Lag3+ regulatory T lymphocytes in critical carotid artery stenosis

Clinical and Experimental Medicine - The aim of this study was to evaluate CD25+ and Lag3+ T regulatory subpopulations in patients with critical carotid artery stenosis (CAS) and Stanford-A acute...     

Mechanical Properties of the Human Tibial and Peroneal Nerves Following Stretch With Histological Correlations

Despite the extensive literature regarding peripheral nerve stretch injuries, there are few studies that compare the nerve histology with the mechanical properties in humans. There is clinical evidence suggesting that the peroneal nerve is at greater risk for injury compared to the tibial nerve following total hip arthroplasty and hip trauma. We examined the two nerves from fresh human cadavers with or without controlled stretch. The mechanical properties, stiffness, and strain were compared with light microscopic preparations in longitudinal sections stained by the trichrome method for collagen and showing the effects of structural deformation. The tibial nerve had an average failure load 1.7× that for the peroneal nerve (P = 0.0001). Although the corresponding average stiffness showed a trend toward being larger (4.39 vs. 3.81 N/mm), the difference was not significant (P = 0.126). Histologically, the perineurium along with the underlying nerve fascicle was undulated in the control specimens and straightened out in the stretched specimens. Peroneal nerves went on to failure at lower loads and exhibited a wavy pattern on pathologic slides after failure, which shows that peroneal nerves fail mechanically before they can unfold. The tibial nerve has a biomechanical and histological advantage compared to the peroneal nerve during tensile testing, which could be the reason why it is less commonly damaged. We conclude that the perineurium is especially protective against deformation changes in human nerves relative to the respective nerve size and number of fascicles. Anat Rec, 302:2030–2039, 2019. © 2019 American Association for Anatomy     

Exceptional Disparity in Australian Agamid Lizards is a Possible Result of Arrival into Vacant Niche

Australia provides abundant examples of continental-scale evolutionary radiations. The collision of two continental shelves around 30 Ma facilitated an influx of squamates and the subsequent squamate radiations resulted in high taxonomic diversity. The morphological disparity seen in these major squamate groups, however, remains underexplored. Here, we examine the major cranial proportions of over 1,000 specimens using 2D linear measurements to explicitly quantify the morphological disparity of Australian agamid lizards (Amphibolurinae) and compare it to that of agamid, acrodont, and iguanian clades from other parts of the world. Our results indicate the Australian Amphibolurinae have exceptionally high cranial disparity, and we suggest that this is linked to the relaxed selective environment that greeted the founders of Amphibolurinae when they first arrived in Australia. Anat Rec, 302:1536–1543, 2019. © 2019 American Association for Anatomy     

In vitro expression of vital virulent genes of clinical and environmental isolates of Cryptococcus neoformans/gattii in endothelial cells of human blood-brain barrier

BackgroundEvaluation of the pathogenesis of clinical and environmental cryptococcal isolates to the central nervous system is necessary for understanding the risk. This study was designed to determine the in vitro expression of six important virulent genes of Cryptococcus neoformans/gattii in Human Brain Microvascular Endothelial cells (hBMEC).MethodsThe hBMEC were infected with Cryptococcus to determine invasion and survival rate at 3, 12 and 24 hours by subsequent colony count of internalized yeasts. The whole RNA of the intracellular Cryptococcus was extracted to quantify the expression of CAP10, PLB1, ENA1, URE1, LAC1, and MATα genes by real-time quantitative PCR for 3 and 12 hours of infection.ResultsInvasion and survival rates were higher in clinical and standard strains of C. neoformans. A significant difference was observed among the clinical and environmental isolates for the expression of CAP10, ENA1, LAC1, MATα and URE1 at 3 hours, and ENA1, LAC1, MATα, PLB1 and URE1 at 12 hours. Clinical isolates showed significant upregulation of all the genes except PLB1, which was higher in environmental isolates. Relative expressions at the two time-points showed statistically significant (P = 0.043) changes for the clinical isolates and no significance (P = 0.063) for environmental isolates.ConclusionThe C. gattii (VGI) isolates showed significantly lower invasion and survival than C. neoformans (VNI, and VNII) irrespective of their sources. Clinical isolates exhibited higher expression for the majority of the virulent genes until 12 hours of infection, probably due to their better adaptation in the host system and enhanced pathogenicity than the environmental counterparts.     

Combining VITEK® 2 with colistin agar dilution screening assist timely reporting of colistin susceptibility

ObjectivesThe rise in carbapenem resistance among Gram-negative bacteria has renewed interest in colistin. Recently, the EUCAST-CLSI Polymyxin Breakpoints Working Group declared that broth microdilution (BMD) is the only valid method for colistin susceptibility testing. BMD is not easily incorporated into the routine work of clinical laboratories, and usually this test is incorporated serially, resulting in delayed susceptibility reporting. We tested a strategy of combining VITEK^® 2 with a 2 μg/mL colistin agar dilution (VITEK^® 2/AD) screening plate to improve performance and time to reporting of colistin susceptibility.MethodsColistin susceptibility for 364 clinical isolates was determined by VITEK^® 2/AD and compared with the reference standard BMD according to the ISO 20776-1:2007 and CLSI guidelines. The EUCAST colistin susceptibility breakpoint of ≤2 μg/mL was used. Escherichia coli NCTC 13846 served as quality control strain. Agreement, very major error (VME) and major error rates were determined using ISO 20776-2:2007.ResultsThe VME rate for VITEK^® 2 alone was 30.6% (15/49, 95% CI 18.3–45.4%), and was reduced to 10.2% (5/49, 95% CI 3.4–22.2%) using the VITEK^® 2/AD combined testing. The combined testing had categorical agreement with BMD of 97% (354/364, 95% CI 95.0–98.7%), and a major error (ME) rate of 1.6% (5/315, 95% CI 0.5–3.7%). Using the combined testing, even against challenging strains, 349 (95.8%, 95% CI 93.3–97.7%) colistin susceptibility results could be reported, and only 15 isolates required further analysis by BMD.DiscussionOur method is simple to apply and allows rapid reporting of colistin susceptibility.     

Fluoroquinolones versus trimethoprim-sulfamethoxazole for the treatment of Stenotrophomonas maltophilia infections: a systematic review and meta-analysis

BackgroundFluoroquinolones are a popular alternative to trimethoprim-sulfamethoxazole for Stenotrophomonas maltophilia infections.ObjectivesTo compare the effects of fluoroquinolones and trimethoprim-sulfamethoxazole on mortality of S. maltophilia infections.Data sourcesPubMed and EMBASE.Study eligibility criteriaClinical studies reporting mortality outcomes of S. maltophilia infections.ParticipantsPatients with clinical infections caused by S. maltophilia.InterventionsFluoroquinolone monotherapy in comparison with trimethoprim-sulfamethoxazole monotherapy.MethodsSystematic review with meta-analysis technique.ResultsSeven retrospective cohort and seven case–control studies were included. Three cohort studies were designed to compare the two drugs, whereas others had other purposes. A total of 663 patients were identified, 332 of which were treated with trimethoprim-sulfamethoxazole (50.1%) and 331 with fluoroquinolones (49.9%). Three cohort studies were designed to compare the effect of the two drugs, whereas the others had other purposes. Levofloxacin was most frequently used among fluoroquinolones (187/331, 56.5%), followed by ciprofloxacin (114/331, 34.4%). The overall mortality rate was 29.6%. Using pooled ORs for the mortality of each study, fluoroquinolone treatment (OR 0.62, 95% CI 0.39–0.99) was associated with survival benefit over trimethoprim-sulfamethoxazole treatment, with low heterogeneity (I² = 18%). Specific fluoroquinolones such as ciprofloxacin (OR 0.44, 95% CI 0.17–1.12) and levofloxacin (OR 0.78, 95% CI 0.48–1.26) did not show a significant difference in comparison with trimethoprim-sulfamethoxazole. In the sub-group analyses of adult and bacteraemic patients, significant differences in mortality were not observed between fluoroquinolones and trimethoprim-sulfamethoxazole.ConclusionsBased on a meta-analysis of non-randomized studies, fluoroquinolones demonstrated comparable effects on mortality of S. maltophilia infection to trimethoprim-sulfamethoxazole, supporting the use of fluoroquinolones in clinical S. maltophilia infections. Although the pooled analysis of overall studies favoured fluoroquinolones over trimethoprim-sulfamethoxazole, the studies included were observational, and sub-group analyses of certain fluoroquinolone agents did not show statistical differences with trimethoprim-sulfamethoxazole. Randomized clinical studies are needed to address these issues.