Displaying publications 1 - 20 of 97 in total

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  1. Röhr S, Pabst A, Riedel-Heller SG, Jessen F, Turana Y, Handajani YS, et al.
    Alzheimers Res Ther, 2020 12 18;12(1):167.
    PMID: 33339532 DOI: 10.1186/s13195-020-00734-y
    BACKGROUND: Subjective cognitive decline (SCD) is recognized as a risk stage for Alzheimer's disease (AD) and other dementias, but its prevalence is not well known. We aimed to use uniform criteria to better estimate SCD prevalence across international cohorts.

    METHODS: We combined individual participant data for 16 cohorts from 15 countries (members of the COSMIC consortium) and used qualitative and quantitative (Item Response Theory/IRT) harmonization techniques to estimate SCD prevalence.

    RESULTS: The sample comprised 39,387 cognitively unimpaired individuals above age 60. The prevalence of SCD across studies was around one quarter with both qualitative harmonization/QH (23.8%, 95%CI = 23.3-24.4%) and IRT (25.6%, 95%CI = 25.1-26.1%); however, prevalence estimates varied largely between studies (QH 6.1%, 95%CI = 5.1-7.0%, to 52.7%, 95%CI = 47.4-58.0%; IRT: 7.8%, 95%CI = 6.8-8.9%, to 52.7%, 95%CI = 47.4-58.0%). Across studies, SCD prevalence was higher in men than women, in lower levels of education, in Asian and Black African people compared to White people, in lower- and middle-income countries compared to high-income countries, and in studies conducted in later decades.

    CONCLUSIONS: SCD is frequent in old age. Having a quarter of older individuals with SCD warrants further investigation of its significance, as a risk stage for AD and other dementias, and of ways to help individuals with SCD who seek medical advice. Moreover, a standardized instrument to measure SCD is needed to overcome the measurement variability currently dominant in the field.

  2. Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, et al.
    Autophagy, 2016;12(1):1-222.
    PMID: 26799652 DOI: 10.1080/15548627.2015.1100356
  3. Slik JWF, Franklin J, Arroyo-Rodríguez V, Field R, Aguilar S, Aguirre N, et al.
    Proc Natl Acad Sci U S A, 2018 02 20;115(8):1837-1842.
    PMID: 29432167 DOI: 10.1073/pnas.1714977115
    Knowledge about the biogeographic affinities of the world's tropical forests helps to better understand regional differences in forest structure, diversity, composition, and dynamics. Such understanding will enable anticipation of region-specific responses to global environmental change. Modern phylogenies, in combination with broad coverage of species inventory data, now allow for global biogeographic analyses that take species evolutionary distance into account. Here we present a classification of the world's tropical forests based on their phylogenetic similarity. We identify five principal floristic regions and their floristic relationships: (i) Indo-Pacific, (ii) Subtropical, (iii) African, (iv) American, and (v) Dry forests. Our results do not support the traditional neo- versus paleotropical forest division but instead separate the combined American and African forests from their Indo-Pacific counterparts. We also find indications for the existence of a global dry forest region, with representatives in America, Africa, Madagascar, and India. Additionally, a northern-hemisphere Subtropical forest region was identified with representatives in Asia and America, providing support for a link between Asian and American northern-hemisphere forests.
  4. Ariffin H, Chen SP, Wong HL, Yeoh A
    Singapore Med J, 2003 Oct;44(10):517-20.
    PMID: 15024455
    In childhood acute lymphoblastic leukaemia (ALL), cytogenetics play an important role in diagnosis, allocation of treatment and prognosis. Conventional cytogenetic analysis, involving mainly karyotyping in our experience, has not been successful in a large proportion of cases due to inadequate metaphase spreads and poor chromosome morphology. Our aim is to develop a highly sensitive and specific method to screen simultaneously for the four most frequent fusion transcripts resulting from specific chromosomal translocations, namely, both the CML- and ALLtype BCR-ABL transcripts of t(9;22), E2A-PBX1 transcript of t(1;19), the MLL-AF4 transcript of t(4;11) and TEL-AML1 (also termed ETV6-CBFA2) of the cryptic t(12;21). A multiplex reverse transcription polymerase chain reaction protocol (RT-PCR) was developed and tested out on archival bone marrow samples and leukaemia cell lines. In all samples with a known translocation detected by cytogenetic techniques, the same translocation was identified by the multiplex-PCR assay. Multiplex RT-PCR assay is an effective, sensitive, accurate and cost-effective diagnostic tool which can improve our ability to accurately and rapidly risk-stratify patients with childhood ALL.
  5. Li R, Chee CS, Kamalden TF, Ramli AS, Yang K
    J Sports Med Phys Fitness, 2024 Jan;64(1):55-65.
    PMID: 37902798 DOI: 10.23736/S0022-4707.23.15220-0
    INTRODUCTION: Blood flow restriction training (BFRT) is an effective training method to improve sports performance in healthy athletes. Nevertheless, a systematic review with meta-analysis regarding how BFRT affects sports performance in athletes is still lacking. Consequently, the study attempted to expand and consolidate the prior studies regarding the effect of BFRT on technical and physical performance in athletes.

    EVIDENCE ACQUISITION: This study was based on PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyzes) statement guidelines for a systematic review of the academic databases Scopus, Web of Science, PubMed, EBSCOhost (SportDiscus), and Google Scholar. The PEDro scale was used to assess the methodological quality of the included publications, which ranged from moderate to high quality. The systematic review protocol was registered on inplasy.com (INPLASY202380049).

    EVIDENCE SYNTHESIS: Out of 249 studies identified, 93 articles were evaluated as eligible, and after the screening, 18 studies were finally included in this systematic review. Meta-analysis results showed a significant enhancement on vertical jump height in the BFRT group compared to the control group (SMD=1.39, 95% CI=0.30-2.49, P=0.01). BFRT was able to significantly increase maximal oxygen uptake (SMD=1.65, 95% CI=0.56-2.74, P<0.01). While no significant improvement in sprint time was observed (SMD= -0.18, 95% CI=-1.18-0.82, P=0.115).

    CONCLUSIONS: The finding suggests that BFRT is beneficial to athletes as this training method can be effective in enhancing physical and technical performance in athletes. Nevertheless, further analysis needs to be conducted to fully determine the effectiveness of the moderators of the intervention on sports performance.

  6. Qian M, Zhang H, Kham SK, Liu S, Jiang C, Zhao X, et al.
    Genome Res, 2017 02;27(2):185-195.
    PMID: 27903646 DOI: 10.1101/gr.209163.116
    Chromosomal translocations are a genomic hallmark of many hematologic malignancies. Often as initiating events, these structural abnormalities result in fusion proteins involving transcription factors important for hematopoietic differentiation and/or signaling molecules regulating cell proliferation and cell cycle. In contrast, epigenetic regulator genes are more frequently targeted by somatic sequence mutations, possibly as secondary events to further potentiate leukemogenesis. Through comprehensive whole-transcriptome sequencing of 231 children with acute lymphoblastic leukemia (ALL), we identified 58 putative functional and predominant fusion genes in 54.1% of patients (n = 125), 31 of which have not been reported previously. In particular, we described a distinct ALL subtype with a characteristic gene expression signature predominantly driven by chromosomal rearrangements of the ZNF384 gene with histone acetyltransferases EP300 and CREBBP ZNF384-rearranged ALL showed significant up-regulation of CLCF1 and BTLA expression, and ZNF384 fusion proteins consistently showed higher activity to promote transcription of these target genes relative to wild-type ZNF384 in vitro. Ectopic expression of EP300-ZNF384 and CREBBP-ZNF384 fusion altered differentiation of mouse hematopoietic stem and progenitor cells and also potentiated oncogenic transformation in vitro. EP300- and CREBBP-ZNF384 fusions resulted in loss of histone lysine acetyltransferase activity in a dominant-negative fashion, with concomitant global reduction of histone acetylation and increased sensitivity of leukemia cells to histone deacetylase inhibitors. In conclusion, our results indicate that gene fusion is a common class of genomic abnormalities in childhood ALL and that recurrent translocations involving EP300 and CREBBP may cause epigenetic deregulation with potential for therapeutic targeting.
  7. Shang X, Peng Z, Ye Y, Asan, Zhang X, Chen Y, et al.
    EBioMedicine, 2017 Sep;23:150-159.
    PMID: 28865746 DOI: 10.1016/j.ebiom.2017.08.015
    Hemoglobinopathies are among the most common autosomal-recessive disorders worldwide. A comprehensive next-generation sequencing (NGS) test would greatly facilitate screening and diagnosis of these disorders. An NGS panel targeting the coding regions of hemoglobin genes and four modifier genes was designed. We validated the assay by using 2522 subjects affected with hemoglobinopathies and applied it to carrier testing in a cohort of 10,111 couples who were also screened through traditional methods. In the clinical genotyping analysis of 1182 β-thalassemia subjects, we identified a group of additional variants that can be used for accurate diagnosis. In the molecular screening analysis of the 10,111 couples, we detected 4180 individuals in total who carried 4840 mutant alleles, and identified 186 couples at risk of having affected offspring. 12.1% of the pathogenic or likely pathogenic variants identified by our NGS assay, which were undetectable by traditional methods. Compared with the traditional methods, our assay identified an additional at-risk 35 couples. We describe a comprehensive NGS-based test that offers advantages over the traditional screening/molecular testing methods. To our knowledge, this is among the first large-scale population study to systematically evaluate the application of an NGS technique in carrier screening and molecular diagnosis of hemoglobinopathies.
  8. Deng L, Pan Y, Wang Y, Chen H, Yuan K, Chen S, et al.
    Mol Biol Evol, 2022 Feb 03;39(2).
    PMID: 34940850 DOI: 10.1093/molbev/msab361
    Tropical indigenous peoples in Asia (TIA) attract much attention for their unique appearance, whereas their genetic history and adaptive evolution remain mysteries. We conducted a comprehensive study to characterize the genetic distinction and connection of broad geographical TIAs. Despite the diverse genetic makeup and large interarea genetic differentiation between the TIA groups, we identified a basal Asian ancestry (bASN) specifically shared by these populations. The bASN ancestry was relatively enriched in ancient Asian human genomes dated as early as ∼50,000 years before the present and diminished in more recent history. Notably, the bASN ancestry is unlikely to be derived from archaic hominins. Instead, we suggest it may be better modeled as a survived lineage of the initial peopling of Asia. Shared adaptations inherited from the ancient Asian ancestry were detected among the TIA groups (e.g., LIMS1 for hair morphology, and COL24A1 for bone formation), and they are enriched in neurological functions either at an identical locus (e.g., NKAIN3), or different loci in an identical gene (e.g., TENM4). The bASN ancestry could also have formed the substrate of the genetic architecture of the dark pigmentation observed in the TIA peoples. We hypothesize that phenotypic convergence of the dark pigmentation in TIAs could have resulted from parallel (e.g., DDB1/DAK) or genetic convergence driven by admixture (e.g., MTHFD1 and RAD18), new mutations (e.g., STK11), or notably purifying selection (e.g., MC1R). Our results provide new insights into the initial peopling of Asia and an advanced understanding of the phenotypic convergence of the TIA peoples.
  9. Cheng J, Wang Y, Hou J, Luo D, Xie Q, Ning Q, et al.
    J Clin Virol, 2014 Dec;61(4):509-16.
    PMID: 25200354 DOI: 10.1016/j.jcv.2014.08.008
    In mainland China, peginterferon (PEG-IFN) alfa-2b 1.0μg/kg/wk for 24 weeks is the approved treatment for HBeAg-positive chronic hepatitis B.
  10. Feng Y, Feng Y, Liu Q, Chen S, Hou P, Poinern G, et al.
    Environ Pollut, 2022 Feb 01;294:118598.
    PMID: 34861331 DOI: 10.1016/j.envpol.2021.118598
    Biochar has been considered as a potential tool to mitigate soil ammonia (NH3) volatilization and greenhouse gases (GHGs) emissions in recent years. However, the aging effect of biochar on soils remains elusive, which introduces uncertainty on the effectiveness of biochar to mitigate global warming in a long term. Here, a meta-analysis of 22 published works of literature with 217 observations was conducted to systematically explore the aging effect of biochar on soil NH3 and GHGs emissions. The results show that, in comparison with the fresh biochar, the aging makes biochar more effective to decrease soil NH3 volatilization by 7% and less risk to contribute CH4 emissions by 11%. However, the mitigation effect of biochar on soil N2O emissions is decreased by 15% due to aging. Additionally, aging leads to a promotion effect on soil CO2 emissions by 25% than fresh biochar. Our findings suggest that along with aging, particularly the effect of artificial aging, biochar could further benefit the alleviation of soil NH3 volatilization, whereas its potential role to mitigate global warming may decrease. This study provides a systematic assessment of the aging effect of biochar to mitigate soil NH3 and GHGs, which can provide a scientific basis for the sustainable green development of biochar application.
  11. Chen S, Wong KY
    Front Psychol, 2022;13:726209.
    PMID: 35602716 DOI: 10.3389/fpsyg.2022.726209
    This study examines preservice music teachers' multicultural personality level and characteristics in the context of multicultural music education in China, focusing on the factors that influence the teachers' multicultural personality traits. We surveyed 433 preservice music teachers who responded via the Multicultural Personality Questionnaire-Short Form survey instrument. The results indicated that the multicultural personality level of preservice music teachers was intermediate, mainly due to a deficiency in the Flexibility and Emotional Stability dimensions, which are necessary for dealing with cultural differences in the face of unknown multicultural conditions. In addition, we also found that the size of a teacher's hometown and the years of studying and teaching are significant factors in shaping preservice music teachers' multicultural personalities. Preservice music teachers whose hometowns are big cities have a higher multicultural personality level than those in rural areas. The more time a preservice music teacher spent studying and teaching, the higher the multicultural personality level. Gender, educational level, and experience playing musical instruments have no statistically significant effect on the multicultural personality of preservice music teachers.
  12. Pham NQ, Barnes I, Chen S, Pham TQ, Lombard L, Crous PW, et al.
    MycoKeys, 2018.
    PMID: 29681735 DOI: 10.3897/mycokeys.32.23754
    Cylindrocladiella spp. are widely distributed especially in tropical and sub-tropical regions, where they are mainly known as saprobes although some species are plant pathogens. Very little is known about these fungi in South-East Asia. The aim of this study was to identify a collection of Cylindrocladiella isolates from soils collected in forest nurseries and plantations in Vietnam and Malaysia. This was achieved using DNA sequence comparisons and morphological observations. The study revealed two previously described species, Cy. lageniformis and Cy. peruviana as well as five novel taxa, described here as Cy. arbustasp. nov., Cy. malesianasp. nov., Cy. obpyriformissp. nov., Cy. parvisporasp. nov. and Cy. solicolasp. nov. A relatively small collection of isolates from a limited geographic sampling revealed an unexpectedly high level of Cylindrocladiella diversity suggesting that many more species in this genus await discovery in South-East Asia.
  13. Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, et al.
    Autophagy, 2021 Jan;17(1):1-382.
    PMID: 33634751 DOI: 10.1080/15548627.2020.1797280
    In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
  14. Sweeney S, Leo BF, Chen S, Abraham-Thomas N, Thorley AJ, Gow A, et al.
    Colloids Surf B Biointerfaces, 2016 Sep 01;145:167-75.
    PMID: 27182651 DOI: 10.1016/j.colsurfb.2016.04.040
    Accompanying increased commercial applications and production of silver nanomaterials is an increased probability of human exposure, with inhalation a key route. Nanomaterials that deposit in the pulmonary alveolar region following inhalation will interact firstly with pulmonary surfactant before they interact with the alveolar epithelium. It is therefore critical to understand the effects of human pulmonary surfactant when evaluating the inhalation toxicity of silver nanoparticles. In this study, we evaluated the toxicity of AgNPs on human alveolar type-I-like epithelial (TT1) cells in the absence and presence of Curosurf(®) (a natural pulmonary surfactant substitute), hypothesising that the pulmonary surfactant would act to modify toxicity. We demonstrated that 20nm citrate-capped AgNPs induce toxicity in human alveolar type I-like epithelial cells and, in agreement with our hypothesis, that pulmonary surfactant acts to mitigate this toxicity, possibly through reducing AgNP dissolution into cytotoxic Ag(+) ions. For example, IL-6 and IL-8 release by TT1 cells significantly increased 10.7- and 35-fold, respectively (P<0.01), 24h after treatment with 25μg/ml AgNPs. In contrast, following pre-incubation of AgNPs with Curosurf(®), this effect was almost completely abolished. We further determined that the mechanism of this toxicity is likely associated with Ag(+) ion release and lysosomal disruption, but not with increased reactive oxygen species generation. This study provides a critical understanding of the toxicity of AgNPs in target human alveolar type-I-like epithelial cells and the role of pulmonary surfactant in mitigating this toxicity. The observations reported have important implications for the manufacture and application of AgNPs, in particular for applications involving use of aerosolised AgNPs.
  15. Chen S, Lin Z, Tan KL, Chen R, Su W, Zhao H, et al.
    Front Psychiatry, 2020;11:564843.
    PMID: 33061920 DOI: 10.3389/fpsyt.2020.564843
    Butyrylcholinesterase (BChE) efficiently hydrolyzes acetylcholine (ACh) at high concentrations when acetylcholinesterase (AChE) is substrate-inhibited. Recent studies have shown that BChE also has a function that is independent of ACh, but it has not been fully explored. Low BChE expression is accompanied with higher stress-induced aggression and ghrelin levels in stress models, and BChE knockout mice exhibit cognitive and memory impairments. However, the role of BChE in posttraumatic stress disorder (PTSD) remains unclear. In the present study, we investigated the role of BChE in contextual fear memory and its regulatory effect on the expression of factors related to the glutamate (Glu)-glutamine (Gln) cycle via knockdown studies. We used AAVs and lentiviruses to knockdown BChE expression in the mouse hippocampal CA1 region and C8D1A astrocytes. Our behavioral data from those mice injected with AAV-shBChE in the hippocampal CA1 region showed strengthened fear memory and increased dendritic spine density. Elevated Glu levels and glutamine synthetase (GS) enzyme activity were detected in contextual fear conditioned-BChE knockdown animals and astrocytes. We observed that an AAV-shBChE induced lowering of BChE expression in the hippocampus CA1 region enhanced contextual fear memory expression and promoted the astrocytic Glu-Gln cycle but did not elevate ACh-hydrolyzing activity. This study provides new insight into the regulatory role of BChE in cognition and suggests potential target for stress-related psychiatric disorder such as PTSD where patients experience fear after exposure to severe life-threatening traumatic events.
  16. Yoochatchaval W, Kumakura S, Tanikawa D, Yamaguchi T, Yunus MF, Chen SS, et al.
    Water Sci Technol, 2011;64(10):2001-8.
    PMID: 22105121 DOI: 10.2166/wst.2011.782
    The biodegradation characteristics of palm oil mill effluent (POME) and the related microbial community were studied in both actual sequential anaerobic ponds in Malaysia and enrichment cultures. The significant degradation of the POME was observed in the second pond, in which the temperature was 35-37 °C. In this pond, biodegradation of major long chain fatty acids (LCFA), such as palmitic acid (C16:0) and oleic acid (C18:1), was also confirmed. The enrichment culture experiment was conducted with different feeding substrates, i.e. POME, C16:0 and C18:1, at 35 °C. Good recovery of methane indicated biodegradation of feeds in the POME and C16:0 enrichments. The methane production rate of the C18:1 enrichment was slower than other substrates and inhibition of methanogenesis was frequently observed. Denaturing gradient gel electrophoresis (DGGE) analyses indicated the existence of LCFA-degrading bacteria, such as the genus Syntrophus and Syntorophomonas, in all enrichment cultures operated at 35 °C. Anaerobic degradation of the POME under mesophilic conditions was stably processed as compared with thermophilic conditions.
  17. Gou Z, Zheng H, He Z, Su Y, Chen S, Chen H, et al.
    Environ Pollut, 2023 Jan 15;317:120790.
    PMID: 36460190 DOI: 10.1016/j.envpol.2022.120790
    This study aims to investigate the positive effects of the combined use of Enterobacter cloacae and biochar on improving nitrogen (N) utilization. The greenhouse pots experimental results showed the synergy of biochar and E. cloacae increased soil total N content and plant N uptake by 33.54% and 15.1%, respectively. Soil nitrogenase (NIT) activity increased by 253.02%. Ammonia monooxygenase (AMO) and nitrate reductase (NR) activity associated with nitrification and denitrification decreased by 10.94% and 29.09%, respectively. The relative abundance of N fixing microorganisms like Burkholderia and Bradyrhizobium significantly increased. Sphingomonas and Ottowia, two bacteria involved in the nitrification and denitrification processes, were found to be in lower numbers. The E. cloacae's ability to fix N2 and promote the growth of plants allow the retention of N in soil and make more N available for plant development. Biochar served as a reservoir of N for plants by adsorbing N from the soil and providing a shelter for E. cloacae. Thus, biochar and E. cloacae form a synergy for the management of agricultural N and the mitigation of negative impacts of pollution caused by excessive use of N fertilizer.
  18. McGrattan AM, Zhu Y, Richardson CD, Mohan D, Soh YC, Sajjad A, et al.
    J Alzheimers Dis, 2021;79(2):743-762.
    PMID: 33361599 DOI: 10.3233/JAD-201043
    BACKGROUND: Mild cognitive impairment (MCI) is a cognitive state associated with increased risk of dementia. Little research on MCI exists from low-and middle-income countries (LMICs), despite high prevalence of dementia in these settings.

    OBJECTIVE: This systematic review aimed to review epidemiological reports to determine the prevalence of MCI and its associated risk factors in LMICs.

    METHODS: Medline, Embase, and PsycINFO were searched from inception until November 2019. Eligible articles reported on MCI in population or community-based studies from LMICs and were included as long as MCI was clearly defined.

    RESULTS: 5,568 articles were screened, and 78 retained. In total, n = 23 different LMICs were represented; mostly from China (n = 55 studies). Few studies were from countries defined as lower-middle income (n = 14), low income (n = 4), or from population representative samples (n = 4). There was large heterogeneity in how MCI was diagnosed; with Petersen criteria the most commonly applied (n = 26). Prevalence of amnesic MCI (aMCI) (Petersen criteria) ranged from 0.6%to 22.3%. Similar variability existed across studies using the International Working Group Criteria for aMCI (range 4.5%to 18.3%) and all-MCI (range 6.1%to 30.4%). Risk of MCI was associated with demographic (e.g., age), health (e.g., cardio-metabolic disease), and lifestyle (e.g., social isolation, smoking, diet and physical activity) factors.

    CONCLUSION: Outside of China, few MCI studies have been conducted in LMIC settings. There is an urgent need for population representative epidemiological studies to determine MCI prevalence in LMICs. MCI diagnostic methodology also needs to be standardized. This will allow for cross-study comparison and future resource planning.

  19. Chen ST, Edsall G, Peel MM, Sinnathuray TA
    Bull World Health Organ, 1983;61(1):159-65.
    PMID: 6601539
    The relationship between the timing of maternal tetanus toxoid immunization and the presence of protective antitoxin in placental cord blood was investigated among women admitted to the obstetrical service of the University Hospital in Kuala Lumpur, Malaysia. The 1st dose was given between 13-39 weeks of gestation, with a median of 29 weeks. The 2nd dose was given an average of 4 weeks later. Protection was conferred on 80% or more of newborns whose mothers received their 1st tetanus toxoid injection 60 days or more before delivery. Protective levels were seen in all cord blood samples from infants whose mothers had received their 1st injection 90 days before delivery. Similarly,protective titers were found in 100% of cord blood samples when the 2nd maternal injection was give 60 days or more before delivery. There was no significant degree of protection when immunization was carried out less than 20 days before delivery. A single-dose schedule provided no protection when less than 70 days before delivery. Cord and maternal antiotoxin titers differed by no more than 1 2-fold dilution for almost all of the individual paired sera. A cord: maternal antitoxin ratio of 2 was more likely to occur with increasing time between the 2nd injection and delivery. Overall, these findings indicate that the 1st injection of a 2-dose maternal tetanus toxoid schedule should be given at least 60 days and preferably 90 days before delivery.
  20. Sarkar S, Leo BF, Carranza C, Chen S, Rivas-Santiago C, Porter AE, et al.
    PLoS One, 2015;10(11):e0143077.
    PMID: 26580078 DOI: 10.1371/journal.pone.0143077
    Exposure to silver nanoparticles (AgNP) used in consumer products carries potential health risks including increased susceptibility to infectious pathogens. Systematic assessments of antimicrobial macrophage immune responses in the context of AgNP exposure are important because uptake of AgNP by macrophages may lead to alterations of innate immune cell functions. In this study we examined the effects of exposure to AgNP with different particle sizes (20 and 110 nm diameters) and surface chemistry (citrate or polyvinlypyrrolidone capping) on cellular toxicity and innate immune responses against Mycobacterium tuberculosis (M.tb) by human monocyte-derived macrophages (MDM). Exposures of MDM to AgNP significantly reduced cellular viability, increased IL8 and decreased IL10 mRNA expression. Exposure of M.tb-infected MDM to AgNP suppressed M.tb-induced expression of IL1B, IL10, and TNFA mRNA. Furthermore, M.tb-induced IL-1β, a cytokine critical for host resistance to M.tb, was inhibited by AgNP but not by carbon black particles indicating that the observed immunosuppressive effects of AgNP are particle specific. Suppressive effects of AgNP on the M.tb-induced host immune responses were in part due to AgNP-mediated interferences with the TLR signaling pathways that culminate in the activation of the transcription factor NF-κB. AgNP exposure suppressed M.tb-induced expression of a subset of NF-κB mediated genes (CSF2, CSF3, IFNG, IL1A, IL1B, IL6, IL10, TNFA, NFKB1A). In addition, AgNP exposure increased the expression of HSPA1A mRNA and the corresponding stress-induced Hsp72 protein. Up-regulation of Hsp72 by AgNP can suppress M.tb-induced NF-κB activation and host immune responses. The observed ability of AgNP to modulate infectious pathogen-induced immune responses has important public health implications.
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