Comparative analysis of pancreatic amylase activity in laboratory rodents.

Alpha-amylase is the main enzyme for starch digestion in the mammalian gastrointestinal tract. There are species differences in the enzymatic activity of pancreatic amylase that are related to the digestive strategy and natural diet of a species. This aspect is well investigated in pet and farm animals, while in common laboratory animal rodents, information is scarce. In the context of the 3R concept, detailed knowledge of the digestive physiology should be the basis of adequate nutrition, experimental planning and data interpretation. The present study aimed to obtain reference data on amylase activity in pancreatic tissue and duodenal digesta in laboratory mice, rats and hamsters. In addition, digesta was stained with Lugol's iodine to visualize starch in the process of degradation throughout the gastrointestinal tract. Amylase activity in pancreatic tissue and duodenal digesta was significantly lower in hamsters than rats and mice. The Lugol staining showed intense starch degradation in the hamsters' forestomachs, presumably by microbial fermentation. A possible explanation is that the prae-duodenal microbial starch fermentation enhances digestibility and reduces the need for pancreatic amylase in hamsters. Rats and mice may rely more on pancreatic amylase for prae-caecal starch digestion, while the microbial fermentation is mainly located in the caecum. The results clearly show species differences in the digestive capacity for starch in mice, rats and hamsters that need to be considered in the feeding of these species in the laboratory setting as well as in the use of rodents as translational animal models.

Modeling Respiratory Syncytial Virus Adult Vaccination in the United States With a Dynamic Transmission Model.

BACKGROUND: Respiratory syncytial virus (RSV) is shown to cause substantial morbidity, hospitalization, and mortality in infants and older adults. Population-level modeling of RSV allows to estimate the full burden of disease and the potential epidemiological impact of novel prophylactics. METHODS: We modeled the RSV epidemiology in the United States across all ages using a deterministic compartmental transmission model. Population-level symptomatic RSV acute respiratory tract infection (ARI) cases were projected across different natural history scenarios with and without vaccination of adults aged ≥60 years. The impact of vaccine efficacy against ARIs, infectiousness and vaccine coverage on ARI incidence were assessed. The impact on medical attendance, hospitalization, complications, death, and other outcomes was also derived. RESULTS: Without a vaccine, we project 17.5-22.6 million symptomatic RSV ARI cases annually in adults aged ≥18 years in the US, with 3.6-4.8 million/year occurring in adults aged ≥60 years. Modeling indicates that up to 2.0 million symptomatic RSV-ARI cases could be prevented annually in ≥60-year-olds with a hypothetical vaccine (70% vaccine efficacy against symptomatic ARI and 60% vaccine coverage) and that up to 0.69 million/year could be prevented in the nonvaccinated population, assuming 50% vaccine impact on infectiousness. CONCLUSIONS: The model provides estimated burden of RSV in the US across all age groups, with substantial burden projected specifically in older adults. Vaccination of adults aged ≥60 years could significantly reduce the burden of disease in this population, with additional indirect effect in adults aged <60 years due to reduced transmissibility.

A systematic review and meta-analysis of the evidence on learning during the COVID-19 pandemic.

To what extent has the learning progress of school-aged children slowed down during the COVID-19 pandemic? A growing number of studies address this question, but findings vary depending on context. Here we conduct a pre-registered systematic review, quality appraisal and meta-analysis of 42 studies across 15 countries to assess the magnitude of learning deficits during the pandemic. We find a substantial overall learning deficit (Cohen's d = -0.14, 95% confidence interval -0.17 to -0.10), which arose early in the pandemic and persists over time. Learning deficits are particularly large among children from low socio-economic backgrounds. They are also larger in maths than in reading and in middle-income countries relative to high-income countries. There is a lack of evidence on learning progress during the pandemic in low-income countries. Future research should address this evidence gap and avoid the common risks of bias that we identify.

Analysis of Slow-Cycling Variants of the Light-Inducible Nuclear Protein Export System LEXY in Mammalian Cells.

The optogenetic tool LEXY consists of the second light oxygen voltage (LOV) domain of Avena sativa phototropin 1 mutated to contain a nuclear export signal. It allows exporting from the nucleus with blue light proteins of interest (POIs) genetically fused to it. Mutations slowing the dark recovery rate of the LOV domain within LEXY were recently shown to allow for better depletion of some POIs from the nucleus in Drosophila embryos and for the usage of low light illumination regimes. We investigated these variants in mammalian cells and found they increase the cytoplasmic localization of the proteins we tested after illumination, but also during the dark phases, which corresponds to higher leakiness of the system. These data suggest that, when aiming to sequester into the nucleus a protein with a cytoplasmic function, the original LEXY is preferable. The iLEXY variants are, instead, advantageous when wanting to deplete the nucleus of the POI as much as possible.

Genetic Engineering of Oligotropha carboxidovorans Strain OM5-A Promising Candidate for the Aerobic Utilization of Synthesis Gas.

Due to climate change and worldwide pollution, development of highly sustainable routes for industrial production of basic and specialty chemicals is critical nowadays. One possible approach is the use of CO2- and CO-utilizing microorganisms in biotechnological processes to produce value-added compounds from synthesis gas (mixtures of CO2, CO, and H2) or from C1-containing industrial waste gases. Such syngas fermentation processes have already been established, e.g., biofuel production using strictly anaerobic acetogenic bacteria. However, aerobic processes may be favorable for the formation of more costly (ATP-intensive) products. Oligotropha carboxidovorans strain OM5 is an aerobic carboxidotrophic bacterium and potentially a promising candidate for such processes. We here performed RNA-Seq analysis comparing cells of this organism grown heterotrophically with acetate or autotrophically with CO2, CO, and H2 as carbon and energy source and found a variety of chromosomally and of native plasmid-encoded genes to be highly differentially expressed. In particular, genes and gene clusters encoding proteins required for autotrophic growth (CO2 fixation via Calvin-Benson-Bassham cycle), for CO metabolism (CO dehydrogenase), and for H2 utilization (hydrogenase), all located on megaplasmid pHCG3, were much higher expressed during autotrophic growth with synthesis gas. Furthermore, we successfully established reproducible transformation of O. carboxidovoransvia electroporation and developed gene deletion and gene exchange protocols via two-step recombination, enabling inducible and stable expression of heterologous genes as well as construction of defined mutants of this organism. Thus, this study marks an important step toward metabolic engineering of O. carboxidovorans and effective utilization of C1-containing gases with this organism.

Understanding the mobility chances of children from working-class backgrounds in Britain: How important are cognitive ability and locus of control?

Research in social stratification has shown that children from working-class backgrounds tend to obtain substantially lower levels of educational attainment and lower labor market positions than children from higher social class backgrounds. However, we still know relatively little about the micro-level processes that account for this empirical regularity. Our study examines the roles of two individual-level characteristics-cognitive ability and locus of control-in mediating the effect of individuals' parental class background on their educational attainment and social class position in Britain. We find that cognitive ability mediates only about 35% of the total parental class effect on educational attainment and only about 20% of the total parental class effect on respondents' social class position, net of their educational attainment. These findings contradict existing claims that differences in the life chances of children from different social class backgrounds are largely due to differences in cognitive ability. Moreover, we find that although individuals' locus of control plays some role in mediating the parental class effect, its role is substantially smaller than the mediating role of cognitive ability. We measure individuals' social class positions at different points in their careers-at labor market entry and at occupational maturity-and find that the mediating roles of cognitive ability and locus of control are remarkably stable across individuals' working lives.

The influence of gaseous microemboli on various biomarkers after minimized cardiopulmonary bypass.

INTRODUCTION: Gaseous microemboli that originate from the cardiopulmonary bypass circuit may contribute to adverse outcome after cardiac surgery. We prospectively evaluated the influence of gaseous microemboli on the release of various biomarkers after use of a minimally invasive extracorporeal technology system. METHODS: In 70 patients undergoing coronary artery bypass grafting with minimized cardiopulmonary bypass, gaseous microemboli were measured intraoperatively with a bubble counter. Intra- and postoperative biomarker levels for inflammatory response (interleukin-6, C5b-9), endothelial damage (von Willebrand factor, soluble vascular cell adhesion molecule-1), oxidative stress (malondialdehyde, 8-isoprostane, neuroketal), and neurological injury (neuron-specific enolase, brain-type fatty acid-binding protein) were analyzed using immune assay techniques. The relationship between gaseous microemboli number or volume and the incremental area under the curve (iAUC24h) or peak change for the biomarkers was calculated. RESULTS: All biomarkers except for malondialdehyde increased at least temporarily after coronary artery bypass grafting with a minimally invasive extracorporeal technology system. The median total gaseous microemboli number was 6,174 (interquartile range: 3,507-10,531) and the median total gaseous microemboli volume was 4.31 µL (interquartile range: 2.71-8.50). There were no significant correlations between total gaseous microemboli number or volume and iAUC24h or peak change for any of the biomarkers. After controlling for the variance of possible other predictor variables, multiple linear regression analysis showed no association between gaseous microemboli parameters and release of biomarkers. CONCLUSION: This study showed no evidence that gaseous microemboli contribute to increased biomarker levels after coronary artery bypass grafting with cardiopulmonary bypass. A reason for the absence of damage by gaseous microemboli may be the relative and considerably small amount of gaseous microemboli entering the patients in this study.

Sonographically Measured Improvement in Diaphragmatic Mobility and Outcomes Among Patients Requiring Prolonged Weaning from the Ventilator.

BACKGROUND: The need of prolonged weaning from the ventilator is a well-known predictor of an unfavorable patients` outcome. Diaphragmatic dysfunction is a serious problem for these patients. We wanted to determine the survival in patients who were already intubated for more than 4 weeks before they were admitted to our weaning unit. In this prospective study, we wanted to investigate if the diaphragmatic function could improve or was related to survival over an 18 months follow up period. METHODS: 84 patients were included when they were able to breathe at least 10 minutes over a t-piece and sit upright for at least 5 minutes. The diaphragmatic function was estimated sonographically using the up and downward movement of the lung silhouette. Sonographic follow-ups were performed for over 18 months. The survival rate, outcome and changes in diaphragm mobility were investigated. RESULTS: a) Survival: 49 patients (58%) survived the 18 months follow up period - 30 had a good outcome; 19 needed assistance. b) Survival in relation to diaphragm mobility: If diaphragmatic mobility improved ≥ 15.5 mm on the left side, the probability of survival was 94% with a probability of 76% to have a satisfying outcome. CONCLUSION: Survival and outcome of prolonged weaning were significantly better when sonographically measured the mobility of left hemidiaphragm improved.

Optical verification and in-vitro characterization of two commercially available acoustic bubble counters for cardiopulmonary bypass systems.

INTRODUCTION: Gaseous microemboli (GME) introduced during cardiac surgery are considered as a potential source of morbidity, which has driven the development of the first bubble counters. Two new generation bubble counters, introduced in the early 2000s, claim correct sizing and counting of GME. This in-vitro study aims to validate the accuracy of two bubble counters using monodisperse bubbles in a highly controlled setting at low GME concentrations. METHODS: Monodisperse GME with a radius of 43 µm were produced in a microfluidic chip. Directly after their formation, they were injected one-by-one into the BCC200 and the EDAC sensors. GME size and count, measured with the bubble counters, were optically verified using high-speed imaging. RESULTS: During best-case scenarios or low GME concentrations of GME with a size of 43 µm in radius in an in-vitro setup, the BCC200 overestimates GME size by a factor of 2 to 3 while the EDAC underestimates the average GME size by at least a factor of two. The BCC200 overestimates the GME concentration by approximately 20% while the EDAC overestimates the concentration by nearly one order of magnitude. Nevertheless, the calculated total GME volume is only over-predicted by a factor 2 since the EDAC underestimates the actual GME size. For the BCC200, the total GME volume was over-predicted by 25 times due to the over-estimation of GME size. CONCLUSIONS: The measured errors in the absolute sizing/counting of GME do not imply that all results obtained using the bubble counters are insignificant or invalid. A relative change in bubble size or bubble concentration can accurately be measured. However, care must be taken in the interpretation of the results and their absolute values. Moreover, the devices cannot be used interchangeably when reporting GME activity. Nevertheless, both devices can be used to study the relative air removal characteristics of CPB components or for the quantitative monitoring of GME production during CPB interventions.

Carbon Dioxide Flush of an Integrated Minimized Perfusion Circuit Prior to Priming Prevents Spontaneous Air Release Into the Arterial Line During Clinical Use.

Recently, an oxygenator with an integrated centrifugal blood pump (IP) was designed to minimize priming volume and to reduce blood foreign surface contact even further. The use of this oxygenator with or without integrated arterial filter was compared with a conventional oxygenator and nonintegrated centrifugal pump. To compare the air removal characteristics 60 patients undergoing coronary artery bypass grafting were alternately assigned into one of three groups to be perfused with a minimized extracorporeal circuit either with the conventional oxygenator, the oxygenator with IP, or the oxygenator with IP plus integrated arterial filter (IAF). Air entering and leaving the three devices was measured accurately with a bubble counter during cardiopulmonary bypass. No significant differences between all groups were detected, considering air entering the devices. Our major finding was that in both integrated devices groups incidental spontaneous release of air into the arterial line in approximately 40% of the patients was observed. Here, detectable bolus air (>500 µm) was shown in the arterial line, whereas in the minimal extracorporeal circulation circuit (MECC) group this phenomenon was not present. We decided to conduct an amendment of the initial design with METC-approval. Ten patients were assigned to be perfused with an oxygenator with IP and IAF. Importantly, the integrated perfusion systems used in these patients were flushed with carbon dioxide (CO2 ) prior to priming of the systems. In the group with CO2 flush no spontaneous air release was observed in all cases and this was significantly different from the initial study with the group with the integrated device and IAF. This suggests that air spilling may be caused by residual air in the integrated device. In conclusion, integration of a blood pump may cause spontaneous release of large air bubbles (>500 µm) into the arterial line, despite the presence of an integrated arterial filter. CO2 flushing of an integrated cardiopulmonary bypass system prior to priming may prevent spontaneous air release and is strongly recommended to secure patient safety.

Circulating microaggregates during cardiac surgery precedes postoperative stroke.

Postoperative stroke and encephalopathy are potentially serious complications associated with coronary artery bypass grafting. In this case report a 78-year-old male patient receiving routine elective cardiac surgery presented with microaggregations in the sublingual microcirculation while on cardiopulmonary bypass that was undetected by routine intraoperative anticoagulation assessment. Microaggregates identified using video microscopy on his sublingual microcirculation during the procedure preceded a stroke postoperatively. Postoperative cerebral and carotid artery examination with computed tomography scanning revealed a left watershed cerebral infarct with carotid stenosis. This report presents intraoperative microcirculation-based evidence suggesting that observations of microaggregations, otherwise undetected by conventional anticoagulation assessment techniques, could serve as an early warning in elderly patients at high risk for postoperative cerebrovascular events.

Clinical evaluation of the air-handling properties of contemporary oxygenators with integrated arterial filter.

Gaseous microemboli (GME) may originate from the extracorporeal circuit and enter the arterial circulation of the patient. GME are thought to contribute to cerebral deficit and to adverse outcome after cardiac surgery. The arterial filter is a specially designed component for removing both gaseous and solid microemboli. Integration of an arterial filter with an oxygenator is a contemporary concept, reducing both prime volume and foreign surface area. This study aims to determine the air-handling properties of four contemporary oxygenator devices with an integrated arterial filter. Two oxygenator devices, the Capiox FX25 and the Fusion, showed significant increased volume of GME reduction rates (95.03 ± 3.13% and 95.74 ± 2.69%, respectively) compared with both the Quadrox-IF (85.23 ± 5.84%) and the Inspire 6F M (84.41 ± 12.93%). Notably, both the Quadrox-IF and the Inspire 6F M as well as the Capiox FX 25 and the Fusion showed very similar characteristics in volume and number reduction rates and in detailed distribution properties. The Capiox FX25 and the Fusion devices showed significantly increased number and volume reduction rates compared with the Quadrox-IF and the Inspire 6F M devices. Despite the large differences in design of all four devices, our study results suggest that the oxygenator devices can be subdivided into two groups based on their fibre design, which results in screen filter (Quadrox-IF and Inspire 6F M) and depth filter (Capiox FX25 and Fusion) properties. Depth filter properties, as present in the Capiox FX25 and Fusion devices, reduced fractionation of air and may ameliorate GME removal.

Effect of Oxygenator Size on Air Removal Characteristics: A Clinical Evaluation.

During cardiopulmonary bypass (CPB), gaseous microemboli (GME) are released into the patients' arterial bloodstream. Gaseous microemboli may contribute to the adverse outcome after cardiac surgery. Recently, two oxygenator models with or without integrated arterial filter (IAF) were designed and only differ in size, leading to a change of 20% in surface area of the hollow fibers and 25% in blood velocities. The aim of this study was to assess the air removal characteristics of the inspire oxygenators with or without IAF. Sixty-eight patients were randomly assigned to four different groups: optimized adult and full adult and an additional IAF. Gaseous microemboli reduction rates were measured with a bubble counter. The number of GME reduction rates showed no differences. However, both models reduced significantly less volume of GME (optimized adult: 40.6% and full adult: 50.3%) compared with both models with IAF (88.7% and 88.5%, respectively). No significant differences of reduction rates were found between both devices without IAF and also not between both models with IAF. In conclusion, the larger inspire oxygenator tends to remove more GME. No effect from size of oxygenator device with integrated screen filter on GME reduction was observed. The inspire oxygenators with IAF may be considered as an adequate GME filter.

The influence of feeding on the evolution of sensory signals: a comparative test of an evolutionary trade-off between masticatory and sensory functions of skulls in southern African horseshoe bats (Rhinolophidae).

The skulls of animals have to perform many functions. Optimization for one function may mean another function is less optimized, resulting in evolutionary trade-offs. Here, we investigate whether a trade-off exists between the masticatory and sensory functions of animal skulls using echolocating bats as model species. Several species of rhinolophid bats deviate from the allometric relationship between body size and echolocation frequency. Such deviation may be the result of selection for increased bite force, resulting in a decrease in snout length which could in turn lead to higher echolocation frequencies. If so, there should be a positive relationship between bite force and echolocation frequency. We investigated this relationship in several species of southern African rhinolophids using phylogenetically informed analyses of the allometry of their bite force and echolocation frequency and of the three-dimensional shape of their skulls. As predicted, echolocation frequency was positively correlated with bite force, suggesting that its evolution is influenced by a trade-off between the masticatory and sensory functions of the skull. In support of this, variation in skull shape was explained by both echolocation frequency (80%) and bite force (20%). Furthermore, it appears that selection has acted on the nasal capsules, which have a frequency-specific impedance matching function during vocalization. There was a negative correlation between echolocation frequency and capsule volume across species. Optimization of the masticatory function of the skull may have been achieved through changes in the shape of the mandible and associated musculature, elements not considered in this study.

Effects of fluoridated milk on root dentin remineralization.

BACKGROUND: The prevalence of root caries is increasing with greater life expectancy and number of retained teeth. Therefore, new preventive strategies should be developed to reduce the prevalence of root caries. The aim of this study was to investigate the effects of fluoridated milk on the remineralization of root dentin and to compare these effects to those of sodium fluoride (NaF) application without milk. METHODS: Thirty extracted human molars were divided into 6 groups, and the root cementum was removed from each tooth. The dentin surface was demineralized and then incubated with one of the following six solutions: Sodium chloride NaCl, artificial saliva, milk, milk+2.5 ppm fluoride, milk+10 ppm fluoride and artificial saliva+10 ppm fluoride. Serial sections were cut through the lesions and investigated with polarized light microscopy and quantitative morphometry, scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS). The data were statistically evaluated using a one-way ANOVA for multiple comparisons. RESULTS: The depth of the lesion decreased with increasing fluoride concentration and was the smallest after incubation with artificial saliva+10 ppm fluoride. SEM analysis revealed a clearly demarcated superficial remineralized zone after incubation with milk+2.5 ppm fluoride, milk+10 ppm fluoride and artificial saliva+10 ppm fluoride. Ca content in this zone increased with increasing fluoride content and was highest after artificial saliva+10 ppm fluoride incubation. In the artificial saliva+10 ppm fluoride group, an additional crystalline layer was present on top of the lesion that contained elevated levels of F and Ca. CONCLUSION: Incubation of root dentin with fluoridated milk showed a clear effect on root dentin remineralization, and incubation with NaF dissolved in artificial saliva demonstrated a stronger effect.

Consensus paper: management of degenerative cerebellar disorders.

Treatment of motor symptoms of degenerative cerebellar ataxia remains difficult. Yet there are recent developments that are likely to lead to significant improvements in the future. Most desirable would be a causative treatment of the underlying cerebellar disease. This is currently available only for a very small subset of cerebellar ataxias with known metabolic dysfunction. However, increasing knowledge of the pathophysiology of hereditary ataxia should lead to an increasing number of medically sensible drug trials. In this paper, data from recent drug trials in patients with recessive and dominant cerebellar ataxias will be summarized. There is consensus that up to date, no medication has been proven effective. Aminopyridines and acetazolamide are the only exception, which are beneficial in patients with episodic ataxia type 2. Aminopyridines are also effective in a subset of patients presenting with downbeat nystagmus. As such, all authors agreed that the mainstays of treatment of degenerative cerebellar ataxia are currently physiotherapy, occupational therapy, and speech therapy. For many years, well-controlled rehabilitation studies in patients with cerebellar ataxia were lacking. Data of recently published studies show that coordinative training improves motor function in both adult and juvenile patients with cerebellar degeneration. Given the well-known contribution of the cerebellum to motor learning, possible mechanisms underlying improvement will be outlined. There is consensus that evidence-based guidelines for the physiotherapy of degenerative cerebellar ataxia need to be developed. Future developments in physiotherapeutical interventions will be discussed including application of non-invasive brain stimulation.

Longitudinal analysis of frequency and reactivity of Epstein-Barr virus-specific T lymphocytes and their association with intermittent viral reactivation.

Persistent Epstein-Barr virus (EBV) infection is controlled tightly by virus-specific T cells. EBV infection is reactivated intermittently over time, even in apparently healthy carriers. Changes in frequency and reactivity of memory T cells, particularly of CD8(+) origin, have not been assessed in this context. It is hypothesized that viral reactivation is facilitated by diminished EBV-specific T-cell immunity. To this end, blood samples from 14 healthy donors were collected at irregular time intervals for a period of about 1 year. Samples were screened for both EBV plasma viremia and increases in viral load in PBMCs as parameters of EBV reactivation. PBMCs were subject to IFN-γ ELISPOT analysis using the autologous EBV-transformed lymphoblastoid cell line (EBV-LCL) or appropriate HLA class I-restricted EBV peptides as stimulators. Frequencies of epitope-specific CD8(+) T cells were monitored further using HLA tetramers and flow cytometry. Twelve of 14 donors exhibited signs of asymptomatic EBV reactivation. Viral reactivation was accompanied by either substantially decreased IFN-γ responses against autologous EBV-LCL (eight of 12 study participants) and/or increased responses against particular EBV peptides (six of 12 donors). In seven persons with HLA-A2 and/or -B8 alleles numbers of HLA tetramer-positive CD8(+) T cells also varied over time, but showed no correlation to episodes of detectable viral activity. In summary, IFN-γ reactivity of EBV-specific T cells is not constant. Viral reactivation is detected preferably at times of diminished EBV-LCL-specific cellular immunity. However, increased reactivity of single immunodominant CD8(+) EBV-specific T-cell clones may occur in response to virus replication.

[Pulmonary hypertension due to chronic lung disease. Recommendations of the Cologne Consensus Conference 2010]. / Pulmonale Hypertonie bei chronischen Lungenerkrankungen. Empfehlungen der Kölner Konsensus-Konferenz 2010.

The 2009 European Guidelines on Pulmonary Hypertension did not cover only pulmonary arterial hypertension (PAH) but also some aspects of pulmonary hypertension (PH) in chronic lung disease. The European Guidelines point out that the drugs currently used to treat patients with PAH (prostanoids, endothelin receptor antagonists and phosphodiesterase-5 inhibitors) have not been sufficiently investigated in other forms of PH. Therefore, the European Guidelines do not recommend the use of these drugs in patients with chronic lung disease and PH. This recommendation, however, is not always in agreement with medical ethics as physicians feel sometimes inclined to treat other form of pulmonary hypertension which may affect quality of life and survival of these patients in a similar manner. In June 2010, a group of German experts met in Cologne, Germany, to discuss open and controversial issues surrounding the practical implementation of the European Guidelines. The conference was sponsored by the German Society of Cardiology, the German Society of Respiratory Medicine and the German Society of Pediatric Cardiology. One of the working groups was dedicated to the diagnosis and treatment of PH in patients with chronic lung disease. The recommendations of this working group are summarized in the present paper.

Basal ganglia dysfunction in OCD: subthalamic neuronal activity correlates with symptoms severity and predicts high-frequency stimulation efficacy.

Functional and connectivity changes in corticostriatal systems have been reported in the brains of patients with obsessive-compulsive disorder (OCD); however, the relationship between basal ganglia activity and OCD severity has never been adequately established. We recently showed that deep brain stimulation of the subthalamic nucleus (STN), a central basal ganglia nucleus, improves OCD. Here, single-unit subthalamic neuronal activity was analysed in 12 OCD patients, in relation to the severity of obsessions and compulsions and response to STN stimulation, and compared with that obtained in 12 patients with Parkinson's disease (PD). STN neurons in OCD patients had lower discharge frequency than those in PD patients, with a similar proportion of burst-type activity (69 vs 67%). Oscillatory activity was present in 46 and 68% of neurons in OCD and PD patients, respectively, predominantly in the low-frequency band (1-8 Hz). In OCD patients, the bursty and oscillatory subthalamic neuronal activity was mainly located in the associative-limbic part. Both OCD severity and clinical improvement following STN stimulation were related to the STN neuronal activity. In patients with the most severe OCD, STN neurons exhibited bursts with shorter duration and interburst interval, but higher intraburst frequency, and more oscillations in the low-frequency bands. In patients with best clinical outcome with STN stimulation, STN neurons displayed higher mean discharge, burst and intraburst frequencies, and lower interburst interval. These findings are consistent with the hypothesis of a dysfunction in the associative-limbic subdivision of the basal ganglia circuitry in OCD's pathophysiology.