A selective sweep in a microsporidian parasite Nosema-tolerant honeybee population, Apis mellifera.

Nosema is a microsporidian parasite of the honeybee, which infects the epithelial cells of the gut. In Denmark, honeybee colonies have been selectively bred for the absence of Nosema over decades, resulting in a breeding line that is tolerant toward Nosema infections. As the tolerance toward the Nosema infection is a result of artificial selection, we screened chromosome 14 for a selective sweep with microsatellite markers, where a major quantitative trait locus (QTL) had been identified to be involved in the reduction in Nosema spores in the honeybees. By comparing the genetic variability of 10 colonies of the selected honeybee strain with a population sample from 22 unselected colonies, a selective sweep was revealed within the previously identified QTL region. The genetic variability of the swept loci was not only reduced in relation to the flanking markers on chromosome 14 within the selected strain but also significantly reduced compared with the same region in the unselected honeybees. This confirmed the results of the previous QTL mapping for reduced Nosema infections. The success of the selective breeding may have driven the selective sweep found in our study.

Reproductive division of labour and thelytoky result in sympatric barriers to gene flow in honeybees (Apis mellifera L.).

Determining the extent and causes of barriers to gene flow is essential for understanding sympatric speciation, but the practical difficulties of quantifying reproductive isolation remain an obstacle to analysing this process. Social parasites are common in eusocial insects and tend to be close phylogenetic relatives of their hosts (= Emery's rule). Sympatric speciation caused by reproductive isolation between host and parasite is a possible evolutionary pathway. Socially parasitic workers of the Cape honeybee, Apis mellifera capensis, produce female clonal offspring parthenogenetically and invade colonies of the neighbouring subspecies A. m. scutellata. In the host colony, socially parasitic workers can become pseudoqueens, an intermediate caste with queenlike pheromone secretion. Here, we show that over an area of approximately 275.000 km², all parasitic workers bear the genetic signature of a clone founded by a single ancestral worker genotype. Any gene flow from the host to the parasite is impossible because honeybee workers cannot mate. Gene flow from the parasite to the host is possible, as parasitic larvae can develop into queens. However, we show that despite sympatric coexistence for more than a decade, gene flow between host and social parasite (F(st) = 0.32) and hybridizations (0.71%) are rare, resulting in reproductive isolation. Our data suggest a new barrier to gene flow in sympatry, which is not based on assortative matings but on thelytoky and reproductive division of labour in eusocial insects, thereby suggesting a new potential pathway to Emery's rule.

Outbreeding and possibly inbreeding depression in a pollinating fig wasp with a mixed mating system.

Mixed mating systems are somewhat of an enigma as most models predict that organisms should either inbreed when inbreeding depression is low, or outbreed when inbreeding depression is high. Many wasps mix routine inbreeding with a little random mating. This random mating is most common when all local sibmating opportunities are exhausted and dispersal is the only way males can further increase their fitness. The males of the pollinating fig wasp, Platyscapa awekei, are slightly different in that they disperse before all sibmating opportunities have been exhausted. To see if this is a response to inbreeding depression we quantify inbreeding depression by comparing females' life time reproductive success to their heterozygosity at multiple microsatellite loci. We find that a female wasp's heterozygosity is an accurate predictor of her inbreeding coefficient and that P. awekei females actually seem to suffer from outbreeding depression and possibly from a little inbreeding depression. Male dispersal is thus not a means to effect the optimal mating system, but more likely a mechanism to reduce competition among brothers. The number of mature offspring a female produces depends on her own heterozygosity and not on that of the offspring, and may be determined by egg and gall quality.

The influence of previous low back trouble, general health, and working conditions on future sick-listing because of low back trouble. A 15-year follow-up study of risk indicators for self-reported sick-listing caused by low back trouble.

STUDY DESIGN: A 15-year follow-up study. OBJECTIVE: To find risk indicators for self-reported sick-listing because of low back trouble and to evaluate which variables were the most important indicators of work incapacity resulting from low back trouble during the follow-up period of 15 years. SUMMARY OF BACKGROUND DATA: The initial data were obtained from a health survey conducted in a general population from the Municipality of Glostrup, Denmark. The follow-up data included information from the Central Person Register, the Early Retirement Pension Register, and a postal questionnaire regarding self-reported sick-listing because of low back trouble. METHODS: An epidemiologic study, in which logistic regression analyses were used for evaluation of the data. The model used consisted of the variable in question, age, gender, and previous experience of low back trouble, along with interactions. RESULTS: It was found that 22 of 37 variables were risk indicators for later self-reported sick-listing because of low back trouble during the preceding year or the 7 years before the date of follow-up evaluation. In analyzing the most significant variables simultaneously, it was found that information from the initial investigation about sick-listing in general during the previous 10 years, sciatic pain, use of analgesics for low back trouble, previous sick-listing because of low back trouble, and occupation were the most important risk indicators for self-reported work incapacity resulting from low back trouble during the follow-up period of 15 years. CONCLUSION: Findings showed that the strongest prognostic indicators of later sick-listing because of low back trouble involve information from the person about previous sick-listing behavior in general and previous experience of low back trouble episodes, especially if these had been accompanied by sciatic pain, use of analgesics, or previous low back trouble sick-listing.

Risk indicators of disability pension. A 15 year follow-up study.

OBJECTIVE: To identify risk indicators for granting of disability pension (DP) during a period of 15 years. DESIGN: Follow-up study. The initial data were obtained from a health survey in a general population 1977/78. Variables were initially collected through questionnaires and objective measurements. Information about the end-point for the follow-up, granting of DP, was obtained from the Registry for Early Retirement Pension in 1992/93. Data analyses were performed by logistic regression and Cox analyses. SETTING: The Glostrup Population Studies, Glostrup University Hospital and The Danish Committee for the Assessment of Substandard Lives. POPULATION: General population of 892 persons, born in 1918, 1928, 1938, and 1948, and living in the municipality of Glostrup, Denmark. Eighty-four were granted DP during the 15 years follow-up. RESULTS: Ninety-six variables from the initial study were analysed, age and 18 variables were found to be risk indicators for DP. These were general health variables, including dyspnoea, colic, nervousness, previous hospitalizations and operations, self-reported poor general health the last year, and low general health risk-score by the doctor. Objective measurements included high Body Mass Index, low peak flow and isometric endurance of the back muscles. Among the occupational variables unemployment and sick leave were found to be risk indicators. In addition, low physical activity in leisure time, self-reported worse physical condition than those at the same age and smoking were also identified as risk indicators. CONCLUSION: The main indicators for granting of DP can be covered by the heading poor physical condition and general health.

[Back problems during military service--significance for later back problems. A 12-year follow-up study]. / Rygbesvaer under aftjening af vaernepligt--betydning for senere rygproblemer. En 12-års followup-undersøgelse.

One thousand and fifty-eight conscripts participating in an investigation of back problems among conscripts in 1979-80 were re-examined 12 years later with an identical questionnaire concerning back problems. The questionnaire was answered by seven hundred and eighty-four persons (74%). The lifetime prevalence for low-back trouble was 73%, the one-year prevalence 53% and the point prevalence 26%. At the time of follow-up the incidence of low-back trouble depended on ever having had back pains and on having an X-ray made because of back problems. The probability for sick leave from work caused by lowback trouble was increased when back troubles had been reported at the time of the initial investigation. A significant amount of the conscripts that had been rejected due to back problems (60%) had been unfit for work because of low-back trouble in the follow-up period, and 95% of them had had low-back trouble in the year before follow-up, compared to 51% of the other conscripts. Previous back trouble increases the risk of getting back trouble once again. The risk of sick leave from work caused by low-back trouble increases with the incidence of back trouble up to the investigation in 1979-80. Rejection from service due to back problems increases the risk of later low-back trouble and sick leave from work caused by low-back troubles.

Intensive dynamic training for females with chronic neck/shoulder pain. A randomized controlled trial.

OBJECTIVES: To compare the clinical effectiveness of an intensive three-month training programme with a less intensive programme on females suffering from chronic neck/shoulder pain. STUDY DESIGN: A prospective observer-blinded clinical trial including 12-month pretreatment follow-up. SETTING: Patients were referred to the Departments of Rheumatology and Physical Medicine at Hvidovre Hospital by their general practitioners. Training was undertaken at a satellite clinic for physiotherapy of Hvidovre Hospital. SUBJECTS: Female patients aged 18-65 years suffering from chronic neck/shoulder pain for a minimum of six months. INTERVENTION: Patients were examined by a physician in order to exclude serious diseases. They were then randomized to either an intensive neck/shoulder training programme or a programme of lesser intensity but of similar duration. MAIN OUTCOME MEASURES: Scales measuring pain and activities of daily living (ADL) were used, and strength and endurance measurements of the cervical and shoulder muscles were carried out at baseline and completion of the study. Follow-up measurements were carried out by postal questionnaire at 6 and 12 months after inclusion, and included pain, ADL and treatment satisfaction measurements. RESULTS: Seventy-seven patients were included in the trial, of whom 27 (69%) completed the intensive programme and 25 (61%) the lighter programme. Forty-one (>80%) completed the follow-up questionnaires. The patients in the two groups did not differ with regard to age, pain, ADL scores and physical measurements prior to training. Patients in both groups that completed the trial demonstrated statistically significant improvements in nearly all of the outcome measurements at completion. ADL scores maintained statistical significance at 12 months in both groups, but pain scores were only significantly improved in the intensive group at 12 months follow-up. There was no statistically significant difference between groups regarding pain or ADL, but overall 50% of all patients showed improvement. CONCLUSIONS: The type of low-tech dynamic training used in either of our two programmes resulted in both subjective and objective improvements in patients suffering from chronic neck/shoulder pain, but there were no statistically significant differences in outcome between the two approaches. The subjective improvements were maintained throughout the follow-up period.

[Epidural glucocorticoid injection in lumbago sciatica]. / Epidural glukokortikoidinjektion ved lumbago-iskias.

Within the past decades, epidural steroid injections have been used in the treatment of severe low back pain and sciatica. In reviewing papers for this article an effort is made to concentrate on those that meet commonly accepted research design criteria, such as being blinded, randomized and prospective. The risks and the advantages of the procedure are discussed. Some of the studies report an efficient reduction in low back pain and sciatica for a longer period. Risks of more serious complications are low using the right technique. However, the results are to some extent conflicting. Future correctly designed studies are necessary to clarify whether the injection should be a supplement to the established treatment of low back pain and sciatica.

Exercises for chronic low back pain: a clinical trial.

Different training models are effective for the treatment of chronic low back pain, but no consensus has been found. Earlier studies have emphasized training of spinal mobility and back strength. To evaluate if other physiological parameters, such as coordination, are of equal importance, we performed a randomized trial on 40 consecutive patients with chronic low back pain. Two training models were compared: 1) intensive training of muscle endurance and 2) muscle training, including coordination. In both groups, training was performed 1 hour twice a week for 3 months. Pain score, disability score, and spinal mobility improved in both training groups without differences between the two groups. Only intensive training of muscle endurance improved isokinetic back muscle strength. At study entry, we found a significant correlation between spinal mobility and dysfunction, but after the training, no correlation was found between improvement of spinal mobility or isokinetic back extension strength and improvement of function or pain level. We conclude that coordination training for patients with chronic low back pain is as equally effective as endurance training.

Effect of intraarticular osmic acid on synovial membrane volume and inflammation, determined by magnetic resonance imaging.

The changes in MR-determined synovial membrane volume, early synovial enhancement, and cartilage and bone erosions after osmic acid knee synovectomy were studied. Gadolinium-DTPA enhanced magnetic resonance imaging (MRI) of 18 knees with persistent arthritis was performed before and 1 month after treatment. The synovial membrane volume was significantly reduced (median -52%) in all 9 patients brought into clinical remission (p < 0.01), while no significant change was found in patients with clinical relapse. The early synovial enhancement was not significantly changed. MRI revealed progressive erosive changes in 2 patients. The time of relapse was correlated to a MR-erosion score, but not to early synovial enhancement or volumes of synovium or effusion (Spearman tests). MRI-determined synovial membrane volumes and early synovial enhancement may be objective quantitative markers of inflammation. MR-scores of cartilage and bone erosions are sensitive to progressive changes occurring within a month.

Supervised endurance exercise training compared to home training after first lumbar diskectomy: a clinical trial.

OBJECTIVE: We performed a randomised trial to evaluate if intensive supervised training of the back should be offered to all patients after a first lumbar diskectomy. METHODS: Forty consecutive patients were, after a first lumbar diskectomy, randomly allocated to 2 groups undergoing "supervised training" twice a week for 3 months in an outpatient clinic or "home training" after 2 hours of instruction. RESULTS: The two rehabilitation models both showed a significant effect on spinal mobility, isokinetic trunk flexion strength, isokinetic trunk extension strength and daily function. These improvements were unchanged at follow up 3 months later. The pain score remained unchanged, however, throughout the trial in both groups. No differences in effect between the two rehabilitation models could be found for any of the assessed parameters. Thirteen patients did not complete the trial, including 9 from the supervised endurance trained group, mainly because of increased pain and reprolaps (n = 4). Four patients dropped out of the home trained group, only one because of increased pain. The differences in drop-out rate and training side effects were, however, not statistically significant. CONCLUSION: We conclude that it is not worthwhile to implement 3 months of supervised intensive endurance training as opposed to home training in all cases of first lumbar diskectomy, although a beneficial effect and better compliance might be found for a selected group of such patients.

Hydroxychloroquine and sulphasalazine alone and in combination in rheumatoid arthritis: a randomised double blind trial.

OBJECTIVES: To compare the effects of hydroxychloroquine and sulphasalazine alone and in combination in rheumatoid arthritis. METHODS: A six month randomised, multicentre, double blind trial with three parallel groups was performed. Ninety one outpatients with active rheumatoid arthritis were included. Monthly assessments of erythrocyte sedimentation rate, morning stiffness, number of swollen joints, a pain score, and global assessments were carried out. Radiographs of hands and wrists were taken before and after the trial. RESULTS: Sixty two patients completed the study. The 29 withdrawals caused no evident bias, and there was no difference in side effects among the three groups. All variables improved significantly with time. Patients treated with a combination of hydroxychloroquine and sulphasalazine responded better and faster than those treated with hydroxychloroquine alone, but there was no statistically significant difference between the combination treatment and single drug treatment with sulphasalazine or between treatment with hydroxychloroquine and sulphasalazine given alone. CONCLUSION: The present results do not support a recommendation to use a combination of hydroxychloroquine and sulphasalazine in the treatment of rheumatoid arthritis.

[Risk factors for development of low back pain]. / Risikofaktorer for udvikling af laenderygsmerter.

The incidence, severity and potential disability of low back pain are related, in particular, to previous back complaints, heavy lifting and the general psychosocial environment and to the physical constitution of the individual, viz the endurance of his back muscles. Recommendations for approach to the problem in future are discussed.

[Osteoporotic fractures of the spine in elderly women. Risk factors, inducing factors and course]. / Osteoporotisk fraktur i columna hos aeldre kvinder. Risikofaktorer, udløsende faktorer og forløb.

Forty-seven women with osteoporotic fractures of the spine were examined consecutively. The age range was 64-91 years with a median of 77 years. Risk factors for osteoporosis such as induced menopause or gastric resection were not present. Four patients had had rheumatoid arthritis. 19% had been treated with glucocorticoid. Only one patient had received long-term oestrogen treatment. The patients had been physically very active at a younger age and 91% had been occupationally employed. The symptoms frequently commenced with a fall or strain by lifting at home. The average period of hospitalization was 22 days. Thirty-four patients were followed-up after 6-12 months. All of them experienced pain and 74% still took analgesics. Fifteen out of the 19 patients who had been fitted with a supportive corset still employed this.

Double blind placebo controlled trial of pulse treatment with methylprednisolone combined with disease modifying drugs in rheumatoid arthritis.

OBJECTIVE: To assess whether monthly treatment with intravenous methylprednisolone enhances or accelerates the effect of disease modifying drugs in patients with rheumatoid arthritis. DESIGN: A 12 month double blind, placebo controlled, multicentre trial in which patients with active rheumatoid arthritis were randomly allocated to receive pulses of either methylprednisolone or saline every four weeks for six months. At the start of the pulse treatment all patients were started on penicillamine or azathioprine. SETTING: Four rheumatology departments in Denmark. PATIENTS: 97 Patients (71 women, 26 men) aged 23-84 (mean 60) who had active rheumatoid arthritis of at least four weeks' duration despite treatment with non-steroidal anti-inflammatory drugs. MAIN OUTCOME MEASURES: Monthly clinical recording of morning stiffness, number of tender and swollen joints, blinded observers' evaluation of therapeutic effect, and patients' self assessed condition. Concomitant laboratory measurements of erythrocyte sedimentation rate and concentrations of C reactive protein and haemoglobin. Radiography to determine the number of erosions at the start of treatment and after 12 months. RESULTS: 57 Patients completed the trial, taking the same disease modifying drug throughout. Evaluation four weeks after each pulse treatment and at 12 month follow up showed no significant differences between the methylprednisolone and placebo groups in any of the clinical or laboratory variables. Radiography showed the same degree of progression of erosions in both groups. Evaluation of the total data on 97 patients and on the 57 who completed the trial showed the same lack of significance between the treatment groups. CONCLUSIONS: Intravenous pulse treatment with steroids can be recommended only for rapid temporary relief of flares of disease in patients with rheumatoid arthritis. The response is short lived. Repeated pulses of methylprednisolone at four week intervals do not improve the results of treatment with drugs that induce remission such as penicillamine and azathioprine.

Reactivation of viral replication in anti-HBe positive chronic HBsAg carriers.

Reactivation of hepatitis B virus replication was investigated in an unselected group of 44 HBV DNA negative, anti-HBe positive chronic HBsAg carriers. Twenty-five patients (54%) were intravenous drug addicts and 7 (16%) were male homosexuals. Sixteen patients had evidence of delta infection and five of the seven male homosexuals had human immunodeficiency virus infection. The patients were followed for 1 to 180 months (median, 24 months) while HBV DNA negative, anti-HBe positive. Reactivation, defined as reappearance of HBV DNA or HBeAg, or both, was detected in six patients corresponding to an annual reactivation rate of 5%. Reactivation in four patients was detected by reversion to HBV DNA positivity only, whereas HBeAg/anti-HBe status remained unchanged. Two patients became both HBV DNA and HBeAg positive. None of the patients developed hepatitis-like symptoms and transaminase elevation was only observed in two patients. Reactivation in two patients was ascribed to human immunodeficiency virus infection and in one patient to chronic lymphatic leukaemia. It is concluded that HBV DNA seems to be superior to HBeAg in the detection of reactivation of HBV replication and that reactivation associated with clinical symptoms leading to progression in chronic liver disease is a rare event in the population studied.