Spinal pain in childhood: prevalence, trajectories, and diagnoses in children 6 to 17 years of age.

This study aimed to investigate the trajectories of spinal pain frequency from 6 to 17 years of age and describe the prevalence and frequency of spinal pain and related diagnoses in children following different pain trajectories. First through fifth-grade students from 13 primary schools were followed for 5.5 years. Occurrences of spinal pain were reported weekly via text messages. Children reporting spinal pain were physically evaluated and classified using International Classification of Disease criteria. Trajectories of spinal pain frequency were modeled from age 6 to 17 years with latent class growth analysis. We included data from 1556 children (52.4% female, mean (SD) baseline age = 9.1 (1.9) years) and identified 10,554 weeks of spinal pain in 329,756 weeks of observation. Sixty-three percent of children reported one or more occurrences of spinal pain. We identified five trajectories of spinal pain frequency. Half the children (49.8%) were classified as members of a "no pain" trajectory. The remaining children followed "rare" (27.9%), "rare, increasing" (14.5%), "moderate, increasing" (6.5%), or "early-onset, decreasing" (1.3%) spinal pain trajectories. The most common diagnoses in all trajectory groups were non-specific (e.g., "back pain"). Tissue-specific diagnoses (e.g., muscle strain) were less common and pathologies (e.g., fracture) were rare.  Conclusion: From childhood through adolescence, spinal pain was common and followed heterogeneous courses comprising stable, increasing, and early-onset trajectories. These findings accord with recommendations from adult back pain guidelines that most children with spinal pain can be reassured that they do not have a serious disease and encouraged to stay active. What is Known: • Spinal pain imposes a large burden on individuals and society. • Although many people first experience the condition in childhood, little is known about the developmental trajectories of spinal pain from childhood to adolescence. What is New: • Data from 1556 children and 329,756 participant weeks showed five unique spinal pain trajectories from 6 to 17 years: most children rarely reported spinal pain, while one in five followed increasing or early-onset trajectories. • Most pain occurrences were non-specific; pathological diagnoses were rare.

Spinal pain is prospectively associated with cardiovascular risk factors in girls but not boys (CHAMPS study-DK).

PURPOSE: To examine the prospective associations between spinal pain exposures and risk factors for cardiovascular disease in children and explore the mediating role of health-related physical activity. METHODS: Students were recruited from ten public primary schools. Each week from November 2008 to October 2010, parents reported spinal pain occurrences in their children via text messaging. Clustered cardiovascular risk was estimated with a composite score comprising fasting serum triglycerides, homeostasis assessment model-estimated insulin resistance (HOMA-IR), total to high-density lipoprotein cholesterol ratio, and systolic blood pressure. Additional outcomes were fasting serum insulin and glucose concentrations and body mass index categories. Associations were explored with multilevel mixed regression models and reported with beta coefficients (ß) and percent difference scores. All models were adjusted for potential confounders. RESULTS: Data from 1022 children (53% female) with mean ± SD age of 8.4 ± 1.4 years were included. Girls with spinal pain had greater clustered cardiovascular risk (ß [95% CI]; percent difference [95% CI] = .41 [.02-.80]; 3.3% [.2-6.4%]) than those without spinal pain. Similar outcomes were observed for log insulin (percent difference [95% CI] = 3.4% [.6-6.2%]) and log HOMA-IR = (percent difference [95% CI] = 3.8% [.4-7.3%]). Remaining associations between spinal pain and cardiovascular risk in girls were nonsignificant. There were no associations between spinal pain and cardiovascular risk in boys. Moderate-to-vigorous-intensity physical activity did not appear to mediate this relationship. CONCLUSION: These findings suggest a potentially important link between spinal pain and cardiovascular risk in girls that may be independent of health-related physical activity. These slides can be retrieved under Electronic Supplementary Material.

Pubertal development and growth are prospectively associated with spinal pain in young people (CHAMPS study-DK).

PURPOSE: To examine the prospective associations of pubertal development and linear growth with spinal pain frequency and duration in children. METHODS: We recruited students from 10 public primary schools. Over 42 months, pubertal development was assessed four times and categorized according to Tanner stages 1-5, and height was measured on seven occasions. Occurrences of spinal pain were reported weekly via text messaging. We constructed variables for spinal pain duration (total weeks with pain) and frequency (number of episodes). Potential associations between pubertal development and growth were examined with generalized estimating equations and reported with incident rate ratios (IRRs). All models were adjusted for potential confounders. RESULTS: Data from 1021 children (53% female; mean [SD] age = 9.4 [1.4] years), with median participation duration of 39 months, were included. Advancing pubertal development was associated with increased spinal pain duration (IRR [95% CI] = 1.90 [1.45, 2.49] to 5.78 [4.03, 8.29]) and frequency of pain episodes (IRR [95% CI] = 1.32 [1.07, 1.65] to 2.99 [2.24, 3.98]). Similar associations were observed for each 1-cm change in height in 6 months with spinal pain duration (IRR [95% CI] = 1.19 [1.15, 1.23]) and frequency (IRR [95% CI] = 1.14 [1.11, 1.17]). The relations between pubertal development and spinal pain, as well as growth and spinal pain, were largely independent. CONCLUSIONS: In young people, pubertal development and linear growth are likely to be independent risk factors for the development of spinal pain. Pubertal development demonstrates evidence of dose-response in its relationship with spinal pain. This knowledge may assist healthcare providers with clinical decision-making when caring for pediatric patients. These slides can be retrieved under Electronic Supplementary Material.

Total body fat percentage and body mass index and the association with lower extremity injuries in children: a 2.5-year longitudinal study.

BACKGROUND: Overweight youths are generally recognised as being at increased risk of sustaining lower extremity injuries in sports. However, previous studies are inconclusive and choices for measuring overweight are manifold. OBJECTIVE: To examine two different measures of overweight, body mass index (BMI) and total body fat percentage (TBF%), as risk factors for lower limb injuries in a school-based cohort. STUDY DESIGN: A longitudinal cohort study. METHODS: A total of 632 school children, baseline age 7.7-12.0 years, were investigated. Whole body dual energy x-ray absorptiometry scans provided measures of TBF%. Measures of BMI were obtained by standard anthropometric methods. Musculoskeletal complaints were reported by parents answering weekly mobile phone text messages during 2.5 years. Injuries were diagnosed by clinicians. Leisure time sports participation was reported weekly using text messaging. RESULTS: During 2.5 years of follow-up, 673 lower extremity injuries were diagnosed. Children being overweight by both BMI and TBF% showed the highest risk of sustaining lower extremity injuries (IRR 1.38 (95% CI 1.05 to 1.81)). Children who were overweight using BMI and TBF% showed the highest risk of sustaining lower extremity injuries (IRR 1.38 (95% CI 1.05 to 1.81)). CONCLUSIONS: The risk of lower extremity injuries appeared to be increased for overweight children. When comparing two different measures of overweight, overweight by TBF% is a higher risk factor than overweight by BMI. This suggests that a high proportion of adiposity is more predictive of lower extremity injuries, possibly due to a lower proportion of lean muscle mass.

Study protocol. The Childhood Health, Activity, and Motor Performance School Study Denmark (The CHAMPS-study DK).

BACKGROUND: An increasingly passive life-style in the Western World has led to a rise in life-style related disorders. This is a major concern for all segments of society. The county council of the municipality of Svendborg in Denmark, created six Sport Schools with increased levels of suitable physical activities, which made it possible to study the health outcomes in these children whilst comparing them to children who attended the 'normal' schools of the region using the design of a "natural experiment". METHODS: Children from the age of 6 till the age of 10, who accepted to be included in the monitoring process, were surveyed at baseline with questionnaires, physical examinations and physical and biological testing, including DXA scans. The physical examination and testing was repeated during the early stage of the study. Every week over the whole study period, the children will be followed with an automated mobile phone text message (SMS-Track) asking questions on their leisure time sports activities and the presence of any musculoskeletal problems. Children who report any such problems are monitored individually by health care personnel. Data are collected on demography, health habits and attitudes, physical characteristics, physical activity using accelerometers, motor performance, fitness, bone health, life-style disorders, injuries and musculoskeletal problems. Data collection will continue at least once a year until the children reach grade 9. DISCUSSION: This project is embedded in a local community, which set up the intervention (The Sport Schools) and thereafter invited researchers to provide documentation and evaluation. Sport schools are well matched with the 'normal' schools, making comparisons between these suitable. However, subgroups that would be specifically targeted in lifestyle intervention studies (such as the definitely obese) could be relatively small. Therefore, results specific to minority groups may be diluted. Nonetheless, the many rigorously collected data will make it possible to study, for example, the general effect that different levels of physical activity may have on various health conditions and on proxy measures of life-style conditions. Specifically, it will help answer the question on whether increased physical activity in school has a positive effect on health in children.

Physical activity is prospectively associated with spinal pain in children (CHAMPS Study-DK).

ABSTARCT: Spinal pain and physical inactivity are critical public health issues. We investigated the prospective associations of physical activity intensity with spinal pain in children. Physical activity was quantified with accelerometry in a cohort of primary school students. Over 19 months, parents of primary school students reported children's spinal pain status each week via text-messaging (self-reported spinal pain). Spinal pain reports were followed-up by trained clinicians who diagnosed each child's complaint and classified the pain as non-traumatic or traumatic. Associations were examined with logistic regression modeling using robust standard errors and reported with odds ratios (OR). Children (n = 1205, 53.0% female) with mean ± SD age of 9.4 ± 1.4 years, participated in 75,180 weeks of the study. Nearly one-third (31%) of children reported spinal pain, and 14% were diagnosed with a spinal problem. Moderate intensity physical activity was protectively associated with self-reported [OR(95%CI) = 0.84(0.74, 0.95)], diagnosed [OR(95%CI) = 0.79(0.67, 0.94)] and traumatic [OR(95%CI) = 0.77(0.61, 0.96)] spinal pain. Vigorous intensity physical activity was associated with increased self-reported [OR(95%CI) = 1.13(1.00, 1.27)], diagnosed [OR(95%CI) = 1.25(1.07, 1.45)] and traumatic [OR(95%CI) = 1.28(1.05, 1.57)] spinal pain. The inclusion of age and sex covariates weakened these associations. Physical activity intensity may be a key consideration in the relationship between physical activity behavior and spinal pain in children.

Leisure-time sport and overuse injuries of extremities in children age 6-13, a 2.5†years prospective cohort study: the CHAMPS-study DK.

OBJECTIVES: It is not known which sports are most likely to cause overuse injuries of the extremities in children. In this study, we report on the incidence of overuse injuries of the upper and lower extremities in children who participate in various leisure-time sports and relate this to the frequency of sport sessions. DESIGN: Natural experiment including a prospective cohort study. SETTING: 10 state schools in 1 Danish municipality: Svendborg. PARTICIPANTS: 1270 children aged 6-13 years participating in the Childhood Health, Activity, and Motor Performance School Study Denmark. OUTCOMES MEASURES: Over 2.5 years, parents answered weekly SMS-track messages (a) on type and frequency of leisure-time sports undertaken by their child, and (b) reporting if their child had experienced any musculoskeletal pain. Children with reported pain were examined by a clinician and diagnosed as having an overuse injury of an extremity or not. The incidence of diagnosed overuse injury was calculated for each of the 9 most common sports in relation to 5-week periods. Incidence by frequency of sessions was calculated, and multivariable analysis was performed taking into account age, sex and frequency of physical education classes at school. RESULTS: Incidence of overuse injuries of the lower extremity ranged from 0.2 to 3.3 for the 9 sports, but was near 0 for overuse injuries of the upper extremities. There was no obvious dose-response. The multivariate analysis showed soccer and handball to be the sports most likely to result in an overuse injury. CONCLUSIONS: Among a general population of schoolchildren, overuse injuries of the lower extremities were not common and overuse injuries of the upper extremities were rare. Organised leisure-time sport, as practised in Denmark, can be considered a safe activity for children.

Seasonal variation in musculoskeletal extremity injuries in school children aged 6-12 followed prospectively over 2.5 years: a cohort study.

OBJECTIVES: The type and level of physical activity in children vary over seasons and might thus influence the injury patterns. However, very little information is available on the distribution of injuries over the calendar year. This study aims to describe and analyse the seasonal variation in extremity injuries in children. DESIGN: Prospective cohort study. SETTING: 10 public schools in the municipality of Svendborg, Denmark. PARTICIPANTS: A total of 1259 school children aged 6-12 years participating in the Childhood Health, Activity, and Motor Performance School Study Denmark. METHODS: School children were surveyed each week during 2.5 school-years. Musculoskeletal injuries were reported by parents answering automated mobile phone text questions (SMS-Track) on a weekly basis and diagnosed by clinicians. Data were analysed for prevalence and incidence rates over time with adjustments for gender and age. RESULTS: Injuries in the lower extremities were reported most frequently (n=1049). There was a significant seasonal variation in incidence and prevalence for lower extremity injuries and for lower and upper extremity injuries combined (n=1229). For the upper extremities (n=180), seasonal variation had a significant effect on the risk of prevalence. Analysis showed a 46% increase in injury incidence and a 32% increase in injury prevalence during summer relative to winter for lower and upper extremity injuries combined. CONCLUSIONS: There are clear seasonal differences in the occurrence of musculoskeletal extremity injuries among children with almost twice as high injury incidence and prevalence estimates during autumn, summer and spring compared with winter. This suggests further research into the underlying causes for seasonal variation and calls for preventive strategies to be implemented in order to actively prepare and supervise children before and during high-risk periods.

Back pain in children surveyed with weekly text messages - a 2.5 year prospective school cohort study.

BACKGROUND: Back pain is reported to occur already in childhood, but its development at that age is not well understood. The aims of this study were to describe BP in children aged 6-12 years, and to investigate any sex and age differences. METHODS: Data on back pain (defined as pain in the neck, mid back and/or lower back) were collected once a week from parents replying to automated text-messages over 2.5 school years from 2008 till 2011. The prevalence estimates were presented as percentages and 95% confidence intervals. Differences between estimates were considered significant if confidence intervals did not overlap. A test for trend, using a multi-level mixed-effects logistic regression extended to the longitudinal and multilevel setting, was performed to see whether back pain reporting increased with age. RESULTS: Depending on the age group, 13-38% children reported back pain at least once per survey year, and 5-23% at least twice per survey year. The average weekly prevalence estimate ranged between 1% and 5%. In the final survey year more girls than boys reported back pain at least twice. The prevalence estimates did not increase monotonically with age but showed a greater increase in children younger than 9/10, after which they remained relatively stable up to the age of 12 years. CONCLUSIONS: We found that back pain was not a common problem in this age group and recommend health professionals be vigilant if a child presents with constant or recurring back pain. Our results need to be supplemented by a better understanding of the severity and consequences of back pain in childhood. It would be productive to study the circumstances surrounding the appearance of back pain in childhood, as well as, how various bio-psycho-social factors affect its onset and later recurrence. Knowledge about the causes of back pain in childhood might allow early prevention.

Injuries in children with extra physical education in primary schools.

PURPOSE: (1) Examine the influence of extra physical education (EPE) on the number of musculoskeletal injuries in public schools accounting for organized sports participation (OSP) outside school. (2) Examine the major injury subgroup: growth-related overuse (GRO) through the overuse-related injury group. METHODS: A longitudinal controlled school-based study among Danish public schools. At baseline, 1216 children participated age 6.2-12.4 yr. Six schools (701 children) with EPE and four control schools (515 children) were followed up with weekly automated mobile phone text messages for information on musculoskeletal problems and OSP. Health care personnel diagnosed the children according to the World Health Organization's International Classification of Diseases, Tenth Revision. Data were analyzed using a two-part zero-inflated negative binomial (ZINB) regression model. RESULTS: School type had no influence on the odds of sustaining an injury but increased the probability of sustaining a higher injury count for children with injuries, with total injuries by a factor of 1.29 (95% confidence interval [CI] = 1.07-1.56), overuse by a factor of 1.29 (95% CI = 1.06-1.55), and GRO by a factor of 1.38 (95% CI = 1.02-1.80). Weekly mean OSP decreased the odds of belonging to the group of children with no injuries, by a factor of 0.29 (95% CI = 0.14-0.58), 0.26 (95% CI = 0.14-0.48), and 0.17 (95% CI = 0.06-0.52) for total, overuse, and GRO, respectively. OSP also increased the probability of sustaining a higher injury count for children with injuries by a factor of 1.11 (95% CI = 1.02-1.22), 1.10 (95% CI = 1.00-1.22), and 1.14 (95% CI = 1.00-1.30), respectively. CONCLUSIONS: Children enrolled in EPE schools with high OSP have the highest odds of injury and a high probability of sustaining a higher injury count compared to their peers at schools with normal PE. Special attention should be assigned to these children during compulsory PE.

Gαi2- and Gαi3-deficient mice display opposite severity of myocardial ischemia reperfusion injury.

G-protein-coupled receptors (GPCRs) are the most abundant receptors in the heart and therefore are common targets for cardiovascular therapeutics. The activated GPCRs transduce their signals via heterotrimeric G-proteins. The four major families of G-proteins identified so far are specified through their α-subunit: Gαi, Gαs, Gαq and G12/13. Gαi-proteins have been reported to protect hearts from ischemia reperfusion injury. However, determining the individual impact of Gαi2 or Gαi3 on myocardial ischemia injury has not been clarified yet. Here, we first investigated expression of Gαi2 and Gαi3 on transcriptional level by quantitative PCR and on protein level by immunoblot analysis as well as by immunofluorescence in cardiac tissues of wild-type, Gαi2-, and Gαi3-deficient mice. Gαi2 was expressed at higher levels than Gαi3 in murine hearts, and irrespective of the isoform being knocked out we observed an up regulation of the remaining Gαi-protein. Myocardial ischemia promptly regulated cardiac mRNA and with a slight delay protein levels of both Gαi2 and Gαi3, indicating important roles for both Gαi isoforms. Furthermore, ischemia reperfusion injury in Gαi2- and Gαi3-deficient mice exhibited opposite outcomes. Whereas the absence of Gαi2 significantly increased the infarct size in the heart, the absence of Gαi3 or the concomitant upregulation of Gαi2 dramatically reduced cardiac infarction. In conclusion, we demonstrate for the first time that the genetic ablation of Gαi proteins has protective or deleterious effects on cardiac ischemia reperfusion injury depending on the isoform being absent.

Interaction of the antibiotic minocycline with liver mitochondria - role of membrane permeabilization in the impairment of respiration.

Several studies have proposed that the antibiotic minocycline (MC) has cytoprotective activities. Nevertheless, when cells have been exposed to MC at micromolar concentrations, detrimental effects have been also observed. Despite the known inhibitory activity of MC on ATP synthesis and the Ca(2+) retention capacity of isolated rat liver and brain mitochondria, the underlying mechanism is still debated. Here, we present further arguments supporting our concept that MC acting on rat liver mitochondria suspended in KCl medium permeabilizes the inner membrane. Supplementation of the medium with cytochrome c and NAD(+) strongly enhanced the respiration of MC-treated mitochondria, thus partly preventing or reversing the inhibitory effect of MC on state 3 or uncoupled respiration. These results indicate that MC produced depletion of mitochondrial cytochrome c and NAD(+) , thus impairing mitochondrial respiration. In addition, NADH oxidation by alamethicin-permeabilized mitochondria supplemented with cytochrome c was insensitive to 200 µm MC, arguing against direct impairment of respiratory chain complexes by MC. Finally, a surprising feature of MC was its accumulation or binding by intact rat liver mitochondria, but not by mitochondria permeabilized with alamethicin or disrupted by freezing and thawing.

The uncoordinated-5 homolog B (UNC5B) receptor increases myocardial ischemia-reperfusion injury.

The UNC5 receptor family are chemorepulsive neuronal guidance receptors with additional functions outside the central nervous system. Previous studies have implicated that the UNC5B receptor influences the migration of leukocytes into sites of tissue inflammation. Given that this process is a critical step during the pathophysiology of myocardial ischemia followed by reperfusion (IR) we investigated the role of UNC5B during myocardial IR. In initial in-vitro experiments, the functional inhibition of UNC5B resulted in a significant reduction of chemotactic migration of neutrophils. In-vivo, using a model of acute myocardial ischemia in UNC5B(+/-) and wild type (WT) animals, we found a significant reduction of infarct sizes in UNC5B(+/-) animals. This was associated with significantly reduced levels of troponin-I and IL-6 in UNC5B(+/-) mice. The repression of UNC5B using siRNA and the functional inhibition of UNC5B significantly dampened the extent of myocardial IR injury. Following depletion of neutrophils, we were not able to observe any further reduction in infarct size through functional inhibition of UNC5B in WT and UNC5B(+/-) mice. In summary our studies demonstrate an important role for UNC5B during myocardial IR injury, and that UNC5B might be a potential therapeutic target to control reperfusion injury in the future.

Resveratrol binds to the sulfonylurea receptor (SUR) and induces apoptosis in a SUR subtype-specific manner.

Sulfonylurea receptors (SURs) constitute the regulatory subunits of ATP-sensitive K+ channels (K(ATP) channels). SUR binds nucleotides and synthetic K(ATP) channel modulators, e.g. the antidiabetic sulfonylurea glibenclamide, which acts as a channel blocker. However, knowledge about naturally occurring ligands of SUR is very limited. In this study, we show that the plant phenolic compound trans-resveratrol can bind to SUR and displace binding of glibenclamide. Electrophysiological measurements revealed that resveratrol is a blocker of pancreatic SUR1/K(IR)6.2 K(ATP) channels. We further demonstrate that, like glibenclamide, resveratrol induces enhanced apoptosis. This was shown by analyzing different apoptotic parameters (cell detachment, nuclear condensation and fragmentation, and activities of different caspase enzymes). The observed apoptotic effect was specific to cells expressing the SUR1 isoform and was not mediated by the electrical activity of K(ATP) channels, as it was observed in human embryonic kidney 293 cells expressing SUR1 alone. Enhanced susceptibility to resveratrol was not observed in pancreatic beta-cells from SUR1 knock-out mice or in cells expressing the isoform SUR2A or SUR2B or the mutant SUR1(M1289T). Resveratrol was much more potent than glibenclamide in inducing SUR1-specific apoptosis. Treatment with etoposide, a classical inducer of apoptosis, did not result in SUR isoform-specific apoptosis. In conclusion, resveratrol is a natural SUR ligand that can induce apoptosis in a SUR isoform-specific manner. Considering the tissue-specific expression patterns of SUR isoforms and the possible effects of SUR mutations on susceptibility to apoptosis, these observations could be important for diabetes and/or cancer research.

Glibenclamide-induced apoptosis is specifically enhanced by expression of the sulfonylurea receptor isoform SUR1 but not by expression of SUR2B or the mutant SUR1(M1289T).

Sulfonylurea receptor 1 (SUR1) is the regulatory subunit of the pancreatic ATP-sensitive K+ channel (K(ATP) channel), which is essential for triggering insulin secretion via membrane depolarization. Sulfonylureas, such as glibenclamide and tolbutamide, act as K(ATP) channel blockers and are widely used in diabetes treatment. These antidiabetic substances are known to induce apoptosis in pancreatic beta-cells or beta-cell lines under certain conditions. However, the precise molecular mechanisms of this sulfonylurea-induced apoptosis are still unidentified. To investigate the role of SUR in apoptosis induction, we tested the effect of glibenclamide on recombinant human embryonic kidney 293 cells expressing either SUR1, the smooth muscular isoform SUR2B, or the mutant SUR1(M1289T) at which a single amino acid in transmembrane helix 17 (TM17) was exchanged by the corresponding amino acid of SUR2. By analyzing cell detachment, nuclear condensation, DNA fragmentation, and caspase-3-like activity, we observed a SUR1-specific enhancement of glibenclamide-induced apoptosis that was not seen in SUR2B, SUR1(M1289T), or control cells. Coexpression with the pore-forming Kir6.2 subunit did not significantly alter the apoptotic effect of glibenclamide on SUR1 cells. In conclusion, expression of SUR1, but not of SUR2B or SUR1(M1289T), renders cells more susceptible to glibenclamide-induced apoptosis. Therefore, SUR1 as a pancreatic protein could be involved in specific variation of beta-cell mass and might also contribute to the regulation of insulin secretion at this level. According to our results, TM17 is essentially involved in SUR1-mediated apoptosis. This effect does not require the presence of functional Kir6.2-containing K(ATP) channels, which points to additional, so far unknown functions of SUR.

Targeted mutagenesis of the farnesylation site of Drosophila Ggammae disrupts membrane association of the G protein betagamma complex and affects the light sensitivity of the visual system.

Activation of phototransduction in the compound eye of Drosophila is mediated by a heterotrimeric G protein that couples to the effector enzyme phospholipase Cbeta. The gamma subunit of this G protein (Ggammae) as well as gamma subunits of vertebrate transducins contain a carboxyl-terminal CAAX motif (C, cysteine; A, aliphatic amino acid; X, any amino acid) with a consensus sequence for protein farnesylation. To examine the function of Ggammae farnesylation, we mutated the farnesylation site and overexpressed the mutated Ggammae in Drosophila. Mass spectrometry of overexpressed Ggammae subunits revealed that nonmutated Ggammae is modified by farnesylation, whereas the mutated Ggammae is not farnesylated. In the transgenic flies, mutated Ggammae forms a dimeric complex with Gbetae, with the consequence that the fraction of non-membrane-bound Gbetagamma is increased. Thus, farnesylation of Ggammae facilitates the membrane attachment of the Gbetagamma complex. We also expressed human Ggammarod in Drosophila photoreceptors. Despite similarities in the primary structure between the transducin gamma subunit and Drosophila Ggammae, we observed no interaction of human Ggammarod with Drosophila Gbetae. This finding indicates that human Ggammarod and Drosophila Ggammae provide different interfaces for the interaction with Gbeta subunits. Electroretinogram recordings revealed a significant loss of light sensitivity in eyes of transgenic flies that express mutated Ggammae. This loss in light sensitivity reveals that post-translational farnesylation is a critical step for the formation of membrane-associated Galphabetagamma required for transmitting light activation from rhodopsin to phospholipase Cbeta.

Motion palpation findings and self-reported low back pain in a population-based study sample.

BACKGROUND: Although the clinical usefulness of motion palpation has not been established, it is one of the most commonly used diagnostic methods by chiropractors. Notably, its sensitivity, specificity, and validity in general have not been adequately studied, and most study samples have consisted of student volunteers. OBJECTIVE: To determine the prevalence of positive motion-palpation findings (so-called fixations and spontaneous pain response) in relation to self-reported low back pain status and to determine the sensitivity and specificity of the motion-palpation technique carried out on the sacroiliac and lumbar joints. DESIGN: Study subjects were examined by 1 examiner (out of 7 possible), who was unaware of their low back pain status. Information on low back pain was then collected in a self-report questionnaire. SETTING: Research laboratory at the Odense University Hospital, Denmark. PARTICIPANTS: One hundred eighty-four twins, consisting of a subset of healthy twins taken from a panel of population-generated twins aged 19 to 42 years, made up the study sample. Examiners consisted of 7 biomechanics (chiropractic) students from the University of Southern Denmark who were proficient in motion palpation. MAIN OUTCOME MEASURES: The prevalence rates of motion palpation-determined fixations and of spontaneous pain reactions in response to motion palpation were studied in relation to anatomic area, self-reported low back pain status, and each other. RESULTS: The point period prevalence of low back pain was 14%. Fixations were found in 43% of the study sample, and 25% appeared to have a painful reaction to motion palpation. There was no logical pattern of fixations and spontaneous pain reactions in relation to the low back pain status. The sensitivity was generally low (always below 60%) for fixations and pain, whereas the specificity was higher, significantly so for pain in the mid lumbar area. There was no strong association between fixations and the examiners' interpretation of a spontaneous pain reaction in response to motion palpation. CONCLUSION: Motion palpation does not appear to be a good method to differentiate persons with or without low back pain. It is possible to dissociate the findings of fixations and those of pain reactions.