Quantifying salinity in heterogeneous coastal aquifers through ERT and IP: Insights from laboratory and field investigations.

The lithological and stratigraphical heterogeneity of coastal aquifers has a great influence on saltwater intrusion (SI). This makes it difficult to predict SI pathways and their persistence in time. In this context, electrical resistivity tomography (ERT) and induced polarization (IP) methods are receiving increasing attention regarding the discrimination between saltwater-bearing and clayey sediments. To simplify the interpretation of ERT data, it is commonly assumed that the bulk conductivity mostly depends on the conductivity of pore-filling fluids, while surface conductivity is generally disregarded in the spatial and temporal variability of the aquifers, particularly, once the aquifer is affected by the presence of saltwater. Quantifying salinities based on a simplified petrophysical relationship can lead to misinterpretation in aquifers constituted by clay-rich sediments. In this study, we rely on co-located data from drilled boreholes to formulate petrophysical relationships between bulk and fluid conductivity for clay-bearing and clay-free sediments. First, the sedimentary samples from the drilled wells were classified according to their particle size distribution and analyzed in the lab using spectral IP in controlled salinity conditions to derive their formation factors, surface conductivity, and normalized chargeability. Second, the deduced thresholds are applied on the field to distinguish clay-bearing sediments from brackish sandy sediments. The results are validated with logging data and direct salinity measurements on water samples. We applied the approach along the Luy River catchment and found that the formation factors and surface conductivity of the different unconsolidated sedimentary classifications vary from 4.0 to 8.9 for coarse-grained sand and clay-bearing mixtures, while normalized chargeability above 1.0 mS.m-1 indicates the presence of clay. The clay-bearing sediments are mostly distributed in discontinuous small lenses. The assumption of homogenous geological media is therefore leading to overestimating SI in the heterogeneous clay-bearing aquifers.

Perioperative quality indicators specific to the practice of anesthesia in noncardiac surgery: an umbrella review.

PURPOSE: Improvement in delivery of perioperative care depends on the ability to measure outcomes that can direct meaningful changes in practice. We sought to identify and provide an overview of perioperative quality indicators specific to the practice of anesthesia in noncardiac surgery. SOURCE: We conducted an umbrella review (a systematic review of systematic reviews) according to Joanna Briggs Institute methodology. We included systematic reviews examining perioperative indicators in patients ≥ 18 yr of age undergoing noncardiac surgery. Our primary outcome was any quality indicator specific to anesthesia. Indicators were classified by the Donabedian system and perioperative phase of care. The quality of systematic reviews was assessed using AMSTAR 2 criteria. Level of evidence of quality indicators was stratified by the Oxford Centre for Evidence-Based Medicine Classification. PRINCIPAL FINDINGS: Our search returned 1,475 studies. After removing duplicates and screening of abstracts and full texts, 23 systematic reviews encompassing 3,164 primary studies met our inclusion criteria. There were 330 unique quality indicators. Process indicators were most common (n = 169), followed by outcome (n = 114) and structure indicators (n = 47). Few identified indicators were supported by high-level evidence (45/330, 14%). Level 1 evidence supported indicators of antibiotic prophylaxis (1a), venous thromboembolism prophylaxis (1a), postoperative nausea/vomiting prophylaxis (1b), maintenance of normothermia (1a), and goal-directed fluid therapy (1b). CONCLUSION: This umbrella review highlights the scarcity of perioperative quality indicators that are supported by high quality evidence. Future development of quality indicators and recommendations for outcome measurement should focus on metrics that are supported by level 1 evidence. Potential targets for evidence-based quality-improvement programs in anesthesia are identified herein. STUDY REGISTRATION: PROSPERO (CRD42020164691); first registered 28 April 2020.

RéSUMé: OBJECTIF: L'amélioration de la prestation des soins périopératoires dépend de la capacité de mesurer les résultats qui peuvent orienter des changements significatifs dans la pratique. Nous avons cherché à identifier et à fournir une vue d'ensemble des indicateurs périopératoires de qualité spécifiques à la pratique de l'anesthésie en chirurgie non cardiaque. SOURCES: Nous avons mené une revue d'ensemble (une revue systématique des revues systématiques) selon la méthodologie de l'Institut Joanna Briggs. Nous avons inclus des revues systématiques examinant les indicateurs périopératoires chez les patient·es âgé·es de 18 ans ou plus bénéficiant d'une chirurgie non cardiaque. Notre critère d'évaluation principal était tout indicateur de qualité spécifique à l'anesthésie. Les indicateurs ont été classés en fonction du système de Donabedian et de la phase périopératoire des soins. La qualité des revues systématiques a été évaluée à l'aide des critères AMSTAR 2. Le niveau de donnée probante des indicateurs de qualité a été stratifié selon l'Oxford Centre for Evidence-Based Medicine Classification. CONSTATATIONS PRINCIPALES: Notre recherche a permis de trouver 1475 études. Après avoir éliminé les doublons et examiné les résumés et les textes intégraux, 23 revues systématiques englobant 3164 études primaires ont répondu à nos critères d'inclusion. Il y avait 330 indicateurs de qualité uniques. Les indicateurs de processus étaient les plus courants (n = 169), suivi des indicateurs de résultats (n = 114) et des indicateurs de structure (n = 47). Peu d'indicateurs identifiés étaient étayés par des données probantes de haut niveau (45/330, 14 %). Les données probantes de niveau 1 ont confirmé les indicateurs de l'antibioprophylaxie (1a), de la prophylaxie pour la thromboembolie veineuse (1a), de la prophylaxie postopératoire pour les nausées/vomissements (1b), du maintien de la normothermie (1a) et de la fluidothérapie ciblée (1b). CONCLUSION: Cet examen d'ensemble met en évidence la rareté des indicateurs périopératoires de qualité qui sont étayés par des données probantes de haute qualité. L'élaboration future d'indicateurs de qualité et de recommandations pour la mesure des résultats devrait être axée sur des paramètres étayés par des données probantes de niveau 1. Les cibles potentielles des programmes d'amélioration de la qualité de l'anesthésie fondés sur des données probantes sont identifiées dans le présent manuscrit. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42020164691); premier enregistrement le 28 avril 2020.

Optimizing phosphorus fertigation management zones using electromagnetic induction, soil properties, and crop yield data under semi-arid conditions.

The impact of climate change on water resource availability and soil quality is more and more emphasized under the Mediterranean basin, mostly characterized by drought and extreme weather conditions. The present study aims to investigate how electromagnetic induction technique and soil mapping combined with crop yield data can be used to optimize phosphorus (P) use efficiency by chickpea crop under drip fertigation system. The study was carried out on a 2.5-ha agricultural plot and the agronomic experiments in two growing cycles of chickpea crop. Soil spatial variability was first assessed by the measurement of soil apparent electrical conductivity (ECa) using the CMD Mini-Explorer sensor, and then, soil physicochemical properties were evaluated based on an oriented soil sampling scheme to explore other soil spatial variabilities influencing chickpea yield and quality. Data from the first agronomic experiment were used in geostatistical, multiple linear regression (MLR), and fuzzy c-means unsupervised classification algorithms to properly identify P drip fertigation management zones (MZs). Results from the Person's correlation analysis revealed that chickpea grain yield was more influenced by soil ECa (r = - 0.56), pH (r = - 0.84), ECe (r = - 0.6), P content (r = 0.72), and calcium (Ca) content (r = - 0.83). The proposed MLR-based model to predict chickpea grain yield showed good performances with a normalized root mean square error (NRMSE) of 0.11% and a coefficient of determination (R2) equal to 0.69. The identified MZs were verified by the one-way variance analysis for the studied soil and plant attributes, revealing that the first MZ1 presents a high grain yield, high soil P content, and low ECa. The low fertility MZ2 located in the south part of the studied site presented a low chickpea grain yield due to the low P content and the high ECa. Moreover, the application of P-variable rate fertigation regimes in the second field experiment significantly improved P use efficiency, chickpea grain yield, seed quality, and farmer income by 18%, 12%, 9%, and 136 $/ha, respectively, as compared to the conventional drip fertigation practices. The approach proposed in this study can greatly contribute to optimizing agro-input use efficiency under drip fertigation system, thereby improving farmers' incomes, preserving the ecosystem, and ensuring sustainable cropping systems in the Mediterranean climate.

Interactive effect of soil moisture content and phosphorus fertilizer form on chickpea growth, photosynthesis, and nutrient uptake.

Water shortage and soil nutrient depletion are considered the main factors limiting crops productivity in the Mediterranean region characterized by longer and frequent drought episodes. In this study, we investigated the interactive effects of P fertilizer form and soil moisture conditions on chickpea photosynthetic activity, water and nutrient uptake, and their consequent effects on biomass accumulation and nutrient use efficiency. Two P fertilizer formulas based on orthophosphates (Ortho-P) and polyphosphates (Poly-P) were evaluated under three irrigation regimes (I1: 75% of field capacity, I2: 50% FC and I3: 25% FC), simulating three probable scenarios of soil water content in the Mediterranean climate (adequate water supply, medium, and severe drought stress), and compared to an unfertilized treatment. The experiment was conducted in a spilt-plot design under a drip fertigation system. The results showed significant changes in chickpea phenotypic and physiological traits in response to different P and water supply regimes. Compared with the unfertilized treatment, the stomata density and conductance, chlorophyll content, photosynthesis efficiency, biomass accumulation, and plant nutrient uptake were significantly improved under P drip fertigation. The obtained results suggested that the P fertilizer form and irrigation regime providing chickpea plants with enough P and water, at the early growth stage, increased the stomatal density and conductance, which significantly improved the photosynthetic performance index (PIABS) and P use efficiency (PUE), and consequently biomass accumulation and nutrient uptake. The significant correlations established between leaf stomatal density, PIABS, and PUE supported the above hypothesis. We concluded that the Poly-P fertilizers applied in well-watered conditions (I1) performed the best in terms of chickpea growth improvement, nutrient uptake and use efficiency. However, their effectiveness was greatly reduced under water stress conditions, unlike the Ortho-P form which kept stable positive effects on the studied parameters.

Chickpea plant responses to polyphosphate fertiliser forms and drip fertigation frequencies: effect on photosynthetic performance and phenotypic traits.

Photosynthesis is the main biophysiological process that governs plant growth and development. Under nutrient deficiency in crops and soils, many photosynthetic reactions can be disturbed. We compared two polyphosphates (Poly-A and Poly-B) and an orthophosphate fertiliser (Ortho-P) to an unfertilised treatment under three drip fertigation frequencies. Results showed that the electron transport chain between PSII and PSI was significantly enhanced in fertigated chickpea plants compared with the control treatment. The polyphosphate fertiliser (Poly-A) enhanced the number of electron acceptors of the photosynthetic linear electron transport chain compared with the other fertiliser forms. Furthermore, the time for reaching the maximum intensity F m was shortened in the fertilised chickpea plant indicating that the rate of light trapping and electron transport was enhanced under phosphorus drip fertigation. Also, the energy needed to close all reaction centres was decreased with P fertigated treatments, as revealed by the electron acceptor pool size of PSII (Sm/tFmax ). However, no significant effects of fertiliser forms or fertigation frequencies were observed on the energetic demand for reaction centres closure. Plants grown under polyphosphate fertigation absorbed significantly more phosphorus. Positive correlations between phosphorus uptake, photosynthetic yield, chickpea podding dynamic, and grain yield showed the beneficial effects of adequate phosphorus nutrition on chickpea growth and productivity.

Replacement of mitochondrion-rich cells during regeneration of the gills and opercular epithelium in zebrafish (Danio rerio).

Transport epithelia maintain the volume, ion concentration and acid-base balance of blood and extracellular fluids. In teleost fish, mitochondrion-rich cells (MRCs) are specialized ionocytes that perform this role. These cells are found in epithelia of the gills and buccal surface of the operculum (the bony structure covering the gills). Proliferation of MRCs in response to changes in water salinity and other environmental stressors is well documented, but the cellular mechanisms underlying MRC proliferation are poorly understood. Recently, regeneration and epithelial cell replacement in the gill filaments was demonstrated in the model vertebrate, zebrafish (Danio rerio), raising the question of whether MRCs are replaced during regrowth of transport epithelia. We chose two anatomical sites where MRCs are found-the gills and the opercular epithelium-to investigate whether MRCs were replaced following surgical resection of these structures. In live imaging experiments, we observed gradual replacement of the branchiostegal valve, an extension of the operculum, in zebrafish over a period of 21 days post-resection (dpr). In regenerating epithelia of both the operculum and gills, we detected MRCs by immunohistochemical localization of the α subunit of plasma membrane Na+/K+-ATPase. In both tissues, MRCs appeared soon after resection, and as early as 1 dpr in the gill filaments. We report regeneration of the operculum and proliferation of MRCs in regenerating tissue in adult zebrafish. These studies may contribute to our understanding of how MRC populations are regulated during the regenerative process, which may occur following exposure to environmental stressors, chemical toxicity or disease.

Site-selection criteria for the Einstein Telescope.

The Einstein Telescope (ET) is a proposed next-generation, underground gravitational-wave detector to be based in Europe. It will provide about an order of magnitude sensitivity increase with respect to the currently operating detectors and, also extend the observation band targeting frequencies as low as 3 Hz. One of the first decisions that needs to be made is about the future ET site following an in-depth site characterization. Site evaluation and selection is a complicated process, which takes into account science, financial, political, and socio-economic criteria. In this paper, we provide an overview of the site-selection criteria for ET, provide a formalism to evaluate the direct impact of environmental noise on ET sensitivity, and outline the necessary elements of a site-characterization campaign.

The Association of Frailty With Adverse Outcomes After Multisystem Trauma: A Systematic Review and Meta-analysis.

BACKGROUND: Frailty strongly predicts adverse outcomes in a variety of clinical settings; however, frailty-related trauma outcomes have not been systematically reviewed and quantitatively synthesized. Our objective was to systematically review and meta-analyze the association between frailty and outcomes (mortality-primary; complications, health resource use, and patient experience-secondary) after multisystem trauma. METHODS: After registration (CRD42018104116), we applied a peer-reviewed search strategy to MEDLINE, EMBASE, and Comprehensive Index to Nursing and Allied Health Literature (CINAHL) from inception to May 22, 2019, to identify studies that described: (1) multisystem trauma; (2) participants ≥18 years of age; (3) explicit frailty instrument application; and (4) relevant outcomes. Excluded studies included those that: (1) lacked a comparator group; (2) reported isolated injuries; and (3) reported mixed trauma and nontrauma populations. Criteria were applied independently, in duplicate to title/abstract and full-text articles. Risk of bias was assessed using the Risk of Bias in Nonrandomized Studies-of Interventions (ROBINS-I) tool. Effect measures (adjusted for prespecified confounders) were pooled using random-effects models; otherwise, narrative synthesis was used. RESULTS: Sixteen studies were included that represented 5198 participants; 9.9% of people with frailty died compared to 4.2% of people without frailty. Frailty was associated with increased mortality (adjusted odds ratio [OR], 1.53; 95% confidence interval [CI], 1.37-1.71), complications (adjusted OR, 2.32; 95% CI, 1.72-3.15), and adverse discharge (adjusted OR, 1.78; 95% CI, 1.29-2.45). Patient function, experience, and resource use outcomes were rarely reported. CONCLUSIONS: The presence of frailty is significantly associated with mortality, complications, and adverse discharge disposition after multisystem trauma. This provides important prognostic information to inform discussions with patients and families and highlights the need for trauma system optimization to meet the complex needs of older patients.

Regeneration of the gill filaments and replacement of serotonergic neuroepithelial cells in adult zebrafish (Danio rerio).

Respiratory epithelia and chemoreceptors of the gills and mammalian lung derive from the same embryonic structures. While the lung is limited to facultative regeneration, the regenerative capacity of the gill has not been adequately explored. We report regeneration of gill filaments and respiratory lamellae in adult zebrafish (Danio rerio). Gill filaments retained a constitutive population of mitotic cells identified by the proliferating cell nuclear antigen (PCNA). Within 24 h of resection, a new mass of PCNA-positive cells appeared at the filament tip. At 40 days post-resection, approximately half of resected tissue was replaced; and at 160 days post-resection, regeneration was nearly complete. Chemoreceptive neuroepithelial cells, identified by serotonin immunohistochemistry, were present in regenerates and established innervation by nerve fibres. Use of the transgenic zebrafish line Tg(fli1a:EGFP), in which the gill vasculature was labelled with enhanced green fluorescent protein, indicated that angiogenesis occurred during the regenerative process. Thus, the zebrafish is capable of substantive gill regeneration and replacement of respiratory chemoreceptors.

Long-term ERT monitoring of biogeochemical changes of an aged hydrocarbon contamination.

Adequate management of contaminated sites requires information with improved spatio-temporal resolution, in particular to assess bio-geochemical processes, such as the transformation and degradation of contaminants, precipitation of minerals or changes in groundwater geochemistry occurring during and after remediation procedures. Electrical Resistivity Tomography (ERT), a geophysical method sensitive to pore-fluid and pore-geometry properties, permits to gain quasi-continuous information about subsurface properties in real-time and has been consequently widely used for the characterization of hydrocarbon-impacted sediments. However, its application for the long-term monitoring of processes accompanying natural or engineered bioremediation is still difficult due to the poor understanding of the role that biogeochemical processes play in the electrical signatures. For in-situ studies, the task is further complicated by the variable signal-to-noise ratio and the variations of environmental parameters leading to resolution changes in the electrical images. In this work, we present ERT imaging results for data collected over a period of two years on a site affected by a diesel fuel contamination and undergoing bioremediation. We report low electrical resistivity anomalies in areas associated to the highest contaminant concentrations likely due transformations of the contaminant due to microbial activity and accompanying release of metabolic products. We also report large seasonal variations of the bulk electrical resistivity in the contaminated areas in correlation with temperature and groundwater level fluctuations. However, the amplitude of bulk electrical resistivity variations largely exceeds the amplitude expected given existing petrophysical models. Our results suggest that the variations in electrical properties are mainly controlled by microbial activity which in turn depends on soil temperature and hydrogeological conditions. Therefore, ERT can be suggested as a promising tool to track microbial activity during bioremediation even though further research is still needed to completely understand the bio-geochemical processes involved and their impact on electrical signatures.

Gravimetric water distribution assessment from geoelectrical methods (ERT and EMI) in municipal solid waste landfill.

The gravimetric water content of the waste material is a key parameter in waste biodegradation. Previous studies suggest a correlation between changes in water content and modification of electrical resistivity. This study, based on field work in Mont-Saint-Guibert landfill (Belgium), aimed, on one hand, at characterizing the relationship between gravimetric water content and electrical resistivity and on the other hand, at assessing geoelectrical methods as tools to characterize the gravimetric water distribution in a landfill. Using excavated waste samples obtained after drilling, we investigated the influences of the temperature, the liquid phase conductivity, the compaction and the water content on the electrical resistivity. Our results demonstrate that Archie's law and Campbell's law accurately describe these relationships in municipal solid waste (MSW). Next, we conducted a geophysical survey in situ using two techniques: borehole electromagnetics (EM) and electrical resistivity tomography (ERT). First, in order to validate the use of EM, EM values obtained in situ were compared to electrical resistivity of excavated waste samples from corresponding depths. The petrophysical laws were used to account for the change of environmental parameters (temperature and compaction). A rather good correlation was obtained between direct measurement on waste samples and borehole electromagnetic data. Second, ERT and EM were used to acquire a spatial distribution of the electrical resistivity. Then, using the petrophysical laws, this information was used to estimate the water content distribution. In summary, our results demonstrate that geoelectrical methods represent a pertinent approach to characterize spatial distribution of water content in municipal landfills when properly interpreted using ground truth data. These methods might therefore prove to be valuable tools in waste biodegradation optimization projects.

Electrical resistivity tomography to monitor enhanced biodegradation of hydrocarbons with Rhodococcus erythropolis T902.1 at a pilot scale.

Petroleum hydrocarbons (HC) represent the most widespread contaminants and in-situ bioremediation remains a competitive treatment in terms of cost and environmental concerns. However, the efficiency of such a technique (by biostimulation or bioaugmentation) strongly depends on the environment affected and is still difficult to predict a priori. In order to overcome these uncertainties, Electrical Resistivity Tomography (ERT) appears as a valuable non-invasive tool to detect soil heterogeneities and to monitor biodegradation. The main objective of this study was to isolate an electrical signal linked to an enhanced bacterial activity with ERT, in an aged HC-contaminated clay loam soil. To achieve this, a pilot tank was built to mimic field conditions. Compared to a first insufficient biostimulation phase, bioaugmentation with Rhodococcus erythropolis T902.1 led to a HC depletion of almost 80% (6900 to 1600ppm) in 3months in the center of the contaminated zone, where pollutants were less bioavailable. In the meantime, lithological heterogeneities and microbial activities (growth and biosurfactant production) were successively discriminated by ERT images. In the future, this cost-effective technique should be more and more transferred to the field in order to monitor biodegradation processes and assist in selecting the most appropriate remediation technique.

A case of hypokalemic paralysis in a patient with neurogenic diabetes insipidus.

Acute hypokalemic paralysis is characterized by muscle weakness or paralysis secondary to low serum potassium levels. Neurogenic diabetes insipidus (DI) is a condition where the patient excretes large volume of dilute urine due to low levels of antidiuretic hormone. Here, we describe a patient with neurogenic DI who developed hypokalemic paralysis without a prior history of periodic paralysis. A 30-year-old right-handed Hispanic male was admitted for refractory seizures and acute DI after developing a dental abscess. He had a history of pituitary adenoma resection at the age of 13 with subsequent pan-hypopituitarism and was noncompliant with hormonal supplementation. On hospital day 3, he developed sudden onset of quadriplegia with motor strength of 0 of 5 in the upper extremities bilaterally and 1 of 5 in both lower extremities with absent deep tendon reflexes. His routine laboratory studies revealed severe hypokalemia of 1.6 mEq/dL. Nerve Conduction Study (NCS) revealed absent compound motor action potentials (CMAPs) with normal sensory potentials. Electromyography (EMG) did not reveal any abnormal insertional or spontaneous activity. He regained full strength within 36 hours following aggressive correction of the hypokalemia. Repeat NCS showed return of CMAPs in all nerves tested and EMG revealed normal motor units and normal recruitment without myotonic discharges. In patients with central DI with polyuria, hypokalemia can result in sudden paralysis. Hypokalemic paralysis remains an important differential in an acute case of paralysis and early recognition and appropriate management is key.

Non-invasive measurement of transparency, arcus senilis, and scleral rim diameter of corneas during eye banking.

We developed a non-invasive device to quantify transparency (T), clear corneal diameter (CCD) excluding arcus senilis, and scleral rim diameter (SRD) of stored corneas. The T value (expressed in % on a relative scale), based on the modulation transfer function principle, referred to the ratio of local contrasts of a special LED backlit chart measured with and without cornea. CCD and SRD (in mm) were automatically calculated by morphologic operations. Firstly, we assessed measurement reproducibility. We then determined the agreement of T and CCD values with 3-level scores given independently by three experts on 179 scientific corneas. Thirdly, an eye bank was equipped with the device, and 358 consecutive organ-cultured (OC) corneas were tested for donor- and storage- related factors possibly influencing T and CCD. Reproducibility of T, CCD and SRD measurements was high, with intraclass correlation coefficients of 0.982, 0.886, and 0.999 respectively. Capacity to discriminate the three levels of transparency and arcus senilis was good, with T of 20.0 (10.0-33.6), 38.3 (24.3-75.4) and 57.9 (33.9-90.0) % respectively for T deemed poor, average, and good (P < 0.001), and CCD of 9.8 (7.3-10.6), 10.5 (8.2-11.5), and 11.1 (9.9-12.0) mm respectively for arcus senilis deemed prominent, moderate or absent (P < 0.001). T was correlated with neither donor age nor endothelial cell density nor storage time, but slightly worsened during OC for corneas assessed twice. In conclusion, the device, which can be easily integrated in the facilities of an eye bank, provides reliable objective measurement of T, CCD, and SRD. This could be a useful tool for standardizing quality assessment of stored corneas and consequently optimizing their selection for penetrating, endothelial or anterior lamellar keratoplasty.

Isolated central nervous system histoplasmosis presenting with ischemic pontine stroke and meningitis in an immune-competent patient.

IMPORTANCE: Histoplasmosis, a systemic mycosis caused by the fungus Histoplasma capsulatum, primarily affects immune-suppressed patients and commonly involves the lung and rarely the central nervous system (CNS). Herein, we report a case of isolated CNS histoplasmosis presenting with pontine stroke and meningitis. OBSERVATIONS: A 35-year-old, white, immune-competent man was transferred from an outside facility with worsening dysarthria and confusion after having presented 4 weeks prior with dysarthria, gait ataxia, and bilateral upper extremity weakness. Brain magnetic resonance imaging revealed bilateral pontine strokes, and the working diagnosis was ischemic infarctions, presumed secondary to small vessel vasculitis. Cerebral spinal fluid (CSF) examination showed marked abnormalities including an elevated protein level (320 mg/dL), low glucose level (2 mg/dL), and high white blood cell count (330/mm(3); 28% lymphocytes, 56% neutrophils, and 16% monocytes) suggestive of a bacterial, fungal, or tuberculosis meningitis. Empirical antibiotics and a second trial of intravenous steroids were started before infectious etiologies of meningitis were ultimately ruled out. Repeated magnetic resonance imaging of the brain revealed no evidence of new ischemic lesions. On hospital day 11, results of his CSF Histoplasma antigen and urine antigen tests were positive. His CSF culture also was positive for H capsulatum. The patient was treated initially with liposomal amphotericin B, 430 mg daily, but changed to voriconazole, 300 mg twice daily, secondary to renal insufficiency and eventually continued treatment with itraconazole cyclodextrin, 100 mg twice daily. Computed tomographic imaging revealed obstructive hydrocephalus, and a ventriculoperitoneal shunt was placed that successfully decompressed the ventricles. At 1 year, the patient demonstrated good clinical improvement and results of follow-up CSF cultures were negative. CONCLUSIONS AND RELEVANCE: While pulmonary involvement of histoplasmosis in immune-suppressed patients is common, systemic presentation of this fungal infection in immune-competent patients is rare and self-limiting. Isolated CNS histoplasmosis is exceedingly rare. Clinicians should consider CNS histoplasmosis in the differential diagnosis in atypical stroke cases, particularly those presenting with meningitis.

α-Synuclein expression in rat substantia nigra suppresses phospholipase D2 toxicity and nigral neurodegeneration.

We present genetic evidence that an in vivo role of α-synuclein (α-syn) is to inhibit phospholipase D2 (PLD2), an enzyme that is believed to participate in vesicle trafficking, membrane signaling, and both endo- and exocytosis. Overexpression of PLD2 in rat substantia nigra pars compacta (SNc) caused severe neurodegeneration of dopamine (DA) neurons, loss of striatal DA, and an associated ipsilateral amphetamine-induced rotational asymmetry. Coexpression of human wild type α-syn suppressed PLD2 neurodegeneration, DA loss, and amphetamine-induced rotational asymmetry. However, an α-syn mutant defective for inhibition of PLD2 in vitro also failed to inhibit PLD toxicity in vivo. Further, reduction of PLD2 activity in SNc, either by siRNA knockdown of PLD2 or overexpression of α-syn, both produced an unusual contralateral amphetamine-induced rotational asymmetry, opposite to that seen with overexpression of PLD2, suggesting that PLD2 and α-syn were both involved in DA release or reuptake. Finally, α-syn coimmunoprecipitated with PLD2 from extracts prepared from striatal tissues. Taken together, our data demonstrate that α-syn is an inhibitor of PLD2 in vivo, and confirm earlier reports that α-syn inhibits PLD2 in vitro. Our data also demonstrate that it is possible to use viral-mediated gene transfer to study gene interactions in vivo.