Antimicrobial resistance in urosepsis: outcomes from the multinational, multicenter global prevalence of infections in urology (GPIU) study 2003–2013

Primary objective was to identify the (1) relationship of clinical severity of urosepsis with the pathogen spectrum and resistance and (2) appropriateness of using the pathogen spectrum and resistance rates of health-care-associated urinary tract infections (HAUTI) as representative of urosepsis. The secondary objective was to provide an overview of the pathogens and their resistance profile in patients with urosepsis. POPULATION AND METHODS: A point prevalence study carried out in 70 countries (2003-2013). Population studied included; 408 individuals with microbiologically proven urosepsis, 1606 individuals with microbiological proof of HAUTI and 27,542 individuals hospitalised in urology wards. Main outcomes are pathogens and resistance identified in HAUTIs and urosepsis including its clinical severity. A statistical model that included demographic factors (study year, geographical location, hospital setting) was used for analysis. RESULTS: Amongst urology practices, the prevalence of microbiologically proven HAUTI and urosepsis was 5.8 and 1.5 %, respectively. Frequent pathogens in urosepsis were E. coli (43 %), Enterococcus spp. (11 %), P. aeruginosa (10 %) and Klebsiella spp. (10 %). Resistance to commonly prescribed antibiotics was high and rates ranged from 8 % (imipenem) to 62 % (aminopenicillin/β lactamase inhibitors); 45 % of Enterobacteriaceae and 21 % of P. aeruginosa were multidrug-resistant. Resistance rates in urosepsis were higher than in other clinical diagnosis of HAUTI (Likelihood ratio <0.05). CONCLUSIONS: It is not appropriate to use the pathogen spectrum and resistance rates of other HAUTIs as representative of urosepsis to decide on empirical treatment of urosepsis. Resistance rates in urosepsis are high, and precautions should be made to avoid further increas

Cerebellum Abnormalities in Idiopathic Generalized Epilepsy with Generalized Tonic-Clonic Seizures Revealed by Diffusion Tensor Imaging

Although there is increasing evidence suggesting that there may be subtle abnormalities in idiopathic generalized epilepsy (IGE) patients using modern neuroimaging techniques, most of these previous studies focused on the brain grey matter, leaving the underlying white matter abnormalities in IGE largely unknown, which baffles the treatment as well as the understanding of IGE. In this work, we adopted multiple methods from different levels based on diffusion tensor imaging (DTI) to analyze the white matter abnormalities in 14 young male IGE patients with generalized tonic-clonic seizures (GTCS) only, comparing with 29 age-matched male healthy controls. First, we performed a voxel-based analysis (VBA) of the fractional anisotropy (FA) images derived from DTI. Second, we used a tract-based spatial statistics (TBSS) method to explore the alterations within the white matter skeleton of the patients. Third, we adopted region-of-interest (ROI) analyses based on the findings of VBA and TBSS to further confirm abnormal brain regions in the patients. At last, considering the convergent evidences we found by VBA, TBSS and ROI analyses, a subsequent probabilistic fiber tractography study was performed to investigate the abnormal white matter connectivity in the patients. Significantly decreased FA values were consistently observed in the cerebellum of patients, providing fresh evidence and new clues for the important role of cerebellum in IGE with GTCS

Connectivity-based parcellation of the thalamus explains specific cognitive and behavioural symptoms in patients with bilateral thalamic infarct

A novel approach based on diffusion tractography was used here to characterise the cortico-thalamic connectivity in two patients, both presenting with an isolated bilateral infarct in the thalamus, but exhibiting partially different cognitive and behavioural profiles. Both patients (G.P. and R.F.) had a pervasive deficit in episodic memory, but only one of them (R.F.) suffered also from a dysexecutive syndrome. Both patients had an MRI scan at 3T, including a T1-weighted volume. Their lesions were manually segmented. T1-volumes were normalised to standard space, and the same transformations were applied to the lesion masks. Nineteen healthy controls underwent a diffusion-tensor imaging (DTI) scan. Their DTI data were normalised to standard space and averaged. An atlas of Brodmann areas was used to parcellate the prefrontal cortex. Probabilistic tractography was used to assess the probability of connection between each voxel of the thalamus and a set of prefrontal areas. The resulting map of corticothalamic connections was superimposed onto the patients' lesion masks, to assess whether the location of the thalamic lesions in R.F. (but not in G. P.) implied connections with prefrontal areas involved in dysexecutive syndromes. In G.P., the lesion fell within areas of the thalamus poorly connected with prefrontal areas, showing only a modest probability of connection with the anterior cingulate cortex (ACC). Conversely, R.F.'s lesion fell within thalamic areas extensively connected with the ACC bilaterally, with the right dorsolateral prefrontal cortex, and with the left supplementary motor area. Despite a similar, bilateral involvement of the thalamus, the use of connectivity-based segmentation clarified that R.F.'s lesions only were located within nuclei highly connected with the prefrontal cortical areas, thus explaining the patient's frontal syndrome. This study confirms that DTI tractography is a useful tool to examine in vivo the effect of focal lesions on interconnectivity brain patterns

Prevalence and Characteristics Associated With Post-COVID-19 Condition Among Nonhospitalized Adolescents and Young Adults

Importance: The prevalence and baseline risk factors of post-COVID-19 condition (PCC) remain unresolved among the large number of young people who experienced mild COVID-19. Objectives: To determine the point prevalence of PCC 6 months after the acute infection, to determine the risk of development of PCC adjusted for possible confounders, and to explore a broad range of potential risk factors. Design, Setting, and Participants: This cohort study included nonhospitalized individuals from 2 counties in Norway between ages 12 and 25 years who underwent reverse transcription-polymerase chain reaction (RT-PCR) testing. At the early convalescent stage and at 6-month follow-up, participants underwent a clinical examination; pulmonary, cardiac, and cognitive functional testing; immunological and organ injury biomarker analyses; and completion of a questionnaire. Participants were classified according to the World Health Organization case definition of PCC at follow-up. Association analyses of 78 potential risk factors were performed. Exposures: SARS-CoV-2 infection. Main Outcomes and Measures: The point prevalence of PCC 6 months after RT-PCR testing in the SARS-CoV-2-positive and SARS-CoV-2-negative groups, and the risk difference with corresponding 95% CIs. Results: A total of 404 individuals testing positive for SARS-CoV-2 and 105 individuals testing negative were enrolled (194 male [38.1%]; 102 non-European [20.0%] ethnicity). A total of 22 of the SARS-CoV-2-positive and 4 of the SARS-CoV-2-negative individuals were lost to follow-up, and 16 SARS-CoV-2-negative individuals were excluded due to SARS-CoV-2 infection in the observational period. Hence, 382 SARS-CoV-2-positive participants (mean [SD] age, 18.0 [3.7] years; 152 male [39.8%]) and 85 SARS-CoV-2-negative participants (mean [SD] age, 17.7 [3.2] years; 31 male [36.5%]) could be evaluated. The point prevalence of PCC at 6 months was 48.5% in the SARS-CoV-2-positive group and 47.1% in the control group (risk difference, 1.5%; 95% CI, -10.2% to 13.1%). SARS-CoV-2 positivity was not associated with the development of PCC (relative risk [RR], 1.06; 95% CI, 0.83 to 1.37; final multivariable model utilizing modified Poisson regression). The main risk factor for PCC was symptom severity at baseline (RR, 1.41; 95% CI, 1.27-1.56). Low physical activity (RR, 0.96; 95% CI, 0.92-1.00) and loneliness (RR, 1.01; 95% CI, 1.00-1.02) were also associated, while biological markers were not. Symptom severity correlated with personality traits. Conclusions and Relevance: The persistent symptoms and disability that characterize PCC are associated with factors other than SARS-CoV-2 infection, including psychosocial factors. This finding raises questions about the utility of the World Health Organization case definition and has implications for the planning of health care services as well as for further research on PCC

Reassessing associations between white matter and behaviour with multimodal microstructural imaging

Several studies have established specific relationships between White Matter (WM) and behaviour. However, these studies have typically focussed on fractional anisotropy (FA), a neuroimaging metric that is sensitive to multiple tissue properties, making it difficult to identify what biological aspects of WM may drive such relationships. Here, we carry out a pre-registered assessment of WM-behaviour relationships in 50 healthy individuals across multiple behavioural and anatomical domains, and complementing FA with myelin-sensitive quantitative MR modalities (MT, R1, R2∗). Surprisingly, we only find support for predicted relationships between FA and behaviour in one of three pre-registered tests. For one behavioural domain, where we failed to detect an FA-behaviour correlation, we instead find evidence for a correlation between behaviour and R1. This hints that multimodal approaches are able to identify a wider range of WM-behaviour relationships than focusing on FA alone. To test whether a common biological substrate such as myelin underlies WM-behaviour relationships, we then ran joint multimodal analyses, combining across all MRI parameters considered. No significant multimodal signatures were found and power analyses suggested that sample sizes of 40-200 may be required to detect such joint multimodal effects, depending on the task being considered. These results demonstrate that FA-behaviour relationships from the literature can be replicated, but may not be easily generalisable across domains. Instead, multimodal microstructural imaging may be best placed to detect a wider range of WM-behaviour relationships, as different MRI modalities provide distinct biological sensitivities. Our findings highlight a broad heterogeneity in WM's relationship with behaviour, suggesting that variable biological effects may be shaping their interaction

Ku70/80 gene expression and DNA-dependent protein kinase (DNA-PK) activity do not correlate with double-strand break (dsb) repair capacity and cellular radiosensitivity in normal human fibroblasts

The expression of the Ku70 and Ku80 genes as well as the activity of the DNA-dependent protein kinase (DNA-PK) were studied in 11 normal human fibroblast lines. The proteins studied are known to be part of a double-strand break (dsb) repair complex involved in non-homologous recombination, as was demonstrated for the radiosensitive rodent mutant cell lines of the complementation groups 5–7. The 11 fibroblast lines used in this study represent a typical spectrum of normal human radiosensitivity with the surviving fraction measured for a dose of 3.5 Gy, SF3.5 Gy, ranging from 0.03 to 0.28. These differences in cell survival were previously shown to correlate with the number of non-repaired dsbs. We found that the mRNA signal intensities of both Ku70 and Ku80 genes were fairly similar for the 11 cell lines investigated. In addition, the DNA-PK activity determined by the pulldown assay was fairly constant in these fibroblast lines. Despite the correlation between cell survival and dsb repair capacity, there was no correlation between dsb repair capacity and DNA-PK activity in the tested normal human fibroblast lines. Obviously, in this respect, other proteins/pathways appear to be more relevant. © 1999 Cancer Research Campaig

Anatomical connectivity patterns predict face selectivity in the fusiform gyrus

A fundamental assumption in neuroscience is that brain structure determines function. Accordingly, functionally distinct regions of cortex should be structurally distinct in their connections to other areas. We tested this hypothesis in relation to face selectivity in the fusiform gyrus. By using only structural connectivity, as measured through diffusion-weighted imaging, we were able to predict functional activation to faces in the fusiform gyrus. These predictions outperformed two control models and a standard group-average benchmark. The structure–function relationship discovered from the initial participants was highly robust in predicting activation in a second group of participants, despite differences in acquisition parameters and stimuli. This approach can thus reliably estimate activation in participants who cannot perform functional imaging tasks and is an alternative to group-activation maps. Additionally, we identified cortical regions whose connectivity was highly influential in predicting face selectivity within the fusiform, suggesting a possible mechanistic architecture underlying face processing in humans.United States. Public Health Service (DA023427)National Institute of Mental Health (U.S.) (F32 MH084488)National Eye Institute (T32 EY013935)Poitras FoundationSimons FoundationEllison Medical Foundatio