Broad and potent neutralizing human antibodies to tick-borne flaviviruses protect mice from disease

Tick-borne encephalitis virus (TBEV) is an emerging human pathogen that causes potentially fatal disease with no specific treatment. Mouse monoclonal antibodies are protective against TBEV, but little is known about the human antibody response to infection. Here, we report on the human neutralizing antibody response to TBEV in a cohort of infected and vaccinated individuals. Expanded clones of memory B cells expressed closely related anti-envelope domain III (EDIII) antibodies in both groups of volunteers. However, the most potent neutralizing antibodies, with IC₅₀s below 1 ng/ml, were found only in individuals who recovered from natural infection. These antibodies also neutralized other tick-borne flaviviruses, including Langat, louping ill, Omsk hemorrhagic fever, Kyasanur forest disease, and Powassan viruses. Structural analysis revealed a conserved epitope near the lateral ridge of EDIII adjoining the EDI–EDIII hinge region. Prophylactic or early therapeutic antibody administration was effective at low doses in mice that were lethally infected with TBEV.     

EphA2-mediated mesenchymal–amoeboid transition induced by endothelial progenitor cells enhances metastatic spread due to cancer-associated fibroblasts

Tumor progression is deeply influenced by epigenetic changes induced by tumor stroma. Cancer-associated fibroblasts (CAFs) have been reported to promote epithelial–mesenchymal transition in cancer cells, thereby enhancing their aggressiveness and stem-like properties. As CAFs are able to recruit endothelial progenitor cells (EPCs) to tumor site, we aim to investigate their interplay for prostate carcinoma progression. Both prostate CAFs and cancer cells actively recruit EPCs, known to affect tumor progression through increased vasculogenesis. EPCs synergize with CAFs to further promote epigenetic plasticity of cancer cells, through a mesenchymal-to-amoeboid transition. Indeed, after fibroblasts have engaged epithelial–mesenchymal transition in cancer cells, a further shift towards amoeboid motility is promoted by EPCs through contact-mediated triggering of the bidirectional ephrinA1/EphA2 signaling. The activation of ephrinA1 reverse pathway enhances EPC-induced neo-vascularization, thus promoting tumor growth, while EphA2 forward signaling elicits mesenchymal–amoeboid transition in cancer cells, favoring their adhesion to endothelium, transendothelial migration, and lung metastatic colonization. We therefore underscore that the metastatic advantage given by tumor microenvironment embraces different motility strategies and propose EphA2-targeted tools as useful adjuvants in anti-metastatic treatments.     

Multivariate analysis of the influence of peri-implant clinical parameters and local factors on radiographic bone loss in the posterior maxilla: a retrospective study on 277 dental implants

Clinical Oral Investigations - The aim of the present study was to investigate whether peri-implant clinical parameters (modified plaque index (mPI), bleeding and/or suppuration on probing (B/SOP))...     

Treatment of benign cold thyroid nodules: a randomized clinical trial of percutaneous laser ablation versus levothyroxine therapy or follow-up.

AIM OF THE STUDY: To compare clinical and ultrasound (US) changes induced in cold thyroid nodules by US-guided percutaneous laser ablation (PLA) versus follow-up or levothyroxine (LT4) suppressive therapy. METHODS: 62 patients randomly assigned to a single PLA (Group 1), LT4 (Group 2), or follow-up (Group 3). Entry criteria: euthyroid patients with a solid thyroid nodule >5 mL and benign cytological findings. TREATMENT: Group 1: PLA was performed with a 1.064 mum neodymium yttrium-aluminum-garnet laser with output power of 3 W for 10 minutes; Group 2: the LT4 dose was adjusted to induce thyrotropin suppression; Group 3: no treatment. RESULTS: In Group 1 a significant nodule reduction was found 6 and 12 months after PLA (delta volume: -42.7 +/- 13.6%; p = 0.001). A reduction >50% was found in 33.3% of cases. In Group 2 a nonsignificant nodule shrinkage was observed. A nonsignificant volume increase was observed in Group 3. Improvement of local symptoms was registered in 81.2% of patients in Group 1 vs. 13.3% in Group 2 and 0.0% in Group 3 ( p = 0.001). No complications were noted. CONCLUSIONS: A single PLA induced significant volume reduction and improvement of local symptoms. PLA was more effective than LT4. Follow-up was associated with nodule growth and progression of local symptoms. PLA should be considered a potential mini-invasive alternative to surgery in symptomatic patients with benign cold thyroid nodules.     

Finding my own way: an fMRI single case study of a subject with developmental topographical disorientation

Developmental topographical disorientation (DTD) causes impaired spatial orientation and navigation from early childhood with no evidence of cerebral damage. Using fMRI and a landmark sequencing task, we investigated the hypothesis that Dr Wai’s abnormal cerebral activation pattern was related to his peculiar behavioral profile. Although Dr Wai was able to correctly perform landmark sequencing, he showed a lack of activity in regions activated in all control subjects and activity in areas that were not activated in any control subject. These results are discussed in light of cognitive and functional model of navigation, with relevant implications for DTD physiology.     

Classification Accuracy of the Portland Digit Recognition Test in Traumatic Brain Injury: Results of a Known-Groups Analysis

The present study used a known-groups design to examine the accuracy of the Portland Digit Recognition Test (PDRT) in the detection of malingering in traumatic brain injury (TBI). Data were derived from 262 TBI patients who were classified as not malingering, possibly malingering, and malingering based on the Slick, Sherman, and Iverson (1999 Slick , D. J. , Sherman , E. M. S. , & Iverson , G. L. ( 1999 ). Diagnostic criteria for malingering neurocognitive dysfunction: Proposed standards for clinical practice and research . The Clinical Neuropsychologist , 13 , 545 – 561 .[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]) criteria. The original PDRT cutoffs detected between 20 and 50% of malingering TBI patients with a false positive error rate of 5% or less. When the false positive error rate was held at 5%, across all item sets, sensitivity was as high as 70%. The results show that the original PDRT cutoffs are conservative and that higher scores detect more MND patients without causing the false positive error rate to become unacceptably high. Clinical application and future research needs are discussed.     

Sensitivity and Specificity of MMPI-2 Validity Scales and Indicators to Malingered Neurocognitive Dysfunction in Traumatic Brain Injury

The present study used a known-groups design to determine the classification accuracy of 10 MMPI-2 validity scales and indicators in the detection of cognitive malingering in traumatic brain injury. Participants were 259 traumatic brain injury and 133 general clinical patients seen for neuropsychological evaluation. The TBI patients were subdivided into groups based on a comprehensive examination of effort following Slick, Sherman, and Iverson's (1999 Slick , D. J. , Sherman , E. M. S. , & Iverson , G. L. ( 1999 ). Diagnostic criteria for malingering neurocognitive dysfunction: Proposed standards for clinical practice and research . The Clinical Neuropsychologist , 13 , 545 – 561 . [INFOTRIEVE] [CSA] [Taylor & Francis Online], [Web of Science ®] , [Google Scholar]) criteria. More extreme scores demonstrated excellent specificity; often impressive sensitivity was seen even while maintaining a low false positive error rate. Specificity was good even in stroke, memory disorder, and psychiatric patients without incentive. The results of this study are presented in frequency tables that can be easily referenced in clinical practice.