Covariation of the amplitude and latency of motor evoked potentials elicited by transcranial magnetic stimulation in a resting hand muscle.

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique used to study human neurophysiology. A single TMS pulse delivered to the primary motor cortex can elicit a motor evoked potential (MEP) in a target muscle. MEP amplitude is a measure of corticospinal excitability and MEP latency is a measure of the time taken for intracortical processing, corticofugal conduction, spinal processing, and neuromuscular transmission. Although MEP amplitude is known to vary across trials with constant stimulus intensity, little is known about MEP latency variation. To investigate MEP amplitude and latency variation at the individual level, we scored single-pulse MEP amplitude and latency in a resting hand muscle from two datasets. MEP latency varied from trial to trial in individual participants with a median range of 3.9 ms. Shorter MEP latencies were associated with larger MEP amplitudes for most individuals (median r = - 0.47), showing that latency and amplitude are jointly determined by the excitability of the corticospinal system when TMS is delivered. TMS delivered during heightened excitability could discharge a greater number of cortico-cortical and corticospinal cells, increasing the amplitude and, by recurrent activation of corticospinal cells, the number of descending indirect waves. An increase in the amplitude and number of indirect waves would progressively recruit larger spinal motor neurons with large-diameter fast-conducting fibers, which would shorten MEP onset latency and increase MEP amplitude. In addition to MEP amplitude variability, understanding MEP latency variability is important given that these parameters are used to help characterize pathophysiology of movement disorders.

Measurement of the Earth tides with a MEMS gravimeter.

The ability to measure tiny variations in the local gravitational acceleration allows, besides other applications, the detection of hidden hydrocarbon reserves, magma build-up before volcanic eruptions, and subterranean tunnels. Several technologies are available that achieve the sensitivities required for such applications (tens of microgal per hertz(1/2)): free-fall gravimeters, spring-based gravimeters, superconducting gravimeters, and atom interferometers. All of these devices can observe the Earth tides: the elastic deformation of the Earth's crust as a result of tidal forces. This is a universally predictable gravitational signal that requires both high sensitivity and high stability over timescales of several days to measure. All present gravimeters, however, have limitations of high cost (more than 100,000 US dollars) and high mass (more than 8 kilograms). Here we present a microelectromechanical system (MEMS) device with a sensitivity of 40 microgal per hertz(1/2) only a few cubic centimetres in size. We use it to measure the Earth tides, revealing the long-term stability of our instrument compared to any other MEMS device. MEMS accelerometers--found in most smart phones--can be mass-produced remarkably cheaply, but none are stable enough to be called a gravimeter. Our device has thus made the transition from accelerometer to gravimeter. The small size and low cost of this MEMS gravimeter suggests many applications in gravity mapping. For example, it could be mounted on a drone instead of low-flying aircraft for distributed land surveying and exploration, deployed to monitor volcanoes, or built into multi-pixel density-contrast imaging arrays.

Long-interval intracortical inhibition is asymmetric in young but not older adults.

Aging is typically accompanied by a decline in manual dexterity and handedness; the dominant hand executes tasks of manual dexterity more quickly and accurately than the nondominant hand in younger adults, but this advantage typically declines with age. Age-related changes in intracortical inhibitory processes might play a role in the age-related decline in manual dexterity. Long-interval intracortical inhibition (LICI) is asymmetric in young adults, with more sensitive and more powerful LICI circuits in the dominant hemisphere than in the nondominant hemisphere. Here we investigated whether the hemispheric asymmetry in LICI in younger adults persists in healthy older adults. Paired-pulse transcranial magnetic stimulation was used to measure LICI in the dominant and nondominant hemispheres of younger and older adults; LICI stimulus-response curves were obtained by varying conditioning stimulus intensity at two different interstimulus intervals [100 ms (LICI100) and 150 ms]. We have replicated the finding that LICI100 circuits are more sensitive and more powerful in the dominant than the nondominant hemisphere of young adults and extend this finding to show that the hemispheric asymmetry in LICI100 is lost with age. In the context of behavioral observations showing that dominant hand movements in younger adults are more fluent than nondominant hand movements in younger adults and dominant hand movements in older adults, we speculate a role of LICI100 in the age-related decline in manual dexterity.NEW & NOTEWORTHY In younger adults, more sensitive and more powerful long-interval intracortical inhibitory circuits are evident in the hemisphere controlling the more dexterous hand; this is not the case in older adults, for whom long-interval intracortical inhibitory circuits are symmetric and more variable than in younger adults. We speculate that the highly sensitive and powerful long-interval intracortical inhibition circuits in the dominant hemisphere play a role in manual dexterity.

Diagnostic Exercise: Circling and Behavioral Changes in a Cat.

A 4-year old spayed male domestic shorthair cat was presented with a history of circling and behavioral changes. Neurologic examination showed mild proprioceptive deficits. The lesion was localized in the forebrain, and magnetic resonance imaging revealed the presence of a large midline intracranial mass extending from the frontal lobe to the tentorial region of the brain. Euthanasia was elected due to poor prognosis. Histopathologic evaluation confirmed the presence of a mass composed by sheets and aggregates of large round/polygonal cells and multinucleate cells associated with deposits of cholesterol clefts, scattered hemorrhages and hemosiderin-laden macrophages. Immunohistochemistry showed that the round/polygonal cells and multinucleate cells were strongly positive for major histocompatibility complex class II antigen, variably positive for CD18, and occasionally positive for S100. Subsets of spindle cells showing variable expression of vimentin, S100, and neuron-specific enolase were also present. The final diagnosis was cholesterol granuloma. Differential diagnosis with meningioma is discussed.

Evaluating the performance of parallel subsurface simulators: An illustrative example with PFLOTRAN.

[1] To better inform the subsurface scientist on the expected performance of parallel simulators, this work investigates performance of the reactive multiphase flow and multicomponent biogeochemical transport code PFLOTRAN as it is applied to several realistic modeling scenarios run on the Jaguar supercomputer. After a brief introduction to the code's parallel layout and code design, PFLOTRAN's parallel performance (measured through strong and weak scalability analyses) is evaluated in the context of conceptual model layout, software and algorithmic design, and known hardware limitations. PFLOTRAN scales well (with regard to strong scaling) for three realistic problem scenarios: (1) in situ leaching of copper from a mineral ore deposit within a 5-spot flow regime, (2) transient flow and solute transport within a regional doublet, and (3) a real-world problem involving uranium surface complexation within a heterogeneous and extremely dynamic variably saturated flow field. Weak scalability is discussed in detail for the regional doublet problem, and several difficulties with its interpretation are noted.

Gold-catalyzed annulations of 2-alkynyl benzaldehydes with vinyl ethers: synthesis of dihydronaphthalene, isochromene, and bicyclo[2.2.2]octane derivatives.

With the suitable selection of a gold catalyst as well as the appropriate control of the reaction conditions, various new gold-catalyzed cyclizations of 2-alkynyl benzaldehyde with acyclic or cyclic vinyl ethers have been developed. Acetal-tethered dihydronaphthalene and isochromenes were obtained from the reactions of 2-alkynyl benzaldehydes with acyclic vinyl ethers under mild conditions. And, more interestingly, the gold-catalyzed reactions of 2-alkynyl benzaldehyde with a cyclic vinyl ether afforded the bicyclo[2.2.2]octane derivative involving two molecules of cyclic vinyl ethers. These products contain interesting substructures that have been found in many biologically active molecules and natural products. In addition, a gold-catalyzed homo-dimerization of 2-phenylethynyl benzaldehyde 1a was observed when the reaction was carried out in the absence of vinyl ether, affording a set of separable diastereomeric products. Plausible mechanisms for these transformations are discussed; a gold-containing benzopyrylium was regarded as the crucial intermediate by which a number of these new transformations took place.

Changes in risk factors for preterm birth in Western Australia 1984-2006.

OBJECTIVE: To characterise changing risk factors of preterm birth in Western Australia between 1984 and 2006. DESIGN: Population-based study. SETTING: Western Australia. POPULATION: All non-Aboriginal women giving birth to live singleton infants between 1984 and 2006. METHODS: Multinomial, multivariable regression models were used to assess antecedent profiles by preterm status and labour onset types (spontaneous, medically indicated, prelabour rupture of membranes [PROM]). Population attributable fraction (PAF) estimates characterized the contribution of individual antecedents as well as the overall contribution of two antecedent groups: pre-existing medical conditions (including previous obstetric history) and pregnancy complications. MAIN OUTCOME MEASURE: Antecedent relationships with preterm birth, stratified by labour onset type. RESULTS: Marked increases in maternal age and primiparous births were observed. A four-fold increase in the rates of pre-existing medical complications over time was observed. Rates of pregnancy complications remained stable. Multinomial regression showed differences in antecedent profiles across labour onset types. PAF estimates indicated that 50% of medically indicated preterm deliveries could be eliminated after removing six antecedents from the population; estimates for PROM and spontaneous preterm reduction were between 10 and 20%. Variables pertaining to previous and current obstetric complications (previous preterm birth, previous caesarean section, pre-eclampsia and antepartum haemorrhage) were the most influential predictors of preterm birth and adverse labour onset (PROM and medically indicated). CONCLUSIONS: Preterm antecedent profiles have changed markedly over the 23 years studied. Some changes may be attributable to true change, others to advances in surveillance and detection. Still others may signify change in clinical practice.

Computed tomographic features of basihyoid ectopic thyroid carcinoma in dogs.

Eight dogs with a firm, nonpainful swelling in the ventral laryngeal region and with a final diagnosis of ectopic thyroid carcinoma were investigated by Computed Tomography (CT) at six different institutions. Computed Tomography findings were reviewed, focusing on lesion volume, shape, margins, relationship with surrounding structures and adjacent vessels, attenuation characteristics, and presence of metastases. Ectopic thyroid carcinomas were seen as oval-to-bilobed masses centered on the basihyoid bone with associated bone lysis, highly vascularized capsules with central poorly contrast enhancing areas. In all cases there was laryngeal wall infiltration, in two dogs invasion of the laryngeal lumen and in one case invasion of the ventral muscular and subcutaneous plane. Metastases were found in retropharyngeal lymph nodes (three cases) and in the lung (two cases). Ectopic thyroid carcinoma should be considered in the differential diagnosis when a mass in the basihyoid region is present. Described CT features may be typical for ectopic thyroid neoplasia and could be used to help decide the therapeutic plan.

Healthy midlife Canadian women: how bone health is considered in their food choice systems.

BACKGROUND: The incidence of osteoporosis is predicted to increase as Western populations age. Diet is considered to be an important modifiable factor in bone health, yet the diets of many women are insufficient in calcium and vitamin D, which comprise two key nutrients for bone health. This focus group study explored ways in which midlife women consider bone health in their personal food choice systems. METHODS: Data were obtained in six audio-recorded focus groups from a total of 36 women from upper, middle and lower income neighbourhoods. Open and axial coding and thematic analysis revealed shared and unique themes across and within the income groups. Use of member checks, peer debriefing, and independent and team data analysis enhanced rigour in the findings. RESULTS: All participants were aware of osteoporosis. Most women idealised making simple food decisions and eating for 'holistic' health, but not specifically for bone health. Most midlife women were not motivated to change their diets, few had deliberately increased their intake of calcium and vitamin D through foods and supplements, and few others had simplified their food decisions. CONCLUSIONS: Midlife women in the present study did not make eating for bone health a priority in their food choice systems. Instead, women wanted to eat for 'holistic' health, and only by implication bone health.

The molecules that initiate cardiac hypertrophy are not species-specific.

Extracts from hypertrophying dog hearts perfused through isolated rat hearts increase the synthesis of messenger RNA and initiate hypertrophy in the treated hearts. Total RNA extracted from experimental and control hearts was translated in vitro and hybridized with polyuridylate. Synthesis of protein and polyadenylate-containing RNA was greater in rat hearts perfused with extracts of hypertrophying dog hearts than in control hearts. The results demonstrate that molecules from hypertrophying dog hearts are not species-specific since they are effective in stimulating transcription of messenger RNA in rat hearts as well as in dog hearts.

Reduced immunotoxicity and preservation of antibacterial activity in a releasable side-chain carbapenem antibiotic.

A carbapenem antibiotic, L-786,392, was designed so that the side chain that provides high-affinity binding to the penicillin-binding proteins responsible for bacterial resistance was also the structural basis for ameliorating immunopathology. Expulsion of the side chain upon opening of the beta-lactam ring retained antibacterial activity while safely expelling the immunodominant epitope. L-786,392 was well tolerated in animal safety studies and had significant in vitro and in vivo activities against methicillin- and vancomycin-resistant Staphylococci and vancomycin-resistant Enterococci.

Radiographic anatomy of the articular process joints of the caudal cervical vertebrae in the horse on lateral and oblique projections.

REASONS FOR PERFORMING STUDY: Plain radiography is the standard imaging technique for investigation of diseases associated with the articular process joints (APJ) of the caudal neck; however, the radiographic anatomy of these structures on both lateral and oblique radiographic projections has not previously been described in detail. OBJECTIVES: To determine the optimal technique for obtaining oblique radiographs of the APJ of the caudal cervical vertebrae (C4-5, C5-6 and C6-7) and to provide a detailed description of their normal radiographic appearance, on both lateral and oblique radiographic projections. METHODS: Radiopaque markers were used to highlight the contours of the APJ on both lateral and oblique radiographs. A novel cineradiographic technique was employed to determine the optimal oblique projection to permit both left and right APJ to be assessed on the same radiograph. Lateral and oblique radiographs of the caudal neck were obtained in 6 live horses under standing sedation to assess the feasibility of the technique. RESULTS: The radiopaque markers facilitated identification of the APJ by clearly outlining the margins of the cranial and caudal articular processes on lateral and oblique radiographs. The optimal range of angles for obtaining oblique radiographs was 50-55 degrees for C4-5, 45-55 degrees for C5-6 and 45-5 degrees for C6-7. Obtaining oblique radiographs within the specified range of angles resulted in a consistent radiographic image of the APJ in the caudal cervical region in the live individual. CONCLUSIONS AND POTENTIAL RELEVANCE: The description of the normal radiographic anatomy of the cervical APJ of the caudal neck region in horses provides a valuable reference for the interpretation of cervical radiographs. Using the standardised technique to obtain oblique radiographs of the equine cervical vertebrae may provide additional diagnostic information about the APJ.

Radiographic analysis of trochlear notch sclerosis in the diagnosis of osteoarthritis secondary to medial coronoid disease.

Trochlear notch sclerosis (TNS) as assessed by radiography has been shown to be increased in elbow dysplasia (ED) associated medial coronoid process disease (MCD). The aims of this study were to investigate whether two defined radiographic tests evaluating TNS would increase the sensitivity of detecting osteoarthritis secondary to MCD, and to assess whether there was a correlation between increasing TNS with severity of MCD. Sixty-one dogs with MCD (121 elbows) were selected from the imaging database. The controls were nine cadavers (18 disease-free elbows). Standard International Elbow Working Group radiographs and CT scans were taken of each elbow. Plain radiographs were analysed using various assessments: osteophyte grade (0-3), coronoid grade (0-3), TNS descriptive grade (0-3) and TNS ratio. The TNS ratio was calculated from the depth of ulnar sclerosis at the level of the disto-cranial margin of the humeral condyles divided by the cranio-caudal ulna depth. The TNS descriptive assessment and ratio both increased the overall sensitivity of diagnosing osteoarthritis secondary to MCD above the other radiographic tests. The sensitivity of the TNS ratio at <0.3 mm was 91%-96% and the TNS descriptive assessment was 77%-96%. Radiographic TNS significantly increased with increasing severity of coronoid disease grade as evaluated by CT p < 0.01. The finding that TNS increases the sensitivity of diagnosing osteoarthritis secondary to MCD is valuable to those that have neither a CT scanner nor arthroscopy readily available. The assessments described in this study are easy to apply and do not require any sophisticated technology in order to detect sclerosis.

Galantamine treatment in Alzheimer's disease with cerebrovascular disease: responder analyses from a randomized, controlled trial (GAL-INT-6).

Alzheimer's disease combined with cerebrovascular disease (AD with CVD) is associated with progressive decline, with CVD impacting AD onset and severity of progression. Subjects with confirmed diagnosis of AD with CVD were treated with galantamine during a six-month, randomized, placebo-controlled trial (N = 285). Responder analyses were performed for cognitive, behavioural and functional outcome measures. Galantamine treatment resulted in significantly greater cognitive and functional improvements compared with placebo at six months, and a significantly higher percentage of treatment responders. The proportion of responders demonstrating improved or maintained cognition on the 11-item AD assessment scale-cognitive subscale (ADAS-cog/11) was 60.5% for galantamine versus 46.0% for placebo (P = 0.013). The proportion of patients responding by at least four-points on the ADAS-cog/11 was significantly greater for the galantamine group compared with placebo (33.6% versus 17.2%; P = 0.003). Seventy-five percent of galantamine-treated subjects improved or remained stable as assessed by CIBIC-plus compared with 53.6% on placebo (P = 0.0006). Significantly higher responder rates were observed with galantamine for behaviour (64.9% versus 56.6%; P = 0.024), and numerically favourable responder rates were seen with galantamine for activities of daily living. Treatment-emergent adverse events were generally related with the gastrointestinal system (nausea 20% versus 10%; vomiting 12% versus 5%; galantamine and placebo groups, respectively). Three deaths occurred during double-blind treatment: 2 of 188 subjects receiving galantamine, and 1 of 97 subjects receiving placebo. These findings are consistent with a broad range of cognitive, functional and behavioural benefits with galantamine across the spectrum of AD and AD with CVD.

Estetrol does not bind sex hormone binding globulin or increase its production by human HepG2 cells.

OBJECTIVES: To determine whether human sex hormone binding globulin (SHBG) binds estetrol (E4), and to assess whether E4 stimulates the production of SHBG by human hepatocytes. METHODS: Competitive ligand binding assays have been used to assess the relative binding affinity of E4 to human SHBG using either [3H]5alpha-dihydrotestosterone or [3H]estradiol as labeled ligands. The effect of E4 on the production of SHBG has been assessed by a fluoroimmunometric assay in wild-type human HepG2 cells and in human Hep89 cells that over-express the human estrogen receptor (ER) alpha, and compared to the effect of ethinylestradiol, estradiol and estriol. RESULTS: There was no detectable binding of E4 to the human SHBG steroid-binding sites. By contrast, testosterone and estradiol were bound with high affinity and the synthetic estrogen ethinylestradiol was found to bind SHBG with low affinity. Estetrol does not stimulate ERalpha-mediated increases in SHBG production by HepG2 or Hep89 cells, in contrast to ethinylestradiol, estradiol and estriol. CONCLUSIONS: These data indicate that SHBG has no influence on the plasma distribution of E4 or its availability to target tissues. In addition, it is shown that E4 has no effect on SHBG production by human hepatocytes.

Molecular rearrangements of the MLL gene are present in most cases of infant acute myeloid leukemia and are strongly correlated with monocytic or myelomonocytic phenotypes.

Cytogenetic studies have previously identified abnormalities of chromosome band 11q23 in many cases of infant acute leukemia. Recent studies by ourselves and others have demonstrated breakpoint clustering in acute leukemias bearing translocations involving 11q23, and a Drosophila trithorax gene homologue (called MLL, HRX, or ALL-1) has been shown to span the 11q23 breakpoints of these translocations. To determine if this gene is affected in infant acute myeloid leukemia (AML), we have analyzed 26 infant AML cases for molecular alterations of this 11q23 gene. 15 out of 26 cases studied (58%) showed rearrangement of the MLL gene at the molecular level, and these rearrangements were clustered within an approximately 11-kb region containing nine exons of this gene. Moreover, 14 of the 15 cases with 11q23 rearrangements (93%) had myelomonocytic or monocytic phenotypes (M4 or M5 FAB subtypes, respectively), both of which are associated with a poor prognosis in childhood AML. In contrast, only 1 of 11 nonrearranged cases had an M4 or M5 phenotype (P = 0.00002). Rearrangement also correlated significantly with hyperleukocytosis (P = 0.02), another clinical parameter associated with poor outcome in this disease. Our results demonstrate that molecular rearrangements of MLL are common in M4 or M5 infant AML, and suggest that alteration of this gene may result in abnormal control of proliferation and differentiation in monocytic progenitor cells.

Comparison of ultrasonography, radiography and a single computed tomography slice for fluid identification within the feline tympanic bulla.

Evaluation of the tympanic bulla (TB) in cases of acute feline otitis media can be a diagnostic challenge, although a feature often associated with this condition is the accumulation of fluid or material within the middle ear cavity. A technique is reported allowing optimum imaging of the feline TB using ultrasound (US) and recording of the appearance of gas and fluid-filled TB. A random number of bullae in 42 feline cadavers were filled with lubricant and rostroventral-caudodorsal oblique radiographs, single slice computed tomography (CT) images and US images were created and interpreted by blinded operators. The content (fluid or gas) of each TB was determined using each technique and the cadavers were then frozen and sectioned for confirmation. CT remained the most accurate diagnostic method, but US produced better results than radiology. Given the advantages of US over other imaging techniques, these results suggest that further work is warranted to determine applications of this modality in the evaluation of clinical cases of feline otitis media.

Assessment of middle ear disease in the dog: a comparison of diagnostic imaging modalities.

OBJECTIVES: To compare radiography and ultrasound for the assessment of the tympanic bulla against computed tomography results. METHODS: Thirty-one dogs had dorsoventral, left and right lateral oblique and rostrocaudal open mouth radiographs compared with ultrasound images and computed tomography scans of the tympanic bullae. RESULTS: Radiography was superior to ultrasonography for the evaluation of the middle ear. However, computed tomography assessment was best predicted by a combination of radiographic and ultrasonographic findings. CLINICAL SIGNIFICANCE: A combination of radiography and ultrasound can provide a more accurate assessment of the bulla than either of them alone. Ultrasound may have a role in the evaluation of middle ear disease in the dog. Results are operator dependent and not reproducible with current recording techniques.

First reported case of multidrug-resistant Candida auris in Canada.

Candida auris is a fungal pathogen that has recently emerged as a global threat to public health. It was first described in Japan in 2009 and has since been reported in 17 countries on five continents. This case report describes the first reported case of multidrug-resistant C. auris in Canada. In May 2017, a 64-year-old individual was evaluated for chronic otitis externa. Past medical history included a recent hospitalization in India for elective oral surgery that was complicated by an odontogenic brain abscess. Upon return to Canada, the individual was admitted to a hospital for neurosurgical drainage of the brain abscess and parenteral antibiotics. Early during hospitalization, the patient was identified as a carrier of carbapenem-resistant Enterobacteriaceae and was placed on contact precautions. Also early during this hospitalization, a chronic otitis media was managed with placement of a typanostomy tube with drainage of clear fluid from the ear, which continued through the admission and after discharge to a post-neurosurgical rehabilitation facility. During outpatient follow-up, swabs of the ear discharge cultured C. auris that was resistant to fluconazole and amphotericin B. There was no clinical response to ototopical antifungal therapy. Surgical evaluation for management of the otomastoiditis is pending. There is a potential for C. auris to cause infection in health care settings. It can persist in hospital environments, has the potential for transmission and can cause invasive disease. It is difficult to identify and is often resistant to antifungal medications. The application of infection prevention and control recommendations can help prevent nosocomial transmission. It is now prudent to consider the risk of C. auris, in addition to the known risk of other antimicrobial resistant organisms, in any traveller who has been hospitalized while outside the country. When identified, contacting local public health can assist in the tracking and management of this emerging disease.