Obesity status and obesity-associated gut dysbiosis effects on hypothalamic structural covariance.

BACKGROUND: Functional connectivity alterations in the lateral and medial hypothalamic networks have been associated with the development and maintenance of obesity, but the possible impact on the structural properties of these networks remains largely unexplored. Also, obesity-related gut dysbiosis may delineate specific hypothalamic alterations within obese conditions. We aim to assess the effects of obesity, and obesity and gut-dysbiosis on the structural covariance differences in hypothalamic networks, executive functioning, and depressive symptoms. METHODS: Medial (MH) and lateral (LH) hypothalamic structural covariance alterations were identified in 57 subjects with obesity compared to 47 subjects without obesity. Gut dysbiosis in the subjects with obesity was defined by the presence of high (n = 28) and low (n = 29) values in a BMI-associated microbial signature, and posthoc comparisons between these groups were used as a proxy to explore the role of obesity-related gut dysbiosis on the hypothalamic measurements, executive function, and depressive symptoms. RESULTS: Structural covariance alterations between the MH and the striatum, lateral prefrontal, cingulate, insula, and temporal cortices are congruent with previously functional connectivity disruptions in obesity conditions. MH structural covariance decreases encompassed postcentral parietal cortices in the subjects with obesity and gut-dysbiosis, but increases with subcortical nuclei involved in the coding food-related hedonic information in the subjects with obesity without gut-dysbiosis. Alterations for the structural covariance of the LH in the subjects with obesity and gut-dysbiosis encompassed increases with frontolimbic networks, but decreases with the lateral orbitofrontal cortex in the subjects with obesity without gut-dysbiosis. Subjects with obesity and gut dysbiosis showed higher executive dysfunction and depressive symptoms. CONCLUSIONS: Obesity-related gut dysbiosis is linked to specific structural covariance alterations in hypothalamic networks relevant to the integration of somatic-visceral information, and emotion regulation.

Neuroinflammation in obesity: circulating lipopolysaccharide-binding protein associates with brain structure and cognitive performance.

BACKGROUND/OBJECTIVES: Growing evidence implicates neuroinflammation in the pathogenesis of diet-induced obesity and cognitive dysfunction in rodent models. Obesity is associated with reduced white matter integrity and cognitive decline. Circulating lipopolysaccharide binding protein (LBP) concentration is known to be increased in patients with obesity. Here, we aimed to evaluate whether circulating LBP is associated longitudinally with white matter structure and cognitive performance according to obesity status. SUBJECTS/METHODS: This longitudinal study analyzed circulating LBP (ELISA), DTI-metrics (axial diffusivity (L1), fractional anisotropy (FA) and radial diffusivity (RD)) in specific regions of the white matter of 24 consecutive middle-aged obese subjects (13 women) and 20 healthy volunteers (10 women) at baseline and two years later. Digit Span Test (DST) was used as a measure of working memory/short-term verbal memory. RESULTS: Circulating LBP concentration was associated with FA and L1 values of several white matter regions both at baseline and follow-up. The associations remained significant after controlling for age, BMI, fat mass and plasma high sensitivity C-reactive protein. Importantly, the increase in LBP over time impacted negatively on FA and L1 values and on DST performance. CONCLUSIONS: Circulating LBP associates with brain white matter integrity and working memory/short-term verbal memory in both obese and non-obese subjects.

Population structure and connectivity in the Mediterranean sponge Ircinia fasciculata are affected by mass mortalities and hybridization.

Recent episodes of mass mortalities in the Mediterranean Sea have been reported for the closely related marine sponges Ircinia fasciculata and Ircinia variabilis that live in sympatry. In this context, the assessment of the genetic diversity, bottlenecks and connectivity of these sponges has become urgent in order to evaluate the potential effects of mass mortalities on their latitudinal range. Our study aims to establish (1) the genetic structure, connectivity and signs of bottlenecks across the populations of I. fasciculata and (2) the hybridization levels between I. fasciculata and I. variabilis. To accomplish the first objective, 194 individuals of I. fasciculata from 12 locations across the Mediterranean were genotyped at 14 microsatellite loci. For the second objective, mitochondrial cytochrome c oxidase subunit I sequences of 16 individuals from both species were analyzed along with genotypes at 12 microsatellite loci of 40 individuals coexisting in 3 Mediterranean populations. We detected strong genetic structure along the Mediterranean for I. fasciculata, with high levels of inbreeding in all locations and bottleneck signs in most locations. Oceanographic barriers like the Almeria-Oran front, North-Balearic front and the Ligurian-Thyrrenian barrier seem to be impeding gene flow for I. fasciculata, adding population divergence to the pattern of isolation by distance derived from the low dispersal abilities of sponge larvae. Hybridization between both species occurred in some populations that might be increasing genetic diversity and somewhat palliating the genetic loss caused by population decimation in I. fasciculata.

Predicting Motor Outcome in Acute Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Predicting motor outcome following intracerebral hemorrhage is challenging. We tested whether the combination of clinical scores and DTI-based assessment of corticospinal tract damage within the first 12 hours of symptom onset after intracerebral hemorrhage predicts motor outcome at 3 months. MATERIALS AND METHODS: We prospectively studied patients with motor deficits secondary to primary intracerebral hemorrhage within the first 12 hours of symptom onset. Patients underwent multimodal MR imaging including DTI. We assessed intracerebral hemorrhage and perihematomal edema location and volume, and corticospinal tract involvement. The corticospinal tract was considered affected when the tractogram passed through the intracerebral hemorrhage or/and the perihematomal edema. We also calculated affected corticospinal tract-to-unaffected corticospinal tract ratios for fractional anisotropy, mean diffusivity, and axial and radial diffusivities. Motor impairment was graded by the motor subindex scores of the modified NIHSS. Motor outcome at 3 months was classified as good (modified NIHSS 0-3) or poor (modified NIHSS 4-8). RESULTS: Of 62 patients, 43 were included. At admission, the median NIHSS score was 13 (interquartile range = 8-17), and the median modified NIHSS score was 5 (interquartile range = 2-8). At 3 months, 13 (30.23%) had poor motor outcome. Significant independent predictors of motor outcome were NIHSS and modified NIHSS at admission, posterior limb of the internal capsule involvement by intracerebral hemorrhage at admission, intracerebral hemorrhage volume at admission, 72-hour NIHSS, and 72-hour modified NIHSS. The sensitivity, specificity, and positive and negative predictive values for poor motor outcome at 3 months by a combined modified NIHSS of >6 and posterior limb of the internal capsule involvement in the first 12 hours from symptom onset were 84%, 79%, 65%, and 92%, respectively (area under the curve = 0.89; 95% CI, 0.78-1). CONCLUSIONS: Combined assessment of motor function and posterior limb of the internal capsule damage during acute intracerebral hemorrhage accurately predicts motor outcome.

The gut mycobiome composition is linked to carotid atherosclerosis.

The mycobiotic component of the microbiota comprises an integral, yet under-researched, part of the gastrointestinal tract. Here, we present a preliminary study of the possible contribution of gut mycobiota to sub-clinical atherosclerosis in a well-characterised group of obese and non-obese subjects in association with the Framingham Risk Score (FRS) and carotid intima-media thickness (cIMT). From all taxa identified, the relative abundance of the phylum Zygomycota, comprising the family Mucoraceae and genus Mucor, was negatively associated with cIMT and this association remained significant after controlling for false discovery rate. Obese subjects with detectable Mucor spp. had a similar cardiovascular risk profile as non-obese subjects. Interestingly, the relative abundance of Mucor racemosus was negatively associated both with FRS and cIMT. Partial least square discriminant analyses modelling, evaluating the potential relevance of gut mycobiota in patients stratified by mean values of cIMT, showed that even a 1 component model had a high accuracy (0.789), with a high R2 value (0.51). Variable importance in projection scores showed that M. racemosus abundance had the same impact in the model as waist-to-hip ratio, high-density lipoprotein-cholesterol, fasting triglycerides or fasting glucose, suggesting that M. racemosus relative abundance in the gut may be a relevant biomarker for cardiovascular risk.

Acquisition of carbapenem-resistant Gram-negative bacilli in intensive care unit: predictors and molecular epidemiology.

OBJECTIVES: We had for aim to determine the risk factors for acquiring carbapenem-intermediate or -resistant Gram-negative bacilli (CR-GNB) in an intensive care unit (ICU) and to identify the resistance mechanisms involved. PATIENTS AND METHODS: We conducted an observational prospective cohort study during 6 months in medical and surgical ICUs of the Besançon Teaching Hospital. Patients with acquired CR-GNB were patients whose cultures (screening or diagnosis) became positive more than 48h after admission to the ICU. The risk factors for ICU-acquired CR-GNB were determined by multivariate logistic regression. CR-GNB isolates were typed by pulsed-field gel electrophoresis (PFGE) and screened for resistance mechanisms with phenotypic and genotypic tests. RESULTS: Twenty-three of the 347 included patients had acquired a CR-GNB. The multivariate analysis revealed significant associations between this acquisition and the duration of previous treatments with piperacillin-tazobactam (adjusted odds ratio [aOR], 1.13, P=0.02) and aminoglycosides (aOR, 1.62; P=0.005), but not with carbapenems. The CR-GNB strains were identified as Pseudomonas aeruginosa (n=10), Stenotrophomonas maltophilia (n=7), and Enterobacter cloacae (n=6). No acquired carbapenemase-producing strain was identified. PFGE typing identified 1 multiple clone among P. aeruginosa isolates (4 patients), whereas for the other bacteria, all the strains were different. CONCLUSION: Our study results suggest that the strategy to prevent the emergence and spread of CR-GNB should not be limited to the sole restriction of carbapenem use in ICU settings.

Inhaled nitric oxide in patients with pulmonary embolism.

OBJECTIVE: To describe the use of inhaled nitric oxide (NO) in four patients with severe pulmonary embolism. SETTING: The intensive care unit (ICU) of a university teaching hospital. PATIENTS: Four patients with severe pulmonary embolism on the basis of clinical, haemodynamic or blood-gas parameters received NO by inhalation either during spontaneous respiration (two cases) or while mechanically ventilated (two cases). INTERVENTIONS: Conventional management of pulmonary embolism in addition to the use of inhaled NO. MEASUREMENTS AND RESULTS: Description of clinical course, haemodynamic and gas-exchange data. Dose-response data are also described for three patients. CONCLUSIONS: We reported four cases of pulmonary embolism where the administration of inhaled NO resulted in an improvement in pulmonary haemodynamic and gas-exchange parameters. Two patients were weaned from NO and survived until discharged from the ICU. Inhaled NO might be a useful adjunct in pulmonary embolism to improve stability of the patient prior to thrombolysis or surgery.

Solution studies of the antitumor complex dichloro 1,2-propylendiaminetetraacetate ruthenium (III) and of its interactions with proteins.

A mixed complex of ruthenium (III) with 1,2-propylendiaminetetraacetate (PDTA) and chloride--RAP hereafter--has been found to exhibit favorable anticancer properties in vivo. To get some insight into the possible mechanism of action of this ruthenium (III) complex, its solution behavior and reactivity with proteins were investigated through absorption, circular dichroism and 1H NMR spectroscopies. Under physiological conditions RAP slowly looses the two coordinated chlorine atoms to produce a number of ruthenium (III) reactive species; a description of the distribution of these species on the dependence of pH has been obtained through 1H NMR studies of the hyperfine shifted signals. Remarkably, through the different solution conditions employed in this study, the ruthenium ion always remains in the 3+ oxidation state and the PDTA ligand is always bound to the metal. Upon reaction with albumin, apotransferrin or diferric transferrin, at a 1:1 ratio, RAP rapidly binds to these proteins to produce substantially equivalent and relatively stable adducts. This behavior is tentatively interpreted in terms of a tight interaction between RAP and surface residues of these proteins. The implications of these findings for the biological action of this novel ruthenium (III) compound are discussed.

Clinical expression of secondary syphilis in a patient with HIV infection.

There are increasing reports of unusual clinical features and atypical courses of syphilis in patients with acquired immunodeficiency syndrome. Recently, we had the opportunity to study an HIV-positive female patient with strong manifestations of secondary syphilis. The case is discussed together with the implications of secondary syphilis in her concomitant ocular affliction. Moreover, we comment on the clinico-therapeutic controversies brought about by the association of infection with Treponema pallidum and HIV.

[Falciparum malaria in French residents in Yaounde]. / Le paludisme a Plasmodium falciparum chez les Français résidants a Yaoundé.

In South Cameroon, malaria is a disquieting problem. It represented 2.6% of consultants and concerned each year 10% among French residents. We have included 310 cases of Falciparum malaria between January 1, 1990 and December 31, 1990. There were 207 adults and 103 children with a mean age of 26 years. The duration of the stay was over one year in 137 cases and lower than 1 year in 183 patients. The chemoprophylaxis was correct in 194 patients according to the dose and duration. Forty-nine patients followed a combination of chloroquine and proguanil. Malaria attack was observed in 272 patients. Among them, there were 95 children. A severe malaria occurred in 38 cases. Mean parasitemia was of 0.24% (range: 0.002-7.5%). Therapy regimen was quinine: 36 cases, halofantrine: 266 cases, amodiaquine: 7 cases and association MFP (Fansimef) in 12 patients. The study shows the importance of malaria in an endemic area among expatriates despite the observance of chemoprophylactics regimens including proguanil.

[Pseudomonas aeruginosa epidemiology in intensive care units: importance of cross-transmission]. / Importance de la transmission croisée dans l'épidémiologie de Pseudomonas aeruginosa en service de soins intensifs.

OBJECTIVES: To update the local epidemiological data of Pseudomonas aeruginosa in intensive care units (ICU) by assessing the colonisation incidence rate and the level of cross-transmission. METHODS: Study carried out in both adult ICUs of the university-hospital of Besançon during a 2 years period. Clinical and surveillance specimens were screened for P. aeruginosa. Pulsed-field-gel-electrophoresis was used as genotyping method to evaluate the rate of cross-transmission. RESULTS: During the study, 314 patients were positive for P. aeruginosa (incidence rate of 19.1 patients per 100 admitted patients). One hundred sixty-six of these patients were detected with a clinical specimen and 148 with a screening specimen. Seventy-seven patients were colonised upon admission in the intensive care unit and 237, negative on admission, became positive during their stay. Of the ICU-acquired cases, the mean length of stay before P. aeruginosa colonisation was acquired was 15.7 days. Genotyping revealed that 53.5% of P. aeruginosa colonisation was acquired via cross-transmission (respectively 48.1% in the medical ICU and 59.2% in the surgical ICU); the other cases probably originated from endogenous sources. CONCLUSION: The incidences of P. aeruginosa colonisation upon admission and during hospitalisation are consistent with other french and european studies. Although we probably over-estimated the rate of cross-transmission, our results demonstrate that cross-transmission may be a major cause of P. aeruginosa dissemination in ICUs.

Appropriate use of carbapenems in the Besançon university hospital.

INTRODUCTION: The excessive and inappropriate use of carbapenems is responsible for the development of resistance. The scientific community has been requiring caution and using these agents in specific cases only. OBJECTIVES: The authors had for aim to evaluate the appropriate use of carbapenems in a French university hospital. DESIGN: A retrospective survey was made over two months as a clinical audit to assess professional practices. The evaluation criteria for this audit were: the appropriateness of the indication, the possibility of alternative therapeutic strategies, the choice of an antibiotic combination, duration of treatment and dosage. RESULTS: During the audit period, 103 carbapenem prescriptions were included. Ninety-nine cases were analyzed. Among the carbapenem prescriptions, 28.3% (28/99) did not meet the criterion "appropriateness of the indication". Carbapenems were mostly prescribed empirically (60/99 [60%]) and most often for lung infections or nosocomial urinary tract infections. Finally, 66.7% (66/99) of all prescriptions were considered inappropriate for at least one criterion. The rate of inappropriateness ranged around 30% for each criterion. CONCLUSIONS: This study allowed us to assess professional practices for carbapenem prescriptions. The overall rate of inappropriateness was quite important. Carbapenems were not always used appropriately. These findings highlight the need of new regional guidelines and regular updating of local best practices recommendations. Finally, a stricter validation of carbapenem prescriptions will be implemented at the hospital pharmacy level.

Quantification of thrombus hounsfield units on noncontrast CT predicts stroke subtype and early recanalization after intravenous recombinant tissue plasminogen activator.

BACKGROUND AND PURPOSE: Little is known about the factors that determine recanalization after intravenous thrombolysis. We assessed the value of thrombus Hounsfield unit quantification as a predictive marker of stroke subtype and MCA recanalization after intravenous rtPA treatment. MATERIALS AND METHODS: NCCT scans and CTA were performed on patients with MCA acute stroke within 4.5 hours of symptom onset. Demographics, stroke severity, vessel hyperattenuation, occlusion site, thrombus length, and time to thrombolysis were recorded. Stroke origin was categorized as LAA, cardioembolic, or indeterminate according to TOAST criteria. Two blinded neuroradiologists calculated the Hounsfield unit values for the thrombus and contralateral MCA segment. We used ROC curves to determine the rHU cutoff point to discriminate patients with successful recanalization from those without. We assessed the accuracy (sensitivity, specificity, and positive and negative predictive values) of rHU in the prediction of recanalization. RESULTS: Of 87 consecutive patients, 45 received intravenous rtPA and only 15 (33.3%) patients had acute recanalization. rHU values and stroke mechanism were the highest predictive factors of recanalization. The Matthews correlation coefficient was highest for rHU (0.901). The sensitivity, specificity, and positive and negative predictive values for lack of recanalization after intravenous rtPA for rHU ≤ 1.382 were 100%, 86.67%, 93.75%, and 100%, respectively. LAA thrombi had lower rHU than cardioembolic and indeterminate stroke thrombi (P = .004). CONCLUSIONS: The Hounsfield unit thrombus measurement ratio can predict recanalization with intravenous rtPA and may have clinical utility for endovascular treatment decision making.

Acute damage to the posterior limb of the internal capsule on diffusion tensor tractography as an early imaging predictor of motor outcome after stroke.

BACKGROUND AND PURPOSE: Early prediction of motor outcome is of interest in stroke management. We aimed to determine whether lesion location at DTT is predictive of motor outcome after acute stroke and whether this information improves the predictive accuracy of the clinical scores. MATERIALS AND METHODS: We evaluated 60 consecutive patients within 12 hours of middle cerebral artery stroke onset. We used DTT to evaluate CST involvement in the motor cortex and premotor cortex, centrum semiovale, corona radiata, and PLIC and in combinations of these regions at admission, at day 3, and at day 30. Severity of limb weakness was assessed by using the motor subindex scores of the National Institutes of Health Stroke Scale (5a, 5b, 6a, 6b). We calculated volumes of infarct and fractional anisotropy values in the CST of the pons. RESULTS: Acute damage to the PLIC was the best predictor associated with poor motor outcome, axonal damage, and clinical severity at admission (P < .001). There was no significant correlation between acute infarct volume and motor outcome at day 90 (P = .176, r = 0.485). The sensitivity, specificity, and positive and negative predictive values of acute CST involvement at the level of the PLIC for motor outcome at day 90 were 73.7%, 100%, 100%, and 89.1%, respectively. In the acute stage, DTT predicted motor outcome at day 90 better than the clinical scores (R(2) = 75.50, F = 80.09, P < .001). CONCLUSIONS: In the acute setting, DTT is promising for stroke mapping to predict motor outcome. Acute CST damage at the level of the PLIC is a significant predictor of unfavorable motor outcome.

[Is surveillance of Pseudomonas aeruginosa carriage in intensive care units useful?]. / Faut-il procéder à un dépistage du portage de Pseudomonas aeruginosa dans les services de réanimation ?

OBJECTIVE: To evaluate the potential interest of screening of Pseudomonas aeruginosa on admission and during hospitalisation in intensive care units patients. METHOD: A retrospective study was carried out in two adult ICU of the University-Hospital of Besançon in 2007. P. aeruginosa screening was performed on admission and once a week during ICU stay. Clinical samples positive with P. aeruginosa were collected. RESULTS: Among the 754 patients included, 146 had a screening sample positive giving an average incidence of 19.4 per 100 patients. Thirty-five were imported and 111 ICU-acquired. Sixty-one patients had at least one positive clinical sample, that is an incidence 8.1 cases per 100 admitted patients. Sensibility, specificity, positive and negative predictive values of screening as an indicator of subsequent infection were 54.1%, 86.9%, 26.6% and 95.6%, respectively. CONCLUSION: Screening samples are necessary to assess P. aeruginosa endemicity in intensive care units. The high negative predictive value of screening suggests that use of specifics anti-Pseudomonas antimicrobials could be reduced. However, the benefit of this strategy remains to be evaluated.

Wallerian degeneration in the corticospinal tract evaluated by diffusion tensor imaging correlates with motor deficit 30 days after middle cerebral artery ischemic stroke.

BACKGROUND AND PURPOSE: The quantification and clinical significance of WD in CSTs following supratentorial stroke are not well understood. We evaluated the anisotropy by using DTI and signal-intensity changes on conventional MR imaging in the CST to determine whether these findings are correlated with limb motor deficit in patients with MCA ischemic stroke. MATERIALS AND METHODS: We studied 60 patients within 12 hours of stroke onset. At admission, day 3, and day 30 of evolution, patients underwent multimodal MR imaging, including DTI sequences. We assessed the severity of limb weakness by using the motor subindex scores (5a, 5b, 6a, 6b) of the m-NIHSS and established 3 groups: I (m-NIHSS scores of 0), II (m-NIHSS, 1-4), and III (m-NIHSS, 5-8). FA values and rFAs were measured on the affected and the unaffected CSTs in the pons. RESULTS: FA values for the CST were significantly lower on the affected side compared with the unaffected side only at day 30 (P < .001), and the rFA was significantly correlated with the motor deficit at day 30 (P < .001; r = -0.793). The sensitivity, specificity, and positive and negative predictive values for motor deficit by rFA < 0.925 were 95.2%, 94.9%, 90.9%, and 97.4%, respectively. CONCLUSIONS: WD in the CST revealed by DTI correlates with motor deficit 30 days after MCA ischemic stroke. This study highlights the utility of imaging follow-up at 30 days and the potential of DTI as a surrogate marker in clinical trials.

[Review of the neuroradiological diagnosis of cerebral venous thrombosis]. / Actualización en el diagnóstico neurorradiológico de la trombosis venosa cerebral.

Cerebral venous thrombosis is an uncommon entity with multiple causes. It must be diagnosed quickly to enable early treatment, avoid severe complications, and improve the patient's prognosis. MRI combined with MR venography is the best diagnostic approach. However, the clinical presentation is usually encountered in the emergency department, so cranial CT combined with CT venography is often the best way to establish the diagnosis because it has high sensitivity for the identification of the cerebral veins and sinuses. Although color-coded transcranial duplex sonography does not play a role in the initial diagnostic work-up, it is useful in the follow-up. We describe the distribution of the territories of venous drainage, analyze the usefulness of the different neuroradiological modalities, analyze the direct and indirect signs of central venous thrombosis, and discuss strategies to avoid the diagnostic pitfalls in patients with clinical suspicion of venous thrombosis.

Semi-automated method for brain hematoma and edema quantification using computed tomography.

In this paper, a semi-automated method for brain hematoma and edema segmentation, and volume measurement using computed tomography imaging is presented. This method combines a region growing approach to segment the hematoma and a level set segmentation technique to segment the edema. The main novelty of this method is the strategy applied to define the propagation function required by the level set approach. To evaluate the method, 18 patients with brain hematoma and edema of different size, shape and location were selected. The obtained results demonstrate that the proposed approach provides objective and reproducible segmentations that are similar to the manually obtained results. Moreover, the processing time of the proposed method is about 4 min compared to the 10 min required for manual segmentation.