Tonotopic Ca2+ dynamics and sound processing in auditory interneurons of the bush-cricket Mecopoda elongata.

Two auditory neurons, TN-1 and ON-1, in the bush-cricket, Mecopoda elongata, have large dendritic arborisations which receive excitatory synaptic inputs from tonotopically organised axonal terminals of auditory afferents in the prothoracic ganglion. By combining intracellular microelectrode recording with calcium imaging we demonstrate that the dendrites of both neurons show a clear Ca2+ signal in response to broad-frequency species-specific chirps. Due to the organisation of the afferents frequency specific auditory activation should lead to local Ca2+ increases in their dendrites. In response to 20 ms sound pulses the dendrites of both neurons showed tonotopically organised Ca2+ increases. In ON-1 we found no evidence for a tonotopic organisation of the Ca2+ signal related to axonal spike activity or for a Ca2+ response related to contralateral inhibition. The tonotopic organisation of the afferents may facilitate frequency-specific adaptation in these auditory neurons through localised Ca2+ increases in their dendrites. By combining 10 and 40 kHz test pulses and adaptation series, we provide evidence for frequency-specific adaptation in TN-1 and ON-1. By reversible deactivating of the auditory afferents and removing contralateral inhibition, we show that in ON-1 spike activity and Ca2+ responses increased but frequency-specific adaptation was not evident.

Multiple deprivation and geographic distance to community physical activity events - achieving equitable access to parkrun in England.

OBJECTIVES: To evaluate geographic access to free weekly outdoor physical activity events ('parkrun') in England, with a particular focus on deprived communities, and to identify optimal locations for future events to further maximise access. STUDY DESIGN: This study is a cross-sectional ecological analysis of the socio-economic disparities in geographic access to parkrun events in England in late 2018. METHODS: We combined geolocation data on all English Lower Layer Super Output Areas and parkrun events to calculate geodesic distances to the nearest event for more than 32,000 communities in England. We use this measure of geographic access to summarise the relationship between access and socio-economic deprivation, measured using the index of multiple deprivation. We then used geographic coordinates of public green spaces in England to conduct a simple location-allocation analysis to identify 200 locations for future event locations that would maximise access. RESULTS: In England, 69% of the population live within 5 km of one of the 465 parkrun events. There is a small negative correlation between distance and deprivation, indicating that access is slightly better in more socio-economically deprived areas. Setting up an additional 200 events in optimal locations would improve access: the average distance to the nearest parkrun event would improve by 1.22 km, from 4.65 km to 3.43 km, and approximately 82% of the English population would live within 5 km of a parkrun event. CONCLUSION: Over two-thirds of the English population live within 5 km of a parkrun event, and contrary to our expectation, we find that geographic access is slightly better for those living in more deprived communities. Creating additional events may improve geographic access, but effective strategies will still be needed to increase engagement in new and existing events by those living in socio-economically deprived areas.

A buckling region in locust hindlegs contains resilin and absorbs energy when jumping or kicking goes wrong.

If a hindleg of a locust slips during jumping, or misses its target during kicking, energy generated by the two extensor tibiae muscles is no longer expended in raising the body or striking a target. How, then, is the energy in a jump (4100-4800 µJ) or kick (1700 µJ) dissipated? A specialised buckling region found in the proximal hind-tibia where the bending moment is high, but not present in the other legs, buckled and allowed the distal part of the tibia to extend. In jumps when a hindleg slipped, it bent by a mean of 23±14 deg at a velocity of 13.4±9.5 deg ms(-1); in kicks that failed to contact a target it bent by 32±16 deg at a velocity of 32.9±9.5 deg ms(-1). It also buckled 8.5±4.0 deg at a rate of 0.063±0.005 deg ms(-1) when the tibia was prevented from flexing fully about the femur in preparation for both these movements. By experimentally buckling this region through 40 deg at velocities of 0.001-0.65 deg ms(-1), we showed that one hindleg could store about 870 µJ on bending, of which 210 µJ was dissipated back to the leg on release. A band of blue fluorescence was revealed at the buckling region under UV illumination that had the two key signatures of the elastic protein resilin. A group of campaniform sensilla 300 µm proximal to the buckling region responded to imposed buckling movements. The features of the buckling region show that it can act as a shock absorber as proposed previously when jumping and kicking movements go wrong.

Relationships between attachment, appraisal, coping and adjustment in men and women experiencing infertility concerns.

BACKGROUND: Attachment style may influence distress and relationship satisfaction in infertile couples. Appraisal and coping have also been linked to adjustment to infertility and may be related to attachment patterns. The study examined these associations in men and women around the time of attending initial appointments at fertility clinics. METHODS: Attachment, appraisal, coping, general well-being, infertility-related stress and relationship satisfaction questionnaires were completed by 98 women and 64 men. Data were analysed by gender comparisons, correlations and path analysis. RESULTS: Attachment anxiety was associated with well-being in women via appraisal of infertility as a loss and use of self-blame and avoidance (SBA) coping. Attachment anxiety was also linked with infertility-related stress through SBA. In men, attachment anxiety was associated with well-being and infertility-related stress again via SBA coping. Attachment anxiety and avoidance were related to lower relationship satisfaction in women, whereas only the former was important for men. CONCLUSIONS: Attachment patterns link to couples' relationship satisfaction and are associated with adjustment via appraisal and coping. Identification of such patterns may assist in identifying need and tailoring cognitive interventions to individuals. Participants were mainly white and well-educated, and wider generalization cannot automatically be assumed.

The long-term treatment of steroid osteoporosis with fluoride.

Twenty-two patients with steroid-induced osteoporosis were studied retrospectively to assess the effects on bone mass of fluoride therapy over 4 years. Thirteen of 19 patients with miscellaneous disorders and 2 with Cushing's syndrome received 1 g calcium/day, 50,000 IU vitamin D (D) weekly, and 40-60 mg/day sodium fluoride (F). Six patients with miscellaneous disorders and one with Cushing's syndrome received only Ca and vitamin D. The mean (+/- SD) cumulative dose of prednisone for fluoride-treated patients at the beginning of the study was 42 +/- 25 g, and for those patients treated with only Ca and vitamin D, 45 +/- 47 g, and during the study the cumulative dose was comparable in both groups. The bone mineral mass of the central skeleton was measured by neutron activation analysis and the results expressed as the calcium bone index (CaBI) which normalizes the results to that of young adults of the same body size (normal range 0.75-1.2). In the 13 patients with miscellaneous disorders treated with fluoride, the mean +/- SD CaBI rose from 0.65 +/- .03 to 0.75 +/- .03 after 3 years p less than 0.001) and to 0.81 +/- .11 at 4 years. Patients without fluoride had an initial mean CaBI of 0.70 +/- .08 and it was not significantly changed over 3 years, 0.68 +/- .09 and 4 years, 0.71 +/- .09. The rise in CaBI in fluoride-treated patients with steroid-induced osteoporosis including Cushing's syndrome was comparable to that of 61 patients with postmenopausal osteoporosis treated with fluoride.(ABSTRACT TRUNCATED AT 250 WORDS)

Fluoride-induced fractures: relation to osteogenic effect.

The possible effects of fluoride in inducing fractures were studied in 61 patients treated with sodium fluoride (NaF), 40-60 mg daily in combination with calcium and vitamin D. Nine patients developed the fluoride-(F) related lower extremity pain syndrome. Four other patients had stress fractures associated with trauma. Seven of the 61 patients had 10 upper femur fractures of which 5 were stress fractures. The bone mineral mass of the central skeleton including the hips was measured by neutron activation and the results expressed as a calcium bone index (CaBI) which normalizes the results to that of young adults of the same body size (normal range 0.75-1.2). At the time of hip fracture, 4 patients with a minimal increase in bone mass (mean delta CaBI 0.01) had 4 femur fractures and 3 patients with a marked increase (mean delta CaBI 0.24) had 6. The 7 patients with upper femur fractures at 4 years had a significantly higher bone fluoride retention, 30 mg/g Ca compared with 23.9 mg/g Ca for the other 54 (p less than 0.02) and were older, 73.1 versus 64.2 years (p less than 0.01). Using all 61 fluoride-treated patients, femur fractures/patient were significantly correlated to bone fluoride (p less than 0.05) and to age (p less than 0.05). By partial correlation, only the correlation between hip fractures/patient and bone fluoride remained significant after controlling for the effect of age (p less than 0.05). These results suggest that fluoride therapy may be implicated in the pathogenesis of hip fractures which may occur in treated patients despite a rapid, marked increase in bone mass. The lower extremity pain syndrome is not frequently associated with stress fractures in this study.

Fluoride treatment of postmenopausal osteoporosis: age, renal function, and other clinical factors in the osteogenic response.

We report on 61 women with postmenopausal osteoporosis who were treated with either plain sodium fluoride (NaF) capsules or enteric-coated NaF tablets for 4 years, in whom possible therapeutic and toxic effects were monitored. In these patients there was a mean increase in axial bone mineral mass, assessed by neutron activation analysis, of 26.2% +/- 2.4% (SEM) during the 4 years. This corresponds to a decrease in the bone deficit (compared with reference values) of 48.6%. The response was linear over 4 years. The main predictors of the osteogenic response were bone fluoride (r = 0.52, p less than 0.01), serum fluoride (r = 0.50, p less than 0.01), and age (0.39, p less than 0.01). Patients over 65 years of age achieved higher bone fluoride (F) levels and a significantly greater increase in bone mineral than younger patients (32.8 vs. 17.9%, p less than 0.01), associated with an age-related decline in renal function; serum fluoride was significantly and negatively correlated to creatinine clearance (r = -0.52, p less than 0.01). Although the effect of NaF on fracture rate could not be assessed in this uncontrolled study, the major factors associated with the occurrence of new vertebral fractures were the number of vertebral fractures and the bone mineral mass at the beginning of therapy. There was no correlation between vertebral fracture rate and serum or bone fluoride or other parameters of the osteogenic response, but patients who did not experience new vertebral fractures achieved a normal bone mineral content sooner than those who had new fractures during therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of fluoride on bone histology in postmenopausal osteoporosis depends on adequate fluoride absorption and retention.

Forty-one women with idiopathic postmenopausal osteoporosis have been followed for 2 years after initiation of sodium fluoride at 40-50 mg/day, given together with a daily calcium supplement of 1 gram and vitamin D2, at 50,000 IU weekly. Histological and histomorphometric analyses were done on bone biopsies taken prior to and after 1 year of treatment (mean 1.25 +/- 0.35 years). Thirty patients (74%) developed the histological fluoride effect of hyperosteoidosis, while the remaining 11 patients (26%) had no change from pretreatment biopsies. Hyperosteoidosis was based on increased values for osteoid volume and/or thickened osteoid with greater than 3 lamellar bands. Based on previously reported findings, this histological evidence of hypersoteoidosis within 12-18 months of initiation of therapy provides a useful predictor of ultimate satisfactory fluoride response in terms of bone mineral accretion. No increases in bone mass (measured by neutron activation analysis) were observed at the time of the posttreatment biopsy but, according to this previous work, increases are anticipated over a further 2-3 years of treatment. Factors affecting the development of hyperosteoidosis were analyzed. Hyperosteoidosis was associated with a significantly higher dose of sodium fluoride and a significantly higher level of bone fluoride retention but without significant increase in fasting serum fluoride. Results suggest that fluoride retention depends not only on fluoride dose but also on body size, renal function, and intestinal absorptions of calcium and fluoride. There were no differences in the initial investigations between patients with and without hyperosteoidosis, with respect to age, years of postmenopause, estrogen use, initial biochemistry, or initial bone histology.(ABSTRACT TRUNCATED AT 250 WORDS)

Relevance of vitamin D metabolite concentrations in supporting the diagnosis of primary hyperparathyroidism.

We compared the relationships between 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] levels in patients with primary hyperparathyroidism (PHPT) and 38 volunteer blood donors. There was no significant difference in mean 25(OH)D levels between patients with PHPT (34 +/- 21 nmol/L; n = 21) and the donor samples (41 +/- 19 nmol/L; n = 38). Serum 1,25(OH)2D levels were higher in the patients with PHPT compared with the donors (122 +/- 61 pmol/L vs 56 +/- 41 pmol/L; p less than 0.001). The 95th percentile 1,25(OH)2D value for the donors was exceeded in 65% of the patients with PHPT. There was a significant correlation between serum 1,25(OH)2D versus 25(OH)D in the patients with PHPT (r = 0.50; p less than 0.05) but not in the donors (r = 0.02). We conclude from the distinct elevation in 1,25(OH)2D levels in the majority of our patients with PHPT that the concentration of this parathyroid hormone-dependent hormone can be of critical value in corroborating the diagnosis of PHPT.

Possible limited bone loss with suppressive thyroxine therapy is unlikely to have clinical relevance.

To determine the effect of suppressive doses of thyroxine (T4) on bone mass, we studied 50 women on suppressive doses of T4 for 3-27 years (mean of 11 years). Twenty-five had nontoxic goiter and 25 had well-differentiated thyroid carcinoma. Fifty controls were matched for age, menopausal status, and body mass index. Bone mineral density (BMD) was measured in the lumbar spine (LS), femoral neck (FN), trunk (TK), and extremities (EXT) by dual-energy X-ray absorptiometry (DXA). In addition, the trunk area was measured by neutron activation analysis and recorded as a calcium bone index (CaBI). Twenty-one patients were restudied with DXA measurements at a mean of 1.5 +/- 0.5 (1 SD) years. The total population of 50 patients showed no difference in bone mass from controls. In patients with nontoxic goiter, there was no evidence of any loss in bone mass. Cancer patients showed insignificant reductions of 2-5% in BMD of LS, FN, and TK and a significant 5% reduction in BMD of EXT, compared to controls, and a 12% reduction in CaBI compared to goiter patients. Cancer patients had a slightly higher (p < 0.001) mean daily dose of T4 than goiter patients (0.23 vs 0.15 mg/day) but had a similar degree of TSH suppression. BMD and CaBI values did not correlate with free T4 index) with the daily T4 dose, accumulative dose, or with duration of T4 therapy. There were no significant changes in bone mass in either goiter or cancer patients restudied after a mean of 1.5 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic bone disease in a patient on long-term total parenteral nutrition: a case report with review of literature.

A 38-yr-old woman with Crohn's disease and short bowel on home total parenteral nutrition was studied. Metabolic bone assessments were done prospectively. Daily total parenteral nutrition included 500 IU vitamin D2, 6 to 8 mmol calcium, 10 to 15 mmol phosphorus, 12 to 16 mmol magnesium, and trace elements including zinc, cooper, and chromium. After 6 months, while asymptomatic, chemistries and x-rays were normal. Calcium bone index was 0.79. The bone biopsy showed mild hyperkinetic picture. At 26 months, she had a spontaneous rib fracture and bone pains in the hands and lower back. Chemistries were normal except that calcium bone index was 0.75. Bone biopsy showed mild osteomalacia. Vitamin D2 was withdrawn for 2 months and then restarted at 1000 IU/wk. She improved symptomatically for 4 months, but then developed rib fractures, and the bone pains recurred. After 48 months, chemistries were normal, except that the calcium bone index was 0.57 and bone biopsy showed regression of osteomalacia toward normal. Vitamin D2 was now withdrawn for 6 months, resulting in loss of bone pain. Vitamin D2 may produce a metabolic bone disease, requiring prolonged withdrawal for improvement.

Portal venous tumor casts causing defect on hepatic imaging.

A dilated portal vein has been reported as a cause of a portal defect on liver scan. This report describes a similar defect caused by tumor thrombus casts invading the portal vein and its main branches.

The hospital component of vocational training for general practice.

Trainees and educationalists in general practice have some grounds for suggesting that the hospital component of vocational training should be restructured and teaching improved. However, the implications for other trainees and secondary care have to be considered. Changes that are needed include a curriculum for senior house officers in each specialty; appointment of training consultants with the necessary skills; and a different attitude by everyone towards study leave, including arrangements for funding. The optimum duration of hospital posts for trainees in general practice might be shorter than now, but the effects on others must be considered and competencies guaranteed in a briefer training period. Changes in the regulations for vocational training could help to improve specialist experience if trainees in general practice were allowed to be supernumerary. Alternatively, senior house officer posts for trainees in general practice could be split between secondary and primary care, thus encouraging a broader perspective.