Miracle-dz/UniFAR-FTUs huggingface dataset:
New drugs for the treatment of attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) is the most common neuropsychiatric disorder of childhood. Recent research indicates that ADHD most often persists into adolescence and adulthood, and is associated with impairments in academic, social and occupational functioning. The ADHD diagnosis is based on history and clinical examination. There are no objective laboratory measures for diagnosis. ADHD is largely heritable. Its underlying pathophysiology has been theorised to include dysregulation of inhibitory noradrenergic frontocortical activity on dopaminergic striatal structures. Evidence shows that ADHD is highly responsive to pharmacological treatments resulting in global functional improvements. Although pharmacotherapy is recognised as the most effective treatment, additional components to optimise ADHD management include proper educational placement, parent management training and social skills development. Central nervous system stimulants, specifically methylphenidate and amphetamine, remain first-line pharmacological treatments. Atomoxetine, a selective noradrenergic re-uptake inhibitor, is the first non-stimulant compound to receive FDA approval for paediatric and adult ADHD. Other medication classes, including α-agonist antihypertensives, tricyclic antidepressants, other antidepressants such as buproprion, and the wake-promoting agent modafinil, are prescribed in off-label therapy. Ongoing development of new ADHD medications is expected to emphasise alternative and extended-release delivery systems and non-stimulant compounds.
Understanding patients with asthma and COPD: insights from a European study.

AIMS To understand the needs of people with asthma and COPD, and to identify opportunities for improved care. METHODS Quantitative questionnaire-based survey performed in five European countries on patients with asthma and COPD. Questionnaires were administered to patients using Computer Assisted Web Interview methodology. RESULTS 1022 patients with asthma (UK [n=190]; Germany [n=214]; France [n=200]; Italy [n=222]; Spain [n=196]) and 719 patients with COPD (UK [n=153]; Germany [n=147]; France [n=145]; Italy [n=140]; Spain [n=134]) were enrolled in the study. 32% of those with asthma and 67% of those with COPD considered that their condition had a significant effect on their quality of life, and stigma and emotional distress was common. Many expressed concern regarding potential medication side effects or that medicines might lose their effect with time. Major discrepancies between expectations and patient satisfaction with the doctor-patient relationship were observed, including a need to be consulted in the choice of inhalers. Consultations were infrequent, and 75% of respondents sought additional information beyond that received during consultations - commonly from the internet. CONCLUSIONS Patient satisfaction was high but information needs were not addressed and the emotional burden of disease is underappreciated.
Application of Equal Area Criterion Conditions in the Time Domain for Out-of-Step Protection

A new procedure for out-of-step protection by mapping the equal area criterion conditions to the time domain is proposed in this paper. The classification between stable and out-of-step swings is done using the accelerating and decelerating energies, which represents the area under the power-time curve. The proposed methodology is simple and overcomes some of the difficulties associated with the previous techniques. The proposed approach is based only on the local electrical quantities available at the relay location, and does not depend on the network configuration and parameters. The proposed algorithm has been tested on a single-machine infinite bus and a three-machine infinite bus system using software simulations. A digital prototype of the relay has also been implemented on the hardware and its performance has been assessed in a closed-loop mode using a real-time digital simulator. The simulation results and the hardware testing results confirm the validity of the approach presented.
Essential Oil of Lavender Inhibited the Decreased Attention during a Long-Term Task in Humans

This study examined the effects of odors on sustained attention during a vigilance task. Two essential oils (lavender and eucalyptus) and two materials (l-menthol and linalyl acetate) were compared with a control. The increase in reaction time was significantly lower with lavender than with the control. The results suggest that the administration of lavender helped to maintain sustained attention during the long-term task.
MtDNA mutations in maternally inherited diabetes: presence of the 3397 ND1 mutation previously associated with Alzheimer's and Parkinson's disease.

Mutations in the mitochondrial tRNA(leu) (UUR) gene have been associated with diabetes mellitus and deafness. We screened for the presence of mtDNA mutations in the tRNA(leu) (UUR) gene and adjacent ND1 sequences in 12 diabetes mellitus pedigrees with a possible maternal inheritance of the disease. One patient carried a G to A substitution at nt 3243 (tRNA(leu) (UUR) gene) in heteroplasmic state. In a second pedigree a patient had an A to G substitution at nt 3397 in the ND1 gene. All maternal relatives of the proband had the 3397 substitution in homoplasmic state. This substitution was not present in 246 nonsymptomatic Caucasian controls. The 3397 substitution changes a highly conserved methionine to a valine at aa 31 and has previously been found in Alzheimer's (AD) and Parkinson's (PD) disease patients. Substitutions in the mitochondrial ND1 gene at aa 30 and 31 have associated with a number of different diseases (e.g. AD/PD, MELAS, cardiomyopathy and diabetes mellitus, LHON, Wolfram-syndrome and maternal inherited diabetes) suggesting that changes at these two codons may be associated with very diverse pathogenic processes. In a further attempt to search for mtDNA mutations outside the tRNAleu gene associated with diabetes, the whole mtDNA genome sequence was determined for two patients with maternally inherited diabetes and deafness. Except for substitutions previously reported as polymorphisms, none of the two patients showed any non-synonymous substitutions either in homoplasmic or heteroplasmic state. These results imply that the maternal inherited diabetes and deafness in these patients must result from alterations of nuclear genes and/or environmental factors.
Design of comb-shaped antenna for the lower profile in L-band

In order to hanker for an antenna with very lower profile feature at the L-band, a planar comb-shaped antenna is proposed. The electrical parameters, such as voltage standing-wave ratio and input impedance, related to size of comb-dents have been investigated. Some empirical equations on these parameters have been derived by using straight line approximation method statistically. Geometry of this structure has been optimized by using full wave analysis. Finally, a fabricated sample is measured to verify the design. Results are in very good agreement with simulation.
Locus ceruleus lesions and eosinophilic inclusions in MPTP‐treated monkeys

Systemic administration of the recently discovered neurotoxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) produces severe clinical parkinsonism and degeneration of the substantia nigra in humans and monkeys. In previous studies, no convincing structural damage to nerve cells outside the substantia nigra could be demonstrated in subhuman primates. Using a protracted MPTP regimen and older animals, we now report locus ceruleus lesions and eosinophilic inclusion bodies in squirrel monkeys. The inclusions were seen only in areas where Lewy bodies are found in human Parkinson's disease. No such abnormalities were seen in control animals. These findings suggest that similarities between the neuropathology of MPTP‐induced parkinsonism in the monkey and human Parkinson's disease are greater than first thought and increase the usefulness of the MPTP monkey model for research in Parkinson's disease.
The overdiagnosis of Lyme disease.

To the Editor. —We were saddened and disturbed by the article by Steere et al.1 There exists in the scientific literature ample evidence of persistent chronic infection despite recommended treatment, documentation of seronegativity as a real phenomenon in Lyme disease, sufficient information regarding the mechanisms of evasion of the organism by antibiotics and the immune system, and evidence for the unreliability of diagnostic tests. This type of study fosters complacency, a hesitancy on the part of physicians to diagnosis and treat, and a decline in the numbers of reported cases with the potential for a reduction in funds for Lyme disease research. We would like you to understand what it is like living in a highly endemic area where Lyme disease affects families, friends, and acquaintances by the score. We are not getting well, and our families and friends are not getting well. There are now many thousands of
The Regulatory Properties of Rubisco Activase Differ among Species and Affect Photosynthetic Induction during Light Transitions1[W][OA]

The regulatory properties of Rubisco activase from different species suggest a new strategy for enhancing photosynthetic performance by increasing the rate of photosynthetic induction. Rubisco’s catalytic chaperone, Rubisco activase (Rca), uses the energy from ATP hydrolysis to restore catalytic competence to Rubisco. In Arabidopsis (Arabidopsis thaliana), inhibition of Rca activity by ADP is fine tuned by redox regulation of the α-isoform. To elucidate the mechanism for Rca regulation in species containing only the redox-insensitive β-isoform, the response of activity to ADP was characterized for different Rca forms. When assayed in leaf extracts, Rubisco activation was significantly inhibited by physiological ratios of ADP to ATP in species containing both α-Rca and β-Rca (Arabidopsis and camelina [Camelina sativa]) or just the β-Rca (tobacco [Nicotiana tabacum]). However, Rca activity was insensitive to ADP inhibition in an Arabidopsis transformant, rwt43, which expresses only Arabidopsis β-Rca, although not in a transformant of Arabidopsis that expresses a tobacco-like β-Rca. ATP hydrolysis by recombinant Arabidopsis β-Rca was much less sensitive to inhibition by ADP than recombinant tobacco β-Rca. Mutation of 17 amino acids in the tobacco β-Rca to the corresponding Arabidopsis residues reduced ADP sensitivity. In planta, Rubisco deactivated at low irradiance except in the Arabidopsis rwt43 transformant containing an ADP-insensitive Rca. Induction of CO2 assimilation after transition from low to high irradiance was much more rapid in the rwt43 transformant compared with plants containing ADP-sensitive Rca forms. The faster rate of photosynthetic induction and a greater enhancement of growth under a fluctuating light regime by the rwt43 transformant compared with wild-type Arabidopsis suggests that manipulation of Rca regulation might provide a strategy for enhancing photosynthetic performance in certain variable light environments.
A population-based case-crossover and case-control study of alcohol and the risk of injury.

OBJECTIVE This study investigated the relationship between alcohol and the risk of acute injury, examining both short-term (drinking over a few hours) and long-term exposures (past-month hazardous drinking and current alcohol use disorders). METHOD The study was a case-crossover and population-based case control study. Cases (N = 2,517; 1,432 men) were injured patients recruited from all three emergency departments in Boone County, Missouri. Each case's alcohol consumption in the 6 hours prior to injury was compared to his or her consumption the day before in a case-crossover analysis. Community controls (N = 1,856; 948 men) were recruited by telephone and matched to cases by age, gender, day of week and hour. Case-control analyses examined recent alcohol consumption (past 6 hours), past-month hazardous drinking and past-year alcohol use disorders. RESULTS The odds ratios (ORs) for injury associated with short-term alcohol exposure were similar, whether cases were compared with themselves (case-crossover analyses) or with others (case-control analyses). After 1 or 2 drinks in a 6-hour interval, the ORs were 1.8 (95% confidence interval [CI]: 1.3-2.6) and 1.5 (0.96-2.2), respectively. Similar dose-response curves were seen in the two comparisons, with ORs of 6.2 and 3.7, respectively, after 3 or 4 drinks and 9.5 and 13.5 after 5 or 6 drinks. For past-month hazardous drinking, the OR was 1.7 (95% CI: 1.2-2.3). Current alcohol dependence was associated with injury (OR = 1.9; 95% CI: 1.5-2.6), but alcohol abuse was not (OR = 0.9; 95% CI: 0.8-1.1). CONCLUSIONS Alcohol's effect on injury risk is related more strongly to acute exposure than to measures of long-term exposure. The risk is significant even at low levels of consumption.
Quantitative evaluation of parameters affecting the accuracy of Microsoft Kinect in GAIT analysis

To date various commercial systems have been used in the GAIT analysis. These systems have some difficulties for clinical use, such as interfering with normal movement and high prices. The possibility of utilization of Kinect as a sensor for GAIT analysis has been studied in this research. The accuracy of Kinect in calculation of GAIT parameters such as lower limb joint angles, stride time, and stride length were computed during normal walking. The effects of the sensor's position and direction relative to the walkway were also investigated. The Kinect sensor was installed at different positions toward the motion path. In each position the data was recorded by both Kinect and a commercial motion capture system. After data recording and noise filtering, GAIT parameters were calculated. According to the results, the best position for the Kinect sensor is in front of the subject. In this arrangement, the error of stride time and stride length were 1.4% and 5.2% respectively. The root mean square errors of knee and hip joint angles in this position were 4.5° and 4.4°, respectively. The error of ankle joint angle was higher than the acceptable amount for clinical applications.
Recombination, repair and replication in the pathogenic Neisseriae: the 3 R′s of molecular genetics of two human‐specific bacterial pathogens

Most of the detailed mechanisms that have been established for the molecular biological processes that mediate recombination, repair and replication of DNA have come from studies of the Escherichia coli paradigm. The human specific pathogens, Neisseria gonorrhoeae and N. meningitidis, are Gram‐negative bacteria that have some molecular processes that are similar to E. coli and others that appear to be divergent. We propose that the pathogenic Neisseriae have evolved a specialized collection of molecular mechanisms to adapt to life limited to human hosts. In this MicroReview, we explore what is known about the basic processes of DNA repair, DNA recombination (genetic exchange and pilin variation) and DNA replication in these human specific pathogens.
Facilitating and obstructing factors for development of learning in clinical practice: a student perspective.

AIM OF THE STUDY The aim of this study was to provide information on what the student nurses found facilitating and obstructing for their learning during clinical practice. BACKGROUND Earlier studies of experiences of learning in clinical practice have shown that factors as the possibilities of variations of experiences, the culture of the workplace, and communication between the educational institution and health care facilities are of importance. Less is known about the opportunities which students are given in order to practise the skills that they will be expected to perform as new graduate nurses. METHODS The experiences of 47 degree student nurses from two colleges in Sweden were gathered in weekly diaries during their final period of clinical practice. A content analysis technique was used to analyse their diaries. RESULTS The students emphasized responsibility and independence, opportunities to practise different tasks, and receiving feedback as facilitating factors. Other perceived promoting factors included perceptions of control of the situation and understanding of the 'total picture'. Examples of obstructing factors were the nurses as supervisors not relying on the students, supervision that lacked continuity and lack of opportunities to practise. Perception of their own insufficiency and low self-reliance were drawbacks for some students. CONCLUSIONS Recommended proposals are presented to lecturers and supervising staff concerning organizational and educational changes, and changes of attitudes for elucidating the students' experiences of different facilitating and obstructing factors. Changes may contribute to making easier the students' transition into the nursing profession.
Truncated Forms of the Human Prion Protein in Normal Brain and in Prion Diseases (*)

The cellular form of the prion protein (PrPc) is a glycoprotein anchored to the cell membrane by a glycosylphosphatidylinositol moiety. An aberrant form of PrPc that is partially resistant to proteases, PrP, is a hallmark of prion diseases, which in humans include Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome, and fatal familial insomnia. We have characterized the major forms of PrP in normal and pathological human brains. A COOH-terminal fragment of PrPc, designated C1, is abundant in normal and CJD brains as well as in human neuroblastoma cells. Sequence analysis revealed that C1 contains alternative NH2 termini starting at His-111 or Met-112. Like PrPc, C1 is glycosylated, anchored to the cell membrane, and is heat-stable. Consistent with the lack of the NH2-terminal region of PrPc, C1 is more acidic than PrPc and does not bind heparin. An additional fragment longer than C1, designated C2, is present in substantial amounts in CJD brains. Like PrP, C2 is resistant to proteases and is detergent-insoluble. Our data indicate that C1 is a major product of normal PrPc metabolism, generated by a cleavage that disrupts the neurotoxic and amyloidogenic region of PrP comprising residues 106-126. This region remains intact in C2, suggesting a role for C2 in prion diseases.
Collagen type I alpha1 Sp1 polymorphism, osteoporosis, and intervertebral disc degeneration in older men and women.

OBJECTIVES To examine whether collagen type I alpha1 (COLIA1) Sp1 polymorphism is associated with osteoporosis and/or intervertebral disc degeneration in older people. METHODS COLIA1 genotype was determined in 966 men and women (>/=65 years) of the Longitudinal Aging Study Amsterdam. The guanine (G) to thymidine (T) polymorphism in the first intron of the COLIA1 gene was detected by PCR and MscI digestion. In the total sample, quantitative ultrasound (QUS) measurements, serum osteocalcin (OC), and urine deoxypyridinoline (DPD/Cr(urine)) were assessed. A follow up of fractures was done every three months. In a subsample, total body bone mineral content (n = 485) and bone mineral density (BMD) of the hip and lumbar spine (n = 512) were measured by dual energy x ray absorptiometry (DXA). Prevalent vertebral deformities and intervertebral disc degeneration were identified on radiographs (n = 517). RESULTS People with the TT genotype had a higher risk of disc degeneration than those with the GG and GT genotypes (OR = 3.6; 95% CI 1.3 to 10). For men, higher levels of OC were found in those with the T allele than in those without it (GG v (GT+TT) 1.96 (0.06) nmol/l v 2.19 (0.09) nmol/l). COLIA1 polymorphism was not significantly associated with other measures of osteoporosis in either men or women. CONCLUSION COLIA1 Sp1 polymorphism may be a genetic risk factor related to intervertebral disc degeneration in older people. Previously reported associations between the COLIAI Sp1 genotype and lower BMD or QUS values, higher levels of DPD/Cr, and an increased fracture risk in either men or women could not be confirmed.
The II-III Loop of the Skeletal Muscle Dihydropyridine Receptor Is Responsible for the Bi-directional Coupling with the Ryanodine Receptor*

The dihydropyridine receptor (DHPR) in the skeletal muscle plasmalemma functions as both voltage-gated Ca2+ channel and voltage sensor for excitation-contraction (EC) coupling. As voltage sensor, the DHPR regulates intracellular Ca2+ release via the skeletal isoform of the ryanodine receptor (RyR-1). Interaction with RyR-1 also feeds back to increase the Ca2+ current mediated by the DHPR. To identify regions of the DHPR important for receiving this signal from RyR-1, we expressed in dysgenic myotubes a chimera (SkLC) having skeletal (Sk) DHPR sequence except for a cardiac (C) II-III loop (L). Tagging with green fluorescent protein (GFP) enabled identification of expressing myotubes. Dysgenic myotubes expressing GFP-SkLC or SkLC lacked EC coupling and had very small Ca2+currents. Introducing a short skeletal segment (α1Sresidues 720–765) into the cardiac II-III loop (replacing α1C residues 851–896) of GFP-SkLC restored both EC coupling and Ca2+ current densities like those of the wild type skeletal DHPR. This 46-amino acid stretch of skeletal sequence was recently shown to be capable of transferring strong, skeletal-type EC coupling to an otherwise cardiac DHPR (Nakai, J., Tanabe, T., Konno, T., Adams, B., and Beam, K.G. (1998) J. Biol. Chem.273, 24983–24986). Thus, this segment of the skeletal II-III loop contains a motif required for both skeletal-type EC coupling and RyR-1-mediated enhancement of Ca2+ current.
Effects of Potassium Channel Blockers on Changes in Refractoriness of Atrial Cardiomyocytes Induced by Stretch

Shortening of the effective refractory period (ERP) is regarded as one of the key mechanisms of atrial fibrillation (AF). Stretch is an important predisposing factor in the pathogenesis of AF. However, effective methods to counteract alteration of ERP induced by stretch still need to be explored. Although potassium channels play important roles in cardiac repolarization and refractoriness, the effects of potassium channel blockers on the alteration of repolarization and refractoriness induced by stretch are still unknown. Action potential duration (APD) and ERP were recorded using the standard intracellular microelectrode technique in the left atrial appendage cardiomyocytes of guinea pigs. Stretch accelerated repolarization of atrial cardiomyocytes and also shortened the ERP (P < 0.05). Dofetilide, a rapid delayed rectifying potassium ion channel (IKr) blocker; 4-AP, a transient outward potassium ion channel (Ito) blocker; and BaCl2, an inward rectifying potassium ion channel (IK1) blocker could counteract the shortening of APD and ERP (P < 0.01). Glibenclamide, an ATP-sensitive potassium ion channel (IKATP) blocker; 293-B, a slow delayed rectifying potassium channel (IKs) blocker; and DPO-1, an ultra-rapid delayed rectifying potassium ion channel (IKur) blocker all had no effect on APD and ERP (P > 0.05). Stretch could accelerate repolarization of atrial cardiomyocytes and shorten their ERP, and the Ito, IKr, and IK1 blockers could counteract the effects of stretch.