Onchocerca jakutensis filariasis in humans

We identified Onchocerca jakutensis as the causative agent of an unusual human filariasis in a patient with lupus erythematosus. To our knowledge, this is the first case of human infection with O. jakutensis and the first human case of zoonotic onchocercosis involving >1 worm.     

Isolation and characterization of dermal lymphatic and blood endothelial cells reveal stable and functionally specialized cell lineages

A plexus of lymphatic vessels guides interstitial fluid, passenger leukocytes, and tumor cells toward regional lymph nodes. Microvascular endothelial cells (ECs) of lymph channels (LECs) are difficult to distinguish from those of blood vessels (BECs) because both express a similar set of markers, such as CD31, CD34, podocalyxin, von Willebrand factor (vWF), etc. Analysis of the specific properties of LECs was hampered so far by lack of tools to isolate LECs. Recently, the 38-kD mucoprotein podoplanin was found to be expressed by microvascular LECs but not BECs in vivo. Here we isolated for the first time podoplanin(+) LECs and podoplanin(-) BECs from dermal cell suspensions by multicolor flow cytometry. Both EC types were propagated and stably expressed VE-cadherin, CD31, and vWF. Molecules selectively displayed by LECs in vivo, i.e., podoplanin, the hyaluronate receptor LYVE-1, and the vascular endothelial cell growth factor (VEGF)-C receptor, fms-like tyrosine kinase 4 (Flt-4)/VEGFR-3, were strongly expressed by expanded LECs, but not BECs. Conversely, BECs but not LECs expressed VEGF-C. LECs as well as BECs formed junctional contacts with similar molecular composition and ultrastructural features. Nevertheless, the two EC types assembled in vitro in vascular tubes in a strictly homotypic fashion. This EC specialization extends to the secretion of biologically relevant chemotactic factors: LECs, but not BECs, constitutively secrete the CC chemokine receptor (CCR)7 ligand secondary lymphoid tissue chemokine (SLC)/CCL21 at their basal side, while both subsets, upon activation, release macrophage inflammatory protein (MIP)-3alpha/CCL20 apically. These results demonstrate that LECs and BECs constitute stable and specialized EC lineages equipped with the potential to navigate leukocytes and, perhaps also, tumor cells into and out of the tissues.     

Vedolizumab for ulcerative colitis:Real world outcomes from a multicenter observational cohort of Australia and Oxford

BACKGROUND Vedolizumab(VDZ),a humanised monoclonal antibody that selectively inhibits alpha4-beta7 integrins is approved for use in adult moderate to severe ulcerative colitis(UC) patients.AIM To assess the efficacy and safety of VDZ in the real-world management of UC in a large multicenter cohort involving two countries and to identify predictors of achieving remission.METHODS A retrospective review of Australian and Oxford,United Kingdom data for UC patients.Clinical response at 3 mo,endoscopic remission at 6 mo and clinical remission at 3,6 and 12 mo were assessed.Cox regression models and Kaplan Meier curves were performed to assess the time to remission,time to failure and the covariates influencing them.Safety outcomes were recorded.RESULTS Three hundred and three UC patients from 14 centres in Australia and United Kingdom,[60% n = 182,anti-TNF na?ve] were included.The clinical response was 79% at 3 mo with more Australian patients achieving clinical response compared to Oxford(83% vs 70% P = 0.01).Clinical remission for all patients was 56%,62% and 60% at 3,6 and 12 mo respectively.Anti-TNF naive patients were more likely to achieve remission than exposed patients at all the time points(3 mo 66% vs 40% P 0.001,6 mo 73% vs 46% P 0.001,12 mo 66% vs 51% P = 0.03).More Australian patients achieved endoscopic remission at 6 mo compared to Oxford(69% vs 43% P = 0.01).On multi-variate analysis,anti-TNF na?ve patients were 1.8(95%CI:1.3-2.3) times more likely to achieve remission than anti-TNF exposed(P 0.001).32 patients(11%) had colectomy by 12 mo.CONCLUSION VDZ was safe and effective with 60% of UC patients achieving clinical remission at 12 mo and prior anti-TNF exposure influenced this outcome.     

Effects of Regular Treadmill Exercise on a DNA Oxidative-Damage Marker and Total Antioxidant Capacity in Rat Hippocampal Tissue

MethodsThis study investigated the effects of 8 weeks of regular treadmill exercise on 8-OHdG and the TAC of hippocampal tissue in lead-acetate-exposed rats. Wistar rats were randomly divided into four groups: baseline, sham (control), lead, and exercise+lead. The exercise program involved running on a treadmill with increasing intensity five times a week for 8 weeks. Animals in the lead and exercise+lead groups received lead acetate at 20 mg/kg body weight intraperitoneally three times weekly for 8 weeks. Animals in the sham group received solvent (ethyl oleate) at 30 mg/kg body weight three times weekly for 8 weeks. TAC and 8-OHdG were measured by spectrophotometric and ELISA techniques, respectively. Data were analyzed by ANOVA and Tukey''s post-hoc test with a significance cutoff of p≤0.05.ResultsThe level of 8-OHdG and the TAC were significantly higher and lower, respectively, in the lead group than in the baseline and sham groups (p<0.01). However, the 8-OHdG level and TAC value in hippocampal tissue were significantly decreased and increased, respectively, in the exercise+lead group relative to the lead group (p<0.05).ConclusionsThe TAC of hippocampal tissue may be directly associated with neural protection mechanisms of exercise following lead acetate injection, and the beneficial effects of regular exercise in preventing hippocampal neuronal damage could be due to decreased hippocampal oxidative stress such as reflected by a lower 8-OHdG level and increased TAC.     

Is Subjective Well-being a Useful Parameter for Allocating Resources among Public Interventions?

Scarce public resources requiretrade-offs between competing programs indifferent sectors, and the careful allocationof fixed resources within a single sector. Thispaper argues that a general quality of lifeinstrument encompassing health-related andnon-health-related components is suitable fordetermining the best trade-offs betweensectors. Further, this paper suggests thatsubjective well-being shows the propertiescrucial to a general quality of life measureand has additional advantages that makes itparticularly useful for the allocation ofpublic and health care resources. The paperargues that Western societies are in anunusually prosperous situation today whichallows to concentrate efforts not only onreducing harm but also on improving positivestates of health. Further, subjectivewell-being can be evaluated from the patient'sperspective and incorporates a valuation oflife expectancy. Criteria required for anappropriate questionnaire that measuressubjective well-being are presented.     

Cost-effectiveness of FDG-PET for the management of potentially operable non-small cell lung cancer: priority for a PET-based strategy after nodal-negative CT results

Decision analysis is used here to establish the most cost-effective strategy for management of potentially operable non-small cell lung cancers (NSCLCs). The strategies compared were conventional staging (strategy A), dedicated systems of positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) in patients with normal-sized (strategy B) or in patients with enlarged mediastinal lymph nodes (part of strategy C), and FDG-PET followed by exclusion from surgical procedures when both computed tomography (CT) and PET were positive for mediastinal lymph nodes (strategy D) or when PET alone was positive (strategy E). Based on published data, the sensitivity and specificity of FDG-PET were estimated at 0.74 and 0.96 for detecting metastasis in normal-sized mediastinal lymph nodes, and at 0.95 and 0.76 when these lymph nodes were enlarged. The calculated probability of up-staging to M1 by using PET was 0.05. The costs quoted correspond to the cost reimbursed in 1999 by the public health provider in Germany. The incremental cost-effectiveness ratio (ICER) of strategy B was much more favourable (143 EUR/LYS; LYS = life year saved) than the ICER of strategy C (36,667 EUR/LYS). In strategy B, the use of PET did not raise the overall costs because the costs of PET were almost balanced by a better selection of patients for beneficial cancer resection. The exclusion from biopsy confirmation in strategies D and E led to cost savings that did not justify the expected reduction in life expectancy. In sensitivity analyses, the ICERs of strategy B were robust to the pretest likelihood of N2/N3, to penalized test parameters of PET and to reimbursement of PET. However, the ICER of strategy B would be raised to 28,000 EUR/LYS through use of thoracic PET without whole-body scanning. To conclude, the implementation of whole-body PET with a full ring of detectors in the preoperative staging of patients with NSCLC and normal-sized lymph nodes is clearly cost-effective. However, patients with nodal-positive PET results should not be excluded from biopsy.