Epileptic activity triggers rapid ROCK1-dependent astrocyte morphology changes.

Long-term modifications of astrocyte function and morphology are well known to occur in epilepsy. They are implicated in the development and manifestation of the disease, but the relevant mechanisms and their pathophysiological role are not firmly established. For instance, it is unclear how quickly the onset of epileptic activity triggers astrocyte morphology changes and what the relevant molecular signals are. We therefore used two-photon excitation fluorescence microscopy to monitor astrocyte morphology in parallel to the induction of epileptiform activity. We uncovered astrocyte morphology changes within 10-20 min under various experimental conditions in acute hippocampal slices. In vivo, induction of status epilepticus resulted in similarly altered astrocyte morphology within 30 min. Further analysis in vitro revealed a persistent volume reduction of peripheral astrocyte processes triggered by induction of epileptiform activity. In addition, an impaired diffusion within astrocytes and within the astrocyte network was observed, which most likely is a direct consequence of the astrocyte remodeling. These astrocyte morphology changes were prevented by inhibition of the Rho GTPase RhoA and of the Rho-associated kinase (ROCK). Selective deletion of ROCK1 but not ROCK2 from astrocytes also prevented the morphology change after induction of epileptiform activity and reduced epileptiform activity. Together these observations reveal that epileptic activity triggers a rapid ROCK1-dependent astrocyte morphology change, which is mechanistically linked to the strength of epileptiform activity. This suggests that astrocytic ROCK1 signaling is a maladaptive response of astrocytes to the onset of epileptic activity.

Epidemiology of epilepsy and relationship with onchocerciasis prevalence in villages of the Ntui Health District of Cameroon.

BACKGROUND: A strong association between epilepsy and onchocerciasis endemicity has been reported. We sought to document the epidemiology of epilepsy in onchocerciasis-endemic villages of the Ntui Health District in Cameroon and investigate how this relates to the prevalence of onchocerciasis. METHODS: In March 2022, door-to-door epilepsy surveys were conducted in four villages (Essougli, Nachtigal, Ndjame, and Ndowe). Ivermectin intake during the 2021 session of community-directed treatment with ivermectin (CDTI) was investigated in all participating village residents. Persons with epilepsy (PWE) were identified through a two-step approach: administration of a 5-item epilepsy screening questionnaire followed by clinical confirmation by a neurologist. Epilepsy findings were analyzed together with onchocerciasis epidemiological data previously obtained in the study villages. RESULTS: We surveyed 1663 persons in the four study villages. The 2021 CDTI coverage for all study sites was 50.9%. Overall, 67 PWE were identified (prevalence of 4.0% (IQR: 3.2-5.1) with one new-onset case during the past 12 months (annual incidence of 60.1 per 100,000 persons). The median age of PWE was 32 years (IQR: 25-40), with 41 (61.2%) being females. The majority (78.3%) of PWE met the previously published criteria for onchocerciasis-associated epilepsy (OAE). Persons with a history of nodding seizures were found in all villages and represented 19.4% of the 67 PWE. Epilepsy prevalence was positively correlated with onchocerciasis prevalence (Spearman Rho = 0.949, p = 0.051). Meanwhile, an inverse relationship was observed between distance from the Sanaga river (blackfly breeding site) and the prevalence of both epilepsy and onchocerciasis. CONCLUSION: The high epilepsy prevalence in Ntui appears to be driven by onchocerciasis. It is likely that decades of CDTI have likely contributed to a gradual decrease in epilepsy incidence, as only one new case occurred in the past year. Therefore, more effective elimination measures are urgently needed in such endemic areas to curb the OAE burden.

The characteristics and perioperative outcomes of children with orofacial clefts managed at an academic hospital in Johannesburg, South Africa.

BACKGROUND: Orofacial clefts (OFCs) are the commonest congenital anomalies of the head and neck. Their aetiology is multifactorial, and prevalence has a geographical variation. This study sought to describe OFC cases that presented for surgery. OBJECTIVES: The study aimed to describe the preoperative characteristics, concomitant congenital anomalies and perioperative outcomes of children presenting for cleft repair surgery over a 5-year period at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH). METHODS: A retrospective descriptive record review for children under the age of 14 years who presented for cleft repair surgery at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) during a 5-year period, from 1 January 2014 to 31 December 2018. Descriptive and comparative statistics were used to report the results. RESULTS: A total of 175 records were included in the study. The median (IQR) age was 11 (6-27) months, with a predominance of males 98 (56%). Most of the children had cleft lip and palate (CLP) 71(41%). The prevalence of concomitant congenital anomalies was 22%, emanating mostly from head and neck congenital anomalies. Nine syndromes were identified in 15 children with syndromic clefts. Twenty-nine percent of children were underweight for age. There were 25 anaesthetic related complications, commonly airway related. Six children with complex multiple congenital anomalies were admitted in the intensive care unit postoperatively. No mortalities were recorded. CONCLUSION: Majority of children with orofacial clefts underwent cleft repair surgery without serious complications and intensive care unit admission. Only six children were diagnosed with significant anomalies needing intensive care management.

Enterococcus durans Cardiac Implantable Electronic Device Lead Infection and Review of Enterococcus durans Endocarditis Cases.

Introduction: Cardiac implantable electronic device (CIED) infections present a growing problem in medicine due to a significant increase in the number of implanted devices and the age of the recipient population. Enterococcus spp. are Gram-positive, facultative anaerobic, lactic acid bacteria; they are relatively common pathogens in humans, but uncommon as the cause of CIED lead infections. Only eight cases of Enterococcus durans endocarditis have been reported in the literature thus far; however, there are no reported cases of Enterococcus durans CIED lead infection. Case presentation: A 58-year-old gentleman with a previously implanted St. Jude Medical single-chamber implantable cardioverter-defibrillator (ICD) due to tachy/brady arrhythmias presented with nonspecific constitutional symptoms (i.e., low-grade fevers, chills, fatigue), and was found to have innumerable bilateral pulmonary nodules via computed tomography angiography of the chest. Many of these pulmonary nodules were cavitated and highly concerning for septic pulmonary emboli and infarcts. Within 24 h from presentation, blood cultures in all four culture bottles grew ampicillin- and vancomycin-susceptible Enterococcus durans. Transthoracic echocardiogram confirmed vegetations on the ICD lead in the right ventricle. The patient underwent laser extraction of the ICD lead with generator removal and recovered completely after a 6-week intravenous antibiotic course. Conclusion: To our knowledge, this is the first report of CIED lead infection caused by Enterococcus durans. In this case, management with antibiotics along with ICD lead extraction led to complete recovery. Clinicians should be aware of this rare but potentially devastating infection in patients with native and artificial valves, but also in those with CIEDs.

Xpert Mycobacterium tuberculosis/Rifampicin-Detected Rifampicin Resistance is a Suboptimal Surrogate for Multidrug-resistant Tuberculosis in Eastern Democratic Republic of the Congo: Diagnostic and Clinical Implications.

BACKGROUND: Rifampicin (RIF) resistance is highly correlated with isoniazid (INH) resistance and used as proxy for multidrug-resistant tuberculosis (MDR-TB). Using MTBDRplus as a comparator, we evaluated the predictive value of Xpert MTB/RIF (Xpert)-detected RIF resistance for MDR-TB in eastern Democratic Republic of the Congo (DRC). METHODS: We conducted a cross-sectional study involving data from new or retreatment pulmonary adult TB cases evaluated between July 2013 and December 2016. Separate, paired sputa for smear microscopy and MTBDRplus were collected. Xpert testing was performed subject to the availability of Xpert cartridges on sample remnants after microscopy. RESULTS: Among 353 patients, 193 (54.7%) were previously treated and 224 (63.5%) were MTBDRplus TB positive. Of the 224, 43 (19.2%) were RIF monoresistant, 11 (4.9%) were INH monoresistant, 53 (23.7%) had MDR-TB, and 117 (52.2%) were RIF and INH susceptible. Overall, among the 96 samples detected by MTBDRplus as RIF resistant, 53 (55.2%) had MDR-TB. Xpert testing was performed in 179 (50.7%) specimens; among these, 163 (91.1%) were TB positive and 73 (44.8%) RIF resistant. Only 45/73 (61.6%) Xpert-identified RIF-resistant isolates had concomitant MTBDRplus-detected INH resistance. Xpert had a sensitivity of 100.0% (95% CI, 92.1-100.0) for detecting RIF resistance but a positive-predictive value of only 61.6% (95% CI, 49.5-72.8) for MDR-TB. The most frequent mutations associated with RIF and INH resistance were S531L and S315T1, respectively. CONCLUSIONS: In this high-risk MDR-TB study population, Xpert had low positive-predictive value for the presence of MDR-TB. Comprehensive resistance testing for both INH and RIF should be performed in this setting.

Deep amplicon sequencing for culture-free prediction of susceptibility or resistance to 13 anti-tuberculous drugs.

Conventional molecular tests for detecting Mycobacterium tuberculosis complex (MTBC) drug resistance on clinical samples cover a limited set of mutations. Whole-genome sequencing (WGS) typically requires culture.Here, we evaluated the Deeplex Myc-TB targeted deep-sequencing assay for prediction of resistance to 13 anti-tuberculous drugs/drug classes, directly applicable on sputum.With MTBC DNA tests, the limit of detection was 100-1000 genome copies for fixed resistance mutations. Deeplex Myc-TB captured in silico 97.1-99.3% of resistance phenotypes correctly predicted by WGS from 3651 MTBC genomes. On 429 isolates, the assay predicted 92.2% of 2369 first- and second-line phenotypes, with a sensitivity of 95.3% and a specificity of 97.4%. 56 out of 69 (81.2%) residual discrepancies with phenotypic results involved pyrazinamide, ethambutol and ethionamide, and low-level rifampicin or isoniazid resistance mutations, all notoriously prone to phenotypic testing variability. Only two out of 91 (2.2%) resistance phenotypes undetected by Deeplex Myc-TB had known resistance-associated mutations by WGS analysis outside Deeplex Myc-TB targets. Phenotype predictions from Deeplex Myc-TB analysis directly on 109 sputa from a Djibouti survey matched those of MTBSeq/PhyResSE/Mykrobe, fed with WGS data from subsequent cultures, with a sensitivity of 93.5/98.5/93.1% and a specificity of 98.5/97.2/95.3%, respectively. Most residual discordances involved gene deletions/indels and 3-12% heteroresistant calls undetected by WGS analysis or natural pyrazinamide resistance of globally rare "Mycobacterium canettii" strains then unreported by Deeplex Myc-TB. On 1494 arduous sputa from a Democratic Republic of the Congo survey, 14 902 out of 19 422 (76.7%) possible susceptible or resistance phenotypes could be predicted culture-free.Deeplex Myc-TB may enable fast, tailored tuberculosis treatment.

The Cascade Reactions of Indigo with Propargyl Substrates for Heterocyclic and Photophysical Diversity.

The synthesis of structurally diverse heterocycles for chemical space exploration was achieved via the cascade reactions of indigo with propargylic electrophiles. New pyrazinodiindolodione, naphthyridinedione, azepinodiindolone, oxazinoindolone and pyrrolodione products were prepared in one pot reactions by varying the leaving group (-Cl, -Br, -OMs, -OTs) or propargyl terminal functionality (-H, -Me, -Ph, -Ar). Mechanistic and density functional theory studies revealed that the unsaturated propargyl moiety can behave as an electrophile when aromatic terminal substitutions are made, and therefore competes with leaving group substitution for new outcomes. Selected products from the cascade reactions were investigated for their absorption and fluorescence properties, including transient absorption spectroscopy. This revealed polarity dependent excited state relaxation pathways, fluorescence, and triplet formation, thus highlighting these reactions as a means to access diverse functional materials rapidly.

Optimal allocation of law enforcement patrol effort to mitigate poaching activities.

Poaching is a global problem causing the decline of species worldwide. Optimizing the efficiency of ranger patrols to deter poaching activity at the lowest possible cost is crucial for protecting species with limited resources. We applied decision analysis and spatial optimization algorithms to allocate efforts of ranger patrols throughout a national park. Our objective was to mitigate poaching activity at or below management risk targets for the lowest monetary cost. We examined this trade-off by constructing a Pareto efficiency frontier using integer linear programming. We used data from a ranger-based monitoring program in Nyungwe National Park, Rwanda. Our measure of poaching risk is based on dynamic occupancy models that account for imperfect detection of poaching activities. We found that in order to achieve a 5% reduction in poaching risk, 622 ranger patrol events (each corresponding to patrolling 1-km2 sites) were needed within a year at a cost of US$49,760. In order to attain a 60% reduction in poaching risk, 15,560 patrol events were needed at a cost of US$1,244,800. We evaluated the trade-off between patrol cost and poaching risk based on our model by constructing a Pareto efficiency frontier and park managers found the solution for a 50% risk reduction to be a practical trade-off based on funding constraints (comparable to recent years) and the diminishing returns between risk mitigation and cost. This expected reduction in risk required 8,558 patrol events per year at a cost of US$684,640. Our results suggest that optimal solutions could increase efficiency compared to the actual effort allocations from 2006 to 2016 in Nyungwe National Park (e.g., risk reductions of ~30% under recent budgets compared to ~50% reduction in risk under the optimal strategy). The modeling framework in this study took into account imperfect detection of poaching risk as well as the directional and conditional nature of ranger patrol events given the spatial adjacency relationships of neighboring sites and access points. Our analyses can help to improve the efficiency of ranger patrols, and the modeling framework can be broadly applied to other spatial conservation planning problems with conditional, multilevel, site selection.

Fear and depression during the COVID-19 outbreak in Cameroon: a nation-wide observational study.

BACKGROUND: The COVID-19 pandemic has been associated with significant psychological and social distress worldwide. We investigated fear and depression among adults in Cameroon during different phases of the COVID-19 outbreak. METHODS: An online survey was conducted in Cameroon from June-December 2020 using a structured questionnaire. Socio-demographic data and information regarding COVID-19 history were obtained. Fear and depressive symptoms were assessed using the Fear of COVID-19 score (FCV-19S) and the Patient Health Questionnaire (PHQ-9), respectively. Responses were clustered in weeks to better appreciate their evolution over time. RESULTS: Overall, 7381 responses from all ten regions of Cameroon were analysed (median age: 30 years, 73.3% male). The prevalence of depression (PHQ-9 score ≥ 10) was 8.4%, and that of high fear of COVID-19 (FCV-19S scores ≥19) was 57.4%. These rates were similar across genders, age-groups, and region of residence. While mean weekly PHQ-9 scores remained fairly stable throughout the study period (range: 2.53-3.21; p = 0.101), mean FCV-19S scores were highest during the early weeks but decreased significantly thereafter (from 20.31 to 18.34; p <  0.001). Multivariate analyses revealed that having a postgraduate degree, a history of quarantine, flu-like symptoms during the past 14 days, and higher FCV-19S scores were associated with more severe depressive symptoms, while obtaining COVID-19 information from various sources reduced the odds for depression. CONCLUSION: Depression amidst the COVID-19 crisis is less prevalent in Cameroon than in other countries. Prompt and widespread dissemination of adequate COVID-19 information may reduce the risks for depression by dispelling fear and anxiety among Cameroonians.

Soil microbial functioning and organic carbon storage: can complex timber tree stands mimic natural forests?

Conversion of natural forest to anthropogenic land use systems (LUS) often leads to considerable loss of carbon, however, proper management of these LUS may reverse the trend. A study was conducted in a semi-deciduous forest zone of Côte d'Ivoire to assess soil microbial functioning and soil organic carbon (SOC) stocks in varying tree stands, and to determine whether complex tree stands can mimic the natural forest in terms of these soil attributes. Tree plantations studied were monocultures of teak (Tectona grandis) and full-sun cocoa (Theobroma cacao L.), and a mixture of four tree species (MTS) with Tectona grandis, Gmelina arborea, Terminalia ivoriensis and Terminalia superba. An adjacent natural forest was considered as the reference. Each of these LUS had five replicate stands where soil (0-10 cm depth) samples were taken for physico-chemical parameters and microbial biomass-C (MBC), microbial activities, MBC/SOC ratio and metabolic quotient (qCO2). SOC and total N stocks were also calculated. The C mineralization rate (mg C-CO2 kg-1) and mineral N concentration (mg kg-1) drastically declined in the monocultures of cocoa (154.9 ± 29.3 and 49.8 ± 9.8, respectively) and teak (179.6 ± 27.1 and 54.1 ± 7.3) compared to the natural forest (258.4 ± 21.9 and 108.7 ± 12). However, values in MTS (194.7 ± 24.6 and 105.4 ± 7.4) were not significantly different from those in the natural forest. Similarly, SOC stocks in MTS (28.8 ± 1.9 Mg ha-1) were not significantly different from those recorded in the natural forest (32.9 ± 1.7 Mg ha-1) whereas teak (25.4 ± 1.7 Mg ha-1) and cocoa (23.1 ± 3.4 Mg ha-1) exhibited significantly lower values. Despite the acidic soil and recalcitrant litter conditions, increased MBC/SOC ratio and decreased qCO2 were recorded in the monocrops, suggesting a probable increase in the fungi/bacteria ratio. The complex MTS stand was found to mimic the natural forest in terms of soil microbial activity and organic status, due to the provision of a diversity of litter quality, which may serve as a basis for developing a climate smart timber system in West and Central Africa.

Mono- and Tripodal Porphyrins: Investigation on the Influence of the Number of Pyrene Anchors in Carbon Nanotube and Graphene Hybrids.

A series of molecular precursors, containing one (1 and 3) or three (2 and 4) pyrene anchors, covalently linked to porphyrins (free base or Zn), were prepared and characterized. All of them enable their π-π stacking onto low-dimensional nanocarbons including single-walled carbon nanotubes (SWCNTs) and nanographene (NG), their individualization, and their characterization. Microscopic (TEM, AFM) and spectroscopic (steady-state UV-vis and fluorescence, spectroelectrochemistry, and transient absorption measurements) techniques were at the forefront of the characterizations and were complemented by Raman spectroscopy and theoretical calculations. Of great importance is the Raman analysis, which corroborated n-doping of the nanocarbons due to the interactions with 1-4 when probed in the solid state. In solution, the situation is, however, quite different. Efficient charge separation was only observed for the graphene-based system NG/3.

Monitoring hippocampal glycine with the computationally designed optical sensor GlyFS.

Fluorescent sensors are an essential part of the experimental toolbox of the life sciences, where they are used ubiquitously to visualize intra- and extracellular signaling. In the brain, optical neurotransmitter sensors can shed light on temporal and spatial aspects of signal transmission by directly observing, for instance, neurotransmitter release and spread. Here we report the development and application of the first optical sensor for the amino acid glycine, which is both an inhibitory neurotransmitter and a co-agonist of the N-methyl-D-aspartate receptors (NMDARs) involved in synaptic plasticity. Computational design of a glycine-specific binding protein allowed us to produce the optical glycine FRET sensor (GlyFS), which can be used with single and two-photon excitation fluorescence microscopy. We took advantage of this newly developed sensor to test predictions about the uneven spatial distribution of glycine in extracellular space and to demonstrate that extracellular glycine levels are controlled by plasticity-inducing stimuli.

Epilepsy-associated neurocognitive disorders (EAND) in an onchocerciasis-endemic rural community in Cameroon: A population-based case-control study.

BACKGROUND: Epilepsy affects at least 50 million individuals worldwide, especially in sub-Saharan Africa (sSA). Cognitive impairment is common in people with epilepsy (PWE) yet, little is known on the burden of cognitive impairment in people with epilepsy in sSA. This study was thus designed to assess cognitive impairment in PWE or epilepsy-associated neurocognitive disorders (EAND) in a rural population in Cameroon. METHODS: This was a case-control study including PWE and age/sex-matched healthy controls from July to September 2017 in Bilomo, a village in the Mbam and Kim Division. The Montreal Cognitive Assessment (MoCA), International HIV Dementia Scale (IHDS), Dubois' Five Word testing, Frontal Assessment Battery (FAB), Isaac's Set Test and the Clock drawing test were administered to the study participants to evaluate global and specific cognitive functions. RESULTS: Eighty participants were included (40 cases and 40 controls) with a mean age of 25.78 years. Using the MoCA, 87.5% of cases had cognitive impairment, against 37.5% of controls (p < 0.001; OR 11.67; CI 3.40-45.09). Using the IHDS, the prevalence of global cognitive impairment was 84.6% among the cases against 40% for the controls (p = <0.001; OR 7.07; CI 2.29-29.19). Specifically, executive function deficits (92.5% of cases vs 40.0% of controls p = <0.001 OR = 18.50 CI; 4.48-105.08) and decreased verbal fluency (100% of cases against 45% of controls p < 0.001) were the most affected cognitive domains. Longer duration of epilepsy and higher seizure frequency were associated with global cognitive impairment. Low level of education was associated with both decreased verbal fluency and executive dysfunction while a longer stay in Bilomo correlated with poor results on the Isaac's Set Test. CONCLUSION: The prevalence of cognitive impairment appears to be much higher in PWE in the Mbam valley, particularly decreased executive function and verbal fluency, than in people without epilepsy. Longer disease duration, higher seizure frequency, low level of education and length of stay in Bilomo are associated with poorer cognitive performance. More studies are needed to refine evaluation tools to better characterize and manage EAND in sSA.

Prevalence, Predictors, and Successful Treatment Outcomes of Xpert MTB/RIF-identified Rifampicin-resistant Tuberculosis in Post-conflict Eastern Democratic Republic of the Congo, 2012-2017: A Retrospective Province-Wide Cohort Study.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) jeopardizes global TB control. The prevalence and predictors of Rifampicin-resistant (RR) TB, a proxy for MDR-TB, and the treatment outcomes with standard and shortened regimens have not been assessed in post-conflict regions, such as the South Kivu province in the eastern Democratic Republic of the Congo (DRC). We aimed to fill this knowledge gap and to inform the DRC National TB Program. METHODS: of adults and children evaluated for pulmonary TB by sputum smear microscopy and Xpert MTB/RIF (Xpert) from February 2012 to June 2017. Multivariable logistic regression, Kaplan-Meier estimates, and multivariable Cox regression were used to assess independent predictors of RR-TB and treatment failure/death. RESULTS: Of 1535 patients Xpert-positive for TB, 11% had RR-TB. Independent predictors of RR-TB were a positive sputum smear (adjusted odds ratio [aOR] 2.42, 95% confidence interval [CI] 1.63-3.59), retreatment of TB (aOR 4.92, 95% CI 2.31-10.45), and one or more prior TB episodes (aOR 1.77 per episode, 95% CI 1.01-3.10). Over 45% of RR-TB patients had no prior TB history or treatment. The median time from Xpert diagnosis to RR-TB treatment initiation was 12 days (interquartile range 3-60.2). Cures were achieved in 30/36 (83%) and 84/114 (74%) of patients on 9- vs 20/24-month MDR-TB regimens, respectively (P = .06). Predictors of treatment failure/death were the absence of directly observed therapy (DOT; adjusted hazard ratio [aHR] 2.77, 95% CI 1.2-6.66) and any serious adverse drug event (aHR 4.28, 95% CI 1.88-9.71). CONCLUSIONS: Favorable RR-TB cure rates are achievable in this post-conflict setting with a high RR-TB prevalence. An expanded Xpert scale-up; the prompt initiation of shorter, safer, highly effective MDR-TB regimens; and treatment adherence support are critically needed to optimize outcomes.

Clinical presentations of onchocerciasis-associated epilepsy (OAE) in Cameroon.

BACKGROUND: A high prevalence of epilepsy has been observed in several onchocerciasis-endemic countries, including Cameroon. However, little is known on the clinical presentations of the affected persons with epilepsy (PWE). A community-based study was conducted with the aim of describing the spectrum of seizures in selected onchocerciasis-endemic villages in Cameroon and documenting relevant medical history in patients with onchocerciasis-associated epilepsy (OAE). METHODS: We carried out door-to-door surveys in 5 onchocerciasis-endemic villages in Cameroon and recruited all consenting PWE. Epilepsy was diagnosed using a 2-step approach consisting of the administration of a standardized 5-item questionnaire followed by confirmation of the suspected cases by a neurologist. Onchocerciasis-associated epilepsy was defined as ≥2 seizures without an obvious cause, starting between the ages of 3-18 years in previously healthy persons having resided for at least 3 years in an onchocerciasis-endemic area. Ivermectin use by PWE was verified. Seizure history, relevant past medical, and family history, as well as neurological findings, were noted. RESULTS: In all, 156 PWE were recruited in the 5 villages. The modal age group for epilepsy onset was 10-14 years. The diagnostic criteria for OAE were met by 93.2% of the PWE. Participants had one or more of the following seizure types: generalized tonic-clonic seizures (89.1%), absences (38.5%), nodding (21.8%), focal nonmotor (7.7%), and focal motor seizures (1.9%). One case (0.6%) with the "Nakalanga syndrome" was identified. More than half (56.4%) of PWE had at least one seizure per month. In one village, 56.2% of PWE had onchocercal skin lesions. CONCLUSION: People with epilepsy in onchocerciasis-endemic villages in Cameroon present with a wide clinical spectrum including nodding seizures and Nakalanga features. A great majority of participants met the diagnostic criteria for OAE, suggesting that better onchocerciasis control could prevent new cases. Epilepsy management algorithms in these areas must be adjusted to reflect the varied seizure types.

Heparan Sulfates Support Pyramidal Cell Excitability, Synaptic Plasticity, and Context Discrimination.

Heparan sulfate (HS) proteoglycans represent a major component of the extracellular matrix and are critical for brain development. However, their function in the mature brain remains to be characterized. Here, acute enzymatic digestion of HS side chains was used to uncover how HSs support hippocampal function in vitro and in vivo. We found that long-term potentiation (LTP) of synaptic transmission at CA3-CA1 Schaffer collateral synapses was impaired after removal of highly sulfated HSs with heparinase 1. This reduction was associated with decreased Ca2+ influx during LTP induction, which was the consequence of a reduced excitability of CA1 pyramidal neurons. At the subcellular level, heparinase treatment resulted in reorganization of the distal axon initial segment, as detected by a reduction in ankyrin G expression. In vivo, digestion of HSs impaired context discrimination in a fear conditioning paradigm and oscillatory network activity in the low theta band after fear conditioning. Thus, HSs maintain neuronal excitability and, as a consequence, support synaptic plasticity and learning.

Shifting through the forest: home range, movement patterns, and diet of the eastern chimpanzee (Pan troglodytes schweinfurthii) in Nyungwe National Park, Rwanda.

Populations of the endangered eastern chimpanzee (Pan troglodytes schweinfurthii) are declining throughout their range. Although Nyungwe National Park (NNP) harbors the largest remaining eastern chimpanzee population in Rwanda, we know little about their space use and dietary patterns. We studied home range, movement, and diet of two communities of chimpanzees in NNP using daily tracking data (6:00 am to 6:00 pm) collected from 2000 to 2015. One community, Mayebe, resided in the forest center, and the other community, Cyamudongo, inhabited a forest fragment located about 10 km from the main forest. Home range estimated with the 95% kernel density estimation (KDE) method was 21 km2 for the Mayebe community and 4 km2 for the Cyamudongo community. Chimpanzee home range sizes were smaller during the dry versus wet season and varied monthly throughout the year. The Mayebe community had an average hourly step length of 75 ± SE 5 m with a daily movement range of 987 ± SE 71 m, while the Cyamudongo community had a shorter hourly step length of 52 ± SE 3 m with a daily movement range of 651 ± SE 71 m. Both chimpanzee communities fed primarily on Ficus spp. Other important dietary items included fruits of Symphonia globulifera, Syzygium guineense, and Chrysophyllum gorungosanum for the Mayebe community and Trilepisium madagascariense for the Cyamudongo community. Food choice varied monthly and seasonally for each chimpanzee community. Our study provides the first estimates of home range size and movement parameters for chimpanzees in Rwanda and documents their food habits and seasonal variations therein. We also identified the 50% core home range for each chimpanzee community and suggest this area as the focus of management actions. These results could help park management reduce threats to chimpanzees and other sympatric species by improving the efficiency of ranger patrols.

Subcellular reorganization and altered phosphorylation of the astrocytic gap junction protein connexin43 in human and experimental temporal lobe epilepsy.

Dysfunctional astrocytes are increasingly recognized as key players in the development and progression of mesial temporal lobe epilepsy (MTLE). One of the dramatic changes astrocytes undergo in MTLE with hippocampal sclerosis (HS) is loss of gap junction coupling. To further elucidate molecular mechanism(s) underlying this alteration, we assessed expression, cellular localization and phosphorylation status of astrocytic gap junction proteins in human and experimental MTLE-HS. In addition to conventional confocal analysis of immunohistochemical staining we employed expansion microscopy, which allowed visualization of blood-brain-barrier (BBB) associated cellular elements at a sub-µm scale. Western Blot analysis showed that plasma membrane expression of connexin43 (Cx43) and Cx30 were not significantly different in hippocampal specimens with and without sclerosis. However, we observed a pronounced subcellular redistribution of Cx43 toward perivascular endfeet in HS, an effect that was accompanied by increased plaque size. Furthermore, in HS Cx43 was characterized by enhanced C-terminal phosphorylation of sites affecting channel permeability. Prominent albumin immunoreactivity was found in the perivascular space of HS tissue, indicating that BBB damage and consequential albumin extravasation was involved in Cx43 dysregulation. Together, our results suggest that subcellular reorganization and/or abnormal posttranslational processing rather than transcriptional downregulation of astrocytic gap junction proteins account for the loss of coupling reported in human and experimental TLE. The observations of the present study provide new insights into pathological alterations of astrocytes in HS, which may aid in the identification of novel therapeutic targets and development of alternative anti-epileptogenic strategies.

Vascular anatomical relationships of the retropubic space and the sacrospinous ligament, using three-dimensional imaging.

INTRODUCTION AND HYPOTHESIS: Pelvic anatomy is complex and intimate knowledge of variabilities in anatomical relationships is critical for surgeons to safely perform surgical procedures. Three-dimensional Imaging provides the opportunity to analyze undisturbed anatomical relationships. The authors hypothesized that three-dimensional models created from pelvic computed tomography angiograms could be used to obtain vascular anatomical measurements, and that the measurements obtained from three-dimensional models would be similar to those from cadaver studies. METHODS: We included all pelvic computed tomography angiograms that were acquired in female patients older than 18 years at our institution within the previous 5 years. Three-dimensional models were created using the Invivo5 software based on the Digital Imaging and Communications in Medicine files. Structures of interest were virtually dissected and measured replicating previous cadaver studies. Statistical analysis of demographics and measurements was performed. RESULTS: The final analysis included 87 studies. The average age of the subjects was 66.9 years and their average BMI was 26.1 kg/m2. Of the 87 subjects, 12.6% had a history of hysterectomy, 2.3% a history of a continence procedure, and 1.1% a history of a prolapse procedure. The range of distance between the ischial spine and the pudendal artery was 3-17 mm. The closest vessels to the lower edge of the symphysis pubis were the obturator vessels. The aberrant corona mortis vessel was present in 27.9% of the subjects. Prior hysterectomy was associated with changes in the measurements of the obturator arteries with minimal changes in other measurements. CONCLUSIONS: Our results indicate that this technology provides similar measurements to those found in previous unembalmed cadaver studies. This technology offers a great opportunity to study anatomical relationships in a native undisturbed state.

Study of filamentation with a high power high repetition rate ps laser at 1.03 µm.

We study the propagation of intense, high repetition rate laser pulses of picosecond duration at 1.03 µm central wavelength through air. Evidence of filamentation is obtained from measurements of the beam profile as a function of distance, from photoemission imaging and from spatially resolved sonometric recordings. Good agreement is found with numerical simulations. Simulations reveal an important self shortening of the pulse duration, suggesting that laser pulses with few optical cycles could be obtained via double filamentation. An important lowering of the voltage required to induce guided electric discharges between charged electrodes is measured at high laser pulse repetition rate.