Miracle-dz/UniFAR-FTUs huggingface dataset:
MELAS ASSOCIATED WITH MUTATIONS IN THE POLG1 GENE

MELAS ASSOCIATED WITH MUTATIONS IN THE POLG1 GENE To the Editor: Deschauer et al.1 describe a patient carrying the POLG1 mutations R627Q and G848S in trans who presented with a stroke-like episode. Visual phenomena and headache preceded the development of focal seizures. Occipital focus was demonstrated on MRI and EEG, and COX-negative fibers (CNF) were found in skeletal muscle. The authors concluded that the case fulfills the diagnostic criteria for mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). 1 This interesting case exposes a problem faced in medicine, specifically the use of abbreviations to make clinical statements. The case does fulfill the traditional, diagnostic criteria for MELAS. However, the phenotype is also typical for the A467T or W748S POLG1mutations. We reported a large number of patients with these mutations who presented in their teens or early 20s with migraine-like headaches, visual disturbances, encephalopathy, epilepsy, and occipital foci both on EEG and MRI.2,3 Whether or not these events should be called stroke-like episodes is more a matter of definition and nomenclature and less of substance. We have chosen not to do so, in order to avoid confusion with MELAS, which is a genetically and clinically distinct entity. That the occipital lesion in the case reported by Deschauer et al. was larger than those previously described in POLG1 disease does not make it typical of MELAS. MELAS stroke-like lesions are often more extensive and although they may occasionally be limited to the occipital lobe, most usually also extend into the temporal and parietal cortices.4 The majority of POLG-related cerebral cortical lesions thus far described are confined to the occipital areas.2,3 There is significant clinical overlap between syndromes caused by different mtDNAmutations and stroke-like episodes have been described in several. That POLG1mutations can cause similar disorders is expected since genetic defects affect the same system, namely the mitochondrial genome. However, there are clinical differences including the lack of diabetes mellitus and cardiomyopathy. The clinical spectrum of POLG1 mutations that we and others have described appears to be clinically consistent and the issue should not be confused by adding terms such as MELAS.
Pharmacy Students' Attitudes Toward Chemical Dependency

Chemical dependency, including alcohol and drug dependency, is a growing concem for all segments of the population. Previous pharmacy research has attempted to quantify the potential for chemical abuse among pharmacy students. Normark and colleagues reported that 17.6% of pharmacy students surveyed were potential or actual substance abusers (1). McAuliffe and colleagues found that about two-thirds of pharmacy students from a New England state reported using a controlled substance without a prescription at some time (about 40% within the past year) (2). Tuck and colleagues found that 44% of pharmacy students at 2 schools reported using psychoactive drugs at some time for nonmedical reasons (3). A study of pharmacy students at 8 southeastem schools found that more than 40% had used illicit drugs at some time (over 25% in the last year), while Rascati and colleagues found that about 30% of Texas pharmacy students used illicit drugs some time in their lives (10% in the past year) (4-6). Various programs and instructional seminars have been developed in response to this problem (7). In our area alone, the Texas Pharmaceutical Association (TPA) has implemented a rehabilitation
HSP60 IS A RARE CAUSE OF HEREDITARY SPASTIC PARAPARESIS, BUT MAY ACT AS A GENETIC MODIFIER

To date, 35 genetic loci have been associated with a hereditary spastic paraplegia (HSP phenotype and the responsible gene has been identified at 13 of these loci.1 Heat shock protein 60 (HSP60) protein is a nuclear encoded mitochondrial chaperone protein, mutation in which has been reported in one family with HSP.2 This study aimed to identify the frequency of HSP60 mutations as a cause of autosomal dominant (AD) HSP and describes an interaction between HSP60 polymorphism and spastin mutations. ### Methods. We selected 100 index patients from AD HSP pedigrees who were negative by direct sequencing for spastin mutations and performed direct sequencing of the coding regions of HSP60 3 (for primer details, see table e-1 on the Neurology ® Web site at www.neurology.org). Having identified a missense change, we performed restriction enzyme digest (enzyme MwoI ) analysis in 131 controls and subsequently in 63 patients with HSP with a known spastin mutation. All patients and controls were of British/Caucasian origin. The Mann-Whitney U test and Student unpaired t test were used to analyze the data as appropriate. This study was approved by the South Sheffield Research Ethics Committee. ### Results. A recently reported heterozygous missense change, c. [1688G>C]/p.Glycine563Alanine (p.[Gly563Ala]),4 was identified in an index case of a large AD HSP pedigree. The p.[Gly563Ala] change was present in 4 out …
Reduced striatal D1 receptor binding in autosomal dominant nocturnal frontal lobe epilepsy

Background: Mutations of the neuronal nicotinic acetylcholine (nACh) receptor identified in patients with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) lead to increased sensitivity to ACh. As activation of presynaptic nicotinic receptors augments the release of dopamine in the striatum and the prefrontal regions, we tested the hypothesis that that the α4-Ser248Phe mutation affects dopaminergic transmission. Methods: We measured D1 receptor binding using [11C]-SCH23390 and PET in 12 subjects with the α4-Ser248Phe mutation (3 men, mean age 41 ± 16 years) and 19 controls (8 men, mean age 36 ± 13 years) matched for gender, smoking status, and age. Parametric images were produced using the simplified reference region method. Both MRI-based regions of interest and voxel based analyses were used. Results: Reduced striatal [11C]-SCH23390 binding occurred with the mutation (controls 1.1 ± 0.1; ADNFLE 0.97 ± 0.2; p < 0.01). Statistical parametric mapping confirmed a region of reduced [11C]-SCH23390 binding in the right putamen in α4-Ser248Phe subjects compared to controls (309 voxels, local maxima 20 16 −2 mm; Zscore 3.57, p < 0.05). Conclusions: Reduced D1 receptor binding may represent increased extracellular dopamine levels or, more likely, receptor downregulation. Alterations in mesostriatal dopaminergic circuits may contribute to nocturnal paroxysmal motor activity in autosomal dominant nocturnal frontal lobe epilepsy.
A novel locus for an autosomal recessive hereditary spastic paraplegia (SPG35) maps to 16q21-q23

Background: The hereditary spastic paraplegias (HSPs) are a group of clinically and genetically heterogeneous neurodegenerative disorders in which the cardinal pathologic feature is upper motor neuron degeneration leading to progressive spasticity and weakness of the lower limbs. To date, 14 autosomal recessive HSP loci have been mapped. Methods: We have identified a large consanguineous Omani family in which an autosomal recessive form of HSP is segregating. The age at onset varied from 6 to 11 years and the course of the disease is progressive with intellectual disability and is associated with seizures in two individuals. To map the chromosomal location of the causative gene we undertook 250K gene chip SNP analyses of all affected individuals assuming that a founder mutation was responsible. Results: All affected individuals shared a 20.4 Mb (3.25 cM) region of homozygosity located on chromosome 16q21-q23.1, defined by SNP markers rs149428 and rs9929635 (peak multipoint lod score of 4.86). Two candidate genes, dynein, cytoplasmic 1, light intermediate chain 2 (DYNC1LI2) and vacuolar protein sorting 4 homolog A (VPS4A), were sequenced but no disease causing mutations were identified. Conclusion: We have mapped the chromosomal location of a novel gene responsible for a form of hereditary spastic paraplegia (HSP) (SPG35) and defined its clinical presentation.
Understanding processes at the origin of species flocks with a focus on the marine Antarctic fauna

Species flocks (SFs) fascinate evolutionary biologists who wonder whether such striking diversification can be driven by normal evolutionary processes. Multiple definitions of SFs have hindered the study of their origins. Previous studies identified a monophyletic taxon as a SF if it displays high speciosity in an area in which it is endemic (criterion 1), high ecological diversity among species (criterion 2), and if it dominates the habitat in terms of biomass (criterion 3); we used these criteria in our analyses. Our starting hypothesis is that normal evolutionary processes may provide a sufficient explanation for most SFs. We thus clearly separate each criterion and identify which biological (intrinsic) and environmental (extrinsic) traits are most favourable to their realization.
The logopenic/phonological variant of primary progressive aphasia

Objective: Primary progressive aphasia (PPA) is characterized by isolated decline in language functions. Semantic dementia and progressive nonfluent aphasia are accepted PPA variants. A “logopenic” variant (LPA) has also been proposed, but its cognitive and anatomic profile is less defined. The aim of this study was to establish the cognitive and anatomic features of LPA. Methods: Six previously unreported LPA cases underwent extensive neuropsychological evaluation and an experimental study of phonological loop functions, including auditory and visual span tasks with digits, letters, and words. For each patient, a voxel-wise, automated analysis of MRI or SPECT data were conducted using SPM2. Results: In LPA, speech rate was slow, with long word-finding pauses. Grammar and articulation were preserved, although phonological paraphasias could be present. Repetition and comprehension were impaired for sentences but preserved for single words, and naming was moderately affected. Investigation of phonological loop functions showed that patients were severely impaired in digit, letter, and word span tasks. Performance did not improve with pointing, was influenced by word length, and did not show the normal phonological similarity effect. Atrophy or decreased blood flow was consistently found in the posterior portion of the left superior and middle temporal gyri and inferior parietal lobule. Conclusions: Logopenic progressive aphasia (LPA) is a distinctive variant of primary progressive aphasia. Cognitive and neuroimaging data indicate that a deficit in phonological loop functions may be the core mechanism underlying the LPA clinical syndrome. Recent studies suggest that Alzheimer disease may be the most common pathology underlying the LPA clinical syndrome. GLOSSARY: AD = Alzheimer disease; BA = Brodmann area; CDR = Clinical Dementia Rating; CVLT-MS = California Verbal Learning Test–Mental Status Edition; ECD = ethyl cysteinate dimer; FWHM = full-width at half-maximum; GM = gray matter; LPA = logopenic progressive aphasia; MMSE = Mini-Mental State Examination; PNFA = progressive nonfluent aphasia; PPA = primary progressive aphasia; Rey-O = Rey–Osterrieth; SemD = semantic dementia; VBM = voxel-based morphometry; WAB = Western Aphasia Battery; WAIS-III = Wechsler Adult Intelligence Scale, Third Edition.
Isokinetic Quadriceps and Hamstring Torque Levels of Adolescent, Female Soccer Players

Using a Cybex II® dynamometer, the quadriceps and hamstring torque levels of 16 female high school soccer players were measured. Both the dominant and nondominant knees were tested at a fast (180° per second) and slow (30° per second) speed. The results were similar to those of previous studies that used men as subjects. The conclusions were: 1) Extension torque is significantly greater than flexion torque for both legs and at both speeds. At 30° per second the hamstring/quadriceps ratio is 0.61. This ratio increases to 0.78 at 180° per second. 2) There is no significant difference between dominant and nondominant legs for either flexion or extension torque at fast or slow speed. 3) At 30° per second, peak quadriceps torque is achieved at approximately 73° of extension, and peak flexion torque is achieved at approximately 38° flexion. 4) Slow speed flexion and extension torque levels are significantly greater than fast speed torque levels for both legs.
Cor triloculares biatritum with tricuspid atresia in an african child

Cor triloculares biatritum is a rare congenital heart disease characterized by a three-chambered heart consisting of two atria and a single ventricle; however the case of a 5-month-old African boy who in addition to this defect had an associated tricuspid atresia and an atrial septal defect is reported.
JLO volume 46 issue 11 Cover and Front matter

T h e E a r . 776 T h e N o s e a n d A c c e s s o r y S i n u s e s . 784 T h e P h a r y n x . 786 T h e C E s o p h a g u s a n d E n d o s c o p y . 790 M i s c e l l a n e o u s . 792 R E V I E W O F B O O K . 794 G E N E R A L N O T E S . 796 DeVilbiss SPRAY NI5 WHEN you prescribe a DeVILBISS Nose and Throat Spray you assure your patient of all the advantages that come from the use of an instrument made with truly scientific precision and in strict conformity with the recommendations of medical science. The adjustable tip of the DeVILBISS No. 15 Spray permits spraying in any direction—a special advantage in the treatment of the bronchial tubes and post-nasal cavities. There are also special DeVILBISS Models for professional use — fully illustrated catalogue free on request. Note the adjustable goldplated tip for spraying in any direction. CVS—25 AEROGRAPH CO. LTD., 43 Holborn Viaduct London, E.C. 1 Sole Distributors of DeVILBISS Products in the U.K.
IMMUNOTHERAPY-REVERSED COMPULSIVE, MONOAMINERGIC, CIRCADIAN RHYTHM DISORDER IN MORVAN SYNDROME

Antibodies to voltage-gated potassium channels (VGKC-Abs) have been recognized in neuromyotonia, limbic encephalitis (LE), and Morvan syndrome (MoS),1,2 a rare condition with insomnia, peripheral, and central and autonomic nervous system involvement. Clinical progression in MoS is variable, but potentially fatal. We describe a patient with VGKC-Abs-positive MoS who showed prominent compulsive behaviors, basal ganglia hypermetabolism, increased catecholamine and serotonin secretion, epileptic seizures, and cardiac and endocrine circadian rhythm suppression. A striking response to immunotherapy paralleled a marked reduction in VGKC-Abs over 15 months. ### Case report. A 64-year-old man with idiopathic pulmonary fibrosis and polyarthrosis developed cramps, lower extremity pain, and sensory loss. Three years later, his sleep was disturbed by chewing, manual stereotypies, and sleep-talking. After an episode of tonic-clonic seizures, EEG revealed a temporal epileptic focus. He developed paroxysmal confusional episodes, with gesturing and irregular breathing, that were unresponsive to multiple anticonvulsants. He became irritable and hypomanic with overwhelming compulsive shopping and stealing. Urinary frequency, anosmia, impotence, and increased appetite appeared. Examination showed bilateral postural tremor, multifocal myoclonus, lower extremity fasciculations, hypoesthesia, hyporeflexia, and mild proximal muscle atrophy. Laboratory investigations, including autoimmune and thyroid profile, were normal except for increased leukocytes, a raised erythrocyte sedimentation rate and creatine phosphokinase, mild hyponatremia, and antinuclear antibodies 1:160. CSF was negative for infections and 14.3. 3 protein, but showed slightly increased …
On Iterative Solution of Elliptic Difference Equations on a Mesh-Connected Array of Processors

Elementary operations such as inner products and vector norms used in conjugate gradient methods and for iteration error checking have an amazingly high complexity (computer time) on mesh connected arrays of processors because they require global information. Therefore iterative methods which require only local, nearest neighbor communications can be more efficient. The simplest such method, the Jacobi iterative method converges too slowly but we show how faster convergent methods based on Chebyshev iterative methods, with or without preconditioning can be applied efficiently for elliptic difference equations The preconditionings provide the bounds for the extreme eigenvalues, which are needed for the Chebyshev method and the number of iterations can be determined a priori, so no error checking is needed.
Parallel Matrix Multiplication on the Connection Machine

Matrix multiplication is a computation and communication intensive problem. Six parallel algorithms for matrix multiplication on the Connection Machine are presented and compared with respect to their performance and processor usage. For n by n matrices, the algorithms have theoretical running times of O(n2 log n), O(n log n), O(n), and O(log n), and require n, n2, n2, and n3 processors, respectively. With careful attention to communication patterns, the theoretically predicted runtimes can indeed be achieved in practice. The parallel algorithms illustrate the tradeoffs between performance, communication cost, and processor usage.
Kanerva's Sparse Distributed Memory: an Associative Memory Algorithm Well-Suited to the Connection Machine

The advent of the Connection Machine profoundly changes the world of supercomputers. Its highly nontraditional architecture makes possible the exploration of algorithms that were impractical for standard Von Neumann architectures. Kanerva’s sparse distributed memory (SDM) is an example of such an algorithm. Sparse distributed memory is a particularly simple and elegant formulation for an associative memory. In this paper I describe the foundations for sparse distributed memory, and give some simple examples of using the memory. I continue by showing the relationship of sparse distributed memory to random-access memory. Finally, I discuss the implementation of the algorithm for sparse distributed memory on the Connection Machine.
Effect of plasma exchange in accelerating natalizumab clearance and restoring leukocyte function

Background: Accelerating the clearance of therapeutic monoclonal antibodies (mAbs) from the body may be useful to address uncommon but serious complications from treatment, such as progressive multifocal leukoencephalopathy (PML). Treatment of PML requires immune reconstitution. Plasma exchange (PLEX) may accelerate mAb clearance, restoring the function of inhibited proteins and increasing the number or function of leukocytes entering the CNS. We evaluated the efficacy of PLEX in accelerating natalizumab (a therapy for multiple sclerosis [MS] and Crohn disease) clearance and α4-integrin desaturation. Restoration of leukocyte transmigratory capacity was evaluated using an in vitro blood–brain barrier (ivBBB). Methods: Twelve patients with MS receiving natalizumab underwent three 1.5-volume PLEX sessions over 5 or 8 days. Natalizumab concentrations and α4-integrin saturation were assessed daily throughout PLEX and three times over the subsequent 2 weeks, comparing results with the same patients the previous month. Peripheral blood mononuclear cell (PBMC) migration (induced by the chemokine CCL2) across an ivBBB was assessed in a subset of six patients with and without PLEX. Results: Serum natalizumab concentrations were reduced by a mean of 92% from baseline to 1 week after three PLEX sessions (p < 0.001). Although average α4-integrin saturation was not reduced after PLEX, it was reduced to less than 50% when natalizumab concentrations were below 1 μg/mL. PBMC transmigratory capacity increased 2.2-fold after PLEX (p < 0.006). Conclusions: Plasma exchange (PLEX) accelerated clearance of natalizumab, and at natalizumab concentrations below 1 μg/mL, desaturation of α4-integrin was observed. Also, CCL2-induced leukocyte transmigration across an in vitro blood–brain barrier was increased after PLEX. Therefore, PLEX may be effective in restoring immune effector function in natalizumab-treated patients.
On the Floating Point Performance of the I860TM Microprocessor

The i860™ microprocessor is a powerful pipelined processor that is being used in the Touchstone project to develop a teraflop computer by the year 2000. It was expected that memory bandwidth would limit performance on certain kernels used with sparse matrices. Measured performances of three kernels were less than what memory bandwidth limitations would predict. This paper develops a model that explains the discrepancy in terms of memory latencies.
Molecular detection of hepatitis B virus: recent developments. Molekularer Nachweis des Hepatitis B-Virus: Aktueller Entwicklungsstand

Abstract Abstract Highly sensitive qualitative and quantitative automated nucleic acid amplification tests (NATs) that are commercially available for the detection of hepatitis B virus (HBV) infection have been developed only in the last few years. The potential indications for HBV NATs are: follow-up of chronic hepatitis B, therapy and antiviral resistance monitoring, determination of infectivity and transmission risk, detection of occult (HBsAg-negative and HBV DNA-positive) infection and mutant virus which may escape serologic diagnosis, blood donor screening, and resolution of unusual or discordant serologic constellations. Although NATs are now widely implemented in the routine diagnosis of clinical laboratories, there are several important issues which need to be further investigated. Standardisation of NATs used for the monitoring of antiviral therapy and follow-up of chronic infection is still lacking, and the clinical significance of HBV DNA levels needs to be clarified. The influence of genetic variability in terms of genotype variation has been poorly investigated so far. Although there are highly sensitive automated NATs for blood donor screening available, their implementation is still subject to discussion and certain countries rejected HBV DNA testing for blood donation for reasons of poor cost-effectiveness.
Extension of Aβ2M amyloid fibrils with recombinant human β2-microglobulin

In order to elucidate the pathogenesis ofAβ2M amyloidosis, we established an experimental system to study the mechanism of amyloid fibril formation or degradation in vitro. We compared the kinetics of Aβ2M amyloid fibril (fAβ2M) extension with native β2microglobulin (n-β2M) purified from the urine of a patient suffering from renal insufficiency, with that with recombinant β2M (r-β2M) in vitro. n-β2M and r-β2M were incubated with fβ32Mpurifiedfrom synovial tissues excised from Aβ2M amyloidosis patients. The fA β2M extension reaction could be explained by a first-order kinetic model in both β2Ms. The extension reaction was greatly dependent on the pH of the reaction mixture and maximum around pH 2.5-3.0 in both p2Ms. ThefAβ2M extended with both p2Ms assumed the similar helical filament structure, although the fibrils extended with r-β2M were slightly wider than those extended with n-β2M and the former fibrils assumed a helical structure more clearly as compared to the latter. In order to obtain pure, unmodifiedfAβ2M, we next extendedfA β2M repeatedly by the algorithmic protocol with r-β2M. As the generation of the extended fibrils proceeded, the initial rate of the extension reaction increased. The ultrastructure of fibrils was completely preserved throughout the repeated extension steps. Sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunoblotting revealed that f A P2M extended repeatedly with r-β2Mwere composed solely ofr-β2M. The use of these r-β2M and fAβ2M will be advantageous to assess the effects of several amyloid-associated molecules in the formation or degradation offAβ2M in vitro.