Spin-Selective Electron Transport Through Single Chiral Molecules.

The interplay between chirality and magnetism is a source of fascination among scientists for over a century. In recent years, chirality-induced spin selectivity (CISS) has attracted renewed interest. It is observed that electron transport through layers of homochiral molecules leads to a significant spin polarization of several tens of percent. Despite the abundant experimental evidence gathered through mesoscopic transport measurements, the exact mechanism behind CISS remains elusive. This study reports spin-selective electron transport through single helical aromatic hydrocarbons that are sublimed in vacuo onto ferromagnetic cobalt surfaces and examined with spin-polarized scanning tunneling microscopy (SP-STM) at a temperature of 5 K. Direct comparison of two enantiomers under otherwise identical conditions revealed magnetochiral conductance asymmetries of up to 50% when either the molecular handedness is exchanged or the magnetization direction of the STM tip or Co substrate is reversed. Importantly, the results rule out electron-phonon coupling and ensemble effects as primary mechanisms responsible for CISS.

RPE65 and retinal dystrophy: Report of new and recurrent mutations.

BACHGROUND: Leber congenital amaurosis (LCA) is a severe and congenital or early onset form of inherited retinitis pigmentosa (RP). To date, approximately 25 genes have been introduced in relation to LCA. In this regard, retinal pigment epithelium-specific 65 kDa (RPE65) is a well-known gene mutation that plays a role in the pathogenesis of 5-10% of LCA cases. METHOS: Two individuals fromseparate families were subjected to ehole exome sequencing (WES). Causativevariants were searched further assessed using Sanger sequencing. RESULTS: Here, two families with mutations in the RPE65 gene show severe and early onset LCA, as expected. In addition to the characterization of the phenotype, by reporting a new mutation (c.1451-1G>A), we further expand the mutation spectrum of RPE65. Likewise, as an interesting aspect of our study, we report on a previously reported RP-linked mutation associated with severe early onset LCA (c.T200G:p.L67R). CONCLUSIONS: Considering this variant in different populations, it is likely that it represents a hotspot and affects the function of the coded protein. The variable expressivity of the phenotype can be assumed by the presence of the modifier allele(s) as a result of a different genetic background or the effect of different environments on phenotype expression.

Expression Pattern of Long Non-coding RNAs in Schizophrenic Patients.

The role of long non-coding RNAs (lncRNAs) in the pathogenesis of neurological disorders including schizophrenia has been highlighted by independent studies. In the present study, we compared peripheral blood expression of seven lncRNAs between schizophrenic patients and sex- and age-matched controls using quantitative real-time PCR technique. FAS-AS1, PVT1 and TUG1 were significantly down-regulated in schizophrenic patients compared with healthy individuals (P = 0.007, 0.003 and 0.001, respectively). The association between FAS-AS1 expression and schizophrenia was significant in male subjects aged more than 50 but not in other subgroups. GAS5, NEAT1 and OIP5-AS1 expressions were not significantly different between patients and controls (P = 0.523, 0.739 and 0.267, respectively). The associations between GAS5, NEAT1 and OIP5-AS1 expressions and schizophrenia were significant in female subjects but not in male subjects. THRIL was up-regulated in schizophrenic patients compared with healthy subjects. Based on the results of bootstraped median regression, and after controlling for the effects of age and sex, the difference in its expression between cases and controls was significant (P = 0.014), while the interaction between group and sex was not significant. The expression of lncRNAs was not correlated with age in any study subgroups. In addition, we found sex-based pairwise correlations between PVT1 expression and expression levels of OIP5-AS1, THRIL and NEAT1. We also demonstrated high sensitivity and specificity of GAS5 for diagnosis of schizophrenia in female patients. The current study provides further evidence for the participation of lncRNAs in the pathogenesis of schizophrenia. Future studies are needed to confirm the suitability of lncRNAs as peripheral biomarkers for this psychiatric disorder.

Socket Interface Pressure and Amputee Reported Outcomes for Comfortable and Uncomfortable Conditions of Patellar Tendon Bearing Socket: A Pilot Study.

The objectives of the current study were to compare intra-socket pressure differences between comfortable and uncomfortable socket conditions, and the usefulness of subject perception of satisfaction, activity limitations, and socket comfort in distinguishing between these two socket conditions. Five unilateral trans-tibial amputees took part in the study. They answered the Socket Comfort Score (SCS) and Trinity Amputation and Prosthetic Experience Scale (TAPES) questionnaires before the interface pressure (in standing and walking) was measured for the uncomfortable socket condition at five regions of the residual limb. Participants were then provided with a comfortable socket and wore it for two weeks. Participants who were satisfied with the socket fit after two weeks repeated the SCS and TAPES questionnaires and interface pressure measurements. The differences between the test results of the two conditions were not statistically significant, except for the interface pressure at the popliteal region during the early stance phase, TAPES socket fit subscale, and the SCS. Due to large variability of the data and the lack of statistical significance, no firm conclusion can be made on the possible relationship between the interface pressure values and the patient-reported outcomes of the two socket conditions. A larger sample size and longer acclimation period are required to locate significant differences.

Enantioselective Adsorption on Magnetic Surfaces.

From the beginning of molecular theory, the interplay of chirality and magnetism has intrigued scientists. There is still the question if enantiospecific adsorption of chiral molecules occurs on magnetic surfaces. Enantiomer discrimination was conjectured to arise from chirality-induced spin separation within the molecules and exchange interaction with the substrate's magnetization. Here, it is shown that single helical aromatic hydrocarbons undergo enantioselective adsorption on ferromagnetic cobalt surfaces. Spin and chirality sensitive scanning tunneling microscopy reveals that molecules of opposite handedness prefer adsorption onto cobalt islands with opposite out-of-plane magnetization. As mobility ceases in the final chemisorbed state, it is concluded that enantioselection must occur in a physisorbed transient precursor state. State-of-the-art spin-resolved ab initio simulations support this scenario by refuting enantio-dependent chemisorption energies. These findings demonstrate that van der Waals interaction should also include spin-fluctuations which are crucial for molecular magnetochiral processes.

Hands-off and hands-on casting consistency of amputee below knee sockets using magnetic resonance imaging.

Residual limb shape capturing (Casting) consistency has a great influence on the quality of socket fit. Magnetic Resonance Imaging was used to establish a reliable reference grid for intercast and intracast shape and volume consistency of two common casting methods, Hands-off and Hands-on. Residual limbs were cast for twelve people with a unilateral below knee amputation and scanned twice for each casting concept. Subsequently, all four volume images of each amputee were semiautomatically segmented and registered to a common coordinate system using the tibia and then the shape and volume differences were calculated. The results show that both casting methods have intra cast volume consistency and there is no significant volume difference between the two methods. Inter- and intracast mean volume differences were not clinically significant based on the volume of one sock criteria. Neither the Hands-off nor the Hands-on method resulted in a consistent residual limb shape as the coefficient of variation of shape differences was high. The resultant shape of the residual limb in the Hands-off casting was variable but the differences were not clinically significant. For the Hands-on casting, shape differences were equal to the maximum acceptable limit for a poor socket fit.

Accuracy verification of magnetic resonance imaging (MRI) technology for lower-limb prosthetic research: utilising animal soft tissue specimen and common socket casting materials.

Lower limb prosthetic socket shape and volume consistency can be quantified using MRI technology. Additionally, MRI images of the residual limb could be used as an input data for CAD-CAM technology and finite element studies. However, the accuracy of MRI when socket casting materials are used has to be defined. A number of six, 46 mm thick, cross-sections of an animal leg were used. Three specimens were wrapped with Plaster of Paris (POP) and the other three with commercially available silicone interface liner. Data was obtained by utilising MRI technology and then the segmented images compared to corresponding calliper measurement, photographic imaging, and water suspension techniques. The MRI measurement results were strongly correlated with actual diameter, surface area, and volume measurements. The results show that the selected scanning parameters and the semiautomatic segmentation method are adequate enough, considering the limit of clinical meaningful shape and volume fluctuation, for residual limb volume and the cross-sectional surface area measurements.

Deposition of Chiral Heptahelicene Molecules on Ferromagnetic Co and Fe Thin-Film Substrates.

The discovery of chirality-induced spin selectivity (CISS), resulting from an interaction between the electron spin and handedness of chiral molecules, has sparked interest in surface-adsorbed chiral molecules due to potential applications in spintronics, enantioseparation, and enantioselective chemical or biological processes. We study the deposition of chiral heptahelicene by sublimation under ultra-high vacuum onto bare Cu(111), Co bilayer nanoislands on Cu(111), and Fe bilayers on W(110) by low-temperature spin-polarized scanning tunneling microscopy/spectroscopy (STM/STS). In all cases, the molecules remain intact and adsorb with the proximal phenanthrene group aligned parallel to the surface. Three degenerate in-plane orientations on Cu(111) and Co(111), reflecting substrate symmetry, and only two on Fe(110), i.e., fewer than symmetry permits, indicate a specific adsorption site for each substrate. Heptahelicene physisorbs on Cu(111) but chemisorbs on Co(111) and Fe(110) bilayers, which nevertheless remain for the sub-monolayer coverage ferromagnetic and magnetized out-of-plane. We are able to determine the handedness of individual molecules chemisorbed on Fe(110) and Co(111), as previously reported for less reactive Cu(111). The demonstrated deposition control and STM/STS imaging capabilities for heptahelicene on Co/Cu(111) and Fe/W(110) substrate systems lay the foundation for studying CISS in ultra-high vacuum and on the microscopic level of single molecules in controlled atomic configurations.

Renal Function in Patients with Thalassemia Major Receiving Exjade® Dispersible Tablets and a New Film-coated Tablet Formulation of Deferasirox (Nanojade®).

Background: In patients with ß-thalassemia major (TM), one of the long-term complications of regular blood transfusion is renal dysfunction. The purpose of the current study was to evaluate the renal function in TM patients receiving Exjade® dispersible tablets and a new film-coated tablet formulation of deferasirox (Nanojade®). Materials and Methods: In this descriptive cross-sectional study, a total of 80 TM patients aged 11-48-year-old entered the study. Patients received 20-30 mg/kg/d (single dose) Exjade® (Exjade group, n = 40) and Nanojade® (Nanojade group, n = 40) orally. To evaluated renal function, serum creatinine (SCr), estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), 24-h urine protein (UPro), UCa/UCr, spot UPro/UCr ratio, and serum ferritin were calculated at baseline and every 3 months to 9 months. Results: There was no significant difference in SCr, BUN, eGFR, 24-h UPro, UPro/UCr ratio, UCa/UCr ratio, and serum ferritin between groups at baseline and end of study (P baseline> 0.05, P end of study> 0.05). There was no significant difference in proteinuria between groups at baseline and end of study (P baseline> 0.05, P end of study> 0.05). Conclusions: The proportion of SCr, BUN, eGFR, 24-h UPro, UPro/UCr ratio, and UCa/UCr ratio was not significantly different in TM patients treated with Nanojade® compared to patients' received Exjade®. Nanojade® had similar effects to Exjade®, and therefore, the use of Nanojade® is safe in TM patients and does not seem to be associated with increased renal failure, proteinuria, and hypercalciuria.

Magnetic Nanoprobes for Spatio-Mechanical Manipulation in Single Cells.

Magnetic nanoparticles (MNPs) are widely known as valuable agents for biomedical applications. Recently, MNPs were further suggested to be used for a remote and non-invasive manipulation, where their spatial redistribution or force response in a magnetic field provides a fine-tunable stimulus to a cell. Here, we investigated the properties of two different MNPs and assessed their suitability for spatio-mechanical manipulations: semisynthetic magnetoferritin nanoparticles and fully synthetic 'nanoflower'-shaped iron oxide nanoparticles. As well as confirming their monodispersity in terms of structure, surface potential, and magnetic response, we monitored the MNP performance in a living cell environment using fluorescence microscopy and asserted their biocompatibility. We then demonstrated facilitated spatial redistribution of magnetoferritin compared to 'nanoflower'-NPs after microinjection, and a higher magnetic force response of these NPs compared to magnetoferritin inside a cell. Our remote manipulation assays present these tailored magnetic materials as suitable agents for applications in magnetogenetics, biomedicine, or nanomaterial research.

GRM7 polymorphisms are not associated with ischemic stroke in Iranian population.

Objectives: Ischemic stroke is the main neurological cause of acquired incapability in adults and a prominent cause of mortality. Several association studies have been conducted to explore the role of candidate genes in this neurological condition.Methods: In the present study, we aimed at identification of association between Glutamate Metabotropic Receptor 7 (GRM7) and risk of ischemic stroke in Iranian population. Two intronic variants within this gene (rs6782011 and rs779867) were genotyped in 318 sporadic ischemic stroke cases and 300 unrelated, healthy controls individuals.Results: No significant difference was found in allele, genotype or haplotype frequencies of these SNPs between cases and controls after correction for multiple comparisons.Conclusion: Consequently, the assessed GRM7 variants are not implicated in risk of ischemic stroke in Iranian population.

Genomic variants within the long non-coding RNA H19 confer risk of breast cancer in Iranian population.

OBJECTIVE: The long non-coding RNA (lncRNA) H19 is an imprinted lncRNA with acknowledged roles in carcinogenesis. METHODS: In the current study, we genotyped two single nucleotide polymorphisms (SNPs) within H19 in 111 breast cancer patients and 130 age-matched healthy subjects using tetra primer-ARMS-PCR technique. The T allele of rs2839698 conferred breast cancer risk in the assessed population (OR (95% CI) = 2.52 (1.75-3.64), adjusted P value = 1.3E-6), while and the T allele of rs217727 had a protective effect (OR (95% CI) = 0.42 (0.27-0.66), adjusted P value = 2.8E-4). Both SNPs were associated with breast cancer risk in recessive, dominant and co-dominant models. The T C haplotype (rs2839698 and rs217727) significantly increased risk of breast cancer (OR (95% CI) = 2.4 (1.65-3.45), adjusted P value = 1.2E-5), while the C T haplotype had a protective role (OR (95% CI) = 0.31 (0.18-0.52), adjusted P value = 2.03E-5). The present study highlights the role of H19 SNPs in conferring risk of breast cancer in Iranian population. Future studies with larger sample sizes are required to verify these data.

Antiglycation and antioxidant activity of four Iranian medical plant extracts.

OBJECTIVE: Diabetes mellitus (DM) is the most common metabolic disorder that defined by chronic hyperglycemia for the deficiency in insulin secretion or resistance. Hyperglycemia could induce non-enzymatic glycation of proteins. It has been suggested that some traditional plants can improve blood glucose and inhibit glycation process. This work evaluates and compares the anti-glycation activities of four Iranian plant extracts in vitro. METHODS: The methanolic extract of "Fumaria officinalis, Stachys lavandulifolia, Salvia hydrangea and Rosa Damascene" was prepared in three different concentrations. Phenolic, flavonoids content and antioxidant activity were evaluated. The multistage glycation markers-fructosamines (early stage), protein carbonyls (intermediate stage) and ß aggregation of albumin were investigated in the bovine serum albumin (BSA)/ glucose systemt. RESULTS: All plants showed the high potency of scavenging free radicals and glycation inhibition in the following order: Fumaria officinalis> Rosa Damascene> Stachys lavandulifolia > Salvia hydrangea. There was a significant correlation between antioxidant and anti-glycation activity. Also, the antioxidant and anti-glycation capacity of extracts correlated with total phenolic and flavonoids content. CONCLUSION: Our findings demonstrated that the studied plants are good sources of anti-glycation and antioxidant compounds and, these properties can primarily attributable to phenolics, particularly flavonoids.

Temperature measurement and control system for transtibial prostheses: Functional evaluation.

The accumulation of heat inside the prosthetic socket increases skin temperature and fosters perspiration, which consequently leads to high tissue stress, friction blister, discomfort, unpleasant odor, and decreased prosthesis suspension and use. In the present study, the prototype of a temperature measurement and control (TM&C) system was designed, fabricated, and functionally evaluated in a phantom model of the transtibial prosthetic socket. The TM&C system was comprised of 12 thermistors divided equally into two groups that arranged internal and external to a prosthetic silicone liner. Its control system was programmed to select the required heating or cooling function of a thermal pump to provide thermal equilibrium based on the amount of temperature difference from a defined set temperature, or the amount of difference between the mean temperature recorded by inside and outside thermistors. A thin layer of aluminum was used for thermal conduction between the thermal pump and different sites around the silicone liner. The results showed functionality of the TM&C system for thermoregulation inside the prosthetic socket. However, enhancing the structure of this TM&C system, increasing its thermal power, and decreasing its weight and cost are main priorities before further development.

Temperature measurement and control system for transtibial prostheses: Single subject clinical evaluation.

The snug fit of a prosthetic socket over the residual limb can disturb thermal balance and put skin integrity in jeopardy by providing an unpleasant and infectious environment. The prototype of a temperature measurement and control (TM&C) system was previously introduced to resolve thermal problems related to prostheses. This study evaluates its clinical application in a setting with reversal, single subject design. The TM&C system was installed on a fabricated prosthetic socket of a man with unilateral transtibial amputation. Skin temperature of the residual limb without prosthesis at baseline and with prosthesis during rest and walking was evaluated. The thermal sense and thermal comfort of the participant were also evaluated. The results showed different skin temperature around the residual limb with a temperature decrease tendency from proximal to distal. The TM&C system decreased skin temperature rise after prosthesis wearing. The same situation occurred during walking, but the thermal power of the TM&C system was insufficient to overcome heat build-up in some regions of the residual limb. The participant reported no significant change of thermal sense and thermal comfort. Further investigations are warranted to examine thermography pattern of the residual limb, thermal sense, and thermal comfort in people with amputation.

FOXP3 gene variations and susceptibility to autism: A case-control study.

Autism Spectrum Disorders (ASD) are a group of heterogeneous neurodevelopmental disorders associated with immune system dysregulation. There are supporting evidences for the role of Forkhead Box P3 (FOXP3) gene as a lineage specification factor of regulatory T cells in the pathogenesis of ASD. The aim of this study was to explore possible relationship between genetic variants rs2232365 and rs3761548 of FOXP3 and ASD in 523 ASD patients versus 472 control individuals. Allele frequency analyses showed significant overpresentation of rs2232365-G allele in cases versus controls. In addition, rs2232365 GG genotype was associated with ASD in dominant inheritance model. Haplotype analysis revealed no significant association of any estimated block of rs2232365/rs3761548 with ASD. Our study indicated that rs2232365 is associated with ASD.

Synaptosome-Associated Protein 25 (SNAP25) Gene Association Analysis Revealed Risk Variants for ASD, in Iranian Population.

Autism spectrum disorder (ASD) is a common, complex neurological condition, affecting approximately 1% of people worldwide. Monogenic neurodevelopmental disorders which showed autistic behavior patterns have suggested synaptic dysfunction, as a key mechanism in the pathophysiology of ASD. Subsequently, genes involved in synaptic signaling have been investigated with a priority for candidate gene studies. A synaptosomal-associated protein 25 (SNAP25) gene plays a crucial role in the central nervous system, contributing to exocytosis by targeting and fusion of vesicles to the cell membrane. Studies have shown a correlation between aberrant expression of the SNAP25 and a variety of brain diseases. Single nucleotide polymorphisms (SNPs) in this gene are associated with several psychiatric diseases, such as bipolar, schizophrenia, and attention-deficit/hyperactivity disorder. The aim of the present study was to investigate whether polymorphisms (rs3746544 and rs1051312) in the regulatory 3'-untranslated region (3'UTR) of the SNAP25 gene have an association with ASD in unrelated Iranian case (N = 524)-control (N = 472) samples. We observed robust association of the rs3746544 SNP and ASD patients, in both allele and haplotype-based analyses. Our results supported the previous observations and indicated a possible role for SNAP25 polymorphisms as susceptibility genetic factors involved in developing ASD.

The prototype of a thermoregulatory system for measurement and control of temperature inside prosthetic socket.

BACKGROUND AND AIM: Thermal related problems with prostheses are common complaints of amputee people. This article aims to introduce a thermoregulatory technique as a potential solution for those problems in prostheses wearers. TECHNIQUE: A smart thermoregulatory system was designed, manufactured, and installed on a phantom model of a prosthetic socket. It captured temperature data from 16 sensors positioned at the interface between the phantom model and a silicone liner and used their average for comparison with a defined set temperature to select required heating or cooling functions for thermal equilibrium. A thin layer of Aluminum was used to transfer temperature between thermal pump and different sites around the phantom model. DISCUSSION: The feasibility of this thermoregulatory technique was confirmed by its ability to provide thermal equilibrium. Further investigations to improve the design of thermoregulatory system are necessary including temperature transfer element and power consumption based on thermal capacity and thermal inertia of the residual limb. CLINICAL RELEVANCE: The smart thermoregulatory system by providing thermal equilibrium between two sides of a prosthetic silicone liner can control residual limb skin temperature and sweating. Consequently, it can improve quality of life in amputee people.

Systematic review of effects of current transtibial prosthetic socket designs-Part 1: Qualitative outcomes.

This review is an attempt to untangle the complexity of transtibial prosthetic socket fit, determine the most important characteristic for a successful fitting, and perhaps find some indication of whether a particular prosthetic socket type might be best for a given situation. Further, it is intended to provide directions for future research. We followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and used medical subject headings and standard key words to search for articles in relevant databases. No restrictions were made on study design or type of outcome measure. From the obtained search results (n = 1,863), 35 articles were included. The relevant data were entered into a predefined data form that incorporated the Downs and Black risk of bias assessment checklist. Results for the qualitative outcomes (n = 19 articles) are synthesized. Total surface bearing sockets lead to greater activity levels and satisfaction in active persons with amputation, those with a traumatic cause of amputation, and younger persons with amputation than patellar tendon bearing sockets. Evidence on vacuum-assisted suction and hydrostatic sockets is inadequate, and further studies are much needed. To improve the scientific basis for prescription, comparison of and correlation between mechanical properties of interface material, socket designs, user characteristics, and outcome measures should be conducted and reported in future studies.

Systematic review of effects of current transtibial prosthetic socket designs--Part 2: Quantitative outcomes.

This review is an attempt to untangle the complexity of transtibial prosthetic socket fit and perhaps find some indication of whether a particular prosthetic socket type might be best for a given situation. In addition, we identified knowledge gaps, thus providing direction for possible future research. We followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, using medical subject headings and standard key words to search for articles in relevant databases. No restrictions were made on study design and type of outcome measure used. From the obtained search results (n = 1,863), 35 articles were included. The relevant data were entered into a predefined data form that included the Downs and Black risk of bias assessment checklist. This article presents the results from the systematic review of the quantitative outcomes (n = 27 articles). Trends indicate that vacuum-assisted suction sockets improve gait symmetry, volume control, and residual limb health more than other socket designs. Hydrostatic sockets seem to create less inconsistent socket fittings, reducing a problem that greatly influences outcome measures. Knowledge gaps exist in the understanding of clinically meaningful changes in socket fit and its effect on biomechanical outcomes. Further, safe and comfortable pressure thresholds under various conditions should be determined through a systematic approach.