METHODS: A population-based case-referent study was performed using cases with congenital anomalies (N = 5,131) from EUROCAT Northern Netherlands, a registry of congenital anomalies. The referent population (N = 31,055) was selected from the pregnancy IADB.nl, a pharmacy prescription database.
RESULTS: Ten placental transporters known to have comparable expression levels in the placenta to that of P-gp, were selected in this study. In total, 147 drugs were identified to be substrates, inhibitors or inducers, of these transporters. Fifty-eight of these drugs were used by at least one mother in our cases or referent population, and 28 were used in both. The highest user rate was observed for the substrates of multidrug resistance-associated protein 1, mainly folic acid (6% of cases, 8% of referents), and breast cancer resistance protein, mainly nitrofurantoin (2.3% of cases, 2.9% of referents). In contrast to P-gp, drug interactions involving substrates of these transporters did not have a significant effect on the risk of congenital anomalies.
CONCLUSIONS: Some of the drugs which are substrates or inhibitors of placental transporters were commonly used during pregnancy. No significant effect of transporter inhibition was found on fetal drug exposure, possibly due to a limited number of exposures.
METHODOLOGY: Parallel virology was used to investigate the phenotypes of duck and mosquito-derived isolates of TMUV. Molecular biology and bioinformatics methods were employed to investigate the genetic characteristics and evolution of TMUV.
PRINCIPAL FINDINGS: The plaque diameter of duck-derived isolates of TMUV was larger than that of mosquito-derived isolates. The cytopathic effect (CPE) in mammalian cells occurred more rapidly induced by duck-derived isolates than by mosquito-derived isolates. Furthermore, duck-derived isolates required less time to reach maximum titer, and exhibited higher viral titer. These findings suggested that poultry-derived TMUV isolates were more invasive and had greater expansion capability than the mosquito-derived isolates in mammalian cells. Variations in amino acid loci in TMUV E gene sequence revealed two mutated amino acid loci in strains isolated from Malaysia, Thailand, and Chinese mainland compared with the prototypical strain of the virus (MM1775). Furthermore, TMUV isolates from the Chinese mainland had six common variations in the E gene loci that differed from the Southeast Asian strains. Phylogenetic analysis indicated that TMUV did not exhibit a species barrier in avian species and consisted of two lineages: the Southeast Asian and the Chinese mainland lineages. Molecular traceability studies revealed that the recent common evolutionary ancestor of TMUV might have appeared before 1934 and that Malaysia, Thailand and Shandong Province of China represent the three main sources related to TMUV spread.
CONCLUSIONS: The current broad distribution of TMUV strains in Southeast Asia and Chinese mainland exhibited longer-range diffusion and larger-scale propagation. Therefore, in addition to China, other Asian and European countries linked to Asia have used improved measures to detect and monitor TMUV related diseases to prevent epidemics in poultry.
CAPSULE: The concentration, distribution sources and fate of microplastics in the global marine environment were discussed, so also was the impact of microplastics on a wide range of marine biota.
METHODS: This is a retrospective review using archived data sets of women seen in the context of two prospective perinatal imaging studies. All subjects had undergone a standardised interview, a clinical examination and 4D translabial ultrasound, 3 months and 2-5 years post-partum. Main outcome measures were pelvic organ descent and hiatal area at maximum Valsalva manoeuvre. Means at the two time points were compared using paired Student's t test. Predictors of change over time in continuous variables were explored using linear modelling methods.
RESULTS: A total of 300 women had at least two postnatal follow-ups. They were first seen on average 0.39 (SD 0.2, range 0.2-2.1) years and again 3.1 (SD 1.5, range 1.4-8) years after the index delivery, with a mean interval of 2.71 (SD 1.5, range 0.7-7.7) years, providing a total of 813 (300 × 2.71) woman-years of observation. On univariate analysis, there was a significant decrease in mobility over time of the bladder neck, bladder, and rectal ampulla (P = < 0.004) and hiatal area (P = 0.012). The degree of improvement was less marked in women with levator avulsion.
CONCLUSIONS: A significant reduction in pelvic organ descent and hiatal area was noted over a mean of 2.7 years after a first birth.
METHOD: MRI brain of patients with a diagnosis of IIDDs presented to the Hospital from 2010 to 2015 was analysed. The MRI was assessed by 2 radiologists blinded to the AQP4 status, on features said to be typical of NMOSD and MS.
RESULTS: Thirty nine patients fulfilled the criteria and were included in the study. They consisted of 19 AQP4 seropositive and 20 AQP4 seronegative patients. The mean age was older (37.0 vs. 28.8 years) among the AQP4 positive group. The majority of the patients were ethnic Chinese (72%), followed by the Malays and Indians. Those with AQP4 seropositive status generally has less brain lesions, and significantly less fulfilling the McDonald DIS criteria as compared to those with AQP4 seronegative status (15.8% vs. 60.0%, p=0.005). None of the seven cerebral MRI features highlighted in NMOSD 2015 diagnostic criteria, said to be characteristic of NMOSD was more common among the AQP4 positive patients. These features were in fact seen less frequently among the AQP4 seropositive patients. An example was the extensive hemispheric lesion seen in 10.5% of AQP4 seropositive patients vs. 45% of that AQP4 seronegative group.
CONCLUSION: There was no characteristic MRI brain features in the Malaysian AQP4 seropositive IIDD patients versus those who are seronegative. This could be a reflection of ethnical difference.
OBJECTIVE: The purpose of this study was to determine the organophosphorus pesticide urinary metabolite levels and its predictors among Orang Asli children of the Mah Meri tribe living in an agricultural island in Kuala Langat, Selangor.
METHODS: Data collection was carried out at an island in Kuala Langat, Selangor, where a total of 180 Orang Asli children of the Mah Meri tribe voluntarily participated in the study. Data were collected via a validated, modified questionnaire. Urinary organophosphate metabolites, namely dimethylphosphate, diethylphosphate, dimethylthiophosphate, dimethyldithiophosphate, diethylthiophosphate, and diethyldithiophosphate were measured to assess organophosphate pesticide exposure in children.
FINDINGS: Eighty-four (46.7%) of the respondents were positive for urine dialkyl phosphate metabolites. In multivariable analysis, children who frequently consumed apples had 4 times higher risk of pesticide detection than those who consumed apple less frequently. In addition, those who frequently ate cucumbers had 4 times higher risk for pesticide detection than those who ate cucumbers less frequently. Children with a father whose occupation involved high exposure to pesticides (agriculture) had 3 times higher risk of pesticide detection than those with a father in a low-risk occupation (nonagriculture).
CONCLUSIONS: Almost half of the children (46.7%) in the study area tested positive for urinary dialkyl phosphate metabolite levels. Most of the metabolite levels were equal to or higher than that reported in other previous studies. Major factors associated with pesticide detection in children in this study were frequent intake of apple and cucumber and fathers who are working in an agricultural area.