Ultra-Violet Light Emission from HPV-G Cells Irradiated with Low Let Radiation From 90Y; Consequences for Radiation Induced Bystander Effects

In this study, we aimed to establish the emission of UV photons when HPV-G cells and associated materials (such as the cell substrate and cell growth media) are exposed to low LET radiation. The potential role of UV photons in the secondary triggering of biological processes led us to hypothesize that the emission and absorption of photons at this wavelength explain some radiation induced “bystander effects” that have previously been thought to be chemically mediated. Cells were plated in Petri-dishes of two different sizes, having different thicknesses of polystyrene (PS) substrate, and were exposed to β-radiation from ⁹⁰Y produced by the McMaster Nuclear Reactor. UV measurements were performed using a single photon counting system employing an interference-type filter for selection of a narrow wavelength range, 340±5 nm, of photons. Exposure of the cell substrates (which were made of polystyrene) determined that UV photons were being emitted as a consequence of β particle irradiation of the Petri-dishes. For a tightly collimated β-particle beam exposure, we observed 167 photons in the detector per unit μCi in the shielded source for a 1.76 mm thick substrate and 158 photons/μCi for a 0.878 mm thick substrate. A unit μCi source activity was equivalent to an exposure to the substrate of 18 β-particles/cm² in this case. The presence of cells and medium in a Petri-dish was found to significantly increase (up to a maximum of 250%) the measured number of photons in a narrow band of wavelengths of 340±5 nm (i.e. UVA) as compared to the signal from an empty control Petri-dish. When coloured growth medium was added to the cells, it reduced the measured count rate, while the addition of transparent medium in equal volume increased the count rate, compared to cells alone. We attribute this to the fact that emission, scattering and absorption of light by cells and media are all variables in the experiment. Under collimated irradiation conditions, it was observed that increasing cell density in medium of fixed volume resulted in a decrease in the observed light output. This followed a roughly exponential decline. We suggest that this may be due to increased scattering at the cell boundary and absorption of the UV in the cells. We conclude that we have measured UVA emitted by cells, cell medium and cell substrates as a consequence of their irradiation by low LET β-particle radiation. We suggest that these secondary UV photons could lead to effects in non-targetted cells. Some effects that had previously been attributed to a chemically mediated “bystander effect” may in fact be due to secondary UV emission. Some radiation bystander effect studies may require re-interpretation as this phenomenon of UV emission is further investigated.     

A Qualitative Analysis of Vaccine Safety Perceptions and Concerns Among Caretakers in Uganda

Parents and caretakers of young children often have concerns about vaccine safety and adverse events following immunization (AEFI). Little is known about vaccine safety perceptions in Uganda and their influence on parental decision-making about infant immunization. The study objectives were: to identify community sources of information on immunization, vaccine safety and AEFI; determine caretakers?? knowledge of immunization; identify community concerns/fears about immunization and AEFI and their influence on caretakers?? decisions to vaccinate; and obtain an understanding of knowledge, perceptions, and experience of health care workers (HCWs) and policy administrators on vaccine safety and AEFI. Twelve focus group discussions with 136 caretakers who were very or somewhat concerned about vaccine safety and 25 key informant interviews were conducted in two districts (1 urban and 1 rural) with district authorities and health facility staff as well as national level decision-makers between December and April 2006. Content analysis was used to analyze the results. The main themes identified related to general lack of information among caretakers about immunization, perceived immunization benefits, immunization concerns, and misconceptions. Specific caretaker concerns related to vaccine administration, immunization services and vaccine safety. Experiences with AEFI and concerns about vaccine safety negatively affected caretakers?? decisions to vaccinate their children, notably in rural areas. HCWs demonstrated knowledge about AEFI and their management although incidences reported to facilities were rare. Inadequate communication between HCWs and caretakers was noted. Concerns and misconceptions about vaccination still exist among caretakers in Uganda and influence decisions to vaccinate. Effective inter personal communication initiated by HCWs towards caretakers is needed.     

Automatic blood pressure measurement: the oscillometric waveform shape is a potential contributor to differences between oscillometric and auscultatory pressure measurements

OBJECTIVE: To explore the differences between oscillometric and auscultatory measurements. METHOD: From a simulator evaluation of a non-invasive blood pressure (NIBP) device regenerating 242 oscillometric blood pressure waveforms from 124 subjects, 10 waveforms were selected based on the differences between the NIBP (oscillometric) and auscultatory pressure measurements. Two waveforms were selected for each of five criteria: systolic over and underestimation; diastolic over and underestimation; and close agreement for both systolic and diastolic pressures. The 10 waveforms were presented to seven different devices and the oscillometric-auscultatory pressure differences were compared between devices and with the oscillometric waveform shapes. RESULTS: Consistent patterns of waveform-dependent over and underestimation of systolic and diastolic pressures were shown for all seven devices. The mean and standard deviation, for all devices, of oscillometric-auscultatory pressure differences were: for the systolic overestimated waveforms, 36 +/- 28/-6 +/- 3 and 23 +/- 2/-1 +/- 3 mmHg (systolic/diastolic differences); for systolic underestimated waveforms, -21 +/- 5/-4 +/- 3 and -11 +/- 4/-3 +/- 3 mmHg; for diastolic overestimated waveforms, 3 +/- 4/12 +/- 5 and 17 +/- 6/10 +/- 2 mmHg; for diastolic underestimated waveforms, 1 +/- 4/-22 +/- 4 and -9 +/- 6/-29 +/- 4 mmHg; and for the two waveforms with good agreement, 0 +/- 6/0 +/- 3 and -2 +/- 4/-4 +/- 3 mmHg. Waveforms for which devices showed good oscillometric and auscultatory agreement had smooth envelopes with clearly defined peaks, compared with the broader plateau and complex shapes of those waveforms for which devices over or underestimated pressures. CONCLUSION: By increasing the understanding of the characteristics and limitations of the oscillometric method and the effects of waveform shape on pressure measurements, simulator evaluation should lead to improvements in NIBP devices.     

Periscope Proteins are variable-length regulators of bacterial cell surface interactions

Changes at the cell surface enable bacteria to survive in dynamic environments, such as diverse niches of the human host. Here, we reveal “Periscope Proteins” as a widespread mechanism of bacterial surface alteration mediated through protein length variation. Tandem arrays of highly similar folded domains can form an elongated rod-like structure; thus, variation in the number of domains determines how far an N-terminal host ligand binding domain projects from the cell surface. Supported by newly available long-read genome sequencing data, we propose that this class could contain over 50 distinct proteins, including those implicated in host colonization and biofilm formation by human pathogens. In large multidomain proteins, sequence divergence between adjacent domains appears to reduce interdomain misfolding. Periscope Proteins break this “rule,” suggesting that their length variability plays an important role in regulating bacterial interactions with host surfaces, other bacteria, and the immune system.

Bacteria encounter complex and dynamic environments, including within human hosts, and have thus evolved various mechanisms that enable a rapid response for survival within, and exploitation of, new conditions. In addition to classical control by regulation of gene expression, bacteria exploit mechanisms that give rise to random variation to facilitate adaptation [e.g., phase and antigenic variation (1)]. In Gram-positive and Gram-negative human pathogens, DNA inversions (2, 3), homologous recombination (4), DNA methylation (1), and promoter sequence polymorphisms (5) govern changes in bacterial surface components, including capsular polysaccharide and protein adhesins, which can impact bacterial survival and virulence in the host (1, 6). Many of these mechanisms are very well studied and widespread across bacteria.A less well-studied mechanism is length variation in bacterial surface proteins. Variability in the number of sequence repeats in the Rib domain (7)–containing proteins on the surface of Group B streptococci has been linked to pathogenicity and immune evasion (8). The repetitive regions of the Staphylococcus aureus surface protein G (SasG) (9) and Staphylococcus epidermidis SasG homolog, Aap (10), also demonstrate sequence repeat number variability. In SasG, this variability regulates ligand binding by other bacterial proteins in vitro (11) in a process that has been proposed to enable bacterial dissemination in the host. Variations in repeat number have also been noted in the biofilm forming proteins Esp from Enterococcus faecalis (12) and, more recently, CdrA from Pseudomonas aeruiginosa (13). High DNA sequence identity in the genes that encode these proteins is likely to facilitate intragenic recombination events that would lead to repeat number variation (14) and, in turn, to protein sequence repetition. However, such sequence repetition is usually highly disfavored in large multidomain proteins (15), so its existence in these bacterial surface proteins suggests that protein length variation provides an evolutionary benefit. SasG, Aap, and Rib contain N-terminal host ligand binding domains and C-terminal wall attachment motifs; thus our recent demonstration that the repetitive regions of both SasG (16) and Rib (17) form unusual highly elongated rods suggests that host-colonization domains will be projected differing distances from the bacterial surface.Here, we show that repeat number variation in predicted bacterial surface proteins is more widespread and we characterize a third rod-like repetitive region in the Streptococcus gordonii protein (Sgo_0707) formed by tandem array of Streptococcal High Identity Repeats in Tandem (SHIRT) domains. Thus, we propose a growing class of “Periscope Proteins,” in which long, highly similar DNA repeats facilitate expression of surface protein stalks of variable length. This mechanism could enable changes in response to selection pressures and confer key advantages to the organism that include evasion of the host immune system (8) and regulation of surface interactions (11) involved in biofilm formation and host colonization.     

Economic evaluation of a randomised trial of early return to normal activities versus cardiac rehabilitation after acute myocardial infarction

Background: Although there have been a number of economic evaluations of cardiac rehabilitation after acute myocardial infarction (AMI), none has considered only low-risk patients or control groups with no rehabilitation at all.Methods: An economic evaluation was included in a randomised controlled trial of patients following uncomplicated AMI. Eligible patients were randomised to return to normal activities after 6 weeks of standard rehabilitation (REHAB, n = 70) or to early return to normal activities 2 weeks after AMI with no formal rehabilitation (ERNA, n = 72). Outcomes were assessed weekly for 6 weeks, then 3, 6 and 12 months post-AMI. Outcomes included four quality of life (QOL) measures (physical abilities, distress, usual/social activities, self-care) and four measures of return to normal activities (paid and unpaid return to any work and to pre-AMI level of work). Statistical analysis included repeated-measures regression (QOL outcomes) and survival analysis (work outcomes).Results: There were no statistically significant differences between the two groups in any of the outcomes measured or in the use of other health services. The net cost that could be saved by the health service by targeting rehabilitation to high-risk patients was approximately $300 (Australian, 1999) per low-risk patient.Conclusions: Early return to normal activities without formal rehabilitation is cost-effective for low-risk patients.     

Autonomic cardiovascular responses are impaired in women with irritable bowel syndrome

GOALS: This study characterizes cardiovascular autonomic function in women with irritable bowel syndrome (IBS), using standardized techniques. BACKGROUND: Autonomic dysfunction is believed to contribute to abnormal gastrointestinal motility and visceral hypersensitivity in IBS. There is mounting evidence of generalized impairment of autonomic activity in patients with IBS. STUDY: Thirty women aged 39 years (95% C.I. 25-53 years) diagnosed with IBS, and 30 age-matched healthy women were studied. The ratio of low frequency to high frequency heart rate variability domains (LF:HF ratio) was used to represent cardiac sympathovagal activity, and orthostatic testing and sustained isometric handgrip exercise were used as sympathetic stimuli. Parasympathetic activity was represented by the expiratory to inspiratory R-R interval (E:I) ratio during deep breathing at 6 minutes. RESULTS: LF:HF responses to handgrip exercise (316%, C.I. 134% to 498% vs. 107%, C.I. 15% to 153%; P < 0.05) and orthostatic testing (648%, C.I. 520% to 904% vs. 330%, C.I. 140% to 520%; P < 0.05) were higher in IBS patients than controls, and the E:I ratio was significantly lower (1.47, C.I. 1.33-1.61 vs. 1.20, C.I. 1.14-1.26; P < 0.01). CONCLUSIONS: Autonomic cardiovascular function is impaired in IBS, manifest as attenuated cardio-vagal tone, and relative sympathetic excess during stimulated conditions.     

Repair of erosions in rheumatoid arthritis does occur. Results from 2 studies by the OMERACT Subcommittee on Healing of Erosions

The committee was charged with determining whether healing of erosions in rheumatoid arthritis (RA) occurs. Two exercises were performed: The first asked the committee members, as a panel of experts, to express agreement or disagreement with the presence of improvement and features of bone reaction to injury in images submitted by members as examples of healing. The second presented panel members with 28 pairs of serial images, 14 chosen to illustrate progression and 14 chosen to illustrate repair. Agreement was tested on 8 items: global judgment on which image in the pair was better, relative size of the erosion in the 2 images, judgment on which image was first, presence and extent of sclerosis, cortication, filling-in, remodeling, and reconstituting normal structure. Our results showed good agreement, among the 15 respondents, on global assessment of which image was better and which image showed the smaller erosion. Correct assignment of sequence was only slightly better than expected by chance (in 65% of the cases). Agreement was poor regarding the presence of morphologic features of bone repair. A majority of a panel of experts agreed on which 2nd images in a set of paired, serial images represented improvement and which showed progression based on global assessment of which was better and on size of erosion. Features of bone repair were not distinctive and did not enable the panel to deduce the correct sequence of the serial images. This study provides evidence that repair of bone damage in RA does occur, resulting in some degree of improvement, which was recognized by a majority of a panel of experts.