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Let V be a vector space over the binary field F 2 = { 0 , 1 } with dim V ≥ 2 . If W = { W 1 , ... , W n } is a family of hyperplanes of V, one says that W is an irredundant covering for V provided that W covers V, that is, ∪ i = 1 n W i = V and no proper subfamily of W covers V. We show that W is an irredundant covering for V if and only if the following three conditions are satisfied: (i) n is odd, (ii) dim V / ∩ i = 1 n W i = n − 1 , and (iii) any (n − 1) -fold intersection of the elements of W has codimension n – 1. Moreover, we show that for any odd integer n with 3 ≤ n ≤ dim V + 1 there is an irredundant hyperplane covering for V with n elements. [ABSTRACT FROM AUTHOR]

Glycation is a nonenzymatic posttranslational modification (PTM) known to be increased in the brains of hyperglycemic patients. Alpha-synuclein (αSN), a central player in the etiology of Parkinson's disease, can be glycated at lysine residues, thereby reducing αSN fibril formation in vitro and modulating αSN aggregation in cells. However, the molecular basis for these effects is unclear. To elucidate this, we investigated the aggregation of αSN modified by eight glycating agents, namely the dicarbonyl compound methylglyoxal (MGO) and the sugars ribose, fructose, mannose, glucose, galactose, sucrose, and lactose. We found that MGO and ribose modify αSN to the greatest extent, and these glycation products are the most efficient inhibitors of fibril formation. We show glycation primarily inhibits elongation rather than nucleation of αSN and has only a modest effect on the level of oligomerization. Furthermore, glycated αSN is not significantly incorporated into fibrils. For both MGO and ribose, we discovered that a level of ~5 modifications per αSN is optimal for inhibition of elongation. The remaining sugars showed a weak but optimal inhibition at ~2 modifications per αSN. We propose that this optimal level balances the affinity for the growing ends of the fibril (which decreases with the extent of modification) with the ability to block incorporation of subsequent αSN subunits (which increases with modification). Our results are not only relevant for other αSN PTMs but also for understanding PTMs affecting other fibrillogenic proteins and may thus open novel avenues for therapeutic intervention in protein aggregation disorders. [ABSTRACT FROM AUTHOR]

Aggregation of the 140-residue protein α-synuclein (αSN) is a key factor in the etiology of Parkinson's disease. Although the intensely anionic C-terminal domain (CTD) of αSN does not form part of the amyloid core region or affect membrane binding ability, truncation or reduction of charges in the CTD promotes fibrillation through as yet unknown mechanisms. Here, we study stepwise truncated CTDs and identify a threshold region around residue 121; constructs shorter than this dramatically increase their fibrillation tendency. Remarkably, these effects persist even when as little as 10% of the truncated variant is mixed with the full-length protein. Increased fibrillation can be explained by a substantial increase in self-replication, most likely via fragmentation. Paradoxically, truncation also suppresses toxic oligomer formation, and oligomers that can be formed by chemical modification show reduced membrane affinity and cytotoxicity. These remarkable changes correlate to the loss of negative electrostatic potential in the CTD and highlight a double-edged electrostatic safety guard. Farzadfard et al. present a comprehensive analysis of a range of C-terminal truncations of aSN, linking the importance of high C-terminus charge for decreased fibrillation rates. The ability to formation oligomers, to disrupt synthetic vesicles and cell toxicity was reduced with truncated aSN, aiding in understanding of the intramolecular interactions of aSN which promote/inhibit aggregation. [ABSTRACT FROM AUTHOR]

Let A be an additive semigroup of real numbers the additive group generated by which is non-cyclic. Let I = (a , b) be an open interval and A = f α : α ∈ A be an iteration semigroup of fixed point free increasing functions of I onto I such that α < β implies f α < f β . We show that A can be embedded in a disjoint continuous iteration group if and only if for any compact subinterval K of I of positive length the set ⋃ f ∈ A f - 1 (K) contains an interval of the form (a, c). To do this we provide some results on the density of certain sets of real numbers which are crucial in establishing the main results. [ABSTRACT FROM AUTHOR]

Alexander Šarkovskiǐ has shown that the only continuous periodic functions satisfying the duplication formula ψ (2x)=2ψ (x)2−1 are of the form ψ (x) = cos (ω x), where ω is a real constant. The aim of this paper is to generalize this result as follows: Let I be a compact interval, ƒ : I → I be a continuous surjection and k > 1 be an integer. Let ψ : R → I and φ : R → I be two solutions of the Poincaré functional equation ψ (kx) = ƒ(ψ (x)) with ψ cosine-like and φ non-constant, continuous and periodic. We will show that there exist a positive real number ω and an integer m such that φ (x) = ψ (ω x + mλ/(k−1)) (x ∈ R), where λ is the principal period of ψ. As a tool, we employ the simultaneous Schröder-difference functional equation σ (kx) = ± kσ (x), σ (x + 1) = ε (x)σ (x) + r(x), where ε(x) = ± 1 and r(x)∈ Z for all x ≥ 0, and determine its solution. [ABSTRACT FROM AUTHOR]

To any complex polynomial f with constant term 1 we associate a special sequence by Newton's identities in terms of the coefficients of f. This sequence constitutes the coefficients of the power series representation of − f ′ / f . We prove the fundamental theorem of algebra by showing that this sequence does not converge to zero, or equivalently, f ′ / f is not an entire function. [ABSTRACT FROM AUTHOR]

Let A be a set of positive reals, I be a real interval and A { f α : α ∈ A } be a set of functions of I into itself. We determine necessary and sufficient conditions on A, A and I for the system of Poincaré functional equation ψ (α x) = f α (ψ (x)) (α ∈ A , x ∈ R +) to have a continuous increasing solution ψ : R + → I which is non-constant. It turns out that such a solution exists whenever A is closed under multiplication and A is a multiplicative iteration semigroup of increasing continuous functions satisfying a specific density condition and I is a half-open interval. Finally, we show that such a solution is unique up to an internal multiplicative constant. [ABSTRACT FROM AUTHOR]

Purpose: MicroRNAs are small single-strand noncoding RNAs that can be deregulated in a variety of cancers. Over the past few years, multiple markers have been discovered in chronic lymphocytic leukemia (CLL). Among these, miRNAs seem to have important roles in the pathogenesis of CLL. The development and validation of miRNA-expression patterns as biomarkers should have a significant impact in cancer diagnosis, therapeutic success, and increasing the life expectancy of patients. In this study, to specify the utility of circulatory miRNA expression as noninvasive and useful biomarkers for CLL, we analyzed the dysregulation of seven miRNAs: miR30d, miR25-3p, miR19a-3p, miR133b, miR451a, miR145, and miR144 in CLL-patient sera. Methods: Thirty untreated patients with flow-cytometry confirmation of CLL were chosen. Serum samples were collected from 30 newly diagnosed CLL patients. Fifteen healthy samples were taken for comparison as controls. RNA was extracted using Trizol. RNA from CLL patient specimens was compared to controls with real-time PCR. Results: Seven miRNAs were differently expressed between CLL and normal specimens using the comparative 2−ΔΔCt method. miRNAs  133b, 25-3p, 451a, 145, 19a-3p, and 144 were overexpressed in sera obtained from CLL patients, and miRNA-30d was underexpressed in patient samples. Among these seven miRNAs, miR19a-3p and miR25-3p showed the most deregulation in CLL patients. Conclusion: Real-time PCR is an applied means to perform high-throughput investigation of serum-RNA samples. We assessed the expression of seven miRNAs in CLL patients by this method. The results demonstrated that the use of miRNA-expression profiling may have an impressive role in the diagnosis of CLL. In addition, miRNA  19a-3p and 25-3p are known oncogenes with therapeutic and potential biomarkers. [ABSTRACT FROM AUTHOR]

Let f : R + → R + be an increasing continuous function having no fixed point such that the differential d : = lim x → 0 + ⁡ f (x) x exists and 0 < d < 1. In this paper we present practical tests to check if the Schröder equation σ (f (x)) = d σ (x) has a regularly varying solution on R +. To do this we associate to f a sequence { u 0 , u 1 , ... } of continuous functions of [ 0 , 1 ] onto itself in such a way that the desired solution exists if and only if the iterative sequence U n : = u n ∘ u n − 1 ∘ ⋯ ∘ u 0 converges uniformly. Concerning this, we present three tests called: The Norm Test, The Root Test of Iterations, The Alternating Iterative Sequence Test. [ABSTRACT FROM AUTHOR]

Let f : R + → R + be an increasing homeomorphism with no fixed point such that the derivative d : = lim x → 0 + f (x) x exists and 0

Background Accurate information about disability rate after stroke remains largely unclear in many countries. Population-based studies are necessary to estimate the rate and determinants of disability after stroke. Methods Patients were recruited from the Mashhad Stroke Incidence Study and followed for five years after their index event. Disability was measured using the modified Rankin scale and functional dependency was measured using the Barthel index. Results Among 684 patients registered in this study, 624 were first-ever strokes. In total, 69.0% (n = 409) of patients either died or remained disabled at five-year follow-up. Among the first-ever stroke survivors, 18.5% (n = 69) at one year and 15.9% (n = 31) at five years required major assistance in their daily activities. Patients with a history of stroke (before the study period) compared with first-ever strokes were more likely to be disabled at one year (modified Rankin scale>2 in 40.0% vs. 19.1%; P < 0.001). Advanced age, severity of stroke at the time of admission, diabetes mellitus, and educational level (<12 years) were independently associated with greater disability and functional dependency. Conclusion We found that significant disability and functional dependency after stroke in Northeast Iran were largely attributable to the effects of stroke severity and prior dependency. [ABSTRACT FROM AUTHOR]

Natural life is encoded by evolvable, DNA-based memory. Recent advances in dynamic genome-engineering technologies, which we collectively refer to as in vivo DNA writing, have opened new avenues for investigating and engineering biology. This Review surveys these technological advances, outlines their prospects and emerging applications, and discusses the features and current limitations of these technologies for building various genetic circuits for processing and recording information in living cells. [ABSTRACT FROM AUTHOR]

Let f be a fixed point free increasing continuous function of the interval into itself such that exists, does not depend on x and belongs to the interval (0, 1). We deal with the Schröder equation in a more general setting by giving necessary and sufficient conditions for it to have a solution which is uniformly regularly varying with respect to (f, a) for some , that is, the relation holds locally uniformly with respect to for some . We show that such a solution is continuous, increasing and regularly varying in the usual sense. [ABSTRACT FROM AUTHOR]

Let f be a fixed point free increasing homeomorphism of R + onto itself such that the limit d : = lim n → ∞ ⁡ f n + 1 ( x ) f n ( x ) exits, belongs to the interval ( 0 , 1 ) and is independent of x ∈ R + . For each α ∈ R + we define the α -bi-iterative limits f α , ∞ _ and f α , ∞ ‾ of f to be the lower and the upper limits of the sequence { f − n ( α f n ( x ) ) : n ∈ N , x ∈ R + } , respectively. We show that the following statements are equivalent: (a) The Schröder equation σ ( f ( x ) ) = d σ ( x ) has a continuous regularly varying solution. (b) The set consisting of the differentials at zero of the bi-iterative limits of f is dense in the multiplicative group R + . (c) There exists α ∈ R + such that β : = lim x → 0 + ⁡ f α , ∞ _ ( x ) / x exists, belongs to R + and log ⁡ β / log ⁡ d is irrational. [ABSTRACT FROM AUTHOR]

Interesting phenomena of reflex epileptic syndromes are characterized by epileptic seizures each one induced by specific stimulus with a variety of types. Simple triggers, which lead to seizures within seconds, are of sensory type (most commonly visual, most rarely tactile or proprioceptive stimuli). Complex triggers, which are mostly of cognitive type such as praxis, reading, talking, and music, usually induce the epileptic event within minutes. It should differ from what most epileptic patients report as provocative precipitants for seizures (such as emotional stress, fatigue, fever, sleep deprivation, alcohol, and menstrual cycle). The identification of a specific trigger is not only important for patients or their parents to avoid seizures, but also it might help neurologists to choose the most effective antiepileptic drug for each case. In addition, research in this area may possibly reveal some underlying pathophysiology of epileptic phenomena in the brain. In this review, we briefly introduce reported reflex epileptic seizures, their clinical features and management. [ABSTRACT FROM AUTHOR]

Let f be an increasing homeomorphism of [0, ∞) onto itself with no nonzero fixed point such that d: =f' (0) exists and 0< d< 1. We investigate the limit fα, ∞ (x): =limn→ ∞ { f- n (α fn (x)) (x≥; 0, α > 0) and its properties. We show that the Schröder equation σ (f (x)) =dσ (x) has a regularly varying solution if and only if for some a> 0 the limit fα, ∞ (a) exists for α in a dense set A in R+ and the map A⊃ α → fα, ∞ (a) is injective. [ABSTRACT FROM AUTHOR]

The structure of disjoint iteration groups of real homeomorphisms has been determined by M. C. Zdun without any regularity condition. In this paper we turn to the regular case and describe the structure of regular disjoint groups of real homeomorphisms which are generalizations of regular disjoint iteration groups. It is shown that such a group is either embedded in a regular iteration group, or it is homeomorphically conjugate to a regular piecewise linear disjoint group. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Complementary and alternative medicine has been increasingly used to treat chronic illnesses, such as diabetes mellitus. However, various limitations in terms of their application and efficacies exist. Furthermore, there is still much to be done to discover the right herbal medicine for diabetes. Aim of the study This paper aims to evaluate previous herbal studies on the management of diabetes mellitus, to address their strengths and weaknesses and propose a general framework for future studies. Approach and methods Data sources such as PubMed, ScienceDirect, Scopus, SpringerLink, and Wiley were searched, limited to Iran, using 36 search terms such as herbal, traditional, medicine, and phytopharmacy in combination with diabetes and related complications. Reviewed articles were evaluated regarding the use of botanical nomenclature and included information on (1) identity of plants and plant parts used, (2) the processing procedure, and (3) the extraction process. The main outcomes were extracted and then surveyed in terms of the efficacies of herbs in the management of diabetes mellitus. Then a comparative study was performed between Iranian and non-Iranian studies with respect to herbs best studied in Iran. Results Of the 82 herbs studied in Iran, only six herbs were endemic and 19 were studied in detail. Although most of the reviewed herbs were found to decrease the level of blood glucose (BG) and/or glycated hemoglobin (HbA1C) in both Iranian and non-Iranian studies, information on their pharmacological mechanisms is scarce. However, the level of HbA1C was measured in a limited number of clinical trials or animal studies. Available information on both short- and long-term use of studied herbs on diabetes related complications and functions of involved organs as well as comorbid depression and/or simultaneous changes in lifesyle is also insufficient. Furthermore, little or no information on their phytochemical, toxicological, and herb–drug interaction properties is available. It is worth noting that the efficacy of the reviewed herbs has been studied scarcely in both humans and animals regarding both Iranian and non-Iranian studies. A significant number of reviewed articles failed to cite the scientific name of herbs and include information on the processing procedure and the extraction process. Conclusions Treatment of diabetes mellitus as a multifactorial disease using herbal medicines requires a comprehensive approach. In order to discover the right herbal medicine for the management of diabetes many other important factors than the levels of BG, HbA1C and insulin should be considered. According to our criteria, all the reviewed herbs suffered from inadequate investigation in human, animal and in vitro models in this respect, whereas they are worth investigating further. However, more research on endemic plants and the traditional history of herbal medicine is warranted. In our opinion, the pharmacological, toxicological, and phytochemical information should be obtained before clinical trials. Furthermore, information such as botanical scientific nomenclature, side effects, and toxicity will improve the quality and validity of publications in herbal research. In particular, designing a database covering all valid information about herbs and/or diseases will decrease unnecessary costs and increase the efficiency of research. [ABSTRACT FROM AUTHOR]

Letbe a topological space,be a right topological group (i.e. a group endowed with a topology under which for everythe mapis continuous) andbe a set of self-homeomorphisms of. We give necessary and sufficient conditions for the system of Shröder/Abel equationsto have a non-constant continuous solution, whereis a given map. Moreover, we describe this solution and formulate it in terms of an appropriate quotient map. As an important special case the simultaneous systems of Abel equations on the Euclidean spaceswill be studied in detail. [ABSTRACT FROM AUTHOR]

Introduction: According to some studies, play therapy and story-telling affect on children's attention and concentration so the purpose of the present study aimed to assess the effect of combination of purposeful play therapy and narrative therapy on attention and concentration of preschool children in a nonclinical sample. Materials and Methods: The statistical community of the clinical trial with pre-test, post-test design is all pre-school children of region 2 in Mashhad. Four kindergartens were selected through multi cluster sampling method and 60 children with IQ score in range of 90-119 (6-6.5 years old girls and boys) were selected by available sampling method and randomly assigned to 4 groups (10 persons) play therapy, narrative therapy, combined purposeful play therapy and narrative therapy and control group. The research instruments were Wechsler IQ test, test of every day attention for children and continuous performance test. Experimental groups received 12 sessions of interventions and the control group did not receive any treatment. The data were analyzed using descriptive statistics and multi variable analysis of covariance. Results: Children's attention increased significantly more in combined play therapy and narrative therapy group than the other groups (P=0.004). However, children's concentration did not increase significantly more than other groups in the combined play therapy and narrative therapy group (P=0.31). Conclusion: According to the results, purposeful play therapy and narrative therapy as attractive and educational tools can promote attention factors and prevent to attention defects among children. [ABSTRACT FROM AUTHOR]

Let I be an open interval. We describe the general structure of groups of continuous self functions on I which are disjoint, that is, the graphs of any two distinct elements of them do not intersect. Initially the class of all disjoint groups of continuous functions is divided in three subclasses: cyclic groups, groups the limit points of their orbits are Cantor-like sets, and finally those the limit points of their orbits are the whole interval I. We will show that (1) each group of the second type is conjugate, via a specific homeomorphism, to a piecewise linear group of the same type; (2) each group of the third type is a subgroup of a continuous disjoint iteration group. We conclude the Zdun's result on the structure of disjoint iteration groups of continuous functions as special case of our results. [ABSTRACT FROM AUTHOR]

Abstract: In the present work, we address the question of whether different amino acids have different β-sheet initiating and terminating characteristics. Using a large scale analysis of parallel and antiparallel β-sheets in a non-redundant dataset of proteins, we observed that most of the amino acids show significant under- or over-representation in at least one of the positions at the two ends of β-sheets, which are denoted as N-cap and C-cap. In addition, based on statistical data and structural comparison, we found that certain amino acids, especially Asp, Asn, Gly and Pro have strong tendencies to block β-sheet continuation. Hence, we can consider these residues as β-sheet terminators. It was also proposed that the dipole moments in parallel β-sheets, whose direction is from C-terminal (partially negative) to N-terminal (partially positive), are much stronger than has previously been suggested. In fact, enhancement of dipole moments in parallel β-sheets is a result of the positioning of positively charged residues at N-cap and negatively charged residues at C-cap. This enhancement in dipole moment magnitude leads to strengthened dipolar interactions between parallel β-sheets dipoles and other partners especially α-helices dipoles. The results provide an explanation for the antiparallel alignment of parallel β-sheets with α-helices. [Copyright &y& Elsevier]

Information encoded in DNA can be stored in, and retrieved from, everyday objects. [ABSTRACT FROM AUTHOR]

Let I be a compact real interval, k > 1 an integer and f : I → I a continuous surjection such that: (i) f achieves its absolute extrema at exactly k + 1 points, and on the k remaining intervals f is strictly monotone, (ii) the set of all points among which the iterations of f attain their absolute extrema is dense in I. We show that the above conditions on f are necessary and sufficient for the Poincaré functional equation ψ (k x) = f (ψ (x)) to have a cosine-like solution ψ : R → R. [ABSTRACT FROM AUTHOR]

Herein, an electrochemical label-free biosensor designed for the detection of glycated albumin (GA) using reduced graphene oxide/Au nanoparticles (RGO/AuNPs) modified by anti-GA aptamer. For fast and simple modification of the electrode, the aptamer chain was thiolated. Transition electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) techniques were used to the characterization of synthesized materials. Structural analysis of nanomaterials shows that graphene sheets were synthesized very fine by average thickness of 2.5 nm and Au nanoparticles distributed on the surface of graphene sheets uniformly. Cyclic voltammetry (CV) square wave voltammetry (SWV) and impedance spectroscopy (EIS) were used to electrochemical study of the decorated electrode. Electrochemical studies described the potential of fabricated rGO/AuNPs-aptamer electrode to selectively determine GA properly in buffer solution at the range of 2–10 μg mL−1 by the detection limit of 0.07 μg. mL−1 for GA. Image 1 • Simple and fast immobilization of aptamer on the surface of electrode. • Determination of GA in Hexacyanoferrate and buffer solutions. • Suitable selectivity and high sensitivity for GA. [ABSTRACT FROM AUTHOR]

The interaction of reducing sugars with proteins leads to the formation of advanced glycation end products (AGE) and reactive oxidative species (ROS). ROS peroxidise free or membrane included unsaturated fatty acids, leading to generate reactive aldehydes as advanced lipid peroxidation end products (ALE). Aldehydes from lipid peroxidation (LPO) react with proteins to cause alteration of protein structure to exacerbate complication of diseases. Here we studied serum albumin glycation in the presence and absence of liposomes as a bio-membrane model to investigate protein structural changes using various techniques including intrinsic and extrinsic fluorescence spectroscopies and electron microscopy analysis. Accordingly, serum albumin glycation and fibrillation were accelerated and intensified in the presence of liposomes through a hypothesized glycation-peroxidation loop (GPL). Together, our results shed light on the necessity of reconsidering diabetic protein glycation to make it close to physiological conditions mimicry, more importantly, proteins structural change due to diabetic glycation is intensified in the proximity of cell membranes which probably potentiates programmed cell death distinct from apoptosis. Image 1 • Lipid peroxidation (LPO) of liposomes produces reactive carbonyl compounds that induce fibrillogenesis in serum albumin. • Glycation of serum albumin induces generation of reactive oxygen species (ROS). • The generated ROSs induce LPO in the presence of liposome that accelerates fibrillation of the glycated serum albumin. • The synergistic effect of protein glycation and LPO on fibrillogenesis was explained by a glycation peroxidation loop (GPL). [ABSTRACT FROM AUTHOR]

An excerpt is presented of an article published online at dx.doi.org/10.1126/science.1256272 regarding the use of genomic DNA as an artificial data storage medium via Synthetic Cellular Recorders Integrating Biological Events (SCRIBE) architecture using single-stranded DNA (ssDNA).

Abstract Background Purpose Method Results Conclusion Patients with extensive left hemisphere damage frequently have ideational apraxia (IA) and transcortical sensory aphasia (TSA). Difficulty with action coordination, phonological processing, and complex motor planning may not be indicative of higher-order motor programming or higher-order complex formation. We report on the effects of IA and TSA on the visual and motor skill of stroke patients.The study aims to address the question of whether IA and TSA in bilingual individuals are the results of an error of motor function alone or due to a combined motor plus and cognitive dysfunction effect.Twelve bilingual patients (seven males, and five females) were diagnosed with IA and TSA, and are divided into two groups of six patients. Then, 12 healthy bilingual controls were evaluated for comparing with both groups. Bilingual aphasia testing (BAT) and appropriate behavioral evaluation were used to assess motor skills, including coordination, visual-motor testing, and phonological processing.Findings (pointing skills) show that the performance of the L1 and L2 languages are consistently significant (p < 0.001) in healthy individuals compared to the IA and TSA groups. Command skills for L1 and L2 languages were significantly higher in healthy individuals compared to IA and TSA controls (p < 0.001). Further, the orthographic skills of IA and TSA vs controls in both groups were significantly reduced (p < 0.01). Visual skills in the L1 language were significantly improved (p < 0.05) in IA and TSA patients compared to healthy controls after 2 months. Unlike orthographic skills which were improved in IA and TSA patients, languages in bilingual patients did not simultaneously improve.Dyspraxia is a condition that affects both motor and visual cognitive functions, and patients who have it often have less referred motor skills. The current dataset shows that accurate visual cognition requires both cognitive-linguistic and sensory-motor processes. Motor issues should be highlighted, and skills and functionality should be reinforced along with the significance of treatment between IA and TSA corresponding to age and education. This can be a good indicator for treating semantic disorders. [ABSTRACT FROM AUTHOR]

Background: The accuracy of current laboratory and imaging studies for diagnosis and monitoring of Parkinson's disease (PD) severity is low and diagnosis is mainly dependent on clinical examination. Proton magnetic resonance spectroscopy (MRS) is a non-invasive technique that can assess the chemical profile of the brain. In this study, we evaluated the utility of proton MRS in diagnosis of PD and determination of its severity. Methods: Patients with PD and healthy age-matched controls were studied using proton MRS. The level of N-acetylaspartate (NAA), total creatine (Cr), and total choline (Cho), and their ratios were calculated in substantia nigra (SN), putamen (Pu), and motor cortex. PD severity was assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) and the Hoehn and Yahr scale. Results: Compared to 25 healthy controls (18 men, age: 59.00 ± 8.39 years), our 30 patients with PD (24 men, age: 63.80 ± 12.00 years, 29 under treatment) showed no significant difference in the metabolite ratios in SN, Pu, and motor cortex. Nigral level of NAA/Cr was significantly correlated with total UPDRS score in patients with PD (r = -0.35, P = 0.08). Moreover, patients with PD with Hoehn and Yahr scale score = 2 had a lower NAA/Cr level in SN compared to patients with a lower stage. Conclusion: This study shows that 1.5 tesla proton MRS is unable to detect metabolite abnormalities in patients with PD who are under treatment. However, the NAA/Cr ratio in the SN might be a useful imaging biomarker for evaluation of disease severity in these patients. [ABSTRACT FROM AUTHOR]

This longitudinal study was designed to evaluate the association between acute pre‐stroke stress and the severity stroke and its outcomes including mortality, recurrence, disability and functional dependency. Patients with first‐ever stroke (FES) were recruited from the Mashhad Stroke Incidence Study. Patients were asked about any acute severe pre‐stroke stress in the 2 weeks prior to index stroke. Disability and functional disability were defined using modified the Rankin Scale and Barthel Index, respectively. We used logistic and ordinal regression tests to assess the association between acute pre‐stroke stress and study outcomes. Among 624 patients with FES, 169 reported acute pre‐stroke stress. Patients with acute pre‐stroke stress were younger than those without stress (60.7 ± 14.4 vs. 66.2 ± 14.7; p < 0.001). The frequency of traditional vascular risk factors was not different in patients with and without acute pre‐stroke stress. We did not find any association between acute pre‐stroke stress and stroke outcomes. Although acute stress was common in our cohort, our results did not support an association between acute pre‐stroke stress and the severity of stroke at admission and long‐term stroke outcomes. [ABSTRACT FROM AUTHOR]

Background: Since the emergence of COVID-19 pandemic, several cases of cerebral venous sinus thrombosis (CVST) have been reported in SARS-CoV-2 infected individuals. Methods: Consecutive patients with documented SARS-CoV-2 infection, as well as clinical and radiological characteristics of CVST, were reported from three teaching hospitals in the South West, North West, and the center of Iran between June and July 2020. We also searched the abstract archives until the end of August 2020 and gathered 28 reported cases. The diagnostic criteria for SARS-CoV-2 infection were determined according to SARS-CoV-2 detection in oropharyngeal or nasopharyngeal samples in clinically suspected patients. Demographics, prominent COVID-19 symptoms, confirmatory tests for SARS-CoV-2 infection diagnosis, the interval between the diagnosis of SARS-CoV-2 infection and CVST, clinical and radiological features of CVST, therapeutic strategies, CVST outcomes, rate of hemorrhagic transformation, and mortality rate were investigated. Results: Six patients (31–62 years-old) with confirmed CVST and SARS-CoV-2 infection were admitted to our centers. Four patients had no respiratory symptoms of SARS-CoV-2 infection. Five patients developed the clinical manifestations of CVST and SARS-CoV-2 infection simultaneously. Three patients had known predisposing factors for CVST. Despite receiving CVST and SARS-CoV-2 infection treatments, four patients died. SARS-COV-2 associated CVST patients were older (49.26 vs. 37.77 years-old), had lower female/male ratio (1.42 vs. 2.19), and higher mortality rate (35.29% vs. 6.07%) than CVST not associated with COVID-19. Conclusions: The role of SARS-CoV-2 as a "cause" versus an "additive contributor" remains to be elucidated. Practitioners should be aware of the possibility of CVST in SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Objective: Few data are available on the associations between the level of pre-stroke physical activity and long-term outcomes in patients with stroke. This study is designed to assess the associations between pre-stroke physical activity and age of first-ever stroke occurrence and long-term outcomes. Methods: Six hundred twenty-four cases with first-ever stroke were recruited from the Mashhad Stroke Incidence Study a prospective population-based cohort in Iran. Data on Physical Activity Level (PAL) were collected retrospectively and were available in 395 cases. According to the PAL values, subjects were classified as inactive (PAL < 1.70) and active (PAL ≥ 1.70). Age at onset of stroke was compared between active and inactive groups. Using logistic model, we assessed association between pre-stroke physical activity and long-term (5-year) mortality, recurrence, disability, and functional dependency rates. We used multiple imputation to analyze missing data. Results: Inactive patients (PAL < 1.70) were more than 6 years younger at their age of first-ever-stroke occurrence (60.7 ± 15.5) than active patients (67.0 ± 13.2; p < 0.001). Patients with PAL< 1.7 also had a greater risk of mortality at 1 year [adjusted odds ratio (aOR) = 2.31; 95%CI: 1.14–4.67, p = 0.02] and 5 years after stroke (aOR = 1.81; 95%CI: 1.05–3.14, p = 0.03) than patients who were more physically active. Recurrence rate, disability, and functional dependency were not statistically different between two groups. Missing data analysis also showed a higher odds of death at one and 5 years for inactive patients. Conclusions: In our cohort, we observed a younger age of stroke and a higher odds of 1- and 5-year mortality among those with less physical activity. This is an important health promotion strategy to encourage people to remain physically active. [ABSTRACT FROM AUTHOR]

Creating and characterizing individual genetic variants remains limited in scale, compared to the tremendous variation both existing in nature and envisioned by genome engineers. Here we introduce retron library recombineering (RLR), a methodology for high-throughput functional screens that surpasses the scale and specificity of CRISPR-Cas methods. We use the targeted reversetranscription activity of retrons to produce single-stranded DNA (ssDNA) in vivo, incorporating edits at >90% efficiency and enabling multiplexed applications. RLR simultaneously introduces many genomic variants, producing pooled and barcoded variant libraries addressable by targeted deep sequencing. We use RLR for pooled phenotyping of synthesized antibiotic resistance alleles, demonstrating quantitative measurement of relative growth rates. We also perform RLR using the sheared genomic DNA of an evolved bacterium, experimentally querying millions of sequences for causal variants, demonstrating that RLR is uniquely suited to utilize large pools of natural variation. Using ssDNA produced in vivo for pooled experiments presents avenues for exploring variation across the genome. [ABSTRACT FROM AUTHOR]

Background: Incidence, risk factors, case fatality and survival rates of ischemic stroke subtypes are unknown in the Middle East due to the lack of community-based incidence stroke studies in this region. Aim: To characterize ischemic stroke subtypes in a Middle Eastern population. Methods: The Mashad Stroke Incidence Study is a community-based study that prospectively ascertained all cases of stroke among the 450,229 inhabitants of Mashhad, Iran between 2006 and 2007. We identified 512 cases of first-ever ischemic stroke [264 men (mean age 65.5±14.4) and 248 women (mean age 64.14±14.5)]. Subtypes of ischemic stroke were classified according to the TOAST criteria. Incidence rates were age standardized to the WHO and European populations. Results: The proportion of stroke subtypes was distributed as follows: 14.1% large artery disease, 15% cardioembolic, 22.5% small artery disease, 43.9% undetermined and 4.5% other. The greatest overall incidence rates were attributed to undetermined infarction (49.97/100,000) followed by small artery disease (25.54/100,000). Prevalence of hypertension, diabetes and atrial fibrillation differed among ischemic stroke subtypes. Overall, there were 268 (52.34%) deaths and 73 (14.25%) recurrent strokes at five years after incident ischemic stroke, with the greatest risk of recurrence seen in the large artery disease (35.6%) and cardioembolic (35.5%) subgroups. Survival was similar in men and women for each stroke subtype. Conclusions:We observed markedly greater incidence rates of ischemic stroke subtypes than in other countries within the Mashad Stroke Incidence Study after age standardization. Our findings should be considered when planning prevention and stroke care services in this region. [ABSTRACT FROM AUTHOR]

Background In developing countries, there are few comprehensive studies of mortality following stroke. Aims and/or hypothesis We aimed to determine the one-year case fatality rate following stroke and to identify factors associated with death in a population-based stroke incidence study in Iran. Methods Six hundred eighty-four patients who had suffered a stroke between November 21, 2006, and November 20, 2007, and were recruited to the Mashhad Stroke Incidence Study were followed up at one-year. Most patients were seen in an outpatient visit. When patients had died, a verbal autopsy was conducted by telephone with the next of kin. Results A total of 226 (34·3%) patients died during the first year following stroke. The cumulative one-year case fatality rate was 30·6% following ischemic stroke and 53·0% following hemorrhagic stroke (55·8% after intracerebral hemorrhage and 35·7% after subarachnoid hemorrhage). The majority of these deaths occurred in the first 28 days after stroke (17·7% with ischemic and 43·0% with hemorrhagic stroke). Factors associated with greater mortality at one-year (excluding those who died during the first week) were hemorrhagic stroke [hazard ratio ( HR) 3·99; 95% confidence interval 1·90-8·37], age ( HR 1·05; 95% confidence interval 1·03-1·08), previous transient ischemic attack ( HR 2·45; 95% confidence interval 1·00-5·99), and National Institutes of Health Stroke Scale on admission ( HR 1·14; 95% confidence interval 1·10-1·17). Conclusion Despite the younger age of stroke occurrence in Iran, the one-year case fatality rate following stroke is similar to that reported in developed countries. [ABSTRACT FROM AUTHOR]

Introduction: Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by high levels of inattention, hyperactivity and impulsivity which may result in mothers' stress. The current study aims to compare stress among 45 mothers of ADHD children who had referred to "Rofeydeh psychiatric center" with 45 mothers of normal children. Methods: Brief demographic researcher-made questionnaire, Child Symptom Inventory-4 (CSI-4), the Child Behavior Checklist (CBCL), and Parental Stress Index-Short Form (PSI/SF) were completed for each mother and child. Results: The results showed that except the component of acceptance, ADHD children had more problems in the field of attention compared with normal children. Mothers of ADHD children had also more stress compared with mothers of normal children. Discussion: ADHD can impair mothers' mental health by inducing stress and this issue has important clinical and treatment implications. Specific treatment programs should be designed and implemented in Iran for the mothers of ADHD children to reduce stress among them and therefore, improve their mental health status. [ABSTRACT FROM AUTHOR]

Background The Hajj Ceremony, the largest annual gathering in the world, is the most important life event for any Muslim. This study was designed to evaluate the incidence of stroke among Iranian pilgrims during the Hajj ceremony. Methods We ascertained all cases of stroke occurring in a population of 92,974 Iranian pilgrims between November 27, 2007 and January 12, 2008. Incidence and risk factors of the first ever stroke in Hajj pilgrims were compared, within the same time frame, to those of the Mashhad residents, the second largest city in Iran. Data for the latter group were extracted from the Mashhad Stroke Incidence Study (MSIS) database. Results During the study period, 17 first-ever strokes occurred in the Hajj pilgrims and 40 first-ever stroke strokes occurred in the MSIS group. Overall, the adjusted incidence rate of first ever stroke in the Hajj cohort was lower than that of the MSIS population (9 vs. 16 per 100,000). For age- and gender-specific subgroups, the Hajj stroke crude rates were in general similar to or lower than the general population of Mashhad, Iran, with the exception of women aged 35 to 44 years and aged >75 years who were at greater risk of having first-ever stroke than the non-pilgrims of the same age. Conclusion The first ever stroke rate among Iranian Hajj pilgrims was lower than that of the general population in Mashhad, Iran, except for females 35-44 or more than 75 years old. The number of events occurring during the Hajj suggests that Islamic countries should consider designing preventive and screening programs for pilgrims. [ABSTRACT FROM AUTHOR]

Summary The genome-wide perturbation of transcriptional networks with CRISPR-Cas technology has primarily involved systematic and targeted gene modulation. Here, we developed PRISM (Perturbing Regulatory Interactions by Synthetic Modulators), a screening platform that uses randomized CRISPR-Cas transcription factors (crisprTFs) to globally perturb transcriptional networks. By applying PRISM to a yeast model of Parkinson’s disease (PD), we identified guide RNAs (gRNAs) that modulate transcriptional networks and protect cells from alpha-synuclein (αSyn) toxicity. One gRNA identified in this screen outperformed the most protective suppressors of αSyn toxicity reported previously, highlighting PRISM’s ability to identify modulators of important phenotypes. Gene expression profiling revealed genes differentially modulated by this strong protective gRNA that rescued yeast from αSyn toxicity when overexpressed. Human homologs of top-ranked hits protected against αSyn-induced cell death in a human neuronal PD model. Thus, high-throughput and unbiased perturbation of transcriptional networks via randomized crisprTFs can reveal complex biological phenotypes and effective disease modulators. [ABSTRACT FROM AUTHOR]

Background: The Hajj Ceremony, the largest annual gathering in the world, is the most important life event for any Muslim. This study was designed to evaluate the incidence of stroke among Iranian pilgrims during the Hajj ceremony.Methods: We ascertained all cases of stroke occurring in a population of 92,974 Iranian pilgrims between November 27, 2007 and January 12, 2008. Incidence and risk factors of the first ever stroke in Hajj pilgrims were compared, within the same time frame, to those of the Mashhad residents, the second largest city in Iran. Data for the latter group were extracted from the Mashhad Stroke Incidence Study (MSIS) database.Results: During the study period, 17 first-ever strokes occurred in the Hajj pilgrims and 40 first-ever stroke strokes occurred in the MSIS group. Overall, the adjusted incidence rate of first ever stroke in the Hajj cohort was lower than that of the MSIS population (9 vs. 16 per 100,000). For age- and gender-specific subgroups, the Hajj stroke crude rates were in general similar to or lower than the general population of Mashhad, Iran, with the exception of women aged 35 to 44 years and aged >75 years who were at greater risk of having first-ever stroke than the non-pilgrims of the same age.Conclusion: The first ever stroke rate among Iranian Hajj pilgrims was lower than that of the general population in Mashhad, Iran, except for females 35-44 or more than 75 years old. The number of events occurring during the Hajj suggests that Islamic countries should consider designing preventive and screening programs for pilgrims. [ABSTRACT FROM AUTHOR]