Prenatal and perinatal factors associated with developing multiple sclerosis later in life: A systematic review and meta-analysis

ObjectiveBoth genetic and environmental factors play roles in Multiple Sclerosis (MS) etiopathogenesis. The relationship between prenatal/perinatal factors/exposures and future MS occurrence in the offspring remains controversial. Here, we aimed to review the available evidence on prenatal/perinatal factors associated with later MS occurrence.MethodWe performed systematic search of PubMed, Web of Science, and Scopus from inception to October 2020. We included original observational studies conducted on human participants addressing the association between prenatal/perinatal factors and MS occurrence. Data were extracted according to the PRISMA guideline. The adjusted odds ratio (OR) with 95% confidence interval (CI) was considered as the desired effect size. The heterogeneity was evaluated by Cochran's Q and I² and the publication bias was assessed. We excluded gestational/neonatal vitamin D level, season of birth, and latitude because of recently published systematic reviews/meta-analyses on these subjects.ResultsOverall, 2306 records were identified in the primary search. After excluding irrelevant studies, we evaluated 34 studies with contributing data on 100 prenatal/perinatal factors associated with an increased or decreased risk of MS occurrence. In the meta-analyses, we found no statistically significant associations between later MS occurrence in offspring and prenatal smoking exposure (OR = 1.01, 95% CI = 0.77–1.34), mode of delivery (OR = 0.90, 95% CI = 0.52–1.56), birth order (OR = 0.85, 95% CI = 0.72–1.00), and maternal age (OR = 1.34, 95% CI = 0.88–2.04). Paternal age and parents' marital status at the time of childbirth, maternal preeclampsia/ toxemia, forceps use, birth weight, plurality, and preterm birth were the other most studied factors, and none reported to affect MS risk.ConclusionWe found that prenatal smoking exposure, mode of delivery, birth order, and maternal age do not affect risk of future MS development. Moreover, most of the other investigated factors were reported not to affect MS risk in the offspring.     

Effects of virgin coconut oil consumption on metabolic syndrome components and asymmetric dimethylarginine: A randomized controlled clinical trial

Background and aimsThere is some promising evidence regarding the beneficial effect of coconut oil on cardiometabolic risk factors. This study aimed to assess the effects of virgin coconut oil (VCO) consumption on metabolic syndrome (MetS) components, as well as, asymmetric dimethylarginine (ADMA) in adults with MetS.Methods and resultsIn this randomized controlled trial, 48 subjects, aged 20–50 years, with MetS were allocated into two groups; the intervention group was given 30 ml of VCO per day to substitute the same amounts of fat in their usual diet for four weeks. The control group was advised to follow their usual diet. VCO consumption significantly reduced serum levels of triglyceride (TG) (P = 0.001), very low-density lipoprotein (VLDL) (P = 0.001), and fasting blood sugar (FBS) (P = 0.015) compared to the control group. The levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC) were significantly increased in the VCO group when compared to the control group (P = 0.001). Circulatory ADMA also increased in the VCO group compared to the control group (P = 0.003). No significant differences were observed in the LDL-C/HDL-C ratio, anthropometric parameters, and blood pressure measurements between the two groups at the end of the study (P > 0.05).ConclusionVCO consumption increased the values of HDL-C while reduced TG and FBS levels. Blood pressure and waist circumference did not change. However, levels of TC, LDL-C, and ADMA elevated by VCO consumption. Caution is warranted until the results of further studies become available to explain the long-term effects of VCO consumption.Registration numberIRCT20131125015536N11.     

Evaluation of LKB1 and Serine-Glycine Metabolism Pathway Genes (SHMT1 and GLDC) Expression in AML

LKB1 is a significant tumor suppressor and epigenetic regulator playing a vital role in different types of cancers. SHMT1 and GLDC are two critical genes of the epigenetic pathway influenced by LKB1. As epigenetic is the major cause of AML pathogenesis, this study aimed at investigating LKB1, SHMT1, and GLDC gene expression levels in acute myeloid leukemia patients. The present study was conducted on LKB1, SHMT1, and GLDC gene expression levels in 60 de novo AML samples and 30 normal controls using real-time RT-PCR. The results showed that LKB1 and SHMT1 have respectively a significantly lower (P < 0.05) and higher (P < 0.05) expression level than that of normal controls. Furthermore, the correlation between LKB1 with SHMT1 and GLDC was significant and positive (P value: 0.015, r: 0.299). Positive findings confirm that metabolic pathways alongside the LKB1 association drive the epigenetic axis and its substrate production. Therefore, it can be concluded that the newly-discovered pathway in the pathogenesis of this disease provides new insights into the design of therapeutic targets.     

A manganese(iii) Schiff base complex immobilized on silica-coated magnetic nanoparticles showing enhanced electrochemical catalytic performance toward sulfide and alkene oxidation

In this study, a novel Mn(iii)–Schiff base complex was synthesized and characterized. The structure of this complex was determined to be a deformed octahedral coordination sphere by single-crystal X-ray diffraction analysis. The Mn(iii)–Schiff base complex was supported on silica-coated iron magnetic nanoparticles via axial coordination by one-step complex anchoring to produce a heterogenized nanocatalyst. After this, the complex was characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), thermogravimetric analysis (TGA), vibrating sample magnetometry (VSM), and powder X-ray diffraction (XRD). Moreover, atomic absorption spectroscopy was used to determine the amount of the loaded metal. The heterogenized nanocatalyst effectively catalyzed the oxidation of a broad range of sulfides and alkenes with H₂O₂ in the presence of a glassy carbon electrode, applying voltage to the reaction mixture. The results showed that the application of a potential to the reaction mixture could significantly decrease the reaction time when compared with the case of similar chemical oxidation reactions. In addition, an excellent value of turnover frequency (17 750 h⁻¹) was achieved for the electrochemical oxidation of styrene. Moreover, the nanocatalyst showed good recoverability without significant loss of its activity within six successive runs in the electrochemical oxidation of methyl phenyl sulfide and cyclooctene. The electrochemical properties and stability of Fe₃O₄@SiO₂-[MnL(OAc)] were investigated by cyclic voltammetry measurements and chronoamperometry technique.

A Mn–Schiff base complex supported on silica-coated iron magnetic nanoparticles was used for the electrochemical oxidation of sulfides and alkenes.     

Exploration of "over kill effect" of high-LET Ar- and Fe-ions by evaluating the fraction of non-hit cell and interphase death

The reason why RBE for cell killing fell to less than unity (1.0) with very high-LET heavy-ions ((40)Ar: 1,640 keV/microm; (56)Fe: 780, 1,200, 2,000 keV/microm) was explored by evaluating the fraction of non-hit cell (time-lapse observation) and cells undergoing interphase death (calculation based on our previous data). CHO cells were exposed to 4 Gy (30% survival dose) of Ar (1,640 keV/microm) or Fe-ions (2,000 keV/microm). About 20% of all cells were judged to be non-hit, and about 10% cells survived radiation damage. About 70% cells died after dividing at least once (reproductive death) or without dividing (interphase death). RBE for reproductive (RBE[R]) and interphase (RBE[I]) death showed a similar LET dependence with maximum around 200 keV/microm. In this LET region, at 30% survival level, about 10% non-survivors underwent interphase death. The corresponding value for very high-LET Fe-ions (2,000 keV/microm) was not particularly high (approximately 15%), whereas that for X-rays was less than 3%. However, reproductive death (67%) predominated over interphase death (33%) even in regard to rather severely damaged cells (1% survival level) after exposure to Fe-ions (2,000 keV/microm). These indicate that interphase death is a type of cell death characteristic for the cells exposed to high-LET radiation and is not caused by "cellular over kill effect". Both NHF37 (non-hit fraction at 37% survival) and inactivation cross-section for reproductive death (sigma[R]) began to increase when LET exceeded 100 keV/microm. The exclusion of non-hit fraction in the calculation of surviving fraction partially prevented the fall of RBE[R] when LET exceeded 200 keV/microm. On the other hand, the mean number of lethal damage per unit dose (NLD/Gy) showed the same LET-dependent pattern as RBE[R]. These suggest that the increase in non-hit fraction and sigma[R] with an increasing LET is caused by enhanced clustering of ionization and DNA damage which lowers the energy efficiency for producing damage and RBE.     

Self-Replicating RNAs Drive Protective Anti-tumor T Cell Responses to Neoantigen Vaccine Targets in a Combinatorial Approach

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Dosimetric properties of a flattening filter-free 6-MV photon beam: a Monte Carlo study

Purpose The dosimetric features of an unflattened 6-MV photon beam of an Elekta SL-25 linac was calculated by the Monte Carlo (MC) method. Material and methods The head of the Elekta SL-25 linac was simulated using the MCNP4C MC code. The accuracy of the model was evaluated using measured dosimetric features, including depth dose values and dose profiles in a water phantom. The flattening filter was then removed, and beam dosimetric properties were calculated by the MC method and compared with those of the flattened photon beam. Results Our results showed a significant (twofold) increase in the dose rate for all field sizes. Also, the photon beam spectra for an unflattened beam were softer, which led to a steeper reduction in depth doses. The decrease in the out-of-field dose and increase in the contamination electrons and a buildup region dose were the other consequences of removing the flattening filter. Conclusion Our study revealed that, for recent radiotherapy techniques, the use of multileaf collimators for beam shaping removing the flattening filter could offer some advantages, including an increased dose rate and decreased out-of-field dose.     

Development of all CD4 T lineages requires nuclear factor TOX

CD8(+) cytotoxic and CD4(+) helper/inducer T cells develop from common thymocyte precursors that express both CD4 and CD8 molecules. Upon T cell receptor signaling, these cells initiate a differentiation program that includes complex changes in CD4 and CD8 expression, allowing identification of transitional intermediates in this developmental pathway. Little is known about regulation of these early transitions or their specific importance to CD4 and CD8 T cell development. Here, we show a severe block at the CD4(lo)CD8(lo) transitional stage of positive selection caused by loss of the nuclear HMG box protein TOX. As a result, CD4 lineage T cells, including regulatory T and CD1d-dependent natural killer T cells, fail to develop. In contrast, functional CD8(+) T cells develop in TOX-deficient mice. Our data suggest that TOX-dependent transition to the CD4(+)CD8(lo) stage is required for continued development of class II major histocompatibility complex-specific T cells, regardless of ultimate lineage fate.