Upper Limb Spasticity Reduction Following Active Training: A Robot-Mediated Study In Patients With Chronic Hemiparesis

sion of the arm. A 3-month follow-up was performed. Results: Statistically significant improvements were found in both groups after treatment. Some differences were found in elbow motor improvement between the 2 groups. Conclusion: Comparison between groups confirms that active movement training does not result in increased hypertonia, but results in spasticity reduction in antagonist muscles by activating the reciprocal inhibition mechanism. Furthermore, robot-mediated therapy contributes to a decrease in motor impairment of the upper limbs in subjects with chronic hemiparesis, resulting in a reduction in shoulder pain

A Synergistic Behavior Underpins Human Hand Grasping Force Control During Environmental Constraint Exploitation

Despite the complex nature of human hands, neuroscientific studies suggested a simplified kinematic control underpinning motion generation, resulting in principal joint angle co-variation patterns, usually called postural hand synergies. Such a low dimensional description was observed in common grasping tasks, and was proven to be preserved also for grasps performed by exploiting the external environment (e.g., picking up a key by sliding it on a table). In this paper, we extend this analysis to the force domain. To do so, we performed experiments with six subjects, who were asked to grasp objects from a flat surface while force/torque measures were acquired at fingertip level through wearable sensors. The set of objects was chosen so that participants were forced to interact with the table to achieve a successful grasp. Principal component analysis was applied to force measurements to investigate the existence of co-variation schemes, i.e. a synergistic behavior. Results show that one principal component explains most of the hand force distribution. Applications to clinical assessment and robotic sensing are finally discussed

Ancient Migratory Events in the Middle East: New Clues from the Y-Chromosome Variation of Modern Iranians

Knowledge of high resolution Y-chromosome haplogroup diversification within Iran provides important geographic context regarding the spread and compartmentalization of male lineages in the Middle East and southwestern Asia. At present, the Iranian population is characterized by an extraordinary mix of different ethnic groups speaking a variety of Indo-Iranian, Semitic and Turkic languages. Despite these features, only few studies have investigated the multiethnic components of the Iranian gene pool. In this survey 938 Iranian male DNAs belonging to 15 ethnic groups from 14 Iranian provinces were analyzed for 84 Y-chromosome biallelic markers and 10 STRs. The results show an autochthonous but non-homogeneous ancient background mainly composed by J2a sub-clades with different external contributions. The phylogeography of the main haplogroups allowed identifying post-glacial and Neolithic expansions toward western Eurasia but also recent movements towards the Iranian region from western Eurasia (R1b-L23), Central Asia (Q-M25), Asia Minor (J2a-M92) and southern Mesopotamia (J1-Page08). In spite of the presence of important geographic barriers (Zagros and Alborz mountain ranges, and the Dasht-e Kavir and Dash-e Lut deserts) which may have limited gene flow, AMOVA analysis revealed that language, in addition to geography, has played an important role in shaping the nowadays Iranian gene pool. Overall, this study provides a portrait of the Y-chromosomal variation in Iran, useful for depicting a more comprehensive history of the peoples of this area as well as for reconstructing ancient migration routes. In addition, our results evidence the important role of the Iranian plateau as source and recipient of gene flow between culturally and genetically distinct population

Severe childhood malaria syndromes defined by plasma proteome profiles

BACKGROUND Cerebral malaria (CM) and severe malarial anemia (SMA) are the most serious life-threatening clinical syndromes of Plasmodium falciparum infection in childhood. Therefore it is important to understand the pathology underlying the development of CM and SMA, as opposed to uncomplicated malaria (UM). Different host responses to infection are likely to be reflected in plasma proteome-patterns that associate with clinical status and therefore provide indicators of the pathogenesis of these syndromes. METHODS AND FINDINGS Plasma and comprehensive clinical data for discovery and validation cohorts were obtained as part of a prospective case-control study of severe childhood malaria at the main tertiary hospital of the city of Ibadan, an urban and densely populated holoendemic malaria area in Nigeria. A total of 946 children participated in this study. Plasma was subjected to high-throughput proteomic profiling. Statistical pattern-recognition methods were used to find proteome-patterns that defined disease groups. Plasma proteome-patterns accurately distinguished children with CM and with SMA from those with UM, and from healthy or severely ill malaria-negative children. CONCLUSIONS We report that an accurate definition of the major childhood malaria syndromes can be achieved using plasma proteome-patterns. Our proteomic data can be exploited to understand the pathogenesis of the different childhood severe malaria syndromes

Structure and Dynamics of Cholesterol-Containing Polyunsaturated Lipid Membranes Studied by Neutron Diffraction and NMR

A direct and quantitative analysis of the internal structure and dynamics of a polyunsaturated lipid bilayer composed of 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (18:0-22:6n3-PC) containing 29 mol% cholesterol was carried out by neutron diffraction, 2H-NMR and 13C-MAS NMR. Scattering length distribution functions of cholesterol segments as well as of the sn-1 and sn-2 hydrocarbon chains of 18:0-22:6n3-PC were obtained by conducting experiments with specifically deuterated cholesterol and lipids. Cholesterol orients parallel to the phospholipids, with the A-ring near the lipid glycerol and the terminal methyl groups 3 Å away from the bilayer center. Previously, we reported that the density of polyunsaturated docosahexaenoic acid (DHA, 22:6n3) chains was higher near the lipid–water interface. Addition of cholesterol partially redistributes DHA density from near the lipid–water interface to the center of the hydrocarbon region. Cholesterol raises chain-order parameters of both stearic acid and DHA chains. The fractional order increase for stearic acid methylene carbons C8–C18 is larger, reflecting the redistribution of DHA chain density toward the bilayer center. The correlation times of DHA chain isomerization are short and mostly unperturbed by the presence of cholesterol. The uneven distribution of saturated and polyunsaturated chain densities and the cholesterol-induced balancing of chain distributions may have important implications for the function and integrity of membrane receptors, such as rhodopsin

Reduction in Phencyclidine Induced Sensorimotor Gating Deficits in the Rat Following Increased System Xc − Activity in the Medial Prefrontal Cortex

Rationale: Aspects of schizophrenia, including deficits in sensorimotor gating, have been linked to glutamate dysfunction and/or oxidative stress in the prefrontal cortex. System xc −, a cystine–glutamate antiporter, is a poorly understood mechanism that contributes to both cellular antioxidant capacity and glutamate homeostasis. Objectives: Our goal was to determine whether increased system xc − activity within the prefrontal cortex would normalize a rodent measure of sensorimotor gating. Methods: In situ hybridization was used to map messenger RNA (mRNA) expression of xCT, the active subunit of system xc −, in the prefrontal cortex. Prepulse inhibition was used to measure sensorimotor gating; deficits in prepulse inhibition were produced using phencyclidine (0.3–3 mg/kg, sc). N-Acetylcysteine (10–100 μM) and the system xc − inhibitor (S)-4-carboxyphenylglycine (CPG, 0.5 μM) were used to increase and decrease system xc − activity, respectively. The uptake of 14C-cystine into tissue punches obtained from the prefrontal cortex was used to assay system xc − activity. Results: The expression of xCT mRNA in the prefrontal cortex was most prominent in a lateral band spanning primarily the prelimbic cortex. Although phencyclidine did not alter the uptake of 14C-cystine in prefrontal cortical tissue punches, intraprefrontal cortical infusion of N-acetylcysteine (10–100 μM) significantly reduced phencyclidine- (1.5 mg/kg, sc) induced deficits in prepulse inhibition. N-Acetylcysteine was without effect when coinfused with CPG (0.5 μM), indicating an involvement of system xc −. Conclusions: These results indicate that phencyclidine disrupts sensorimotor gating through system xc − independent mechanisms, but that increasing cystine–glutamate exchange in the prefrontal cortex is sufficient to reduce behavioral deficits produced by phencyclidine

MiR-19b non-canonical binding is directed by HuR and confers chemosensitivity through regulation of P-glycoprotein in breast cancer

MicroRNAs and RNA-binding proteins exert regulation on >60% of coding genes, yet interplay between them is little studied. Canonical microRNA binding occurs by base-pairing of microRNA 3′-ends to complementary “seed regions” in mRNA 3′UTRs, resulting in translational repression. Similarly, regulatory RNA-binding proteins bind to mRNAs, modifying stability or translation. We investigated post-transcriptional regulation acting on the xenobiotic pump ABCB1/P-glycoprotein, which is implicated in cancer therapy resistance. We characterised the ABCB1 UTRs in primary breast cancer cells and identified UTR sequences that responded to miR-19b despite lacking a canonical binding site. Sequences did, however, contain consensus sites for the RNA-binding protein HuR. We demonstrated that a tripartite complex of HuR, miR-19b and UTR directs repression of ABCB1/P-glycoprotein expression, with HuR essential for non-canonical miR-19b binding thereby controlling chemosensitivity of breast cancer cells. This exemplifies a new cooperative model between RNA-binding proteins and microRNAs to expand the repertoire of mRNAs that can be regulated. This study suggests a novel therapeutic target to impair P-glycoprotein mediated drug efflux, and also indicates that current microRNA binding predictions that rely on seed regions alone may be too conservative

Follicular fluid levels of vascular endothelial growth factor and early corpus luteum function during assisted reproductive technology cycles

BACKGROUND: The relation between vascular endothelial growth factor (VEGF) and early luteal function has rarely been proven in humans. The purpose of this study was to define the relation between follicular fluid concentrations of VEGF (FF VEGF) and early luteal function at the preimplantation stage during assisted reproductive technology (ART) cycles. METHODS: 71 women were divided into two groups, based on reproductive outcome: women who became pregnant after embryo transfer (ET) (n = 18, Group A) and non-pregnant women (n = 53, Group B). Serum progesterone (Se P) and inhibin A on ET day, and FF VEGF levels were measured in all women. Data were expressed as mean ± standard deviation. Statistical analysis was performed using Excel Office 98 for Student's t-test, linear regression test and chi-square test. A p value of < 0.05 was considered statistically significant. RESULTS: The groups were comparable for age, ovarian reserve, number and quality of the oocytes retrieved and of the embryos obtained and transferred. FF VEGF levels were increased (4235 ± 1433 vs 3432 ± 1231 pg/ml), while Se P and inhibin A levels were significantly reduced (83.1 ± 34.1 vs 112.0 ± 58.8 ng/ml and 397.4 ± 223 vs 533.5 ± 283 pg/ml, respectively) in the non-pregnant group and were negatively correlated with FF VEGF (r = -0.482, p < 0.05; r = -0.468, p < 0.05) only in pregnant women. CONCLUSION: Much has to be learned about the regulation and role of VEGF during the early luteal phase. We advance the hypothesis that the existence of a negative correlation between FF VEGF/Se P and FF VEGF/inhibin A in pregnant women might indicate the existence of a normal VEGF-mediated paracrine response when Se P and inhibin A levels are decreased. Excess production of FF VEGF and the absence of a correlation between FF VEGF/Se P and FF VEGF/inhibin A in non-pregnant women may be a paracrine reaction to immature luteal vasculature, resulting in luteal dysfunction

Birth outcomes in Colorado's undocumented immigrant population

BACKGROUND: The birth outcomes of undocumented women have not been systematically studied on a large scale. The growing number of undocumented women giving birth in the United States has important implications for clinical care and public health policy. The objective of this study was to describe birth outcomes of undocumented immigrants in Colorado. METHODS: Retrospective descriptive study of singleton births to 5961 undocumented women using birth certificate data for 1998–1999. RESULTS: Undocumented mothers were younger, less educated, and more likely to be single. They had higher rates of anemia, were less likely to gain enough weight, and less likely to receive early prenatal care. They were much less likely to use alcohol or tobacco. Undocumented women had a lower rate of low birth weight (5.3% v 6.5%, P < .001) or preterm infants (12.9% v 14.5%; p = .001). Undocumented women experienced higher rates of labor complications including excessive bleeding (2.3% v 0.8%, p < .001) and fetal distress (8.7% v 3.6%, p < .001). CONCLUSION: Undocumented women have lower rates of preterm delivery and low birth weight infants, but higher rates of pregnancy related risk factors. Higher prevalence of some risk factors which are amenable to medical intervention reveals the need for improved prenatal care in this group