Optimization of sniff nasal inspiratory pressure (SNIP) measurement methodology in healthy subjects.

BACKGROUND: Maximal inspiratory pressure (MIP) is currently the most commonly used measure for respiratory muscle strength (RMS) estimation, however, requires significant effort. Falsely low values are therefore common, especially in fatigue-prone subjects, such as neuromuscular disorder patients. In contrast, sniff nasal inspiratory pressure (SNIP) requires a short, sharp sniff; this is a natural manoeuvre, decreasing required effort. Consequently, it has been suggested that use of SNIP could confirm the accuracy of MIP measurements. However, no recent guidelines regarding the optimal method of SNIP measurement exist, and varied approaches have been described. OBJECTIVES: We compared SNIP values from three conditions, namely with 30, 60 or 90 s time intervals between repeats, the right (SNIPR) and left (SNIPL) nostril, and the contralateral nostril occluded (SNIPO) or non-occluded (SNIPNO). Additionally, we determined the optimal number of repeats for accurate SNIP measurement. METHOD: 52 healthy subjects (23 males) were recruited for this study, of which a subset of 10 subjects (5 males) completed tests comparing the time interval between repeats. SNIP was measured from functional residual capacity via a probe in one nostril, while MIP was measured from residual volume. RESULTS: There was no significant difference in SNIP depending on the interval between repeats (P = 0.98); subjects preferred the 30 s. SNIPO was significantly higher than SNIPNO (P < 0.00001) but SNIPL and SNIPR did not significantly differ (P = 0.60). There was an initial learning effect for the first SNIP test; SNIP did not decline during 80 repeats (P = 0.64). CONCLUSIONS: We conclude that SNIPO is a more reliable RMS indicator than SNIPNO, as there is reduced risk of RMS underestimation. Allowing subjects to choose which nostril to use is appropriate, as this did not significantly affect SNIP, but may increase ease of performance. We suggest that twenty repeats is sufficient to overcome any learning effect and that fatigue is unlikely after this number of repeats. We believe these results are important in aiding the accurate collection of SNIP reference value data in the healthy population.

Advances in the management of TTP.

Thrombotic thrombocytopenic purpura is an acute life-threatening disorder, associated with a mortality of 90% if unrecognised and untreated. The hallmark is thrombocytopenia and microangiopathic hemolytic anemia, with a blood film characterised by fragmented red cells and end organ damage. The mainstay of treatment is ADAMTS13 replacement, currently with plasma exchange (PEX) and immunosuppression. High dose steroids are used from presentation and anti-CD20 monoclonal antibody therapy, specifically rituximab, is initiated early in the acute disease pathway. The use of the nanobody caplacizumab on confirmation of TTP, by severe ADAMTS13 deficiency (<10iu/dL), has revolutionised acute patient care. Caplacizumab binds the A1 domain, the site on VWF normally occupied by platelets. This results in a quicker normalisation of the platelet count, prevention of exacerbations and refractory disease, reduced PEX and inpatient stay. There is a significant risk of relapse and monitoring of patients allows prophylactic rituximab to be given to prevent further acute admissions.

Srs2 helicase prevents the formation of toxic DNA damage during late prophase I of yeast meiosis.

Proper repair of double-strand breaks (DSBs) is key to ensure proper chromosome segregation. In this study, we found that the deletion of the SRS2 gene, which encodes a DNA helicase necessary for the control of homologous recombination, induces aberrant chromosome segregation during budding yeast meiosis. This abnormal chromosome segregation in srs2 cells accompanies the formation of a novel DNA damage induced during late meiotic prophase I. The damage may contain long stretches of single-stranded DNAs (ssDNAs), which lead to aggregate formation of a ssDNA binding protein, RPA, and a RecA homolog, Rad51, as well as other recombination proteins inside of the nuclei, but not that of a meiosis-specific Dmc1. The Rad51 aggregate formation in the srs2 mutant depends on the initiation of meiotic recombination and occurs in the absence of chromosome segregation. Importantly, as an early recombination intermediate, we detected a thin bridge of Rad51 between two Rad51 foci in the srs2 mutant, which is rarely seen in wild type. These might be cytological manifestation of the connection of two DSB ends and/or multi-invasion. The DNA damage with Rad51 aggregates in the srs2 mutant is passed through anaphases I and II, suggesting the absence of DNA damage-induced cell cycle arrest after the pachytene stage. We propose that Srs2 helicase resolves early protein-DNA recombination intermediates to suppress the formation of aberrant lethal DNA damage during late prophase I.

Exploring transition metal fluoride chelates - synthesis, properties and prospects towards potential PET probes.

The coordination chemistry of the first row transition metal trifluorides with terpy (2,2':6',2''-terpyridine) and Me3-tacn (1,4,7-trimethyl-1,4,7-triazacyclononane) was explored to identify potential systems for 18F radiolabelling. The complexes [MF3(L)] (M = Cr, Mn, Fe, Co; L = Me3-tacn, terpy) were synthesised and fully characterised by UV-vis and IR spectroscopy, microanalysis, and, for the diamagnetic [CoF3(L)], using 1H, 19F{1H} and 59Co NMR spectroscopy. Single crystal X-ray analyses are reported for [MF3(Me3-tacn)] (M = Mn, Co), [FeF3(terpy)] and [FeF3(BnMe2-tacn)]. Stability tests on [MF3(Me3-tacn)] (M = Cr, Mn, Fe) and [M'F3(terpy)] (M' = Cr, Fe) were performed and Cl/19F halide exchange reactions on [CrCl3(Me3-tacn)] using [Me4N]F in anhydrous MeCN solution, and [FeCl3(Me3-tacn)] using [Me4N]F in anhydrous MeCN or KF in aqueous MeCN solution were also carried out. Halide exchange reactions proved to be successful in forming [FeF3(Me3-tacn)] in aqueous MeCN solution within 30 minutes. Based upon the clean Cl/F exchange and the good stability observed for [FeF3(Me3-tacn)] in a range of competitive media, this was identified as a possible candidate for radiolabelling. 18F/19F isotopic exchange was achieved by addition of [18F]F- in the cyclotron target water to a MeCN solution of the benzyl-substituted analogue, [FeF3(BnMe2-tacn)], at a range of concentrations down to 24 nM with heating to 80 °C for 10 min.; the resulting [Fe18F19F2(BnMe2-tacn)] shows radiochemical purity (RCP) ≥90% after 2 h in a range of formulations, including 10% EtOH/phosphate buffered saline (PBS) and 10% EtOH/human serum albumin (HSA). This is the first reported complex with a transition metal directly bonded to [18F]F-.

International union of physiological sciences physiology teaching workshop, March 31-April 1, 2012, Arabian Gulf University, Kingdom of Bahrain.

Since 2009, the Department of Physiology had planned an International Union of Physiological Sciences Physiology Teaching Workshop at Arabian Gulf University. The date was set for March 5-6, 2011; however, due to civil unrest, the workshop was postponed to March 31-April 1, 2012. The workshop was a success, bringing together 92 speakers and participants from 23 countries. Twenty-eight participants from economically disadvantaged countries were given travel support. The workshop included plenary lectures, breakout workshops, poster sessions, dinners, and a social trip. On April 2, 2012, an AD Instruments satellite workshop on data-acquisition systems for laboratory teaching was held, with 60 participants from 12 countries.

Lesson plan on new method of teeth identification introduced at dental schools in Malaysia and Pakistan.

This article describes a new tooth notation system designed to be implemented for educational purposes in dental schools in Malaysia and Pakistan for identification of teeth and subsequently dental communication for wellness of dental patients. Its format is constructed as a lesson plan to present an uncomplicated tooth notation system by first letter of each tooth class (I-incisor, C-canine, P-premolar, and M-molar) to describe and communicate dental information. The new system is a promising and potential educational lesson that is innovative in its contents, easily understandable, and usable in dental charting as indicated by the results of a pilot study. However, further studies are required to investigate the strength of this new system.

An assessment of the prescribing skills of undergraduate dental students in malaysia.

Most dental schools lack a module on prescription writing in pharmacology. This study assessed the prescription writing skills of a group of Malaysian dental students at the end of their undergraduate training program. A quantitative study of a two-group posttest experiment was designed, and thirty-seven fifth-year (final-year) dental students were divided into two groups (A [n=18] and B [n=19]). Group A received a didactic lecture on how to write a complete prescription, while Group B served as a control group. For prescription writing, three standardized dental scenarios with a diagnosis of irreversible pulpitis associated with a child and a pregnant woman and periapical pulpitis for an adult man were administered. Thus, a total of 111 prescriptions (Group A [n=54] and Group B [n=57]) were collected. Twelve elements in each prescription were assessed by frequency and a chi-square test. Improvements in eight out of the twelve elements were observed in prescriptions written by students in Group A. The significantly improved elements were provision of the symbol R(x) (39.8 percent) (p<0.001), inclusion of the prescriber's signature (75.3 percent) (p<0.001), inclusion of the date with the prescriber's signature (54.6 percent) (p<0.001), and inclusion of the prescriber's registration (30.5 percent) (p<0.001). Overall, Group A gained almost a 50 percent improvement in writing complete prescriptions due to the intervening lecture. It appeared a traditional lecture led to the more accurate writing of a complete prescription. It was suggested that a module on prescription writing be added to the school's pharmacology curriculum, so that dental graduates will be competent in prescription writing for the sake of their patients' health.

Lung function in Pakistani welding workers.

Our objective was to study the effects of welding fumes and their duration of exposure on lung function. This was a matched case-control cross-sectional study of spirometry in 50 nonsmoking manual metal arc welders who work without the benefit of welding fume control ventilation or respiratory protective devices. Welding workers, with exposures longer than 9 years, showed a significant reduction in spirometry (forced expiratory volume in one second [FEV1], FEV1/forced vital capacity [FVC%], and peak expiratory flow [PEF]) relative to controls. Lung function in nonsmoking welding workers is impaired and stratification of results shows a dose-effect of years of welding on lung function. This effect primarily shows an obstructive pattern of airways disease. Preventive measures in developing countries have to be adopted to avert long-term lung damage in welders.

Cardiac acceleration as a marker of vagal withdrawal in heart rate control during exercise in humans.

OBJECTIVE: To investigate whether the time rate of change in heart rate i.e. cardiac acceleration, during aerobic exercise in human subjects could be used to differentiate vagal withdrawal from sympathetic stimulation. METHODS: Fifteen male subjects exercised on a bicycle ergometer at 50 Watts (Step 1), then 100 Watts (Step 2), for 2 minutes each. RESULTS: Heart rate (HR) was monitored from a resting value (mean +/- SD) of 80.3 +/- 12.9 to 113.8 +/- 13.6 beats min-1 in Step 1. In Step 2 exercise, HR increased from 113.8 +/- 13.6 to 145 +/- 20 beats min-1. At the initiation of Step 1, a rapid acceleration of HR was observed in the form of an overshoot response. In contrast to Step 1, a small overshoot response of cardiac acceleration was observed during Step 2. The difference between the mean cardiac acceleration at 10 seconds in Steps 1 and 2 was significant (2.40 +/- 0.19 and 0.71 +/- 0.12 beats min-1 sec-1, p<0.0001). CONCLUSION: The initial vagal withdrawal of exercise-induced tachycardia, as a frontline adaptive mechanism, can be indirectly identified from HR transients using cardiac acceleration as a new marker.

Computer and experimental simulation of a cortical end-plate phase cancellation artefact in the measurement of BUA at the calcaneus.

It has been experimentally demonstrated that for the measurement of broadband ultrasound attenuation (BUA) at the human calcaneus the cortical end-plate creates a measurement artefact of the order of 7 dB MHz(-1). It has been suggested that the origin of this artefact may be a phase cancellation of the ultrasound pulse resulting from inconsistencies in propagation time across the ultrasound beam. Experimental and computer simulations were performed on samples of varying degrees of curvature and hence varying propagation times across the ultrasound beam. The experimental simulation incorporated Perspex samples of 35, 50 and 75 mm radius. The computer simulation was implemented using Matlab and Simulink, with the propagation time represented by a transport delay. The wavelet-based simulation incorporated a digitized transmitted ultrasound pulse derived from the experimental simulation. The experimental and computer-derived frequency spectra for the varying radii samples were comparable, demonstrating, firstly, that there is a significant dependence of measured BUA upon radius of curvature and, secondly, that the response in measured BUA to radius of curvature is similar in magnitude and trend for both experimental and computer simulations. The current study suggests that the BUA artefact observed in vitro corresponds to a radius of approximately 58 mm. Although the radius of curvature was not recorded in the original in vitro study, this value appears to be reasonable. This study indicates that the assumptions within the computer simulation were manifested within the experimental validation, and, hence, the observed BUA measurement artefact is related to the presence of the calcaneal cortical end-plate and is due to phase cancellation of the propagating ultrasound pulse.

Baroreflex function in sedentary and endurance-trained elderly people.

OBJECTIVE: to determine the differences associated with age and endurance exercise training on the baroreflex function of healthy subjects. DESIGN: cross-sectional study. SETTING: university research department. PARTICIPANTS: 26 (10 female) sedentary, healthy, normotensive elderly subjects (mean age 67 years, range 62-81), eight (two female) elderly endurance-trained athletes (66 years, 62-69) and eight (two female) young (30 years, 25-34) subjects. MEASUREMENTS: baroreflex sensitivity was quantified by the alpha-index, at high frequency (HF, 0.15-0.35 Hz) and mid frequency (MF, 0.05-0.15 Hz), derived from spectral and cross-spectral analysis of spontaneous fluctuations in heart rate and blood pressure. RESULTS: resting heart rate was significantly lower in endurance-trained athletes than sedentary elderly people (58 +/- 12 versus 68 +/- 11 min(-1), P < 0.05) but not different to that in healthy young subjects (63 +/- 9 min[-1]). alpha(HF) in sedentary elderly subjects (8.1 +/- 4.2 ms.mm Hg[-1]) was lower than both endurance-trained elderly athletes (14.8 +/- 4.8 ms.mm Hg(-1), P < 0.05) and healthy young subjects (28.3 +/- 21.8 ms.mm Hg(-1), P < 0.05) and was not significantly different between endurance-trained elderly athletes and healthy young subjects (P = 0.10). alpha(MF) in healthy young subjects (15.4 +/- 8.8 ms.mm Hg[-1]) was greater than in sedentary elderly subjects (6.5 +/- 3.2 ms.mm Hg(-1), P < 0.01) and endurance-trained elderly athletes (6.9 +/- 2.0 ms.mmHg(-1), P < 0.01), while there was no significant difference between the two elderly groups (P = 0.66). CONCLUSIONS: both components of the baroreflex measured by the alpha-index show a decrease with age. Elderly endurance-trained athletes have less reduction in the high, but not mid, frequency component of the alpha-index compared with sedentary elderly subjects. Some of the age-related changes in baroreflex sensitivity may be related to physical fitness and activity levels.

Effects of aerobic exercise training and yoga on the baroreflex in healthy elderly persons.

It is unclear whether the age-associated reduction in baroreflex sensitivity is modifiable by exercise training. The effects of aerobic exercise training and yoga, a non-aerobic control intervention, on the baroreflex of elderly persons was determined. Baroreflex sensitivity was quantified by the alpha-index, at high frequency (HF; 0.15-0.35 Hz, reflecting parasympathetic activity) and mid-frequency (MF; 0.05-0.15 Hz, reflecting sympathetic activity as well), derived from spectral and cross-spectral analysis of spontaneous fluctuations in heart rate and blood pressure. Twenty-six (10 women) sedentary, healthy, normotensive elderly (mean 68 years, range 62-81 years) subjects were studied. Fourteen (4 women) of the sedentary elderly subjects completed 6 weeks of aerobic training, while the other 12 (6 women) subjects completed 6 weeks of yoga. Heart rate decreased following yoga (69 +/- 8 vs. 61 +/- 7 min-1, P < 0.05) but not aerobic training (66 +/- 8 vs. 63 +/- 9 min-1, P = 0.29). VO2 max increased by 11% following yoga (P < 0.01) and by 24% following aerobic training (P < 0.01). No significant change in alpha MF (6.5 +/- 3.5 vs. 6.2 +/- 3.0 ms mmHg-1, P = 0.69) or alpha HF (8.5 +/- 4.7 vs. 8.9 +/- 3.5 ms mmHg-1, P = 0.65) occurred after aerobic training. Following yoga, alpha HF (8.0 +/- 3.6 vs. 11.5 +/- 5.2 ms mmHg-1, P < 0.01) but not alpha MF (6.5 +/- 3.0 vs. 7.6 +/- 2.8 ms mmHg-1, P = 0.29) increased. Short-duration aerobic training does not modify the alpha-index at alpha MF or alpha HF in healthy normotensive elderly subjects. alpha HF but not alpha MF increased following yoga, suggesting that these parameters are measuring distinct aspects of the baroreflex that are separately modifiable.

Effects of inhaled nebulized morphine on ventilation and breathlessness during exercise in healthy man.

1. Nebulized inhaled morphine has been reported to increase exercise endurance in patients with chronic lung disease and to relieve dyspnoea in patients with malignant disease. Potential mechanisms include a central effect occurring after systemic drug absorption or a local action mediated by receptors in the lung. 2. The ventilatory effects of nebulized morphine (10 and 25 mg) were therefore compared with those of intravenous morphine (1.0 and 2.5 mg) and placebo in a double-blind study involving 12 young healthy males. Submaximal cycle ergometry with respiratory gas analysis was performed 15 min after drug administration and breathlessness assessed using a linear visual analogue scale. 3. Neither dose of inhaled morphine had statistically significant effects on spirometry, heart rate, ventilation, respiratory gases or breathlessness at any level of exercise. The slopes and intercepts of the lines relating ventilation to breathlessness were also unaffected. 4. Intravenous morphine 2.5 mg reduced breathlessness slightly at the highest equivalent workload [mean (least significant range) 33 mm (26-40 mm)] compared with placebo [41 mm (34-48 mm), P < 0.05] but had no other significant effects. 5. These results do not support the hypothesis that intrapulmonary opiate receptors modulate the sensation of breathlessness in healthy man. The possibility that inhaled morphine may affect breathlessness caused by other factors, such as disease, has not been excluded.