Vaccine‐Induced Antibody Responses Prevent the Induction of Interferon Type I Responses Upon a Homotypic Live Virus Challenge

During acute viral infections, innate immunity provides essential protective measures to minimize virus dissemination and regulate adaptive immunity. This helps to successfully eliminate the pathogen and establish long‐term memory. Here, we investigated the effect of vaccine‐induced antibody responses on the induction of IFN‐I responses and the associated lymphocyte activation using influenza A virus vaccination and challenge models. Mice were vaccinated with gamma‐irradiated influenza A virus (γ‐FLU) and challenged three weeks later with live virus. Our data show a significant reduction in IFN‐I responses and lymphocyte activation following a homotypic virus challenge. We confirmed the role of vaccine‐induced antibody responses in the observed impairment of IFN‐I and the associated lymphocyte activation using adoptive transfer of immune sera and the administration of sera‐treated viruses prior to challenge. Overall, we addressed a fundamental concept in immunology and provided experimental data illustrating the inhibition of IFN‐I responses in vaccinated animals upon a homotypic virus challenge.     

Automated whole‐brain N‐acetylaspartate proton MRS quantification

Concentration of the neuronal marker, N‐acetylaspartate (NAA), a quantitative metric for the health and density of neurons, is currently obtained by integration of the manually defined peak in whole‐head proton (¹H)‐MRS. Our goal was to develop a full spectral modeling approach for the automatic estimation of the whole‐brain NAA concentration (WBNAA) and to compare the performance of this approach with a manual frequency‐range peak integration approach previously employed. MRI and whole‐head ¹H‐MRS from 18 healthy young adults were examined. Non‐localized, whole‐head ¹H‐MRS obtained at 3 T yielded the NAA peak area through both manually defined frequency‐range integration and the new, full spectral simulation. The NAA peak area was converted into an absolute amount with phantom replacement and normalized for brain volume (segmented from T₁‐weighted MRI) to yield WBNAA. A paired‐sample t test was used to compare the means of the WBNAA paradigms and a likelihood ratio test used to compare their coefficients of variation. While the between‐subject WBNAA means were nearly identical (12.8 ± 2.5 mm for integration, 12.8 ± 1.4 mm for spectral modeling), the latter's standard deviation was significantly smaller (by ~50%, p = 0.026). The within‐subject variability was 11.7% (±1.3 mm ) for integration versus 7.0% (±0.8 mm ) for spectral modeling, i.e., a 40% improvement. The (quantifiable) quality of the modeling approach was high, as reflected by Cramer–Rao lower bounds below 0.1% and vanishingly small (experimental ‐ fitted) residuals. Modeling of the whole‐head ¹H‐MRS increases WBNAA quantification reliability by reducing its variability, its susceptibility to operator bias and baseline roll, and by providing quality‐control feedback. Together, these enhance the usefulness of the technique for monitoring the diffuse progression and treatment response of neurological disorders. Copyright © 2014 John Wiley & Sons, Ltd.     

Mild-to-moderate obesity: implications for respiratory mechanics at rest and during exercise in young men

OBJECTIVE: To investigate the effect of mild-to-moderate obesity on respiratory mechanics at rest and during exercise in obese men. We hypothesized that the simple mass loading of obesity would alter both end-expiratory lung volume (EELV) and respiratory pressures (gastric, P(ga) and transpulmonary, P(TP)) in resting body positions and during graded cycle ergometry to exhaustion. SUBJECTS: A total of 10 obese (38+/-5% body fat; mean+/-s.d.) and nine lean (18+/-4%) men were studied. METHODS: Body composition (by body circumferences and hydrostatic weighing) and pulmonary function were measured at rest. Breathing mechanics were measured at rest in the upright-seated position, supine, and during cycling exercise. Data were analyzed by independent t-test. RESULTS: EELV was significantly lower in the obese men in the supine (30+/-4 vs 37+/-6% total lung capacity (TLC)) and seated (39+/-6 vs 47+/-5%TLC) positions and at ventilatory threshold (35+/-5 vs 45+/-7%TLC) (P<0.01). In contrast, at peak exercise, EELV was not different between groups. Respiratory pressures (P(ga) and P(TP)) were elevated (P<0.05) during one or more phases of the breathing cycle at rest and during exercise in obese men. CONCLUSION: These data demonstrate that mild-to-moderate obesity in young men results in reduced lung volumes and alterations in respiratory mechanics when supine, seated at rest, and during exercise. During moderate exercise, obesity does not appear to limit changes in EELV; however, the regulation of EELV during heavy exercise appears to be affected.     

Bioethical considerations of monoclonal B-cell lymphocytosis: donor transfer after haematopoietic stem cell transplantation

Monoclonal B-cell lymphocytosis (MBL) is a recently described laboratory finding in otherwise healthy individuals. In MBL, a light chain-restricted, clonal B-cell population, often with a chronic lymphocytic leukaemia (CLL) phenotype, is identified by flow cytometry. Although the prognostic significance remains unclear, there is an increased incidence in ageing populations and those with a family history of CLL. During the past decade of MBL study, three families have come to our attention in which prospective sibling haematopoietic stem cell donors were found to have an MBL. These families raise complex bioethical issues with regard to disclosure of research data, eligibility for clinical trials and potential donor transfer of MBL. These issues are explored in this report. Identification of MBL among prospective sibling transplant donors will become a common occurrence in transplant practice as transplantation is increasingly offered to older individuals and those with CLL.     

Airflow limitation and control of end-expiratory lung volume during exercise

To test the hypothesis that the presence of airflow limitation (AFL) influences the control of end-expiratory lung volume (EELV) during exercise, 11 subjects with normal lung function, performed submaximal exercise (SM) on a cycle ergometer, with and without AFL. AFL was achieved during exercise by increasing the density of the air via a hyperbaric chamber, compressed to a depth of 3 atm (3 ATA; with AFL). Five subjects achieved AFL during SM exercise at 3 ATA while the remaining six subjects did not achieve AFL. SM exercise was performed with the same apparatus in the hyperbaric chamber at sea level pressure with none of the subjects achieving AFL (SL; no-AFL). EELV (% of TLC, BTPS), was significantly larger during exercise at 3 ATA than during exercise at SL for the AFL group (SL = 44 +/- 6%; 3 ATA-AFL = 51 +/- 9%, P < 0.05; but, was not for the no-AFL group (SL = 46 +/- 6%; 3 ATA-no AFL = 46 +/- 7%). End inspiratory lung volume was significantly elevated during exercise at 3 ATA compared with SL in the AFL group (SL = 80 +/- 6%; 3 ATA-AFL = 86 +/- 6%; P = 0.01) but not in the no-AFL group (SL = 82 +/- 4%; 3 ATA-no AFL = 84 +/- 4%). Tidal volume and ventilation were not different for any condition. These data suggest that the occurrence of AFL influences the control of EELV.     

Creating a business backbone. A first person recount of the planning process involved in laying the foundation of a successful rehabilitation clinic

Opening your own outpatient therapy center will likely seem an insurmountable task at times. Broken down into the stages of mission establishment, planning and goal setting, establishing financial viability, choosing equipment, promoting your product, and, finally, hiring staff, this task will become less onerous. Remember, it is your practice. True to your vision, and just like high school, be prepared for an emotional roller-coaster ride. Done correctly, this experience will be just as thrilling and ultimately much more gratifying.     

Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets

Interleukin-7 (IL-7) is a homeostatic cytokine for resting T cells with increasing serum and tissue levels during T cell depletion. In preclinical studies, IL-7 therapy exerts marked stimulating effects on T cell immune reconstitution in mice and primates. First-in-human clinical studies of recombinant human IL-7 (rhIL-7) provided the opportunity to investigate the effects of IL-7 therapy on lymphocytes in vivo. rhIL-7 induced in vivo T cell cycling, bcl-2 up-regulation, and a sustained increase in peripheral blood CD4(+) and CD8(+) T cells. This T cell expansion caused a significant broadening of circulating T cell receptor (TCR) repertoire diversity independent of the subjects' age as naive T cells, including recent thymic emigrants (RTEs), expanded preferentially, whereas the proportions of regulatory T (T reg) cells and senescent CD8(+) effectors diminished. The resulting composition of the circulating T cell pool more closely resembled that seen earlier in life. This profile, distinctive among cytokines under clinical development, suggests that rhIL-7 therapy could enhance and broaden immune responses, particularly in individuals with limited naive T cells and diminished TCR repertoire diversity, as occurs after physiological (age), pathological (human immunodeficiency virus), or iatrogenic (chemotherapy) lymphocyte depletion.     

The effects of cochlear implantation on speech perception in older adults

OBJECTIVES: To determine whether significant differences in cochlear implant (CI) performance exist between older and younger CI recipients. DESIGN: Retrospective comparison of audiometric data. SETTING: University hospital center. PARTICIPANTS: Sixty participants who received CIs at age 70 and older and 48 younger adults implanted between age 18 and 69. MEASUREMENTS: Speech outcome scores (Consonant‐Nucleus‐Consonant words and phonemes and City University of New York Sentence test in quiet and noise). RESULTS: Older participants show significant improvement in speech perception scores after implantation. Although on average they do not perform as well as younger adults, this difference correlates with duration of deafness rather than age. In contrast to younger adults, significant differences in CI performance are seen in older recipients depending on the side of implantation, with those implanted on the right performing better than those implanted on the left. CONCLUSION: Postlingually deafened older adults obtained significant speech perception benefits from CIs, although differences in speech outcomes were seen between younger recipients and those implanted after age 70. In older adults considering CIs, hearing benefits appear greater if they are implanted in the right ear.     

Frequency of Intraductal Papillary Mucinous Neoplasm in Patients with and without Pancreas Cancer

Purpose: To determine the frequency of intraductal papillary mucinous neoplasm (IPMN) in patients with and without invasive ductal adenocarcinoma (IDAC). Methods: 82 patients underwent pancreatectomy for pancreas adenocarcinoma. 68/82 subjects underwent at least one preoperative imaging study including CT (n = 43), MRI (n = 25), or both (n = 12). Imaging studies were retrospectively evaluated to determine if IPMN was present in the gland at a location distant from IDAC. In 183 different adult patients undergoing MRI for renal mass, images were evaluated to determine the frequency of IPMN. Fisher's exact test was used to test whether the prevalence of IPMN was greater among patients with pancreas cancer than those without. Results: Five of 68 (7.3%) patients who underwent pancreatic resection for IDAC had IPMN at a site distant from the cancer. Two of 182 (1.1%) patients undergoing MRI for renal cancer had imaging evidence of IPMN. There was a significant difference (p = 0.017) in the prevalence of IPMN between patients with and without IDAC. The odds ratio for IPMN as a predictor of pancreas cancer was estimated as 7.18. Conclusion: IPMN occurs with increased frequency in patients with pancreas cancer as opposed to those without pancreas cancer.