Intranasal vaccination with an adjuvanted Norwalk virus-like particle vaccine elicits antigen-specific B memory responses in human adult volunteers

Noroviruses are the most frequent cause of acute gastroenteritis in humans of all ages. No vaccines are currently available. An intranasally delivered Norwalk (NV) virus-like particle (VLP) vaccine was recently shown to be well tolerated, immunogenic and to protect against infection in Phase 1 studies. Here, we examined B memory (B(M)) responses in volunteers who received the highest dosage levels of the NV-VLP vaccine (50 μg and 100 μg). We measured the frequency of NV-specific IgG and IgA-secreting B(M) cells in peripheral blood and the level of antibodies produced by these cells in culture. All subjects immunized with 100 μg of the NV-VLP vaccine and 90% of those who received 50 μg had significant IgA or IgG B(M) responses. The B(M) cell frequencies correlated with serum antibody levels and mucosally-primed antibody-secreting cell responses. This is the first demonstration of dose-dependent, functional B(M) responses in humans immunized intranasally with a NV-VLP vaccine.     

Resistance to ciprofioxacin in non-typhoidal salmonellas from humans in England and Wales—the current situation

Objective: To report on the prevalence of isolates with ciprofloxacin resistance in non-typhoidal salmonellas from humans in England and Wales in 1997.
Methods: All non-typhoidal salmonellas referred to the Laboratory of Enteric Pathogens in 1997 were screened for resistance to ciprofloxacin at 0.125 and 1.0 mg/L and nalidixic acid at 16 mg/L, and results were compared to those for 1994. Full minimal inhibitory concentrations (MICs) of these antimicrobials were also determined for a selection of isolates resistant to ciprofloxacin at 0.125 mg/L but sensitive at 1.0 mg/L, and for all isolates resistant at 1.0 mg/L.
Results: Since 1994 there have been increases in the occurrence of resistance to ciprofloxacin (MICs: 0.25–1.0 mg/L) in Salmonella enterica serotypes Enteritidis, Typhimurium, Virchow and Hadar. Of particular importance have been increases in the occurrence of resistance in multiresistant S. Typhimurium DT 104, and also in S. virchow, a serotype with a propensity for causing extraintestinal infections in humans. High-level resistance (MIC≥2.0 mg/L) was uncommon and was identified in only a few strains, all from patients with a history of recent foreign travel.
Conclusions: There is a strong temporal association between increases in the occurrence of ciprofloxacin resistance in Salmonella serotypes Typhimurium, Virchow and Hadar from humans in England and Wales and with the licensing for use in food animals in the UK of the related fluoroquinolone antibiotic enrofloxacin; in contrast, for S. enteritidis ciprofloxacin resistance was most common in a phage type associated with foreign travel. It is hoped that recent recommendations for the use of fluoroquinolone antimicrobials in food animals in the UK will result in a reduction in the occurrence of resistance to ciprofloxacin in zoonotic salmonellas causing infections in humans.     

Childhood swine flu vaccination uptake in a Welsh general practice: a prospective study

Background

Immunisation of infants is effective and benefits the health of the children immunised as well as the community where uptake is high. Any social inequality in uptake will worsen any social inequalities that already exist.

Aim

To investigate the demographic characteristics of families attending for swine flu vaccination.

Design and setting

A prospective study in a semi-rural general practice in South Wales.

Method

Data were collected by questionnaire, and logistic regression models were used to test for associations between potential risk factors (including family demographic characteristics and the child''s previous vaccination history) and swine flu vaccination uptake.

Results

No evidence was found of any significant associations between potential risk factors and the outcome.

Conclusion

This suggests that social inequality did not affect vaccination uptake in this sample.     

Eosinophils: multifaceted biological properties and roles in health and disease

Eosinophils are leukocytes resident in mucosal tissues. During T-helper 2 (Th2)-type inflammation, eosinophils are recruited from bone marrow and blood to the sites of immune response. While eosinophils have been considered end-stage cells involved in host protection against parasite infection and immunopathology in hypersensitivity disease, recent studies changed this perspective. Eosinophils are now considered multifunctional leukocytes involved in tissue homeostasis, modulation of adaptive immune responses, and innate immunity to certain microbes. Eosinophils are capable of producing immunoregulatory cytokines and are actively involved in regulation of Th2-type immune responses. However, such new information does not preclude earlier observations showing that eosinophils, in particular human eosinophils, are also effector cells with proinflammatory and destructive capabilities. Eosinophils with activation phenotypes are observed in biological specimens from patients with disease, and deposition of eosinophil products is readily seen in the affected tissues from these patients. Therefore, it would be reasonable to consider the eosinophil a multifaceted leukocyte that contributes to various physiological and pathological processes depending on their location and activation status. This review summarizes the emerging concept of the multifaceted immunobiology of eosinophils and discusses the roles of eosinophils in health and disease and the challenges and perspectives in the field.     

Nasal Septal and Premaxillary Developmental Integration: Implications for Facial Reduction in Homo

The influence of the chondrocranium in craniofacial development and its role in the reduction of facial size and projection in the genus Homo is incompletely understood. As one component of the chondrocranium, the nasal septum has been argued to play a significant role in human midfacial growth, particularly with respect to its interaction with the premaxilla during prenatal and early postnatal development. Thus, understanding the precise role of nasal septal growth on the facial skeleton is potentially informative with respect to the evolutionary change in craniofacial form. In this study, we assessed the integrative effects of the nasal septum and premaxilla by experimentally reducing facial length in Sus scrofa via circummaxillary suture fixation. Following from the nasal septal‐traction model, we tested the following hypotheses: (1) facial growth restriction produces no change in nasal septum length; and (2) restriction of facial length produces compensatory premaxillary growth due to continued nasal septal growth. With respect to hypothesis 1, we found no significant differences in septum length (using the vomer as a proxy) in our experimental (n = 10), control (n = 9) and surgical sham (n = 9) trial groups. With respect to hypothesis 2, the experimental group exhibited a significant increase in premaxilla length. Our hypotheses were further supported by multivariate geometric morphometric analysis and support an integrative relationship between the nasal septum and premaxilla. Thus, continued assessment of the growth and integration of the nasal septum and premaxilla is potentially informative regarding the complex developmental mechanisms that underlie facial reduction in genus Homo evolution. Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.     

Human sex differences in d‐amphetamine self‐administration

Women and men may respond differently to the effects of stimulants such as amphetamine and cocaine. Aim In order to assess potential sex differences in the reinforcing effects of d‐amphetamine, a retrospective‐analysis was conducted on data collected from three studies that employed similar d‐amphetamine self‐administration procedures and used identical subject‐rated drug‐effect measures. Methods Data from 10 women and 15 men were included in the analysis. In all studies, participants sampled placebo, low (8–10 mg) or high (16–20 mg) dose oral d‐amphetamine. Following sampling sessions, participants worked for capsules containing one eighth of the previously sampled dose on a modified progressive‐ratio schedule of reinforcement. We hypothesized that women and men would be differentially sensitive to the reinforcing effects of d‐amphetamine. A two‐way mixed‐model analysis of variance (sex and dose) and planned comparisons were used in the statistical analyses. Results The low dose of d‐amphetamine functioned as a reinforcer in women, but not men, whereas the high dose of d‐amphetamine functioned as a reinforcer in men, but not women. Men self‐administered significantly more capsules under the high dose condition than women. Conclusion The results of this study suggest that men are more sensitive to the reinforcing effects of a high dose of d‐amphetamine than women. Future research is needed that determines prospectively the reinforcing effects of weight‐adjusted doses of d‐amphetamine in women and men while controlling for menstrual cycle phase.     

Effects of tryptophan depletion on central and peripheral chemoreflexes in man

Klein (Arch. Gen. Psychiatry 50, 306-317, 1993) suggests that panic attacks are the result of a defective 'suffocation alarm' threshold that presents with carbon dioxide (CO(2)) hypersensitivity, exaggerated ventilatory response and panic in panic disorder (PD) patients. Serotonergic deficiencies enhance this ventilatory response in PD patients, as per 'suffocation alarm' theory predictions, suggesting that serotonin (5-HT) normalizes the ventilatory response. Other research supports a serotonin system-mediated stimulation of ventilation. Knowledge of 5-HT's role on ventilatory output and its neurophysiological sources impacts on the 'suffocation alarm' theory validity and predictive value. We used tryptophan depletion (TRP-) in concert with a modified Read rebreathing test to determine the effect of deficient serotonergic modulation on the central and peripheral chemoreflex threshold and sensitivity of response to CO(2) in 11 healthy men. TRP- did not affect central or peripheral chemoreflex threshold or sensitivity of response to CO(2). However, basal ventilation was significantly elevated during TRP-. In contrast to 'suffocation alarm' theory predictions, decreased 5-HT neurotransmission does not significantly affect the respiratory chemoreflex response to CO(2), impacting on non-chemoreflex drives to breathe. Panic associated respiratory abnormalities may be related to defective 5-HT modulation of non-chemoreflex drives to breathe, unrelated to any respiratory chemoreflex abnormality.     

Oxygen uptake kinetics during high-intensity arm and leg exercise

The purpose of the present study was to examine the oxygen uptake kinetics during heavy arm exercise using appropriate modelling techniques, and to compare the responses to those observed during heavy leg exercise at the same relative intensity. We hypothesised that any differences in the response might be related to differences in muscle fibre composition that are known to exist between the upper and lower body musculature. To test this, ten subjects completed several bouts of constant-load cycling and arm cranking exercise at 90% of the mode specific V(O(2)) peak. There was no difference in plasma [lactate] at the end of arm and leg exercise. The time constant of the fast component response was significantly longer in arm exercise compared to leg exercise (mean+/-S.D., 48+/-12 vs. 21+/-5 sec; P < 0.01), while the fast component gain was significantly greater in arm exercise (12.1+/-1.0 vs. 9.2+/-0.5 ml min(-1) W(-1); P < 0.01). The V(O(2)) slow component emerged later in arm exercise (126+/-27 vs. 95+/-20 sec; P < 0.01) and, in relative terms, increased more per unit time (5.5 vs. 4.4% min(-1); P < 0.01). These differences between arm crank and leg cycle exercise are consistent with a greater and/or earlier recruitment of type II muscle fibres during arm crank exercise.     

A simple breathing circuit to maintain isocapnia during measurements of the hypoxic ventilatory response

We report the development and testing of a simple breathing circuit that maintains isocapnia in human subjects during hypoxic hyperpnea. In addition, the circuit permits rapid switching between two gas mixtures with different partial pressures of oxygen. Eleven volunteers breathed repeated cycles of exposure to air (2 min of 21% O(2), balance N(2)) and hypoxia (2 min of 8.3+/-0.1% O(2), balance N(2)). Hypoxia induced significant increases in minute ventilation, breathing frequency and tidal volume (P < 0.05) that were consistent over repeated cycles of hypoxia (P > 0.1, one-way ANOVA). The system successfully maintained isocapnia in all subjects, with an average change in end-tidal CO(2) of only -0.2 mmHg during hyperventilation in hypoxia (range 0.4 to -0.8 mmHg). This system may be suitable for repeated tests of the hypoxic ventilatory response (HVR) and may prove useful for exploring intra- and inter-individual variability of HVR in humans.     

Condylar process contributes to mandibular asymmetry: In vivo 3D MRI study

The purpose of this study was to investigate the differences in mandibular morphology between the deviated and nondeviated sides in patients with noncongenital skeletal mandibular asymmetry. Divergences from control values were assessed to determine which region of the mandible contributes most to mandibular asymmetry. We measured various dimensions of the mandible in 20 young patients and 20 controls using noninvasive high‐quality three‐dimensional (3D) volumetric magnetic resonance imaging. Mandibular dimensions including the length of the condylar process were significantly greater on the nondeviated side of patients than the deviated side. Measurements of the deviated side were similar to control values, but measurements of the nondeviated side including condylar process length differed significantly from control values. These findings strongly suggest that overgrowth of the condylar process on the nondeviated side in these patients results in mandibular asymmetry, and therefore needs attention in orthodontic treatment, orthognathic surgery, and follow‐up. Clin. Anat. 585–591, 2014. © 2013 Wiley Periodicals, Inc.