Is MTHFR 677 C>T Polymorphism Clinically Important in Polycystic Ovarian Syndrome (PCOS)? A Case-Control Study,Meta-Analysis and Trial Sequential Analysis

Background

Optimum efficiency of the folate pathway is considered essential for adequate ovarian function. 677 C>T substitution in the 5, 10-methylene tertrahydrofolatereductase (MTHFR) gene compromises activity of the MTHFR enzyme by about 50%. The significance of correlation between 677C>T substitution and PCOS remains dubious due to the low power of published studies.

Methods and Results

We analyzed MTHFR 677 C>T site in ethnically two different PCOS case-control groups (total 261 cases and 256 controls) from India. The data analysis revealed a lack of association between this polymorphism and PCOS [OR = 1.11 (95%CI = 0.71–1.72), P = 0.66]. Group-wise analysis on the basis of ethnicity also revealed no association in any of the ethnic groups [Indo-Europeans, P = 1; Dravidians, P = 0.70]. Homocysteine levels did not differ significantly between cases (15.51 μmol/L, SD = 2.89) and controls (15.89 μmol/L, SD = 2.23). We also undertook a meta-analysis on 960 cases and 1028 controls, which suggested a significant association of the substitution with PCOS in the dominant model of analysis (OR = 1.47 (95%CI = 1.04–2.09), P = 0.032]. Trial sequential analysis corroborated findings of the traditional meta-analysis. However, we found that the conclusions of meta-analysis were strongly influenced by studies that deviated from the Hardy Weinberg equilibrium. A careful investigation of each study and a trial sequential analysis suggested that 677 C>T substitution holds no clinical significance in PCOS in most of the populations.

Conclusion

In conclusion, MTHFR 677 C>T polymorphism does not affect PCOS risk in India. The association seen in the meta-analysis is due to an outlier study and studies showing deviation from the Hardy Weinberg equilibrium.     

Dendrimers Target the Ischemic Lesion in Rodent and Primate Models of Nonarteritic Anterior Ischemic Optic Neuropathy

IntroductionPolyamidoamine dendrimer nanoparticles (~ 4 nanometers) are inert polymers that can be linked to biologically active compounds. These dendrimers selectively target and accumulate in inflammatory cells upon systemic administration. Dendrimer-linked compounds enable sustained release of therapeutic compounds directly at the site of damage. The purpose of this study was to determine if dendrimers can be used to target the optic nerve (ON) ischemic lesion in our rodent and nonhuman primate models of nonarteritic anterior ischemic optic neuropathy (NAION), a disease affecting >10,000 individuals in the US annually, and for which there currently is no effective treatment.MethodsNAION was induced in male Long-Evans rats (rNAION) and in one adult male rhesus monkey (pNAION) using previously described procedures. Dendrimers were covalently linked to near-infrared cyanine-5 fluorescent dye (D-Cy5) and injected both intravitreally and systemically (in the rats) or just systemically (in the monkey) to evaluate D-Cy5 tissue accumulation in the eye and optic nerve following induction of NAION.ResultsFollowing NAION induction, Cy-5 dendrimers selectively accumulated in astrocytes and circulating macrophages. Systemic dendrimer administration provided the best penetration of the ON lesion site when injected shortly after induction. Systemic administration 1 day post-induction in the pNAION model gave localization similar to that seen in the rats.ConclusionsDendrimers selectively target the ischemic ON lesion after induction of both rNAION and pNAION. Systemic nanoparticle-linked therapeutics thus may provide a powerful, targeted and safe approach to NAION treatment by providing sustained and focused treatment of the cells directly affected by ischemia.     

Exploring Health Literacy in Medical University Students of Chongqing,China: A Cross-Sectional Study

Health literacy is important in public health and healthcare, particularly in effective communication between patients and health professionals. Although most medical students will eventually work as health professionals after graduation, research on health literacy of medical students is scarce. This study aimed to assess the health literacy level of medical students in Chongqing, China, and its influencing factors. A cross-sectional study was conducted and 1,275 participants (250 males and 1,022 females) who majored in five different disciplines were involved. The Health Literacy Questionnaire was used as the survey tool. The junior students obtained the highest scores, whereas the freshman students had the lowest scores on each scale. The average score of males was higher than that of females except in “feeling understood and supported by healthcare providers,” and the average score of students who reside in urban areas was higher than that of students in rural areas. Moreover, the average score of engineering students was higher than that of medical or health sciences students. Multiple linear regression models (R_adj² = 0.435, P = 0.000) showed that the grade, socioeconomic status, and parent’s highest level of education were positively correlated with health literacy. In conclusion, the health literacy levels of the medical students are insufficient and need improvement.     

Expressions of visual pigments and synaptic proteins in neonatal chick retina exposed to light of variable photoperiods

Light causes damage to the retina, which is one of the supposed factors for age-related macular degeneration in human. Some animal species show drastic retinal changes when exposed to intense light (e.g. albino rats). Although birds have a pigmented retina, few reports indicated its susceptibility to light damage. To know how light influences a cone-dominated retina (as is the case with human), we examined the effects of moderate light intensity on the retina of white Leghorn chicks (Gallus g. domesticus). The newly hatched chicks were initially acclimatized at 500 lux for 7 days in 12 h light: 12 h dark cycles (12L:12D). From posthatch day (PH) 8 until PH 30, they were exposed to 2000 lux at 12L:12D, 18L:6D (prolonged light) and 24L:0D (constant light) conditions. The retinas were processed for transmission electron microscopy and the level of expressions of rhodopsin, S- and L/M cone opsins, and synaptic proteins (Synaptophysin and PSD-95) were determined by immunohistochemistry and Western blotting. Rearing in 24L:0D condition caused disorganization of photoreceptor outer segments. Consequently, there were significantly decreased expressions of opsins and synaptic proteins, compared to those seen in 12L:12D and 18L:6D conditions. Also, there were ultrastructural changes in outer and inner plexiform layer (OPL, IPL) of the retinas exposed to 24L:0D condition. Our data indicate that the cone-dominated chick retina is affected in constant light condition, with changes (decreased) in opsin levels. Also, photoreceptor alterations lead to an overall decrease in synaptic protein expressions in OPL and IPL and death of degenerated axonal processes in IPL.     

Is the fracto‐mechanoluminescence of ZnS:Mn phosphor dominated by charged dislocation mechanism or piezoelectrification mechanism?

Mathematical approaches made for both the charged dislocation model and piezoelectrically induced electron bombardment model of fracto‐mechanoluminescence (FML), the luminescence induced by fracture of solids, in ZnS:Mn phosphor indicate that the piezoelectrically induced electron bombardment model provides a dominating process for the FML of ZnS phosphors. The concentration of 3000 ppm Mn²⁺ is optimal for ML intensity of ZnS:Mn phosphor. The decay time of ML gives the relaxation time of the piston used to deform the sample and the time t_m of maximum of ML is controlled by both the relaxation time of the piston and decay time of charges on the newly created surfaces of crystals. As the product of the velocity of dislocations and pinning time of dislocations gives the mean free path of a moving dislocation. Both factors play an important role in the ML excitation of impurity doped II–VI semiconductors. The linear increase of total ML intensity I_T with the impact velocity indicates that the damage increases linearly with impact velocity of the load. Thus, the ML measurement can be used remotely to monitor the real‐time damage in the structures, and therefore, the ML of ZnS:Mn phosphor has also the potential for a structural health monitoring system. Copyright © 2015 John Wiley & Sons, Ltd.     

Biobased technologies for the efficient extraction of biopolymers from waste biomass

Bioprocess and Biosystems Engineering - Regardless of considerable progress in synthetic plastic or polymer-based industry, its low biodegradability is a critical issue. Nevertheless, natural...     

Binding interaction study on human serum albumin with bactericidal gold nanoparticles synthesized from a leaf extract of Musa balbisiana: a multispectroscopic approach

This study describes the eco‐friendly, low‐cost and room‐temperature synthesis of gold nanoparticles from Musa balbisiana leaf extract, which acts as both reducing and stabilizing agent, and characterized by ultraviolet?visible (UV–vis) light spectroscopy, fourier transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FE‐SEM), analytical transmission electron microscopy (TEM), energy‐dispersive X‐ray spectroscopy (EDAX) and dynamic light scattering (DLS) instruments. These nanoparticles showed an average diameter of 33.83 ± 3.39 nm, which was confirmed from the size distribution histogram. The bactericidal activity of these nanoparticles was confirmed using bacteria Escherichia coli and Staphylococcus aureus at 1 and 2 nM minimum inhibitory concentrations, respectively. The interaction between nanoparticles and human serum albumin (HSA) was investigated, as this plays significant roles in biological systems. The nature of interaction, binding parameters and structural variation of HSA in the presence of these nanoparticles have been evaluated using several useful spectroscopic approaches such as UV–vis, FTIR, time‐resolved and steady‐state fluorescence, and circular dichroism in addition to the measurement of zeta potential. This interaction study revealed that static quenching occurs in this process with minimal alteration in the secondary structure, but the native structure of HSA remained unaltered. The binding constant and thermodynamic parameters of this interaction process were also evaluated.     

Mono- and digalactosyldiacylglycerol composition of dinoflagellates. VIII. Temperature effects and a perspective on the curious case of Karenia mikimotoi as a producer of the unusual, ‘green algal’ fatty acid hexadecatetraenoic acid [16:4(n-3)]

Previous studies have shown that dinoflagellates with different plastid ancestries have distinct differences in the fatty acid compositions and regiochemistries of their chloroplast-associated galactolipids, mono- and digalactosyldiacylglycerol (MGDG and DGDG, respectively), thus reflecting plastid origin as a major factor in plastid membrane composition. Specifically, dinoflagellates with aberrant plastids (e.g. Karenia brevis, Kryptoperidinium foliaceum and Lepidodinium chlorophorum) possess certain MGDG- and DGDG-associated fatty acids which are not found in peridinin-containing dinoflagellates (the largest group of photosynthetic dinoflagellates with a red algal plastid ancestry which is thought to be an evolutionary precursor to aberrant plastids), but which are common to other algal groups. For example, hexadecatetraenoic acid (16:4(n-3)) is common to green algae and is found in the MGDG and DGDG of L. chlorophorum, which agrees with its green algal plastid ancestry, while hexadecatrienoic acid (16:3) and hexadecadienoic acid (16:2) are found in the MGDG and DGDG of K. foliaceum, which agrees with its diatom plastid ancestry. Notably, 16:4 has been found by others in the total fatty acids and galactolipids of Karenia mikimotoi, but in no other examined members of the Kareniaceae (all of which have plastids of haptophyte origin). However, these findings lack information as to the regiochemistry of 16:4. We have utilized positive-ion electrospray ionization/mass spectrometry (ESI/MS) and ESI/MS/MS to demonstrate that 16:4, which aside from L. chlorophorum is not found conclusively in the MGDG and DGDG of any other dinoflagellates examined to date irrespective of plastid ancestry, is found in K. mikimotoi as 18:5/16:4 (sn-1/sn-2 regiochemistry) MGDG and DGDG, and that its presence is not modulated (i.e. does not become more saturated) with an increase in growth temperature. Considering an aberrant pigment composition as described by others, we present a perspective where galactolipid-associated 16:4 in K. mikimotoi indicates a plastid ancestry more convoluted than for other members of the Kareniaceae.