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Many vertebrate species act as both plant pollinators and seed-dispersers, thus interconnecting these processes, particularly on islands. Ecological multilayer networks are a powerful tool to explore interdependencies between processes; however, quantifying the links between species engaging in different types of interactions (i.e. inter-layer edges) remains a great challenge. Here, we empirically measured inter-layer edge weights by quantifying the role of individually marked birds as both pollinators and seed-dispersers of Galápagos plant species over an entire year. Although most species (80%) engaged in both functions, we show that only a small proportion of individuals actually linked the two processes, highlighting the need to further consider intra-specific variability in individuals' functional roles. Furthermore, we found a high variation among species in linking both processes, i.e. some species contribute more than others to the modular organization of the multilayer network. Small and abundant species are particularly important for the cohesion of pollinator seeddispersal networks, demonstrating the interplay between species traits and neutral processes structuring natural communities. [ABSTRACT FROM AUTHOR]

Objectives: To investigate if quantitative apparent diffusion coefficient (ADC) measurements can predict genetic subtypes of non-gadolinium-enhancing gliomas, comparing whole tumour against single slice analysis.Methods: Volumetric T2-derived masks of 44 gliomas were co-registered to ADC maps with ADC mean (ADCmean) calculated. For the slice analysis, two observers placed regions of interest in the largest tumour cross-section. The ratio (ADCratio) between ADCmean in the tumour and normal appearing white matter was calculated for both methods.Results: Isocitrate dehydrogenase (IDH) wild-type gliomas showed the lowest ADC values throughout (p < 0.001). ADCmean in the IDH-mutant 1p19q intact group was significantly higher than in the IDH-mutant 1p19q co-deleted group (p < 0.01). A volumetric ADCmean threshold of 1201 × 10-6 mm2/s identified IDH wild-type with a sensitivity of 83% and a specificity of 86%; a volumetric ADCratio cut-off value of 1.65 provided a sensitivity of 80% and a specificity of 92% (area under the curve (AUC) 0.9-0.94). A slice ADCratio threshold for observer 1 (observer 2) of 1.76 (1.83) provided a sensitivity of 80% (86%), specificity of 91% (100%) and AUC of 0.95 (0.96). The intraclass correlation coefficient was excellent (0.98).Conclusions: ADC measurements can support the distinction of glioma subtypes. Volumetric and two-dimensional measurements yielded similar results in this study.Key Points: • Diffusion-weighted MRI aids the identification of non-gadolinium-enhancing malignant gliomas • ADC measurements may permit non-gadolinium-enhancing glioma molecular subtyping • IDH wild-type gliomas have lower ADC values than IDH-mutant tumours • Single cross-section and volumetric ADC measurements yielded comparable results in this study. [ABSTRACT FROM AUTHOR]

Information about the relative importance of competitive or facilitative pollinator-mediated interactions in a multi-species context is limited. We studied interspecific pollen transfer ( IPT) networks to evaluate quantity and quality effects of pollinator sharing among plant species on three high-Andean communities at 1600, 1800 and 2000 m a.s.l. To estimate the sign of the effects (positive, neutral or negative), the relation between conspecific and heterospecific pollen deposited on stigmas was analysed with GLMMs. Network analyses showed that communities were characterised by the presence of pollen hub-donors and receptors. We inferred that facilitative and neutral pollinator-mediated interactions among plants prevailed over competition. Thus, the benefits from pollinator sharing seem to outweigh the costs (i.e. heterospecific deposition and conspecific pollen loss). The largest proportion of facilitated species was found at the highest elevation community, suggesting that under unfavourable conditions for the pollination service and at lower plant densities facilitation can be more common. [ABSTRACT FROM AUTHOR]

The article presents a study which investigates the volume dynamics of the brain in patients who are treated with natalizumab after the initiation of therapy. The study uses the magnetic resonance imaging scans and multivariate models for the investigation of the link between the baseline inflammation and the changes to the volume and disability of the brain. Results show that the measures of the volume of the brain is affected by the baseline inflammation after the initiation of natalizumab.

We aimed to single out multiple sclerosis (MS) cases with poor outcome after natalizumab withdrawal and to identify predictive variables. We ascertained 47 withdrawals, and compared their pre- and post-natalizumab periods. We objectively defined significant clinical worsening after natalizumab withdrawal as a 2-step increase in Expanded Disability Status Scale (EDSS). We performed regression models. As a group, post-natalizumab annualized relapse rate (ARR) was lower in the post-natalizumab period, and there were no differences in the mean number of gadolinium (Gd)-enhancing lesions between pre- and post-natalizumab magnetic resonance imaging (MRI). Corticosteroid treatment did not change the outcomes. Eight patients (19%) presented significant clinical worsening after natalizumab withdrawal, which was predicted by a higher baseline EDSS and a 1-step EDSS increase while on natalizumab. [ABSTRACT FROM AUTHOR]

Antifungal activity and in vitro inhibition time for sertaconazole (STZ) and 9 other topical drugs, namely amorolfine, bifonazole, clotrimazole, econazole, ketoconazole, miconazole, oxiconazole, terbinafine, and tioconazole were determined against 124 clinical isolates of dermatophyte (12 species) fungi by the microdilution method in a liquid medium and the measurement of optical density. STZ's antifungal activity was not always affected by the tested dermatophyte genus, as was the case with the remaining antifungals. In vitro antifungal activity was at the same level for all the studied azole derivatives, but, in terms of partial inhibitory concentrations, STZ starts its in vitro inhibitory activity in a shorter time than the other tested substances, particularly in those incubation periods when the growth of the dermatophyte fungi was more developed. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Antifungal activity and in vitro inhibition time for sertaconazole (STZ) and 9 other topical drugs, namely amorolfine, bifonazole, clotrimazole, econazole, ketoconazole, miconazole, oxiconazole, terbinafine, and tioconazole were determined against 124 clinical isolates of dermatophyte (12 species) fungi by the microdilution method in a liquid medium and the measurement of optical density. STZ's antifungal activity was not always affected by the tested dermatophyte genus, as was the case with the remaining antifungals. In vitro antifungal activity was at the same level for all the studied azole derivatives, but, in terms of partial inhibitory concentrations, STZ starts its in vitro inhibitory activity in a shorter time than the other tested substances, particularly in those incubation periods when the growth of the dermatophyte fungi was more developed. [ABSTRACT FROM AUTHOR]

Background: Therapy for multiple sclerosis (MS) has a partial efficacy, and a significant proportion of treated patients will develop a suboptimal response with first-line disease-modifying drugs (DMD). Therapy switch in patients with MS can be a strategy after a treatment failure. We studied the change in clinical activity after switching of first-line DMD because of a treatment failure. Methods: Relapsing-remitting multiple sclerosis (RRMS) patients treated with interferon-beta (IFNB) or glatiramer acetate (GA) were divided into (i) patients without change in DMD, (ii) patients with a change in DMD because of a poor response, and (iii) those with a change in DMD without relation with response. Annualized relapse rate (ARR) and relapse-free proportions were analyzed. Results: We identified 923 patients with RRMS. Of the 180 who experienced a change because of suboptimal response, 90 switched to another first-line DMT, 38 to mitoxantrone, and 52 to natalizumab. Median ARR in the pre-DMD period on first DMD and second DMD was the following: 1, 1, and 0 for switchers from IFNB to another IFNB ( P = 0.0001); 0.67, 1, and 0 for switchers from GA to IFNB ( P = 0.01); 1, 1, and 0 for switchers from an IFNB to GA ( P = 0.02); 1.1, 1.5, 0.2 for switchers from IFNB or GA to mitoxantrone ( P = 0.0001); 0.9, 1, 0 for switchers from IFNB or GA to natalizumab ( P = 0.0001). Conclusions: In patients with RRMS who have a poor response, switch to another DMD may reduce the clinical activity of the disease. [ABSTRACT FROM AUTHOR]

Objectives: To identify associations between cognitive impairment and imaging measures in a cross-sectional study of patients with primary progressive multiple sclerosis (PPMS).Methods: Neuropsychological tests were administered to 27 patients with PPMS and 31 controls. Patients underwent brain conventional magnetic resonance imaging (MRI) sequences, volumetric scans and magnetization transfer (MT) imaging; MT ratio (MTR) parameters, grey matter (GM) and normal-appearing white matter (NAWM) volumes, and WM T2 lesion load (T2LL) were obtained. In patients, multiple linear regression models identified the imaging measure associated with the abnormal cognitive tests independently from the other imaging variables. Partial correlation coefficients (PCC) were reported.Results: Patients performed worse on tests of attention/speed of visual information processing, delayed verbal memory, and executive function, and had a worse overall cognitive performance index, when compared with controls. In patients, a lower GM peak location MTR was associated with worse overall cognitive performance (p < 0.001, PCC = 0.77). GM mean and peak height MTR showed the strongest association with the estimated verbal intelligence quotient (IQ) decline (p < 0.001, PCC = -0.62), and executive function (p < 0.001, PCC = 0.79). NAWM volume was associated with attention/speed of visual information processing (p < 0.001, PCC = 0.74), while T2LL was associated with delayed verbal memory (p = 0.007, PCC = -0.55).Conclusions: The finding of strong associations between GM MTR, NAWM volume and T2LL and specific cognitive impairments suggests that models that predict cognitive impairment in PPMS should include comprehensive MRI assessments of both GM and WM. However, GM MTR appears to be the main correlate of overall cognitive dysfunction, underlining the role of abnormal GM integrity in determining cognitive impairment in PPMS. [ABSTRACT FROM AUTHOR]

Recognition of multiple sclerosis (MS) attacks relies mostly on clinical assessment. However, their definition based on McDonald criteria refers mostly to timing and when dealing with clinical features is rather ambiguous: “...of the kind seen in multiple sclerosis.” This is heightened in clinically isolated syndromes of the brainstem/cerebellum (CISB), where clinical manifestations can be manifold. This study aimed to describe the clinical features of patients with CISB to improve clinical recognition of patients with brainstem manifestations at the onset of their MS. To this end, we conducted a retrospective analysis of case notes of consecutively recruited patients with CISB assessed within 3 months of symptoms onset. Seventy-five patients were included. Most common brainstem-specific symptoms were: diplopia (68%), facial sensory symptoms (32%) and gait disturbance (31%). Adjusting for follow-up times, total number of symptoms and presence of other brainstem-specific symptoms, only the presence of facial sensory symptoms was predictive of (a lower risk of) conversion to clinically definite (CD) MS (Odds ratio: 0.086; p = 0.007). Neither the total number of brainstem-specific, non brainstem-specific nor the sum of both predicted conversion to CDMS. Results indicate that diplopia, facial sensory symptoms and gait disturbance occur in more than 30% of patients with CISB. Facial sensory symptoms are less associated with conversion to CDMS. [ABSTRACT FROM AUTHOR]

The role of multimodal evoked potentials (MMEPs) in establishing multiple sclerosis (MS) diagnosis and prognosis has diminished nowadays. The objective of this article is to evaluate whether MMEPs add information to MRI in identifying patients with higher risk of relapse or development of disability after a clinically isolated syndrome (CIS). Patients who underwent visual, somato-sensory and brainstem auditory evoked potentials (EPs) were identified from a cohort of consecutive CIS. Patients also underwent brain MRI within 3 months of first attack. We analysed time to second attack and to Expanded Disability Status Scale (EDSS) score of 3.0 according to number of Barkhof criteria and number of abnormal MMEPs. A complete study was performed in 245 patients who were followed for a mean of 76.4 months (interquartile range: 61 to 96). Seventy-one patients (29%) had the three EPs normal, 115 patients (47%) had one abnormal EP; 40 patients (16%) had two; and 19 patients (8%) had three abnormal EPs. Baseline MRI determined the risk for converting to clinically definite MS and correlated with disability according to previous studies. EPs individually did not modify the risk of conversion or disability. However, the presence of three abnormal EPs increased the risk of reaching moderate disability (hazard ratio 7.0; 1.4-34.9) independently of baseline MRI. In conclusion, in the presence of three abnormal EPs could help identify CIS patients with a higher risk of developing disability, independently of MRI findings. However, the utility of MMEPs is limited by the low percentage of CIS patients having the three abnormal at baseline. [ABSTRACT FROM AUTHOR]

The diagnostic criteria used in primary progressive (PP) and relapsing-remitting (RR) multiple sclerosis (MS) show substantial differences. This introduces complexity in the diagnosis of MS which could be resolved if these criteria could be unified in terms of the requirements for dissemination in space (DIS). The aim of this study was to assess whether a single algorithm may be used to demonstrate DIS in all forms of MS. Five sets of RRMS criteria for DIS were applied to a cohort of 145 patients with established PPMS (mean disease duration: 11 years - PPMS-1): C1: Barkhof-Tintoré (as in 2005 McDonald's criteria); C2: Swanton et al. (as in JNNP 2006); C3: presence of oligoclonal bands plus two lesions (as in McDonald's criteria); C4 and C5: a two-step approach was also followed (patients not fulfilling C1 or C2 were then assessed for C3). Two sets of PPMS criteria for DIS were applied: C6: Thompson et al. (as in 2001 McDonald's criteria); C7: 2005 McDonald criteria. A second sample of 55 patients with less than 5 years of disease duration (PPMS-2) was also analysed using an identical approach. For PPMS-1/PPMS-2, fulfilment was: C1:73.8%/66.7%; C2:72.1%/59.3%; C3:89%/79.2%; C4:96%/92.3%; C5:96%/85.7%; C6:85.8%/78.7%; C7:91%/80.4%. Levels of fulfilment suggest that the use of a single set of criteria for DIS in RRMS and PPMS might be feasible, and reinforce the added value of cerebrospinal fluid (CSF) findings to increase fulfilment in PPMS. Unification of the DIS criteria for both RRMS and PPMS could be considered in further revisions of the MS diagnostic criteria. [ABSTRACT FROM AUTHOR]

A pest management programme using the chemosterilant lufenuron against the Mediterranean fruit fly, Ceratitis capitata in Mallorca (Spain) is reported. The aim of this field trial was to monitor the reduction on C. capitata population and fruit infestation during the second and third years of an overall pest control programme. The insect growth regulator lufenuron (a phenylbenzoylurea) was placed within a Sevep device baited with the synthetic, female attractants (ammonium acetate, putrescine and amines), as well as the male attractant trimedlure (TML). A total of 7200 devices were placed on 300 ha within the municipalities of the Sóller Valley, at a density of 24 devices/ha. In order to measure the effectiveness of the chemosterilization, the C. capitata population was evaluated by Probodelt traps, baited either with the synthetic food attractants or TML, placed in three citrus orchards located at different altitudes. Fruit infestation was also evaluated. Results showed an average of 20% reduction in adult medfly population (37.2% for males vs. 2.7% for females). However, high differences were observed among the different orchards. In Site 1, where fallen oranges fruits were removed and phytosanitary treatments were applied, female captures decreased by 63.28%. Whereas at Site 2, where fallen fruits were neglected and no insecticide was applied, female captures increased by 19.90%. Ceratitis capitata population increase placed in Site 2 was probably due to the presence of unmanaged or mismanaged surrounding orchards. Summing up, it seems that the method based on lufenuron applied in the Sóller Valley was successful in decreasing medfly population, but the presence of the nearby improperly managed citrus orchards, as well as other hosts fruit trees for C. capitata, decrease the efficacy of the method. [ABSTRACT FROM AUTHOR]

Objective To evaluate the clinical significance of the 2005 modified imaging criteria for dissemination in time in multiple sclerosis stating that detection of a new T2 lesion appearing at any time compared with a reference scan done at least 30 days after the onset of a clinically isolated syndrome implies dissemination in time. Methods We included consecutive patients younger than 50 years examined at our center within 3 months of a clinical syndrome suggestive of central nervous system demyelination of the type seen in multiple sclerosis and followed for at least 3 years. We classified patients into one of two groups, according to the timing when reference scan was performed: less than 30 days and at least 30 days after symptom onset. We analyzed the interaction in time to relapse between timing of reference scan and new T2 lesion effect. Results A total of 218 patients were included. The hazard ratio (95% confidence interval) of this interaction was 0.90 (0.31-2.62) (or 1.02 (0.27-3.91) in patients with dissemination in space). Conclusions We conclude that new T2 lesions increased relapse risk regardless of timing of the reference scan, supporting the use of scans performed at any time within 30 days of symptom onset for dissemination in time demonstration. [ABSTRACT FROM AUTHOR]

Objective Our objective in this study is to evaluate whether brain magnetic resonance imaging (MRI) performed at interferon-beta (IFN-β) onset and after 12 months allow us to identify relapsing-remitting multiple sclerosis (RRMS) patients with a disability increase in the first 2 years of therapy. Methods This is a prospective and longitudinal study of patients with RRMS treated with IFN-β. All patients included underwent brain MRI before the onset of therapy with IFN-β and 12 months after. MRI measures (T2, unenhanced T1-weighted and gadolinium-enhancing T1-weighted brain lesion load, brain parenchymal fraction) were undertaken at baseline and after 12 months. The number of active lesions (new or enlarging T2 plus gadolinium-enhancing brain lesions) was also assessed on the 12 months MRI scan. Expanded Disability Status Scale (EDSS) was scored every 3 months. We defined an increase in disability as an increase of at least 1 EDSS point confirmed and sustained during the first 2 years of therapy with IFN-β. Regression analysis was performed in order to identify MRI variables of response. Results We included 152 patients who were followed-up for at least 2 years. After 2 years of therapy, 24 patients (16%) had an increase in disability. The logistic regression model showed that active lesions in the scan performed at 12 months were the most important factor related with the increase of disability after 2 years of therapy (odds ratio 8.3, 95% confidence interval 3.1-21.9; p < 0.0001). Conclusions In RRMS patients treated with IFN-β the MRI changes occurring during the first year may have a prognostic value for identifying patients with a confirmed increase of disability after 2 years of therapy. [ABSTRACT FROM AUTHOR]

This article presents information on in vitro activity of a new liposomal nystatin formulation against opportunistic fungal pathogens. Amphotericin B (AMB) desoxycholate, lipid formulations of AMB flucytosine, and azoles are currently approved for the treatment of systemic fungal infections; yet, none of these drugs is uniformly effective in the treatment of systemic mycoses. This indicates there is a need for additional antifungal agents, the current range of which is relatively small in comparison with antibacterial agents.

The in-vitro susceptibilities of 120 clinical isolates of yeasts to liposomal nystatin were compared with those to amphotericin B lipid complex (ABLC), liposomal amphotericin B (LAB), amphotericin B cholesteryl sulphate (ABCD), amphotericin B desoxycholate, nystatin, fluconazole and itraconazole. Yeast isolates examined included strains of Candida albicans, Candida parapsilosis, Candida glabrata, Candida krusei, Candida guilliermondii, Candida tropicalis, Candida kefyr, Candida viswanathii, Candida famata, Candida rugosa, Rhodotorula rubra, Trichosporon spp., Cryptococcus laurentii and Cryptococcus neoformans. The mean MICs for all strains examined were: liposomal nystatin 0.96 mg/L; nystatin 0.54 mg/L; ABLC 0.65 mg/L; LAB 1.07 mg/L; ABCD 0.75 mg/L; amphotericin B 0.43 mg/L; fluconazole 5.53 mg/L; and itraconazole 0.33 mg/L. No significant differences were seen between the activity of liposomal nystatin and the polyene drugs or itraconazole, but liposomal nystatin was more active than fluconazole. MICs were lower than the reported blood concentrations following therapeutic doses of this drug, indicating the potential for a therapeutic use of liposomal nystatin in humans. These results indicate good activity in vitro against medically important yeasts, which compares favourably with the activities of other currently available antifungal drugs. Liposomal nystatin may have a role in the treatment of disseminated and systemic mycoses. [ABSTRACT FROM AUTHOR]

The in-vitro antifungal activity of sertaconazole against 110 strains of Candida yeasts (50 Candida albicans, 15 Candida glabrata, 2 Candida guilliermodii, 8 Candida krusei, 1 Candida kefyr, 8 Candida parapsilosis and 26 Candida tropicalis) was assessed in comparison with bifonazole, ketoconazole, econazole and miconazole. The majority of the strains were clinical isolates; some reference strains were included. A commercial agar diffusion method (NeoSensitabs, Rosco, Taastrup, Denmark) in Shadomy's modified medium pH 7 was used. Using the manufacturer's criteria, 86.4% of the strains were classified as “sensitive” to sertaconazole. The only strain classified as “resistant” to sertaconazote was the control reference strain of C. albicans. The remaining strains were classified as moderately sensitive. The sensitivity/resistance percentages for the other antifungals tested were 75.5/1.8 for ketoconazole, 71.8/2.7 for miconazole, 63.7/13.6 for econazole, and 59.1/5.5 for bifonazole. Sertaconazole showed a higher antifungal activity than that of the other antimycotics, tested in vitro which was statistically significant (P<0.001), as well as a lower resistance rate than that of econazole, bifonazole and ketoconazole. [ABSTRACT FROM PUBLISHER]

The author reflects on the impact of oral laquinimod for multiple sclerosis. He talks about several newly approved drugs for relapsing-remitting multiple sclerosis (RRMS) that has notably increased over the last years. He also highlights three findings that support the potential neuroprotective power of oral laquinimod. He also highlights or relates the evidence of the broad impact that laquinimod has on brain tissue damage.