, partly because of population growth, but also the ageing of populations. The largest absolute increases in total numbers of YLDs globally were between the ages of 40 and 69 years. Age-standardised YLD rates for all conditions combined were 10·4% (95% UI 9·0-11·8) higher in women than in men. Iron-deficiency anaemia, migraine, Alzheimer's disease and other dementias, major depressive disorder, anxiety, and all musculoskeletal disorders apart from gout were the main conditions contributing to higher YLD rates in women. Men had higher age-standardised rates of substance use disorders, diabetes, cardiovascular diseases, cancers, and all injuries apart from sexual violence. Globally, we noted much less geographical variation in disability than has been documented for premature mortality. In 2016, there was a less than two times difference in age-standardised YLD rates for all causes between the location with the lowest rate (China, 9201 YLDs per 100 000, 95% UI 6862-11943) and highest rate (Yemen, 14 774 YLDs per 100 000, 11 018-19 228).
    INTERPRETATION: The decrease in death rates since 1990 for most causes has not been matched by a similar decline in age-standardised YLD rates. For many large causes, YLD rates have either been stagnant or have increased for some causes, such as diabetes. As populations are ageing, and the prevalence of disabling disease generally increases steeply with age, health systems will face increasing demand for services that are generally costlier than the interventions that have led to declines in mortality in childhood or for the major causes of mortality in adults. Up-to-date information about the trends of disease and how this varies between countries is essential to plan for an adequate health-system response.
    FUNDING: Bill & Melinda Gates Foundation, and the National Institute on Aging and the National Institute of Mental Health of the National Institutes of Health.
    Malaysian collaborators: School of Medicine, Xiamen University Malaysia Campus, Sepang, Malaysia (Y J Kim PhD); School of Medical Sciences, University of Science Malaysia, Kubang Kerian, Malaysia (K I Musa MD); Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia (R Sahathevan PhD); Department of Community Medicine, International Medical University, Kuala Lumpur, Malaysia (C T Sreeramareddy MD)
    Matched MeSH terms: Child, Preschool
  19. Yusuf A, Mamun ASMA, Kamruzzaman M, Saw A, Abo El-Fetoh NM, Lestrel PE, et al.
    BMC Pediatr, 2019 06 29;19(1):213.
    PMID: 31255172 DOI: 10.1186/s12887-019-1581-9
    BACKGROUND: Anemia is not only a major public health problem among children in developing countries, it is also an important predictor for their future growth and development. The objective of this study was to identify possible factors associated with anemia among pre-school children in Bangladesh after removing a cluster effect of the population, and to determine the prevalence of this condition.

    METHODS: Data for this study was extracted from the 2011 Bangladesh Demographic and Health Survey (BDHS-2011). In this survey, data was collected using a two-stage stratified cluster sampling approach. The chi-square test and a two-level logistic regression model were used for further analysis.

    RESULTS: Data from 2231 children aged 6-59 months were included for analysis. The prevalence of child anemia was noted to be 52.10%. Among these anemic children, 48.40% where from urban environment and 53.90% were from rural areas. The prevalence of mild, moderate and severe anemia among children was 57.10, 41.40 and 1.50% respectively. The two-level logistic regression model revealed that the following factors were associated with childhood anemia: children of anemic mothers (p 

    Matched MeSH terms: Child, Preschool
  20. Poh BK, Lee ST, Yeo GS, Tang KC, Noor Afifah AR, Siti Hanisa A, et al.
    BMC Public Health, 2019 Jun 13;19(Suppl 4):541.
    PMID: 31196019 DOI: 10.1186/s12889-019-6856-4
    BACKGROUND: Socioeconomic factors and nutritional status have been associated with childhood cognitive development. However, previous Malaysian studies had been conducted with small populations and had inconsistent results. Thus, this present study aims to determine the association between socioeconomic and nutritional status with cognitive performance in a nationally representative sample of Malaysian children.

    METHODS: A total of 2406 Malaysian children aged 5 to 12 years, who had participated in the South East Asian Nutrition Surveys (SEANUTS), were included in this study. Cognitive performance [non-verbal intelligence quotient (IQ)] was measured using Raven's Progressive Matrices, while socioeconomic characteristics were determined using parent-report questionnaires. Body mass index (BMI) was calculated using measured weight and height, while BMI-for-age Z-score (BAZ) and height-for-age Z-score (HAZ) were determined using WHO 2007 growth reference.

    RESULTS: Overall, about a third (35.0%) of the children had above average non-verbal IQ (high average: 110-119; superior: ≥120 and above), while only 12.2% were categorized as having low/borderline IQ ( 3SD), children from very low household income families and children whose parents had only up to primary level education had the highest prevalence of low/borderline non-verbal IQ, compared to their non-obese and higher socioeconomic counterparts. Parental lack of education was associated with low/borderline/below average IQ [paternal, OR = 2.38 (95%CI 1.22, 4.62); maternal, OR = 2.64 (95%CI 1.32, 5.30)]. Children from the lowest income group were twice as likely to have low/borderline/below average IQ [OR = 2.01 (95%CI 1.16, 3.49)]. Children with severe obesity were twice as likely to have poor non-verbal IQ than children with normal BMI [OR = 2.28 (95%CI 1.23, 4.24)].

    CONCLUSIONS: Children from disadvantaged backgrounds (that is those from very low income families and those whose parents had primary education or lower) and children with severe obesity are more likely to have poor non-verbal IQ. Further studies to investigate the social and environmental factors linked to cognitive performance will provide deeper insights into the measures that can be taken to improve the cognitive performance of Malaysian children.

    Matched MeSH terms: Child, Preschool
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