Factors associated with depression and anxiety in children with intellectual disabilities.

BACKGROUND: Individuals with intellectual disabilities (ID) are at increased risk for depression and anxiety disorders; however, there is a paucity of research that pertains to associative factors for these mental health disorders in this population. The objective of this investigation was to determine factors associated with depression and anxiety problems in children with ID. METHODS: Children 6-17 years with ID (n = 423; 63% male) from the 2016 National Survey of Children's Health were included in this cross-sectional study. Outcome measures included depression and anxiety problems. Predictor variables included sociodemographics, ID severity, co-morbid conditions (autism spectrum disorders, epilepsy, cerebral palsy, Down syndrome and attention-deficit/hyperactivity disorder), physical factors (i.e. physical activity, sleep duration and pain) and social factors (e.g. participation in activities and bully victimisation). Multivariable logistic regression was performed to determine the association between all factors and depression and/or anxiety problems among children with ID. RESULTS: The prevalence of depression and/or anxiety problems was 35.4%. After adjusting for sociodemographics, Hispanic race was associated with lower odds [odds ratio (OR), 0.3; 95% confidence interval (CI), 0.1-0.8] of depression and/or anxiety problems. After adjusting for race, co-morbid conditions, and physical and social factors, autism spectrum disorders (OR, 4.4; 95% CI, 1.1-10.1), Down syndrome (OR, 0.2; 95% CI, 0.1-0.8), attention-deficit/hyperactivity disorder (OR, 5.9; 95% CI, 2.5-14.3), pain (OR, 7.0; 95% CI, 2.9-17.1) and bully victimisation (OR 2.3; 95% CI, 1.0-5.3) were each associated with depression and/or anxiety problems. CONCLUSIONS: The present study identified both treatable and modifiable, as well as unmodifiable, factors associated with depression and/or anxiety problems in children with ID.

Handgrip and knee extension strength as predictors of cancer mortality: A systematic review and meta-analysis.

The specific role of different strength measures on mortality risk needs to be clarified to gain a better understanding of the clinical importance of different muscle groups, as well as to inform intervention protocols in relation to reducing early mortality. The aim of the systematic review and meta-analysis was to determine the relationship between muscular strength and risk of cancer mortality. Eligible cohort studies were those that examined the association between muscular strength, as assessed using validated tests, and cancer mortality in healthy youth and adults. The hazard ratio (HR) estimates obtained were pooled using random effects meta-analysis models. The outcome was cancer mortality assessed using the HR (Cox proportional hazards model). Eleven prospective studies with 1 309 413 participants were included, and 9787 cancer-specific deaths were reported. Overall, greater handgrip (HR = 0.97, 95% CI, 0.92-1.02; P = .055; I2  = 18.9%) and knee extension strength (HR = 0.98, 95% CI, 0.95-1.00; P = .051; I2  = 60.6%) were barely significant associated with reduced risk of cancer mortality. Our study suggests that higher level of muscular strength is not statistically associated with lower risk of cancer mortality.

Treadmill training in Parkinson's patients after deep brain stimulation: Effects on gait kinematic.

OBJECTIVE: The purpose of this study was to evaluate the effect of treadmill training with body weight support on gait kinematics parameters in patients with PD using DBS. DESIGN: Twelve patients completed the protocols (age: 60.9±10.6 years; disease duration: 20±7 years; and time since DBS surgery: 20±4 months). The same set of patients underwent two trainings protocols and four gait analyses (before and after each training). They received eight weeks of treadmill training without body weight support (16 sessions) in conjunction with physiotherapy program followed by six weeks of wash out period, followed by eight weeks of body-weight-supported treadmill training in conjunction with a same physiotherapy program. The Gait Kinematic Analysis involved eight infrared cameras that detected 19 reflective spherical markers attached in limb lower of patients. Statistical analysis used the Wilcoxon test (p≤0.05). RESULTS: Both the training no showed significant differences in linear variables. As the angular variables, only training with support showed significant increase of ranges of motion: pelvis tilt, obliquity and rotation amplitude; hip adduction-abduction and rotation amplitude; percentage of peak flexion in swing phase; foot progression amplitude. CONCLUSION: The body weight supported treadmill training may promote increase of mobility of lower limbs during gait and it could be a targeted intervention for PD patients treated with DBS.

Muscle Weakness and Physical Disability in Older Americans: Longitudinal Findings from the U.S. Health and Retirement Study.

IMPORTANCE: Muscle weakness is an important indicator of disability, chronic disease and mortality. While we recently proposed sex/race specific grip strength cutpoints for clinical muscle weakness in a diverse, nationally representative sample of older Americans, the extent to which these cutpoints predict physical disability remains unknown. OBJECTIVE: To examine whether sex/race specific muscle weakness cutpoints predict physical disability status in a nationally representative sample of Americans age 65+. DESIGN: We used data from the 2006-2010 Health and Retirement Study. Fully-adjusted, weighted multinomial logistic regression models were used to quantify the odds of experiencing the onset, progression or persistence of disability in activities of daily living (ADL) among weak versus non-weak individuals over a 2-year period. SETTING: General community, nationally representative sample of older Americans. PARTICIPANTS: Population-based, community dwelling sample of older American adults aged 65-years+; 57 percent were women, 91% were White and the mean age was 75 years. Main Outcome(s) and Measure(s): The primary outcome of interest was disability dynamics, defined by changes in ADL status across at 2- year period. The primary exposure was clinical muscle weakness as defined by previously identified cutpoints. Hypotheses were formulated before analyses were conducted. RESULTS: In this nationally representative sample (n= 8,725), 44% of individuals were classified as weak at baseline. At follow-up, 55% remained independent with no change in their ADL status, 11% had an onset of disability and 4% progressed in their disability status. The odds of experiencing an onset of ADL disability was 54% higher among weak individuals compared those who were not weak at baseline (OR= 1.54, 95% CI= 1.54, 1.5, p<.0001); the odds of experiencing a progression in physical disability status was 2.16 times higher among those who were weak at baseline compared to non-weak individuals (OR= 2.16, 95% CI= 2.15, 2.16, p<.0001). CONCLUSIONS: This is the first study to use grip strength weakness cut-points to identify those who may be at greatest risk for experiencing physical disability in later life. Results underscore the importance of using population-specific cutpoints for clinical weakness in order to identify individuals at greatest risk for adverse health outcomes.

Chronic disease risk among adults with cerebral palsy: the role of premature sarcopoenia, obesity and sedentary behaviour.

Premature declines in function among adults with cerebral palsy (CP) are generally attributed to weakness, spasticity and orthopaedic abnormalities, as well as chronic pain and fatigue. Very little research or clinical attention has been devoted to the confluence and consequences of early muscle wasting and obesity as mediators of secondary comorbidity in this population, and perhaps more importantly, to the role of lifestyle to potentiate these outcomes. At present, there are no national surveillance programmes that monitor chronic health in adults with CP; however, mortality records have demonstrated a greater prevalence of coronary heart disease as compared with the general population. Although by definition, CP is a 'non-progressive' condition, secondary factors such as habitual sedentary behaviour, obesity, and premature sarcoepenia may increase the severity of functional impairment throughout adulthood, and lead to cardiometabolic disease, fragility and/or early mortality. Herein we describe the heightened health risk represented in adults with CP, and discuss the hallmark phenotypic features that coincide with ageing, obesity and cardiometabolic disorders. Moreover, we provide discussion regarding the protective role of habitual physical activity to stimulate anti-inflammatory pathways and to ameliorate global risk. Although physical therapeutic modalities are already widely acknowledged as a vital component to improve movement quality in CP, the purpose of this review was to present a compelling case for the value of lifelong physical activity participation for both function and cardiometabolic health preservation.

Adiposity attenuates muscle quality and the adaptive response to resistance exercise in non-obese, healthy adults.

BACKGROUND: Emerging data have revealed a negative association between adiposity and muscle quality (MQ). There is a lack of research to examine this interaction among young, healthy individuals, and to evaluate the contribution of adiposity to adaptation after resistance exercise (RE). OBJECTIVE: The purpose of this investigation was to examine the influence of subcutaneous adipose tissue (SAT) on muscle function among non-obese individuals before and after RE. DESIGN: Analyses included 634 non-obese (body mass index <30 kg m(-2)) subjects (253 males, 381 females; age=23.3 ± 5.2 years). SAT and muscle mass (magnetic resonance imaging-derived SAT and biceps muscle volume), isometric and dynamic biceps strength, and MQ (strength/muscle volume), were analyzed at baseline and after 12 weeks of unilateral RE. RESULTS: At baseline, SAT was independently associated with lower MQ for males (ß=-0.55; P<0.01) and females (ß=-0.45; P<0.01), controlling for body mass and age. Adaptation to RE revealed a significant negative association between SAT and changes for strength capacity (ß=-0.13; p=0.03) and MQ (ß=-0.14; P<0.01) among males. No attenuation was identified among females. Post-intervention SAT remained a negative predictor of MQ for males and females (ß=-0.47; P<0.01). CONCLUSIONS: The findings reveal that SAT is a negative predictor of MQ among non-obese, healthy adults, and that after 12 weeks of progressive RE this association was not ameliorated. Data suggest that SAT exerts a weak, negative influence on the adaptive response to strength and MQ among males.

Pharmacokinetics of sufentanil in patients undergoing coronary artery bypass graft surgery.

OBJECTIVE: To determine the pharmacokinetics of sufentanil in patients undergoing coronary artery bypass graft surgery. DESIGN: Prospective, multigroup study. SETTING: University-affiliated hospital. PARTICIPANTS: Patients with good left ventricular function undergoing elective surgery (n = 103). INTERVENTIONS: Sufentanil was administered by target-controlled infusion, with target effect-site concentrations ranging from 0.4 to 4.5 ng/mL. Isoflurane was administered as required to maintain stable hemodynamics. Sufentanil pharmacokinetics were determined by population modeling. The potential effects of gender, weight, different premedications (lorazepam, morphine-scopolamine, or clonidine), and coinduction with propofol on sufentanil pharmacokinetics were explored. MEASUREMENTS AND MAIN RESULTS: The first model determined was a simple 3-compartment model, without any covariates, which had these parameters: V(1) = 5.7 L, V(2) = 18.1 L, V(3) = 225 L, Cl(1) = 0.69 L/min, Cl(2) = 3.1 L/min, and Cl(3) = 1.4 L/min. The overall predictive ability during the entire pre-cardiopulmonary bypass period of this model was excellent, with virtually no bias (median prediction error, -0.4%) and good precision (median absolute prediction error, 18.4%). More complex models with the various premedications used or coinduction with propofol as covariates did not improve the predictive accuracy or precision compared with the simple 3-compartment model. Similarly, including either gender or weight as a covariate did not improve predictive ability. CONCLUSION: The authors have determined a pharmacokinetic model for sufentanil that can be used to maintain desired target concentrations of sufentanil before cardiopulmonary bypass, with a high degree of accuracy and acceptable variability. Concomitantly administered medications (lorazepam, morphine-scopolamine, clonidine, or propofol) do not appear to have any clinically important effects on distribution-phase sufentanil pharmacokinetics.

The embryonic expression pattern of labial, posterior homeotic complex genes and the teashirt homologue in an apterygote insect.

During embryogenesis of the fruit fly, Drosophila melanogaster, the homeotic genes are required to specify proper cell fates along the anterior-posterior axis of the embryo. We cloned partial cDNAs of homologues of the Drosophila homeotic gene teashirt and five of the homeotic-complex (HOM-C) genes from the thysanuran insect, Thermobia domestica, and assayed their embryonic expression patterns. The HOM-C genes we examined were labial, Antennapedia, Ultrabithorax, abdominal-A and Abdominal-B. As the expression pattern of these HOM-C genes is largely conserved among insects and as Thermobia is a member of a phylogenetically basal order of insects, we were able to infer their ancestral expression patterns in insects. We compare the expression patterns of the Thermobia HOM-C genes with their expression in Drosophila and other insects and discuss the potential roles these genes may have played in insect evolution. Interestingly, the teashirt homologue shows greater variability between Thermobia and Drosophila than any of the HOM-C genes. In particular, teashirt is not expressed strongly in the Thermobia abdomen, unlike Drosophila teashirt. We propose that teashirt expression has expanded posteriorly in Drosophila and contributed to a homogenization of the Drosophila larval thorax and abdomen.

The expression of two engrailed-related genes in an apterygote insect and a phylogenetic analysis of insect engrailed-related genes.

Homologues of the Drosophila segment polarity gene engrailed have been cloned from many insect species, as well as other arthropods and non-arthropods. We have cloned partial cDNAs of two engrailed homologues, which we call engrailed-related genes, from the phylogenetically basal insect, Thermobia domestica (Order Thysanura) and possibly as many as four engrailed-related genes from the phylogenetically intermediate insect, Oncopeltus fasciatus (Order Hemiptera). Previous to our findings, only single engrailed-related homologues had been found in phylogenetically intermediate insect species (Tribolium and Schistocerca) and in the crustacean Artemia, while two engrailed-related homologues have been found in more derived orders (Hymenoptera and the engrailed and invected genes of lepidopterans and dipterans). Consequently, we performed a phylogenetic analysis of insect engrailed-related genes to determine whether insects ancestrally had one or two engrailed-related genes. We have found evidence of concerted evolution among engrailed-related paralogues, however, that masks the true phylogenetic history of these genes; the phylogeny may only be decipherable, therefore, by examining the presence or absence of engrailed-specific and invected-specific motifs, which will require cloning the full length cDNAs from more species. In addition, we examined the embryonic expression pattern of the two Thermobia engrailed-related genes; like Drosophila engrailed and invected, they are expressed in very similar patterns, but show one temporal difference in pregnathal segments that correlates with the tentative phylogenetic placement of the genes. Thermobia engrailed-related expression also confirms that the dorsal ridge is an ancient structure in insects.

Compensatory spinopelvic balance over the hip axis and better reliability in measuring lordosis to the pelvic radius on standing lateral radiographs of adult volunteers and patients.

STUDY DESIGN: Sagittal alignments, including lumbar lordosis and spinopelvic balance (measured from C7, S1, and hip axis reference points for the relative positions of the spine and sacropelvis over the hips), were studied on standing 36-in. lateral radiographs of adult volunteers (control subjects) and patients who had specific spinal disorders. OBJECTIVES: To determine the most reliable methods for measuring lumbopelvic lordosis and to define significant spinopelvic compensations for sagittal balance. SUMMARY OF BACKGROUND DATA: Measurements for standing sagittal balance, obtained using a C7 plumb line, and segmental angulations of the spinal vertebrae, including lordosis to the sacrum, have been reported. Absolute values, even for normative data, have had wide variation and limited clinical usefulness. Correlations of sagittal balance with the reported spinopelvic angulations (spinal vertebral and sacropelvic angulations) have not been well defined. In addition, determinates of balance (spinal and pelvic) have not been studied for reliability, and compensatory mechanisms for maintenance of balance have not been carefully evaluated. Better recognition of the correlations and more reliable methods to measure lordosis and balance and the spinopelvic compensations for its maintenance may be beneficial in treating patients who have spinal disorders. METHODS: Measurements on standing 36-in. lateral radiographs were made for sagittal alignments in adult volunteers (n = 50) and in adult patients who had symptomatic degenerative lumbar disc disease (n = 50), low grade L5-S1 isthmic (lytic) spondylolisthesis (n = 30), and idiopathic or degenerative scoliosis (n = 30). All participants exhibited clinical compensation for balance. Data were analyzed for significant correlations within each group to determine compensatory correlations of spinopelvic balance with the other sagittal alignments. Intraobserver and interobserver reliability for the parameters evaluated were calculated. This included two methods for determining lordosis (S1 end-plate and pelvic radius techniques). RESULTS: Plumb line measurements for balance from the S1 and hip axis reference points, as defined, were similar in all four groups. However, the groups appeared to adjust for balance by using common and distinctive spinopelvic compensations that resulted in significantly and characteristically different angular alignments among the four groups. Lordosis and balance measurements were closely correlated, and the correlation was characterized by pelvic rotation and translation around the hip axis. The subjects with less lordosis typically stood with the C7 plumb line anterior to and at a longer distance from the sacral reference point. This was primarily because of posterior sacropelvic translation around the hip axis and not because the sagittal plumb line initially moved anteriorly away from the sacrum. This was true in all four groups and gave the appearance that the sacropelvis was less well balanced over the hips in the subjects with less lordosis. Even small differences in lordosis appeared to be associated with considerable adjustments in the other spinopelvic alignments. Therefore, it was important to determine that lordosis was lumbopelvic more reliably measured by the pelvic radius technique. CONCLUSIONS: Lower lumbar lordosis, by the pelvic radius technique, and compensatory sacropelvic translation around a hip axis, in addition to measurements from this axis to the C7 plumb line, were the primary determinates and most reliable radiographic assessments for sagittal balance. Understanding the common and characteristically different compensations that occur with balance in these patients who had specific spinal disorders may help to improve their care.

A comparison of clonidine with conventional preanesthetic medication in patients undergoing coronary artery bypass grafting.

UNLABELLED: In this controlled study, we compared clonidine with conventional premedication in 35 patients undergoing coronary artery bypass grafting (CABG). After premedication with clonidine 5 microg/kg p.o. (Group C, n = 11), lorazepam 60 microg/kg p.o. (Group L, n = 13), or morphine 0.1 mg/kg plus scopolamine 6 microg/kg i.m. (Group M, n = 11), sedation, anxiety, and quality of premedication were graded. After the administration of sufentanil 2.0 microg/kg over 12.5 min, a computer-assisted infusion device targeted a sufentanil effect-site concentration of 0.75 ng/mL. Hemodynamic variables, end-tidal isoflurane concentration (ET-ISO), the electroencephalographic spectral edge, and the serum sufentanil concentration (SUF) were measured. There were no intergroup differences in anxiety, sedation, quality of premedication, the dose of sufentanil causing unconsciousness, or the electroencephalographic (EEG) response to induction. Intraoperative SUF was stable, with no intergroup difference. The average prebypass ET-ISO was lower in Group C than in Group M. The ET-ISO and peak ET-ISO after intense surgical stimulation were lower in Group C versus Groups L and M. Mean arterial blood pressure was lower in Group C versus Groups L and M. There were no intergroup differences in pharmacologic intervention, time to extubation, or intensive care unit stay. Clonidine produces sedation, anxiolysis, and quality of premedication comparable to conventional premedication. Compared with other drugs, clonidine does not alter the dose of sufentanil inducing unconsciousness or EEG slowing, but it uniquely reduces isoflurane requirements. IMPLICATIONS: In patients undergoing coronary artery bypass grafting, clonidine produces sedation and relieves anxiety as effectively as conventional premedication. Clonidine does not uniquely alter the dose of sufentanil inducing unconsciousness or electroencephalographic slowing, but it significantly reduces isoflurane requirements.

Instrumented posterolateral lumbar fusion. Results and comparison with anterior interbody fusion.

STUDY DESIGN: Prospective case series. OBJECTIVES: To assess the results of instrumented posterolateral lumbar fusion, using recognized outcome assessment techniques, to evaluate the correlation between technical and clinical results and the effects of assessment techniques, and to compare the outcome with that of anterior lumbar fusion. SUMMARY OF BACKGROUND DATA: Assessments of lumbar spinal fusion results have frequently been published in forms that render direct comparison difficult and thus have not provided optimal assistance in the selection of a preferred method of treatment. METHODS: One hundred and thirty-five patients with intractable back pain underwent instrumented posterolateral lumbar spinal fusion performed by a single surgeon. Review of results was undertaken by independent observers, using a recognized outcome assessment measure. RESULTS: A solid bony fusion was obtained in 82% of patients. The method of outcome assessment profoundly affected the results; whereas 65% of patients rated themselves significantly improved by the procedure, only 19% achieved a good or excellent result on the Low Back Outcome Score. Patients undergoing a second procedure did not do well, and "salvage" surgery is not recommended. Compensation status was a significant prognostic factor. Psychological distress at review had a profound effect on the disability score and on patient satisfaction ratings. Overall, the results were inferior to those in a similar series treated by anterior lumbar fusion. CONCLUSION: It is recommended that in future studies a recognized outcome score be used and that the analysis specifically include compensation status and psychological distress.

Evolution of the insect body plan as revealed by the Sex combs reduced expression pattern.

The products of the HOM/Hox homeotic genes form a set of evolutionarily conserved transcription factors that control elaborate developmental processes and specify cell fates in many metazoans. We examined the expression of the ortholog of the homeotic gene Sex combs reduced (Scr) of Drosophila melanogaster in insects of three divergent orders: Hemiptera, Orthoptera and Thysanura. Our data reflect how the conservation and variation of Scr expression has affected the morphological evolution of insects. Whereas the anterior epidermal expression of Scr, in a small part of the posterior maxillary and all of the labial segment, is found to be in common among all four insect orders, the posterior (thoracic) expression domains vary. Unlike what is observed in flies, the Scr orthologs of other insects are not expressed broadly over the first thoracic segment, but are restricted to small patches. We show here that Scr is required for suppression of wings on the prothorax of Drosophila. Moreover, Scr expression at the dorsal base of the prothoracic limb in two other winged insects, crickets (Orthoptera) and milkweed bugs (Hemiptera), is consistent with Scr acting as a suppressor of prothoracic wings in these insects. Scr is also expressed in a small patch of cells near the basitarsal-tibial junction of milkweed bugs, precisely where a leg comb develops, suggesting that Scr promotes comb formation, as it does in Drosophila. Surprisingly, the dorsal prothoracic expression of Scr is also present in the primitively wingless firebrat (Thysanura) and the leg patch is seen in crickets, which have no comb. Mapping both gene expression patterns and morphological characters onto the insect phylogenetic tree demonstrates that in the cases of wing suppression and comb formation the appearance of expression of Scr in the prothorax apparently precedes these specific functions.

Acute slipped capital femoral epiphysis: the value and safety of urgent manipulative reduction.

A 40-year experience consisting of 91 cases of acute slipped capital femoral epiphysis (SCFE) was reviewed to assess the safety of manipulative reduction and to determine whether urgent reduction has an effect on the development of avascular necrosis (AVN) of the capital femoral epiphysis. All patients had a history of sudden onset of severe hip pain and were documented to have an unstable (acute) slipped epiphysis. Treatment modalities included manipulative reduction under general anesthesia followed by internal fixation (41 hips), epiphysiodesis and internal fixation (15 hips), epiphysiodesis and cast immobilization (31 hips), and cast immobilization alone (three hips). One case was treated with cast immobilization after reduction by skeletal traction. Patient follow-up averaged 44 months, and ranged from 12 to 216 months. Radiographic review identified 13 (14%) cases of AVN in the series of 91 hips. Of 42 hips reduced in <24 h from presentation, AVN developed in three (7%). Of 49 hips reduced in >24 h from presentation, AVN developed in 10 (20%). Manipulative reduction of the acute SCFE may be accomplished without increased risk of AVN. Time to reduction may be an important risk factor for development of AVN after acute SCFE.

Dictyostelium discoideum myoJ: a member of a broadly defined myosin V class or a class XI unconventional myosin?

The simple eukaryote Dictyostelium discoideum contains at least 12 unconventional myosin genes. Here we report the characterization of one of these, myoJ, a gene initially identified through a physical mapping screen. The myoJ gene encodes a high molecular weight myosin, and analysis of the available deduced amino acid sequence reveals that it possesses six IQ motifs and sequences typical of alpha helical coiled coils in the tail region. Therefore, myoJ is predicted to exist as a dimer with up to 12 associated light chains (six per heavy chain). The 7.8 kb myoJ mRNA is expressed all throughout the life cycle of D. discoideum. The myoJ gene has been disrupted and a phenotypic analysis of the mutant cells initiated. Finally, phylogenetic analysis of the head region reveals that myoJ is most similar to two plant myosin genes, Arabidopsis MYA1 and MYA2, that have been alternatively suggested to be either members of the myosin V class or founding members of the myosin XI class.

Examination of the endosomal and lysosomal pathways in Dictyostelium discoideum myosin I mutants.

The role of myosin Is in endosomal trafficking and the lysosomal system was investigated in a Dictyostelium discoideum myosin I double mutant myoB-/C-, that has been previously shown to exhibit defects in fluid-phase endocytosis during growth in suspension culture (Novak et al., 1995). Various properties of the endosomal pathway in the myoB-/C- double mutant as well as in the myoB- and myoC- single mutants, including intravesicular pH, and intracellular retention time and exocytosis of a fluid phase marker, were found to be indistinguishable from wild-type parental cells. The intimate connection between the contractile vacuole complex and the endocytic pathway in Dictyostelium, and the localization of a myosin I to the contractile vacuole in Acanthamoeba, led us to also examine the structure and function of this organelle in the three myosin I mutants. No alteration in contractile vacuole structure or function was observed in the myoB-, myoC- or myoB-/C- cell lines. The transport, processing, and localization of a lysosomal enzyme, alpha-mannosidase, were also unaltered in all three mutants. However, the myoB- and myoB-/C- cell lines, but not the myoC- cell line, were found to oversecrete the lysosomal enzymes alpha-mannosidase and acid phosphatase, during growth and starvation. None of the mutants oversecreted proteins following the constitutive secretory pathway. Two additional myosin I mutants, myoA- and myoA-/B-, were also found to oversecrete the lysosomally localized enzymes alpha-mannosidase and acid phosphatase. Taken together, these results suggest that these myosins do not play a role in the intracellular movement of vesicles, but that they may participate in controlling events that occur at the actin-rich cortical region of the cell. While no direct evidence has been found for the association of myosin Is with lysosomes, we predict that the integrity of the lysosomal system is tied to the fidelity of the actin cortex, and changes in cortical organization could influence lysosomal-related membrane events such as internalization or transit of vesicles to the cell surface.

Dictyostelium myosin I double mutants exhibit conditional defects in pinocytosis.

The functional relationship between three Dictyostelium myosin Is, myoA, myoB, and myoC, has been examined through the creation of double mutants. Two double mutants, myoA-/B- and myoB-/C-, exhibit similar conditional defects in fluid-phase pinocytosis. Double mutants grown in suspension culture are significantly impaired in their ability to take in nutrients from the medium, whereas they are almost indistinguishable from wild-type and single mutant strains when grown on a surface. The double mutants are also found to internalize gp126, a 116-kD membrane protein, at a slower rate than either the wild-type or single mutant cells. Ultrastructural analysis reveals that both double mutants possess numerous small vesicles, in contrast to the wild-type or myosin I single mutants that exhibit several large, clear vacuoles. The alterations in fluid and membrane internalization in the suspension-grown double mutants, coupled with the altered vesicular profile, suggest that these cells may be compromised during the early stages of pinocytosis, a process that has been proposed to occur via actin-based cytoskeletal rearrangements. Scanning electron microscopy and rhodamine-phalloidin staining indicates that the myosin I double mutants appear to extend a larger number of actin-filled structures, such as filopodia and crowns, than wild-type cells. Rhodamine-phalloidin staining of the F-actin cytoskeleton of these suspension-grown cells also reveals that the double mutant cells are delayed in the rearrangement of cortical actin-rich structures upon adhesion to a substrate. We propose that myoA, myoB, and myoC play roles in controlling F-actin filled membrane projections that are required for pinosome internalization in suspension.

The effect of operative position on lumbar lordosis. A radiographic study of patients under anesthesia in the prone and 90-90 positions.

STUDY DESIGN: The effect of intraoperative positioning on lumbar lordosis was retrospectively studied by radiographic analysis of 40 patients under general anesthesia. OBJECTIVES: The aim of this study was to document changes in segmental and total lumbar lordosis between preoperative standing and intraoperative radiographs taken in the "90-90" and prone positions. SUMMARY OF BACKGROUND: Preservation of physiologic lordosis was an important consideration in reconstructive lumbar spine surgery. To avoid iatrogenic loss of lordosis when using spinal instrumentation and to facilitate decompressive procedures, it was necessary to understand how segmental alignments were affected by intraoperative positioning. Although many positioning techniques were used, the effect on lumbar lordosis was not well established. METHODS: Preoperative (standing 36" lateral spine) and intraoperative radiographs (lateral lumbar spine L1 to the sacrum) in either the "90-90" position on a Hastings frame (n = 20) or the prone position on a Jackson table (n = 20) were measured twice by two independent observers using Cobb methodology for total and segmental lordosis between L1 and S1. Data were analyzed for intra- and interobserver reliability and changes in segmental and total lordosis between standing and intraoperative radiographs. RESULTS: Analysis of intra- and interobserver reliability revealed measurements were accurate and reproducible. The "90-90" position produced significant loss (P < or = 0.01) of total and segmental lordosis at all levels except L1-L2, which showed no change. Segmental lordosis was reduced nearly 60% at L2-L3, L3-L4, and L4-L5, and total lordosis was reduced by more than 35%. The prone position on the Jackson table increased segmental lordosis at L5-S1 by 22% (P < or = 0.01) and preserved total and segmental standing lordosis at all other levels. CONCLUSIONS: The "90-90" position on the Hastings frame was associated with significant reduction of total and segmental lordosis in the middle and lower lumbar spine. Positioning prone on a Jackson table maintained standing lumbar lordosis and increased lumbosacral lordosis.

Molecular genetic analysis of myoC, a Dictyostelium myosin I.

The protozoan myosin Is are widely expressed actin-based motors, yet their in vivo roles remain poorly understood. Molecular genetic studies have been carried out to determine their in vivo function in the simple eukaryote Dictyostelium, an organism that contains a family of four myosin Is. Here we report the characterization of myoC, a gene that encodes a fifth member of this family. Analysis of the deduced amino acid sequence reveals that the myoC gene encodes a myosin that is homologous to the well-described Acanthamoeba myosin Is as well as to Dictyostelium myoB and -D. The expression pattern of the myoC mRNA is similar to that of myoB and myoD, with a peak of expression at times of maximal cell migration, around 6 hours development. Deletion of the myoB gene has been previously shown to result in mutant cells that are defective in pseudopod extension and phagocytosis. However, no obvious differences in cell growth, development, phagocytosis or motility were detected in cells in which the myoC gene had been disrupted by homologous recombination. F-actin localization and ultrastructural organization also appeared unperturbed in myoC- cells. This apparent 'lack' of phenotype in a myosin I single knockout cannot be simply explained by redundancy of function. Our results rather suggest that the present means of assessing myosin I function in vivo are insufficient to identify the unique roles of these actin-based motors.