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Transcranial magnetic stimulation (TMS) is an FDA-approved therapeutic option for treatment resistant depression. However, exact mechanisms-of-action are not fully understood and individual responses are variable. Moreover, although previously suggested, the exact network effects underlying TMS' efficacy are poorly understood as of today. Although, it is supposed that DLPFC stimulation indirectly modulates the sgACC, recent evidence is sparse.Here, we used concurrent interleaved TMS-fMRI and state-of-the-science purpose-designed MRI head coils to delineate networks and downstream regions activated by DLPFC-TMS.We show that regions of increased acute BOLD signal activation during TMS resemble a resting-state brain network previously shown to be modulated by offline TMS. There was a topographical overlap in wide spread cortical and sub-cortical areas within this specific RSN#17 derived from the 1000 functional connectomes project.These data imply a causal relation between DLPFC-TMS and activation of the ACC and a broader network that has been implicated in MDD. In the broader context of our recent work, these data implicates a direct relation between initial changes in BOLD activity mediated by connectivity to the DLPFC target site, and later consolidation of connectivity between these regions. These insights advance our understanding of the mechanistic targets of DLPFC-TMS and may provide novel opportunities to characterize and optimize TMS therapy in other neurological and psychiatric disorders.

Characterization of patterns of wheezing and allergic sensitization in early life may allow for identification of specific environmental exposures impacting asthma development.To define respiratory phenotypes in inner-city children and their associations with early-life environmental exposures.Data were collected prospectively from 442 children in the URECA (Urban Environment and Childhood Asthma) birth cohort through age 7 years, reflecting symptoms (wheezing), aeroallergen sensitization, pulmonary function, and body mass index. Latent class mixed models identified trajectories of wheezing, allergic sensitization, and pulmonary function. Cluster analysis defined nonoverlapping groups (termed phenotypes). Potential associations between phenotypes and early-life environmental exposures were examined.Five phenotypes were identified and mainly differentiated by patterns of wheezing and allergic sensitization (low wheeze/low atopy; low wheeze/high atopy; transient wheeze/low atopy; high wheeze/low atopy; high wheeze/high atopy). Asthma was most often present in the high-wheeze phenotypes, with greatest respiratory morbidity among children with frequent wheezing and allergic sensitization. These phenotypes differentially related to early-life exposures, including maternal stress and depression, antenatal environmental tobacco smoke, house dust microbiome, and allergen content (all P 0.05). Prenatal smoke exposure, maternal stress, and depression were highest in the high-wheeze/low-atopy phenotype. The high-wheeze/high-atopy phenotype was associated with low household microbial richness and diversity. Early-life aeroallergen exposure was low in high-wheeze phenotypes.Patterns of wheezing, allergic sensitization, and lung function identified five respiratory phenotypes among inner-city children. Early-life environmental exposure to stress, depression, tobacco smoke, and indoor allergens and microbes differentially associate with specific phenotypes.

To describe a small subset of canine solitary cutaneous histiocytoma in which lymph node metastasis has been documented.Cases of dogs with solitary cutaneous histiocytoma lesions and regional lymph node metastasis diagnosed via histopathology were found through a retrospective search of the databases of IDEXX Laboratories and the University of California, Davis Veterinary Medical Teaching Hospital Clinical Diagnostic Laboratories. Information on signalment, history and clinical follow-up was obtained from the submittal form and/or via a questionnaire to the submitting veterinarian. Slides were available for review in seven cases and when possible immunohistochemistry was reviewed or performed by a single pathologist.Eight cases met the inclusion criteria. The neoplasms had the typical appearance of histiocytomas. All tested samples were immunoreactive for CD18 and lacked immunoreactivity for other lymphocyte markers and CD11d. Immunoreactivity for E-cadherin varied among the neoplasms tested. Outcome was known for five dogs and at the time of manuscript preparation three of those dogs were alive 1682 days, 570 days and 318 days post-diagnosis. Of the other two dogs with known outcome, one was euthanased shortly after diagnosis and another was hit by a car. Of the dogs that were eventually lost to follow-up, one was reported to be disease-free 1003 days after diagnosis.Metastatic histiocytoma is rarely reported and distinction from aggressive disease processes such as histiocytic sarcoma may be difficult. Based upon a small number of cases with known outcomes, some dogs with solitary metastatic histiocytoma may experience favourable outcomes.

Summary A 10-year-old captive male Siberian tiger (Panthera tigris altaica) presented with acute onset collapse, vomiting and dyspnoea, preceded by a 6-month period of progressive muscle wasting. Following humane destruction, post-mortem examination revealed a large multilobulated mass in the cranial mediastinum, which was diagnosed as a T-lymphocyte-rich thymoma with the aid of immunohistochemistry. Retrospective serology for acetylcholine receptor antibodies (titre 3.90 nmol/l) confirmed a diagnosis of thymoma-associated myasthenia gravis. Thymomas are reported rarely in wild carnivores, but when detected they appear to be similar in morphology to those seen in domestic carnivores and may also be accompanied by paraneoplastic syndromes. The clinical signs of myasthenia gravis in the tiger were consistent with those reported in cats and dogs and the condition is proposed as an important differential diagnosis for generalized weakness in captive Felidae.

Experiencing feelings of helplessness has repeatedly been reported to contribute to depressive symptoms and negative affect. In turn, depression and negative affective states are associated, among others, with impairments in performance monitoring. Thus, the question arises whether performance monitoring is also affected by feelings of helplessness. To this end, after the induction of feelings of helplessness via an unsolvable reasoning task, 37 participants (20 females) performed a modified version of a Flanker task. Based on a previously validated questionnaire, 17 participants were classified as helpless and 20 as not-helpless. Behavioral measures revealed no differences between helpless and not-helpless individuals. However, we observed enhanced Error-Related Negativity (ERN) amplitude differences between erroneous and correct responses in the helpless compared to the not-helpless group. Furthermore, correlational analysis revealed that higher scores of helplessness were associated with increased ERN difference scores. No influence of feelings of helplessness on later stages of performance monitoring was observed as indicated by Error-Positivity (Pe) amplitude. The present study is the first to demonstrate that feelings of helplessness modulate the neuronal correlates of performance monitoring. Thus, even a short-lasting subjective state manipulation can lead to ERN amplitude variation, probably via modulation of mesencephalic dopamine activity., Highlights ► Research on neural performance monitoring correlates after helplessness induction. ► Increased feelings of helpless induced ERN amplitude enhancement. ► Behavioral measures were not affected by feelings of helplessness. ► Subjective state manipulation manifests itself in increased ERN amplitudes.

Childhood obesity is an international epidemic with many long-term health consequences. The many comorbid conditions associated with obesity underscore the need to explore the different etiologies of obesity which may lead to potential therapeutic interventions. There is growing evidence both that obesity affects sleep, and that sleep patterns and disorders may have an effect on weight. Both respiratory and non-respiratory sleep disorders are associated with obesity; those that have gotten the most attention are the relationships between obesity and obstructive sleep apnea syndrome and short sleep duration. Other forms of sleep-disordered breathing and narcolepsy have also been associated with childhood obesity. Due to the many comorbidities of obesity, this subset of the pediatric population has frequent health care visits across a variety of subspecialties. It is likely that a non-sleep physician will be the first to recognize a sleep-related problem. The aim of this review was to discuss sleep disorders that may be encountered by the general pediatrician and the pediatric subspecialists in their obese pediatric patients and to describe the evidence that links these disorders to obesity.

Corpora amylacea in the prostate are a frequent finding in benign acini, but are only rarely observed in adenocarcinoma. To determine the incidence and comparative histopathology of this finding, we prospectively reviewed all consecutive needle core biopsies (excluding consultations) received at Bostwick Laboratories between December 2001 and July 2003. Among 5130 cases of adenocarcinoma (34% of 15,279 total needle biopsy cases), we identified 19 (31 biopsy specimens) with corpora amylacea within cancerous acini (0.4% incidence). Patients ranged in age from 51 to 89 years (mean, 68 years). The corpora amylacea were located within cancers with Gleason pattern 3 (28 of 31 specimens), Gleason pattern 4 (one specimen), and Gleason pattern 5 (two specimens), and ranged from less than 0.1-0.3 mm in diameter. Coexistent eosinophilic proteinaceous debris was noted in all 31 specimens, luminal mucin in 19, crystalloids in 15, and collagenous micronodules in two specimens. Our results indicate that the incidence of corpora amylacea in adenocarcinoma is low, but the presence of such inclusions cannot be used to exclude malignancy.

Accurate co-registration of MRI and EEG data is indispensable for the correct interpretation of EEG maps or source localizations in relation to brain anatomy derived from MRI. In this study, a method for the co-registration of EEG and MRI data is presented. The method consists of an iterative matching of EEG-electrode based reconstructions of the scalp surface to scalp-segmented MRIs. EEG-electrode based surface reconstruction is achieved via spline interpolation of individually digitized 3D-electrode coordinates. In contrast to other approaches, neither fiducial determination nor any additional provisions (such as bite bars, other co-registration devices or head shape digitization) are required, and co-registration errors associated with inaccurate fiducial determination are avoided. The accuracy of the method was estimated by calculating the root-mean-square (RMS) deviation of spline interpolated and MRI-segmented surface reconstructions in 20 subjects. In addition, the distance between co-registered and genuine electrode coordinates was assessed via a simulation study, in which surface reconstruction was based on virtual electrodes determined on the scalp surface of a high-resolution MRI data set. The mean RMS deviation of surface reconstructions was 2.43 mm, and the maximal distance between any two matched surface points was 5.06 mm. The simulated co-registration revealed a mean deviation of genuine and co-registered electrode coordinates of 0.61 mm. It is concluded that surface matching using spline interpolated reconstructions of scalp surfaces is a precise and highly practicable method to co-register EEG and MRI data.

Aims To identify risk factors for the development of coronary artery disease after heart transplantation. Methods and Results In consecutive heart transplanted patients, who underwent coronary angiography at the first year follow-up, the aetiology of heart failure in 113 was ischaemic heart disease or dilated cardiomyopathy. Development of clinically significant graft coronary artery disease was analysed vs recipient and donor pre- and post-transplantation variables. At 1, 5 and 9 years follow-up, coronary artery disease had developed in 4%, 16%, and 20% of the included patients, respectively. Among patients with ischaemic heart disease as the aetiology of heart failure, 38% developed graft coronary artery disease, while the corresponding figure for patients with dilated cardiomyopathy was 9% ( P

Long-term survival after replacement of the aortic root with a composite graft is improving. Late deaths are in several cases due to complications related to the previous surgery or to pathologies of the remaining aorta. Regular follow-up of these patients is of paramount importance. The purpose of this study is to evaluate the reliability of magnetic resonance imaging (MRI) in such cases. Twenty-seven patients (9 dissections and 18 aneurysms) who had undergone replacement of the aortic root with a composite graft were studied 20 to 167 months after surgery using magnetic resonance imaging with a 1.5 Tesla magnet. The left-ventricular outflow tract, the mechanical valve function, the proximal part of the coronary arteries, the graft, and the remaining aorta could be examined. No aortic insufficiency, ectasy of the proximal part of the coronaries, or pseudoaneurysms were seen. A widening of the remaining ascending aorta was noted in 4 cases. A still open, dissected pipe was visualized in 7 patients. Our conclusions are that MRI provides excellent images of the thoracic and abdominal aorta following surgical repair. The examination is becoming cost-competitive. More import is its very low risk for the patient group considered here: since it is non-invasive and requires no contrast medium or X-ray exposure, examinations can be repeated as required.

A fibreoptic pressure sensor mounted on an 0.018 inch guidewire (Pressure Guide, RadiMedical Systems, Uppsala, Sweden) was used to measure the trans-stenotic pressure gradient in 20 patients admitted for percutaneous transluminal coronary angioplasty (PTCA) of a single, discrete stenosis. Pressure measurements were made both at rest and during maximal vasodilatation induced by intracoronary injection of papaverine. From the ratio of distal coronary pressure divided by the proximal pressure, the relative coronary flow reserve was calculated. The aim of the study was to compare the different pressure-derived parameters by correlating them to stenosis geometry estimated by quantitative coronary angiography. There was a moderate correlation between baseline pressure gradient and percent area stenosis; r = 0.64, P0.001 and minimal cross-sectional area; r = 0.45, P0.005. A higher correlation was found between hyperaemic pressure gradient and area stenosis (r = 0.80, P0.001) and minimal cross-sectional areas, respectively (r = 0.55, P0.005). The best correlation was found between relative coronary flow reserve and area stenosis (r = 0.86, P0.001) and minimal cross-sectional area (r = 0.70, P0.001). In conclusion, pressure measurement using a pressure guidewire is useful as a complement to angiography in evaluation of coronary stenoses during PTCA. Pressures should be measured during maximal vasodilatation. Relative coronary flow reserve calculated from the pressure measurements provides additional information about the fraction of normal maximal flow possible in the presence of a stenosis.

To determine on a state by state, province by province basis what diagnostic and treatment procedures are allowed by statute in the various practice acts.A survey administered by mail.All state and provincial licensing boards.The response rate to the survey was 90%. More than 50% of the responding licensing boards allow chiropractors to order or perform clinical lab procedures, conduct components of a routine physical exam, examine the female pelvis, perform rectal exams, and conduct electromyographic, electrocardiographic and nerve conduction studies. More than 80% can perform a variety of X-ray procedures, use thermography, administer a vascularizer (Doppler) and order CT or MRI studies. More than 90% of the respondents permit chiropractors to employ some form of physiotherapy, adjust soft tissue or extremities, supplement with vitamins and conduct impairment ratings.These findings demonstrate that the chiropractic profession offers a broad range of diagnostic and treatment procedures.

The recent better recognition of children with sleep-disordered breathing has led to the evaluation of more patients in the sleep laboratory and thence to the definition of sleep problems among children in a variety of clinical situations. Further investigation of these abnormalities is necessary to ascertain the clinical significance of these disorders.

In der vorliegenden Studie sollte uberpruft werden, inwieweit ein massiver Larmschaden, der bekanntlich zu einer Destruktion des Corti-Organs fuhrt, einen Einflus auf das Durchblutungsverhalten und den Sauerstoffpartialdruck im Innenohr hat.

The alpha 2-adrenoceptor agonist, UK14304, dose-dependently inhibited the electrically stimulated release of dopamine (DA) from rat nucleus accumbens slices. This effect was antagonized by idazoxan, confirming that it was an alpha 2-adrenoceptor mediated effect. There was no evidence of endogenous activation of noradrenergic receptors suggesting that the alpha 2-adrenoceptor agonist was not acting presynaptically to inhibit noradrenaline release. An in vitro superfusion technique was used to investigate whether there was any interaction between alpha 2-adrenoceptors and DA D2-receptors in mediating their inhibitory effects on [3H]DA release from rat nucleus accumbens slices. alpha 2-Adrenoceptors and DA D2-receptors interact with similar second messenger systems and it was considered that they may compete for a common pool of G-proteins. The inhibitory effects of the alpha 2-adrenoceptor agonist, UK14304, and the DA receptor agonists, quinpirole, apomorphine and pergolide were not independent. However, there was no evidence of any interaction between UK14304 and the DA D2-receptor antagonists, sulpiride or haloperidol, suggesting that the two receptors do not compete for a common pool of G-proteins in mediating their inhibitory effects on DA release.

Dem praktisch tatigen Hals-Nasen-Ohrenarzt fallt auf, das Patienten mit akuten idiopathischen Labyrinthstorungen sehr haufig unter einer Hypotonie leiden. Folgerichtig stellt sich fur den Experimentator die Frage: Haben Veranderungen des Blutdruckes eine Wirkung auf die Durchblutung, Oxygenierung und Funktion des Innenohres? Deswegen fuhrten wir mit narkotisierten und beatmeten Meerschweinchen folgende Versuche durch: 1. akute Hypertension (6 min) mit 0,2 ml bolus i. v. einer Losung aus 8 ml Epinephrin 1:1000 in 50 ml 0,9% NaCl (13 Tiere); 2. kontrollierte langsame Hypertension (30 min) mit einer intravenos infundierten Losung aus 8 ml Epinephrin 1:1000 in 50 ml 0,9% NaCl (27 Tiere); 3. akute Hypotension (6 min) mit 1 ml Bicarbonat bolus i.v. (26 Tiere); 4. kontrollierte langsame Hypotension (30 min) mit 0,4 bis 5 Vol% Isofluran-Beatmung (23 Tiere).

Mit unserem Tierversuchsmodell (Meerschweinchen) ist es erstmals gelungen, folgende — auch klinisch wichtigen Parameter — simultan zu untersuchen

In 14 guinea pigs the pO2 in the perilymph of the scala tympani fell to 50%-80% of the original value during exposure to noise consisting of 4,000 Hz clicks with a repetition rate of 20/s, 100 dB CHL = 120 dB SPL p.e., repeated twice over a period of 24 minutes each time. For the measurements of the pO2 we used the thin 0.5 micron micro-coaxial needle electrode described by Baumgärtl and Luebbers, which was placed through the round-window membrane in the scala tympani to a depth of 600 micron. The simultaneously recorded CAP latency times were prolonged by 0.8 ms at a test loudness of 60 and 80 dB CHL. The amplitudes of the CM had declined by 60%-70% of the original values at a test loudness of 80 dB SPL p.e. The intra-arterial blood pressure in the common carotid artery of all animals remained constant. As the cortilymph spaces communicate with the perilymph of the scala tympani, our measured decline of pO2 in the perilymph could indicate a cortilymph hypoxia. During exposure to noise the oxygen-dependent Na+ and K+ pumps, which maintain the ion balance and function of the organ of Corti, can decompensate due to lack of oxygen. That would lead to a K+ contamination of the cortilymph and to an intracellular Na+ accumulation, which can cause microstructural damage (hair cell-cilia fusion, hair cell, synaptic and dendritic swelling, hair cell contraction and sustained depolarization), which would be reflected in the CMs and CAPs.

Our earlier animal experiments on guinea pigs showed that instrumental perforation of the round window membrane by a 0.2 mm platinum wire leads to an instant loss of the inner ear functions. The membrane defect healed in a few days, the cochlear structures remained intact, and the compound action potential of the auditory nerve and the brain-stem responses could be evoked again with normal latency times within 2 weeks. 1. In the studies reported here we first carried out microperforations with a 1 micron needle electrode, which caused no changes of the hearing potentials (cochlear microphonics, compound action potential of the auditory nerve, brain-stem responses), and no visible defect of the round window membrane and no perilymph outflow. 2. The removal of the round window membrane and the withdrawal of the perilymph led to a loss of the cochlear microphonics and to a considerable increase of the latency times of wave I (Jewett). The hearing potential regained their original values after 2 weeks without closure of the round window niche. The round window membrane had regenerated spontaneously and the scala tympani was again filled with perilymph. After covering the round window niche with a connective tissue graft, the hearing potentials regained their original values after 2 weeks, as they had done without cover of the round window niche. The round window membrane regenerated below the tissue graft and the scala tympani was also filled again with perilymph.(ABSTRACT TRUNCATED AT 250 WORDS)

An unusually aggressive Mycobacterium marinum infection of the hand that progressed despite surgical and medical treatment is presented. The infection progressed over a 3-week period after the patient had surgical treatment and received isoniazid (INH), rifampin, and ethambutol hydrochloride. The patient had a collar-button abscess, destruction of the metacarpophalangeal (MCP) joint capsule, flexor and extensor tenosynovitis, and metacarpal and proximal phalanx bone destruction at the MCP joint and metacarpal shaft. Although atypical mycobacterial infections of the hand are usually indolent but persistent, this Mycobacterium marinum hand infection progressed rapidly, even with surgical and medical treatment. A judgment was made to perform an index ray amputation. With a more complete excision of the infected tissue, there was a higher probability of controlling this severe infection. The patient was treated with antituberculosis medications for 6 months and is doing well 1 year after the operation.

The purpose of this study was to examine the influence of hyperbaric oxygen on the oxygen tension (pO2) in the normal inner ear. We examined 16 anaesthetised guinea pigs by means of an oxygen-sensitive micro-coaxial needle electrode, using the method described by Baumgaertl and Luebbers. In all animals the pO2 in the perilymph of the scala tympani fell by 34% of the original value during insertion of the sensor into the scala tympani. After we had flooded the hyperbaric chamber with pure oxygen under normobaric conditions the pO2 increased by 244.3% of the original values. Furthermore the pO2 increased by 9.4 times the original values during hyperbaric oxygen at 1.6 bar.

Nineteen guinea pigs were exposed to impulse noise from gunfire (G3 of the Federal German Army, 156 dB peak SPL), 6+6 shots or 12+6 shots, with a 3-s pulse interval. For simultaneous measurements of pO2, cochlea microphonics (CM) and compound action potentials of the auditory nerve (CAP), we used the thin 0.5 microns microcoaxial needle electrode described by Baumgaertl and Luebbers, which was placed through the roundwindow membrane into the scala tympani to a depth of 1000 microns. After exposure to the first 6 or 12 gunshots, the pO2 increased by about 20% of the original values in 12 guinea pigs (63%). In the following 30 min of recovery time the pO2 decreased, stabilized or showed a further decline. There were only 3 animals with a pO2 loss of 70% of the original values. Most animals showed a decline of 25% at the end of the recovery period. In all animals after 6 additional shots, the pO2 only decreased by another 5% of the original values. Amplitudes of CM and CAP were reduced by about 40% of the original values after 6 or 12 shots and by another 20%-24% (CM) and 5%-15% (CAP) after 6 additional shots. The intra-arterial blood pressure in the common carotid artery remained constant. The results are discussed with respect to the well-known morphological damage, subsequent ion imbalance and hypoxia within the cortilymph after exposure to gunfire. These changes are reflected in the loss of CMs and CAPs.

Cardiac output was determined with an indicator dilution technique during digital venous angiography of the left ventricle in 11 patients. The contrast medium injected into the right atrium was used as indicator. During and after the injection of contrast medium one blood sample per second was obtained through a catheter placed in the descending aorta. The samples were analyzed for iodine content with x-ray fluorescence analysis and cardiac output determined ad modum Stewart-Hamilton. Thermodilution was used as a reference method. The results indicate that the indicator dilution method with the use of contrast medium might be used for calibration of videodensitometric methods for blood flow measurements.

The neurotoxicity of delta-aminolaevulinic acid (ALA), porphobilinogen (PBG), glutamic acid, gamma-aminobutyric acid and kainic acid was compared in order to investigate the possibility of a common neurotoxic mechanism. Only ALA (10 microM) and glutamic acid (1 mM) were toxic towards neurons in culture, as measured by cell survival after 5 days' exposure. 3H-kainic acid binds to striatal membranes with an equilibrium dissociation constant (KD) of 57 nM and the number of binding sites was found to be 20 pmol/g striatal tissue. However, neither of the porphyrin precursors could displace kainic acid from these binding sites. Kainic acid alone caused neuronal degeneration after intrastriatal administration, as determined by 3H-spiroperidol binding to striatal membranes. The porphyrin precursors ALA and PBG thus do not share a common neurotoxic mechanism with the well-known neurotoxin kainic acid.

International audience; Are mental additions of single-digit numbers solved through direct retrieval from long-term memory or through persistent use of an automatized counting procedure along a mental line? In this paper, we present an experiment based on small additions along an artificial mental line, which tends to show that for very small addends (+2 to +4), counting may still be used at the end of a 3-week training. To investigate this issue, we developed the AutoCoP computational model, which describes how small additions could be solved, based on attention, working memory and experience. The simulations of AutoCoP based on this experiment showed that the effects detected at the behavioral level are reproduced and consistent with the theory, which assumes the use of a counting procedure in experts.