Publications by authors named "Paul O"

240 Publications

Effect of decompression surgery for lumbar spinal stenosis on aerobic capacities during a 6-min walk test: a preliminary cohort study.

Ann Phys Rehabil Med 2022 Apr 27:101673. Epub 2022 Apr 27.

INSERM U1093, Cognition Action et Plasticité Sensorimotrice, Université de Bourgogne Franche Comté, Dijon, France; INSERM, CIC 1432, Module Plurithématique, Plateforme d'Investigation Technologique, Dijon, France.

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http://dx.doi.org/10.1016/j.rehab.2022.101673DOI Listing
April 2022

Pulmonary vascular inflammation with fatal coronavirus disease 2019 (COVID-19): possible role for the NLRP3 inflammasome.

Respir Res 2022 Feb 10;23(1):25. Epub 2022 Feb 10.

Institute for Environmental Medicine and Department of Physiology, University of Pennsylvania Perelman School of Medicine, 3620 Hamilton Walk, Philadelphia, PA, 19104, USA.

Background: Pulmonary hyperinflammation is a key event with SARS-CoV-2 infection. Acute respiratory distress syndrome (ARDS) that often accompanies COVID-19 appears to have worse outcomes than ARDS from other causes. To date, numerous lung histological studies in cases of COVID-19 have shown extensive inflammation and injury, but the extent to which these are a COVID-19 specific, or are an ARDS and/or mechanical ventilation (MV) related phenomenon is not clear. Furthermore, while lung hyperinflammation with ARDS (COVID-19 or from other causes) has been well studied, there is scarce documentation of vascular inflammation in COVID-19 lungs.

Methods: Lung sections from 8 COVID-19 affected and 11 non-COVID-19 subjects, of which 8 were acute respiratory disease syndrome (ARDS) affected (non-COVID-19 ARDS) and 3 were from subjects with non-respiratory diseases (non-COVID-19 non-ARDS) were H&E stained to ascertain histopathological features. Inflammation along the vessel wall was also monitored by expression of NLRP3 and caspase 1.

Results: In lungs from COVID-19 affected subjects, vascular changes in the form of microthrombi in small vessels, arterial thrombosis, and organization were extensive as compared to lungs from non-COVID-19 (i.e., non-COVID-19 ARDS and non-COVID-19 non-ARDS) affected subjects. The expression of NLRP3 pathway components was higher in lungs from COVID-19 ARDS subjects as compared to non-COVID-19 non-ARDS cases. No differences were observed between COVID-19 ARDS and non-COVID-19 ARDS lungs.

Conclusion: Vascular changes as well as NLRP3 inflammasome pathway activation were not different between COVID-19 and non-COVID-19 ARDS suggesting that these responses are not a COVID-19 specific phenomenon and are possibly more related to respiratory distress and associated strategies (such as MV) for treatment.
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http://dx.doi.org/10.1186/s12931-022-01944-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8830114PMC
February 2022

Otoscopy and tympanometry outcomes from the National Health and Nutrition Examination Survey (NHANES).

Am J Otolaryngol 2022 Mar-Apr;43(2):103332. Epub 2021 Dec 14.

University of Mississippi Medical Center, Department of Otolaryngology Head and Neck Surgery, 2500 N. State St., Jackson, MS 39216, United States of America. Electronic address:

Purpose: The purpose of the study was to estimate the prevalence of conductive pathologies based on tympanometric and otoscopic findings in adults in the U.S. and examine relationships between abnormal findings and audiometrically defined or reported perceived hearing loss and tinnitus.

Materials And Methods: Data from 3409 individuals aged 20-69 years from the 1999-2000 and 2000-2002 cycles of the National Health and Nutrition Examination Survey (NHANES) were analyzed. Outcomes included report of ear tubes, self-perceived hearing loss, and tinnitus (yes or no). Otoscopy involved screening for presence of cerumen (ear wax) and physical abnormality for each ear. Ear-specific tympanometry included measures of middle ear pressure, external ear volume, tympanometric width, and admittance/compliance for each ear. Mean and prevalence estimates are provided applying sample weights. A multivariate ordinal regression model adjusting for age, sex, race/ethnicity, and education was used to examine relationships between otoscopy or tympanometry measures with hearing loss and tinnitus.

Results: Approximately 12% of the sample showed evidence of abnormal tympanometry and 12% showed evidence of abnormal otoscopy in at least one ear. Measured hearing loss was consistently related to tympanometry outcomes, in both univariate and adjusted models, but perceived hearing loss and tinnitus were not related to abnormal tympanometry or otoscopy. The most common reason for abnormal otoscopy was presence of excessive or impacted cerumen, representing an estimated 10% of the population.

Conclusions: With 1 out of 10 adults having excessive cerumen, adults considering over-the-counter (OTC) hearings aids may benefit from an ear examination prior to purchase.
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http://dx.doi.org/10.1016/j.amjoto.2021.103332DOI Listing
March 2022

Applying State-of-the-Art Deep-Learning Methods to Classify Urban Cities of the Developing World.

Sensors (Basel) 2021 Nov 10;21(22). Epub 2021 Nov 10.

Center for Spatial Information Science, The University of Tokyo, Chiba 277-8568, Japan.

This paper shows the efficacy of a novel urban categorization framework based on deep learning, and a novel categorization method customized for cities in the global south. The proposed categorization method assesses urban space broadly on two dimensions-the states of urbanization and the architectural form of the units observed. This paper shows how the sixteen sub-categories can be used by state-of-the-art deep learning modules (fully convolutional network FCN-8, U-Net, and DeepLabv3+) to categorize formal and informal urban areas in seven urban cities in the developing world-Dhaka, Nairobi, Jakarta, Guangzhou, Mumbai, Cairo, and Lima. Firstly, an expert visually annotated and categorized 50 × 50 km Google Earth images of the cities. Each urban space was divided into four socioeconomic categories: (1) highly informal area; (2) moderately informal area; (3) moderately formal area, and (4) highly formal area. Then, three models mentioned above were used to categorize urban spaces. Image encompassing 70% of the urban space was used to train the models, and the remaining 30% was used for testing and validation of each city. The DeepLabv3+ model can segment the test part with an average accuracy of 90.0% for Dhaka, 91.5% for Nairobi, 94.75% for Jakarta, 82.0% for Guangzhou city, 94.25% for Mumbai, 91.75% for Cairo, and 96.75% for Lima. These results are the best for the DeepLabv3+ model among all. Thus, DeepLabv3+ shows an overall high accuracy level for most of the measuring parameters for all cities, making it highly scalable, readily usable to understand the cities' current conditions, forecast land use growth, and other computational modeling tasks. Therefore, the proposed categorization method is also suited for real-time socioeconomic comparative analysis among cities, making it an essential tool for the policymakers to plan future sustainable urban spaces.
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http://dx.doi.org/10.3390/s21227469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621463PMC
November 2021

Multifunctional optrode for opsin delivery, optical stimulation, and electrophysiological recordings in freely moving rats.

J Neural Eng 2021 11 15;18(6). Epub 2021 Nov 15.

Department of Microsystems Engineering (IMTEK), University of Freiburg, Freiburg, Germany.

. Optogenetics involves delivery of light-sensitive opsins to the target brain region, as well as introduction of optical and electrical devices to manipulate and record neural activity, respectively, from the targeted neural population. Combining these functionalities in a single implantable device is of great importance for a precise investigation of neural networks while minimizing tissue damage.. We report on the development, characterization, andvalidation of a multifunctional optrode that combines a silicon-based neural probe with an integrated microfluidic channel, and an optical glass fiber in a compact assembly. The silicon probe comprises an 11-m-wide fluidic channel and 32 recording electrodes (diameter 30m) on a tapered probe shank with a length, thickness, and maximum width of 7.5 mm, 50m, and 150m, respectively. The size and position of fluidic channels, electrodes, and optical fiber can be precisely tuned according to theapplication.With a total system weight of 0.97 g, our multifunctional optrode is suitable for chronicexperiments requiring simultaneous drug delivery, optical stimulation, and neural recording. We demonstrate the utility of our device in optogenetics by injecting a viral vector carrying a ChR2-construct in the prefrontal cortex and subsequent photostimulation of the transduced neurons while recording neural activity from both the target and adjacent regions in a freely moving rat for up to 9 weeks post-implantation. Additionally, we demonstrate a pharmacological application of our device by injecting GABA antagonist bicuculline in an anesthetized rat brain and simultaneously recording the electrophysiological response.. Our triple-modality device enables a single-step optogenetic surgery. In comparison to conventional multi-step surgeries, our approach achieves higher spatial specificity while minimizing tissue damage.
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http://dx.doi.org/10.1088/1741-2552/ac3206DOI Listing
November 2021

Intracortical probe arrays with silicon backbone and microelectrodes on thin polyimide wings enable long-term stable recordings.

J Neural Eng 2021 11 30;18(6). Epub 2021 Nov 30.

Microsystem Materials Laboratory, Department of Microsystems Engineering (IMTEK), University of Freiburg, Freiburg, Germany.

Recording and stimulating neuronal activity across different brain regions requires interfacing at multiple sites using dedicated tools while tissue reactions at the recording sites often prevent their successful long-term application. This implies the technological challenge of developing complex probe geometries while keeping the overall footprint minimal, and of selecting materials compatible with neural tissue. While the potential of soft materials in reducing tissue response is uncontested, the implantation of these materials is often limited to reliably target neuronal structures across large brain volumes.We report on the development of a new multi-electrode array exploiting the advantages of soft and stiff materials by combining 7-m-thin polyimide wings carrying platinum electrodes with a silicon backbone enabling a safe probe implantation. The probe fabrication applies microsystems technologies in combination with a temporal wafer fixation method for rear side processing, i.e. grinding and deep reactive ion etching, of slender probe shanks and electrode wings. The wing-type neural probes are chronically implanted into the entorhinal-hippocampal formation in the mouse forrecordings of freely behaving animals.Probes comprising the novel wing-type electrodes have been realized and characterized in view of their electrical performance and insertion capability. Chronic electrophysiologicalrecordings of the entorhinal-hippocampal network in the mouse of up to 104 days demonstrated a stable yield of channels containing identifiable multi-unit and single-unit activity outperforming probes with electrodes residing on a Si backbone.The innovative fabrication process using a process compatible, temporary wafer bonding allowed to realize new Michigan-style probe arrays. The wing-type probe design enables a precise probe insertion into brain tissue and long-term stable recordings of unit activity due to the application of a stable backbone and 7-m-thin probe wings provoking locally a minimal tissue response and protruding from the glial scare of the backbone.
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http://dx.doi.org/10.1088/1741-2552/ac39b7DOI Listing
November 2021

The diagnostic accuracy of truncated cardiovascular MR protocols for detecting non-ischemic cardiomyopathies.

Int J Cardiovasc Imaging 2021 Nov 9. Epub 2021 Nov 9.

Department of Cardiology, Angiology and Pneumonology, University Hospital Heidelberg, Heidelberg, Germany.

Cardiovascular magnetic resonance imaging is one of the most important diagnostic modalities in the evaluation of cardiomyopathies. However, significant limitations are the complex and time-consuming workflows and the need of contrast agents. The aim of this multi-center retrospective study was to assess workflows and diagnostic value of a short, contrast agent-free cardiac magnetic resonance protocol. 160 patients from Heidelberg, Germany and 119 patients from Montreal, Canada with suspected cardiomyopathy and 20 healthy volunteers have been enrolled. Scans were performed at a 1.5Tesla or 3Tesla scanner in Heidelberg and at a 3Tesla scanner in Montreal. We used single-slice T1 map only. A stepwise analysis of images has been performed. The possible differential diagnosis after each step has been defined. T1-values and color-encoded T1 maps significantly contributed to the differential diagnosis in 54% of the cases (161/299); the final diagnosis has been done without late gadolinium enhancement images in 83% of healthy individuals, in 99% of patients with dilated cardiomyopathy, in 93% of amyloidosis patients, in 94% of patients with hypertrophic cardiomyopathy and in 85% of patients with hypertensive heart disease, respectively. Comparing the scan time with (48 ± 7 min) vs. without contrast agent (23 ± 5 min), significant time saving could be reached by the short protocol. Subgroup analysis showed the most additional diagnostic value of T1 maps in amyloidosis and hypertrophic cardiomyopathy or in confirmation of normal findings. In patients with unclear left ventricular hypertrophy, a short, non-contrast protocol can be used for diagnostic decision-making, if the quality of the T1 map is diagnostic, even if only one slice is available.
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http://dx.doi.org/10.1007/s10554-021-02462-2DOI Listing
November 2021

Microfluidic chip connected to porous microneedle array for continuous ISF sampling.

Drug Deliv Transl Res 2022 02 5;12(2):435-443. Epub 2021 Nov 5.

Institute of Industrial Science, the University of Tokyo, Tokyo, Japan.

Minimally invasive biosensing using microneedles (MNs) is a desirable technology for continuous healthcare monitoring. Among a wide range of MNs, porous MNs are expected to be applied for sampling of interstitial fluids (ISF) by connecting the internal tissue to external measurement devices. In order to realize a continuous measurement of biomarkers in ISF through porous MNs, their integration with a microfluidic chip is a promising approach due to its applicability to micro-total analysis system (μTAS) technology. In this study, we developed a fluidic system to directly interface porous MNs to a microfluidic chip consisting of a capillary pump for the continuous sampling of ISF. The porous and flexible MNs made of PDMS are connected to the microfluidic chip fabricated by standard microelectro-mechanical system (MEMS) processes, showing a continuous flow of phosphate buffered saline (PBS). The developed device will lead to the minimally invasive and continuous biosampling for long-term healthcare monitoring.
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http://dx.doi.org/10.1007/s13346-021-01050-0DOI Listing
February 2022

High rates of culture conversion and low loss to follow-up in MDR-TB patients managed at Regional Referral Hospitals in Uganda.

BMC Infect Dis 2021 Oct 12;21(1):1060. Epub 2021 Oct 12.

University Research Co., LLC, Kampala, Uganda.

Background: Multi-drug resistant-tuberculosis (MDR-TB) is an emerging public health concern in Uganda. Prior to 2013, MDR-TB treatment in Uganda was only provided at the national referral hospital and two private-not-for profit clinics. From 2013, it was scaled up to seven regional referral hospitals (RRH). The aim of this study was to measure interim (6 months) treatment outcomes among the first cohort of patients started on MDR-TB treatment at the RRH in Uganda.

Methods: This was a cross-sectional study in which a descriptive analysis of data collected retrospectively on a cohort of 69 patients started on MDR-TB treatment at six of the seven RRH between 1st April 2013 and 30th June 2014 and had been on treatment for at least 9 months was conducted.

Results: Of the 69 patients, 21 (30.4%) were female, 39 (56.5%) HIV-negative, 30 (43.5%) resistant to both isoniazid and rifampicin and 57 (82.6%) category 1 or 2 drug susceptible TB treatment failures. Median age at start of treatment was 35 years (Interquartile range (IQR): 27-45), median time-to-treatment initiation was 27.5 (IQR: 6-89) days and of the 30 HIV-positive patients, 27 (90.0%) were on anti-retroviral treatment with a median CD4 count of 206 cells/microliter of blood (IQR: 113-364.5). Within 6 months of treatment, 59 (85.5%) patients culture converted, of which 45 (65.2%) converted by the second month and the other 14 (20.3%) by the sixth month; one (1.5%) did not culture convert; three (4.4%) died; and six (8.8%) were lost-to-follow up. Fifty (76.8%) patients experienced at least one drug adverse event, while 40 (67.8%) gained weight. Mean weight gained was 4.7 (standard deviation: 3.2) kilograms.

Conclusions: Despite MDR-TB treatment initiation delays, most patients had favourable interim treatment outcomes with majority culture converting early and very few getting lost to follow-up. These encouraging interim outcomes indicate the potential for success of a scale-up of MDR-TB treatment to RRH.
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http://dx.doi.org/10.1186/s12879-021-06743-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507334PMC
October 2021

Vascular Inflammation in Lungs of Patients with Fatal Coronavirus Disease 2019 (COVID-19): Possible Role for the NLRP3 Inflammasome.

Res Sq 2021 Sep 1. Epub 2021 Sep 1.

Penn: University of Pennsylvania.

Hyperinflammation is a key event that occurs with SARS-CoV-2 infection. In the lung, hyperinflammation leads to structural damage to tissue. To date, numerous lung histological studies have shown extensive alveolar damage, but there is scarce documentation of vascular inflammation in postmortem lung tissue. Lung sections from 8 COVID-19 affected and 11 non-COVID-19 subjects [of which 8 were acute respiratory disease syndrome (ARDS) affected and 3 were from subjects with non-respiratory diseases] were stained for H & E to ascertain histopathological features including presence of thrombi/microthrombi. Inflammation along the vessel wall was also monitored by quantification of the expression of moieties of the NLRP3 inflammasome pathway (NLRP3 and caspase-1). In lungs from "fatal COVID-19", vascular changes in the form of microthrombi in small vessels, arterial thrombosis, and organization were extensive as compared to lungs from "non-COVID-19 non respiratory disease" affected subjects. The NLRP3 pathway components were significantly higher in lungs from COVID-19 subjects as compared to non-COVID-19 fatal cases without respiratory disease. No significant differences were observed between COVID-19 lungs and non-COVID-19 ARDS lungs. We posit that inflammasome formation along the vessel wall is a characteristic of lung inflammation that accompanies COVID-19. Thus, the NLRP3 inflammasome pathway seems to be probable candidate that drives amplification of inflammation post SARS-CoV-2 infection.
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http://dx.doi.org/10.21203/rs.3.rs-842167/v1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423225PMC
September 2021

Occurrence and aetiology of subclinical mastitis in water buffalo in Bangladesh.

J Dairy Res 2021 Aug 20;88(3):314-320. Epub 2021 Aug 20.

Department of Medicine and Surgery, Chattogram Veterinary and Animal Sciences University, Chattogram, Bangladesh.

Subclinical mastitis (SCM) in water buffalo is a production disease associated with decreased milk yield and impaired milk quality and safety. Water buffalo is an important livestock species in Bangladesh, but information about the occurrence and aetiology of SCM in this species is scarce. A cross-sectional study was conducted as part of the Udder Health Bangladesh Programme to (i) determine the occurrence of SCM and bulk milk somatic cell count (SCC) in water buffalo in Bangladesh, (ii) identify pathogens causing SCM and (iii) evaluate penicillin resistance in isolated staphylococci strains. Sixteen buffalo farms in the Bagerhat and Noakhali regions of Bangladesh were selected for study and a bulk milk sample was collected from each farm. In addition, 299 udder quarter milk samples were collected from 76 animals. The bulk milk samples were assessed by direct SCC and the quarter milk samples by California mastitis test (CMT). The occurrence of SCM calculated at quarter and animal level was 42.5 and 81.6%, respectively. Milk samples from 108 CMT-positive quarters in 48 animals and 38 randomly selected CMT-negative quarters in 24 animals were investigated using bacteriological culture. Estimated mean bulk milk SCC was 195 000 cells/ml milk (range 47 000- 587 000 cells/ml milk). On culture, estimated quarter-level intramammary infection (IMI) was 40.4%. The identity of isolated bacteria was confirmed by MALDI-TOF mass spectrometry. Non-aureus staphylococci (NAS) were the most common pathogens (24.7%) and, among 36 NAS tested, 36.1% were resistant to penicillin. Thus there was high occurrence of SCM on the study farms, with relatively high penicillin resistance in NAS. Further studies are needed to identify underlying risk factors and develop an udder health control strategy for water buffalo in Bangladesh.
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http://dx.doi.org/10.1017/S0022029921000698DOI Listing
August 2021

The impact of Wilson disease on myocardial tissue and function: a cardiovascular magnetic resonance study.

J Cardiovasc Magn Reson 2021 06 24;23(1):84. Epub 2021 Jun 24.

Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital, Heidelberg, Germany.

Background: Systemic effects of altered serum copper processing in Wilson Disease (WD) might induce myocardial copper deposition and consequently myocardial dysfunction and structural remodeling. This study sought to investigate the prevalence, manifestation and predictors of myocardial tissue abnormalities in WD patients.

Methods: We prospectively enrolled WD patients and an age-matched group of healthy individuals. We applied cardiovascular magnetic resonance (CMR) to analyze myocardial function, strain, and tissue characteristics. A subgroup analysis of WD patients with predominant neurological (WD-neuro) or hepatic manifestation only (WD-neuro) was performed.

Results: Seventy-six patients (37 years (27-49), 47% women) with known WD and 76 age-matched healthy control subjects were studied. The prevalence of atrial fibrillation in WD patients was 5% and the prevalence of symptomatic heart failure was 2.6%. Compared to healthy controls, patients with WD had a reduced left ventricular global circumferential strain (LV-GCS), and also showed abnormalities consistent with global and regional myocardial fibrosis. WD-neuro patients presented with more severe structural remodeling and functional impairment when compared to WD-neuro patients.

Conclusions: In a large cohort, WD was not linked to a distinct cardiac phenotype except CMR indexes of myocardial fibrosis. More research is warranted to assess the prognostic implications of these findings.

Trial Registration: This trial is registered at the local institutional ethics committee (S-188/2018).
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http://dx.doi.org/10.1186/s12968-021-00760-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223377PMC
June 2021

African Children Vulnerabilities in COVID-19 Era: A Review.

Afr J Reprod Health 2020 Jun;24(s1):154-171

Université Toulouse Jean Jaurès, Département Psychologie du développement, France.

The pandemic of COVID-19 has spread from China to the whole world. Here we address the vulnerability of African children in the context of this health crisis. Based on medical, socio-economic and anthropological studies, we present a thematic review that examines the issue at three levels. Firstly, we address the question of the effect of the virus on children in regard to strategies implemented to limit its spread and the capacity of medical devices in Africa. Second, we address the issue of the additional disruptions that the virus could generate by infecting the parents or guardians of children who often find themselves subject to the disquietudes of an informal economy. Finally, we discuss the long-term effects of the crisis on children about food security issues, particularly in relation to overweight and obesity. Based on studies that have documented the long-term overweight risks that can occur due to school cessation as a result of lockdown measures, we provide strategies to address this emerging public health problem in Africa. We conclude the study by suggesting that all these forms of vulnerabilities remain proactive areas of work to better prepare Africa for future pandemics.
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http://dx.doi.org/10.29063/ajrh2020/v24i2s.19DOI Listing
June 2020

Vascular Inflammation in Lungs of Patients with Fatal Coronavirus Disease 2019 (COVID-19) Infection: Possible role for the NLRP3 inflammasome.

medRxiv 2021 Mar 22. Epub 2021 Mar 22.

Hyperinflammation is a key event that occurs with SARS-CoV-2 infection. In the lung, hyperinflammation leads to structural damage to tissue. To date, numerous lung histological studies have shown extensive alveolar damage, but there is scarce documentation of vascular inflammation in postmortem lung tissue. Here we document histopathological features and monitor the NLRP3 inflammasome in fatal cases of disease caused by SARS Cov2 (COVID-19). We posit that inflammasome formation along the vessel wall is a characteristic of lung inflammation that accompanies COVID-19 and that it is a probable candidate that drives amplification of inflammation post infection.
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http://dx.doi.org/10.1101/2021.03.19.21253815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010767PMC
March 2021

Inflammation in Periodontal Disease: Possible Link to Vascular Disease.

Front Physiol 2020 14;11:609614. Epub 2021 Jan 14.

Institute for Environmental Medicine, Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA, United States.

Inflammation is a well-organized protective response to pathogens and consists of immune cell recruitment into areas of infection. Inflammation either clears pathogens and gets resolved leading to tissue healing or remains predominantly unresolved triggering pathological processes in organs. Periodontal disease (PD) that is initiated by specific bacteria also triggers production of inflammatory mediators. These processes lead to loss of tissue structure and function. Reactive oxygen species and oxidative stress play a role in susceptibility to periodontal pathogenic bacterial infections. Periodontal inflammation is a risk factor for systemic inflammation and eventually cardiovascular disease (CVD). This review discusses the role of inflammation in PD and its two way association with other health conditions such as diabetes and CVD. Some of the mechanisms underpinning the links between inflammation, diabetes, CVD and PD are also discussed. Finally, we review available epidemiological data and other reports to assess possible links between oral health and CVD.
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http://dx.doi.org/10.3389/fphys.2020.609614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841426PMC
January 2021

Histological assessment of a chronically implanted cylindrically-shaped, polymer-based neural probe in the monkey.

J Neural Eng 2021 02 26;18(2). Epub 2021 Feb 26.

Dipartimento di Medicina e Chirurgia, Università degli Studi di Parma, Parma, IT, Italy.

Previous studies demonstrated the possibility to fabricate stereo-electroencephalography probes with high channel count and great design freedom, which incorporate macro-electrodes as well as micro-electrodes offering potential benefits for the pre-surgical evaluation of drug resistant epileptic patients. These new polyimide probes allowed to record local field potentials, multi- and single-unit activity (SUA) in the macaque monkey as early as 1 h after implantation, and yielded stable SUA for up to 26 d after implantation. The findings opened new perspectives for investigating mechanisms underlying focal epilepsy and its treatment, but before moving to possible human application, safety data are needed. In the present study we evaluate the tissue response of this new neural interface by assessing post-mortem the reaction of brain tissue along and around the probe implantation site.Three probes were implanted, independently, in the brain of one monkey () at different times. We used specific immunostaining methods for visualizing neuronal cells and astrocytes, for measuring the extent of damage caused by the probe and for relating it with the implantation time.The size of the region where neurons cannot be detected did not exceed the size of the probe, indicating that a complete loss of neuronal cells is only present where the probe was physically positioned in the brain. Furthermore, around the probe shank, we observed a slightly reduced number of neurons within a radius of 50m and a modest increase in the number of astrocytes within 100m.In the light of previous electrophysiological findings, the present data suggest the potential usefulness and safety of this probe for human applications.
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http://dx.doi.org/10.1088/1741-2552/abdd11DOI Listing
February 2021

[Parental Resolution of the Child's Disability Diagnosis in the Reaction to Diagnosis Interview (RDI) and Effects on the Play Interaction with the Child].

Authors:
Oliver Paul

Prax Kinderpsychol Kinderpsychiatr 2020 Oct;69(7):625-642

Institut für Musikwissenschaft und Musikpädagogik - Fach Musiktherapie Philippistr. 2 48149 Münster Deutschland Institut für Musikwissenschaft und Musikpädagogik - Fach Musiktherapie.

Examining 37 qualitative interviews with mothers and fathers of a child with intellectual disability it was observed that the emotions and traumatic experiences, associated with the child's diagnosis, still burden the relationship with the child even after several years, so that many affected cannot come to resolution. On the other hand, resolution of the diagnosis was indicated for 65 % of the parents, enabling them to reclaim lost space for building a relationship with their child. While these parents significantly more often report purposeless and responsive play interaction with their children, non-resolved parents still seem to be driven to counteract the disability by playing educational games or playing games, which promote the development. In a parallel music therapeutic study, the effects of parental resolution also are monitored in children's free play interaction: Children of resolved parents interact more often in a dialogic relationship, whereas children of non-resolved parents are less able to balance dyadic turn-taking and interaction control in free music play.
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http://dx.doi.org/10.13109/prkk.2020.69.7.625DOI Listing
October 2020

Customized Thinning of Silicon-based Neural Probes Down to 2 µm.

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:3388-3392

This paper reports on the customized thinning of neural probes based on silicon (Si) using deep reactive ion etching (DRIE) as a post-processing step. The reduced probe dimensions are expected to minimize local tissue trauma, while guaranteeing probe integrity during implantation. For DRIE, the probes are partially masked by a micromachined Si cover chip comprising tailored cavities enabling any desired thinned length l and probe thickness t by a proper choice of cover chip design and DRIE parameters, respectively. A broad variety of probe designs were realized with shank tip thicknesses ranging from 35 µm down to 2 µm. All probes could successfully be implanted into a brain tissue phantom, demonstrating a pronounced reduction in insertion force from 0.55 mN for unprocessed probes to 0.08 mN for 2-µm-thin shanks. When the dura mater was mimicked by a polyethylene (PE) membrane, forces were reduced from 28.9 mN to 16.6 mN for 15-µm-thin shanks.
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http://dx.doi.org/10.1109/EMBC44109.2020.9176523DOI Listing
July 2020

Multichannel optogenetic stimulation of the auditory pathway using microfabricated LED cochlear implants in rodents.

Sci Transl Med 2020 07;12(553)

Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, 37099 Göttingen, Germany.

When hearing fails, electrical cochlear implants (eCIs) provide the brain with auditory information. One important bottleneck of CIs is the poor spectral selectivity that results from the wide current spread from each of the electrode contacts. Optical CIs (oCIs) promise to make better use of the tonotopic order of spiral ganglion neurons (SGNs) inside the cochlea by spatially confined stimulation. Here, we established multichannel oCIs based on light-emitting diode (LED) arrays and used them for optical stimulation of channelrhodopsin (ChR)-expressing SGNs in rodents. Power-efficient blue LED chips were integrated onto microfabricated 15-μm-thin polyimide-based carriers comprising interconnecting lines to address individual LEDs by a stationary or mobile driver circuitry. We extensively characterized the optoelectronic, thermal, and mechanical properties of the oCIs and demonstrated stability over weeks in vitro. We then implanted the oCIs into ChR-expressing rats and gerbils, and characterized multichannel optogenetic SGN stimulation by electrophysiological and behavioral experiments. Improved spectral selectivity was directly demonstrated by recordings from the auditory midbrain. Long-term experiments in deafened ChR-expressing rats and in nontreated control animals demonstrated specificity of optogenetic stimulation. Behavioral studies on animals carrying a wireless oCI sound processor revealed auditory percepts. This study demonstrates hearing restoration with improved spectral selectivity by an LED-based multichannel oCI system.
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http://dx.doi.org/10.1126/scitranslmed.abb8086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611895PMC
July 2020

μLED-based optical cochlear implants for spectrally selective activation of the auditory nerve.

EMBO Mol Med 2020 08 29;12(8):e12387. Epub 2020 Jun 29.

Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, Germany.

Electrical cochlear implants (eCIs) partially restore hearing and enable speech comprehension to more than half a million users, thereby re-connecting deaf patients to the auditory scene surrounding them. Yet, eCIs suffer from limited spectral selectivity, resulting from current spread around each electrode contact and causing poor speech recognition in the presence of background noise. Optogenetic stimulation of the auditory nerve might overcome this limitation as light can be conveniently confined in space. Here, we combined virus-mediated optogenetic manipulation of cochlear spiral ganglion neurons (SGNs) and microsystems engineering to establish acute multi-channel optical cochlear implant (oCI) stimulation in adult Mongolian gerbils. oCIs based on 16 microscale thin-film light-emitting diodes (μLEDs) evoked tonotopic activation of the auditory pathway with high spectral selectivity and modest power requirements in hearing and deaf gerbils. These results prove the feasibility of μLED-based oCIs for spectrally selective activation of the auditory nerve.
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http://dx.doi.org/10.15252/emmm.202012387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411546PMC
August 2020

Composition of browses consumed by Matschie's tree kangaroo (Dendrolagus matschiei) sampled from home ranges in Papua New Guinea.

Zoo Biol 2020 Jul 22;39(4):271-275. Epub 2020 Apr 22.

Tree Kangaroo Conservation Program, Lae, Papua New Guinea.

Twenty-six samples (n = 24 spp.) of foods eaten, including ferns, shrubs, vines, orchids, herbaceous plants, and tree leaves, were collected from the Yopno, Uruwa, and Som Conservation Area at approximately 1,800 m altitude on the Huon Peninsula, Papua New Guinea (PNG). Samples were weighed fresh in the field and transported to the Lae National Herbarium in PNG for drying and confirmed identification, before transporting to the US for analysis of primary nutrient composition and minerals. Water content averaged 76 ± 10% (mean ± standard deviation); on a dry matter (DM) basis, foods averaged moderate protein (11 ± 5%), and soluble carbohydrate (27 ± 8%) content, along with exceptionally low starch (1 ± 1%) and crude fat (3 ± 2%) values, and moderate to high values in fiber fractions (neutral detergent fiber 52 ± 13%, acid detergent fiber 39 ± 10%, lignin 15 ± 6%). Calculated metabolizable energy content of native forages averaged 1.9 ± 0.3 Mcal/kg DM (ruminant model). Macromineral concentrations (DM basis) were not exceptional (calcium 1.1 ± 1.0%, phosphorus 0.2 ± 0.1%, magnesium 0.3 ± 0.2%, potassium 1.8 ± 0.9%, sodium 0.02 ± 0.02%), and select trace minerals were within anticipated ranges for herbivores (copper 12 ± 13 mg/kg, iron 48 ± 26 mg/kg, zinc 34 ± 18 mg/kg) with the exception of manganese (268 ± 225 mg/kg), which could be considered on the high end of dietary adequacy for most herbivores. These data provide useful information that can be used to adjust nutrient targets for dietary development and feeding management of captive populations of tree kangaroos.
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http://dx.doi.org/10.1002/zoo.21543DOI Listing
July 2020

High-density electrophysiological recordings in macaque using a chronically implanted 128-channel passive silicon probe.

J Neural Eng 2020 04 29;17(2):026036. Epub 2020 Apr 29.

Ernst Strüngmann Institute (ESI) gGmbH for Neuroscience in Cooperation with Max Planck Society, Deutschordenstraße 46, D-60528, Frankfurt am Main, Germany. Max Planck Institute for Brain Research, Max-von-Laue-Str. 4, D-60438, Frankfurt am Main, Germany. Institute of Cell Biology and Neuroscience, Goethe-University Frankfurt, Max von Laue Str. 13, D-60438, Frankfurt am Main, Germany. These authors have contributed equally to this work.

Objective: The analysis of interactions among local populations of neurons in the cerebral cortex (e.g. within cortical microcolumns) requires high resolution and high channel count recordings from chronically implanted laminar microelectrode arrays. The request for high-density recordings of a large number of recording sites can presently only be accomplished by probes realized using complementary metal-oxide-semiconductor (CMOS) technology. In preparation for their use in non-human primates, we aimed for neural probe validation in a head-fixed approach analyzing the long-term recording capability.

Approach: We examined chronically implanted silicon-based laminar probes, realized using a CMOS technology in combination with micromachining, to record from the primary visual cortex (V1) of a monkey. We used a passive CMOS probe that had 128 electrodes arranged at a pitch of 22.5 µm in four columns and 32 rows on a slender shank. In order to validate the performance of a dedicated microdrive, the overall dimensions of probe and interface boards were chosen to be compatible with the final active CMOS probe comprising integrated circuitry.

Main Results: Using the passive probe, we recorded simultaneously local field potentials (LFP) and spiking multiunit activity (MUA) in V1 of an awake behaving macaque monkey. We found that an insertion through the dura and subsequent readjustments of the chronically implanted neural probe was possible and allowed us to record stable LFPs for more than five months. The quality of MUA degraded within the first month but remained sufficiently high to permit mapping of receptive fields during the full recording period.

Significance: We conclude that the passive silicon probe enables semi-chronic recordings of high quality of LFP and MUA for a time span exceeding five months. The new microdrive compatible with a commercial recording chamber successfully demonstrated the readjustment of the probe position while the implemented plug structure effectively reduced brain tissue movement relative to the probe.
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http://dx.doi.org/10.1088/1741-2552/ab8436DOI Listing
April 2020

Compact Optical Neural Probes With Up to 20 Integrated Thin-Film μLEDs Applied in Acute Optogenetic Studies.

IEEE Trans Biomed Eng 2020 09 13;67(9):2603-2615. Epub 2020 Jan 13.

This paper reports on the development, characterization and in vivo validation of compact optical neural probes. These novel intracerebral devices comprise micro light-emitting diodes ( μLEDs) integrated along their slender probe shanks with up to 20  μLEDs per device. Blue light with a peak wavelength of 455 nm is emitted from circular apertures 100  μm in diameter. The μLEDs are structured on GaN-on-sapphire wafers and subsequently transferred onto silicon (Si) carrier wafers. The wafer-scale transfer process provides the opportunity to process the functional GaN layer stack from both sides and hence enables maximizing the efficiency of the μLEDs. Combined with standard MEMS fabrication processes for Si, linear μLED arrays with small inter- μLED distances are achieved on thin probe shanks with cross-sections measuring [Formula: see text]. Devices are interconnected using highly flexible polyimide cables in order to mechanically decouple them from the peripheral electronics during in vivo experiments. Assembled probes emit a peak optical radiant flux of 440  μW (emittance 56 mW mm ) at 5 mA driving current. Thermal characterization of test probes reveals a temperature increase of 1.5 K measured using an integrated thermistor. Electrical functionality stress tests have been carried out to evaluate the device passivation against the physiological environment. It is estimated to endure at least 48 h during continuously pulsed μLED operation. A compact driving circuitry enables low-noise μLED operation in in vivo optogenetic experiments. The radiant flux necessary to elicit an acceptable neuronal response is determined between 1.36  μW and 17.5  μW. Probe validation successfully demonstrates the layer-specific stimulation in the cortex in multiple in vivo trials.
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http://dx.doi.org/10.1109/TBME.2020.2966293DOI Listing
September 2020

Thermodilution vs estimated Fick cardiac output measurement in an elderly cohort of patients: A single-centre experience.

PLoS One 2019 20;14(12):e0226561. Epub 2019 Dec 20.

Department of Internal Medicine and Cardiology, Campus Virchow Klinikum (CVK), Charité-University Medicine, Berlin, Germany.

Aims: Patients referred to the cath-lab are an increasingly elderly population. Thermodilution (TD, gold standard) and the estimated Fick method (eFM) are interchangeably used in the clinical routine to measure cardiac output (CO). However, their correlation in an elderly cohort of cardiac patients has not been tested so far.

Methods: A single, clinically-indicated right heart catheterization was performed on each patient with CO estimated by eFM and TD in 155 consecutive patients (75.1±6.8 years, 57.7% male) between April 2015 and August 2017. Whole Body Oxygen Consumption (VO2) was assumed by applying the formulas of LaFarge (LaF), Dehmer (De) and Bergstra (Be). CO was indexed to body surface area (Cardiac Index, CI).

Results: CI-TD showed an overall moderate correlation to CI-eFM as assessed by LaF, De or Be (r2 = 0.53, r2 = 0.54, r2 = 0.57, all p < .001, respectively) with large limits of agreement (-0.64 to 1.09, -1.07 to 0.77, -1.38 to 0.53 l/m2/min, respectively). The mean difference of CI between methods was 0.22, -0.15 and -0.42 (all p<0.001 for difference to TD), respectively. A rate of error ≥20% occurred with the equations by LaF, De or Be in 40.6%, 26.5% and 36.1% of patients, respectively. A CI <2.2 l/m2min was present in 42.6% of patients according to TD and in 60.0%, 31.0% and in 16.1% of patients according to eFM by the formulas of LaF, De or Be.

Conclusion: Although CI-eFM shows an overall reasonable correlation with CI-TD, the predictive value in a single patient is low. CI-eFM cannot replace CI-TD in elderly patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226561PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924680PMC
March 2020

Data enabled prediction analysis assigns folate/biopterin transporter (BT1) family to 36 hypothetical membrane proteins in Leishmania donovani.

Bioinformation 2019 18;15(10):697-708. Epub 2019 Oct 18.

National Centre for Biological Sciences, Tata Institute of Fundamental Research,Bangalore.

Leishmaniasis is a neglected tropical disease caused by the pathogenic protozoan Leishmania donovani and it is transmitted by an infected sand fly. Approximately 0.4 million cases of Visceral Leishmaniasis are reported across the globe every year, of which 67% is from the Indian subcontinent. The currently available drugs have not been effective owing to their high toxicity levels, inadequate specificity, drug resistance, extended treatment periods and/or prohibitive prices. For this reason, hypothetical proteins in this pathogen, which constitute about 67% of its proteome, must be distinctly characterized and studied for their potential role as drug targets for Leishmaniasis. Domain information from PFAM and functional information from GO has been used to assign putative functions to 36 hypothetical membrane proteins in this protozoan. Furthermore, as a case study, we have performed a thorough sequence level characterization of a hypothetical protein E9BPD7 from the BT1 family of membrane proteins that transports folate/biopterin. Phylogenetic analyses of E9BPD7 have revealed interesting evolutionary correlations to BT1 family and MFS superfamily, which have significant roles in a number of diseases and drug resistance pathways.
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http://dx.doi.org/10.6026/97320630015697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900323PMC
October 2019

Cardiac pacing using transmural multi-LED probes in channelrhodopsin-expressing mouse hearts.

Prog Biophys Mol Biol 2020 08 16;154:51-61. Epub 2019 Nov 16.

Department of Microsystems Engineering, University of Freiburg, Freiburg, Germany; Cluster of Excellence BrainLinks-BrainTools, University of Freiburg, Freiburg, Germany.

Optogenetics enables cell-type specific monitoring and actuation via light-activated proteins. In cardiac research, expressing light-activated depolarising ion channels in cardiomyocytes allows optical pacing and defibrillation. Previous studies largely relied on epicardial illumination. Light penetration through the myocardium is however problematic when moving to larger animals and humans. To overcome this limitation, we assessed the utility of an implantable multi light-emitting diode (LED) optical probe (IMLOP) for intramural pacing of mouse hearts expressing cardiac-specific channelrhodopsin-2 (ChR2). Here we demonstrated that IMLOP insertion needs approximately 20 mN of force, limiting possible damage from excessive loads applied during implantation. Histological sections confirmed the confined nature of tissue damage during acute use. The temperature change of the surrounding tissue was below 1 K during LED operation, rendering the probe safe for use in situ. This was confirmed in control experiments where no effect on cardiac action potential conduction was observed even when using stimulation parameters twenty-fold greater than required for pacing. In situ experiments on ChR2-expressing mouse hearts demonstrated that optical stimulation is possible with light intensities as low as 700 μW/mm; although stable pacing requires higher intensities. When pacing with a single LED, rheobase and chronaxie values were 13.3 mW/mm2 ± 0.9 mW/mm and 3 ms ± 0.6 ms, respectively. When doubling the stimulated volume the rheobase decreased significantly (6.5 mW/mm2 ± 0.9 mW/mm). We have demonstrated IMLOP-based intramural optical pacing of the heart. Probes cause locally constrained tissue damage in the acute setting and require low light intensities for pacing. Further development is necessary to assess effects of chronic implantation.
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http://dx.doi.org/10.1016/j.pbiomolbio.2019.11.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322525PMC
August 2020

CMOS-Compatible, Flexible, Intracortical Neural Probes.

IEEE Trans Biomed Eng 2020 05 21;67(5):1366-1376. Epub 2019 Aug 21.

Flexible intracortical neural probes elicit a lower foreign body response when compared to rigid implants. However, by incorporating complementary metal-oxide-semiconductor (CMOS) circuitry, silicon-based neural probes can offer an improved scalability and more functionalities than any other currently available technology.

Objective: Our goal is the development of a novel neural probe that combines flexibility with the functionalities of active CMOS-based probes.

Methods: We interface CMOS-based probe tips of only a few millimeters in length with flexible polyimide cables, which enable the complete implantation of the tips into brain tissue. The multilayer platinum metallization of the cables is patterned using a novel combination of ion beam and plasma etching. Implantation of the flexible probes is verified in brain models using stiff insertion shuttles.

Result: We assembled neural probes from passive and active tips as short as 1.5 mm and less than 180 μm in width. Active probes feature electrode arrays with 72 recording sites and multiplexing to 16 parallel output lines. We reliably patterned cables with signal lines of 2 μm in width and 3 μm in spacing. Ion beam etching deteriorated the composition of the polyimide substrate and its resistance to around 1 kΩ. An additional plasma treatment re-established high insulation resistances and recovered the chemical composition. Probes were successfully implanted to a depth of 7 mm using insertion shuttles and withstood forces of 63 mN.

Conclusions: This study presents the methods required for the fabrication and application of a new generation of neural probes.

Significance: The synergetic approach surpasses the limitation of each individual probe technology and should be considered in future developments.
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http://dx.doi.org/10.1109/TBME.2019.2936740DOI Listing
May 2020

Transposon Mutagenesis of Listeria monocytogenes.

Methods Mol Biol 2019 ;2016:63-71

Department of Cell and Molecular Biology, The University of Southern Mississippi, Hattiesburg, MS, USA.

Listeria monocytogenes is a Gram-positive, facultative intracellular foodborne pathogen that enters the human digestive tract after the consumption of contaminated food. Much research has been done to understand the virulence factors of Listeria monocytogenes. One useful tool to study these virulence factors has been transposon mutagenesis. Many mutants can be generated at a time by performing high-throughput mutagenesis using transposons and later screening these mutants to identify features related to particular functions in the bacteria. Many transposon delivery systems are not ideal for transposon studies in Listeria monocytogenes, as the transposon system is too large, has lower transposition efficiency, and a high rate of plasmid retention. Therefore, a new mariner-based transposition system has been developed for Listeria monocytogenes. This system is an ideal high-throughput transposon mutagenesis as the rate of transposition is high and random, along with very low plasmid retention capacity.
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http://dx.doi.org/10.1007/978-1-4939-9570-7_6DOI Listing
March 2020

Recording Quality of Mechanically Decoupled Floating Versus Skull-Fixed Silicon-Based Neural Probes.

Front Neurosci 2019 21;13:464. Epub 2019 May 21.

Department of Microsystems Engineering (IMTEK), University of Freiburg, Freiburg im Breisgau, Germany.

Throughout the past decade, silicon-based neural probes have become a driving force in neural engineering. Such probes comprise sophisticated, integrated CMOS electronics which provide a large number of recording sites along slender probe shanks. Using such neural probes in a chronic setting often requires them to be mechanically anchored with respect to the skull. However, any relative motion between brain and implant causes recording instabilities and tissue responses such as glial scarring, thereby shielding recordable neurons from the recording sites integrated on the probe and thus decreasing the signal quality. In the current work, we present a comparison of results obtained using mechanically fixed and floating silicon neural probes chronically implanted into the cortex of a non-human primate. We demonstrate that the neural signal quality estimated by the quality of the spiking and local field potential (LFP) recordings over time is initially superior for the floating probe compared to the fixed device. Nonetheless, the skull-fixed probe also allowed long-term recording of multi-unit activity (MUA) and low frequency signals over several months, especially once pulsations of the brain were properly controlled.
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http://dx.doi.org/10.3389/fnins.2019.00464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536660PMC
May 2019

[Urinary incontinence revealing vescicouterine fistula: about a case].

Pan Afr Med J 2018 14;31:32. Epub 2018 Sep 14.

Service d'Urologie, CHU Hassan II, Fès, Maroc.

Vescicouterine fistula (VUF) is a rare lesion accounting for only 4% of all urogenital fistulas. It is most often secondary to cesarean section and forms a connection between the bladder and the uterus. We report the case of a young patient with VUF secondary to cesarean section. This study aims to investigate the clinical and therapeutic features of this disorder.
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http://dx.doi.org/10.11604/pamj.2018.31.32.15595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430854PMC
April 2019
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