Electrically Powered Locomotion of Dual-Nature Colloid-Hedgehog and Colloid-Umbilic Topological and Elastic Dipoles in Liquid Crystals.

Colloidal particles in liquid crystals tend to induce topological defects and distortions of the molecular alignment within the surrounding anisotropic host medium, which results in elasticity-mediated interactions not accessible to their counterparts within isotropic fluid hosts. Such particle-induced coronae of perturbed nematic order are highly responsive to external electric fields, even when the uniformly aligned host medium away from particles exhibits no response to fields below the realignment threshold. Here we harness the nonreciprocal nature of these facile electric responses to demonstrate colloidal locomotion. Oscillations of the electric field prompt repetitive deformations of the corona of dipolar elastic distortions around the colloidal inclusions, which upon appropriately designed electric driving synchronize the displacement directions. We observe the colloid-hedgehog dipole accompanied by an umbilical defect in the tilt directionality field (c-field), along with the texture of elastic distortions that evolves with a change in the applied voltage. The temporal out-of-equilibrium evolution of the director and c-field distortions around particles when the voltage is turned on and off is not invariant upon reversal of time, prompting lateral translations and interactions that markedly differ from those accessible to these colloids under equilibrium conditions. Our findings may lead to both technological and fundamental science applications of nematic colloids as both model reconfigurable colloidal systems and as mesostructured materials with predesigned temporal evolution of structure and composition.

Caesarean birth in women with infertility: population-based cohort study.

OBJECTIVE: Caesarean section (CS) is more common following infertility treatment (IT) but the reasons why remain unclear and confounded. The Robson 10-Group Classification System (TGCS) may further explain variation in CS rates. We assessed the association between mode of conception and CS across Robson groups. DESIGN: Population-based cohort study. SETTING: Ontario, Canada, in a public healthcare system. POPULATION: 921 023 births, 2006-2014. METHODS: Modified Poisson regression produced relative risks (RR) and 95% confidence intervals, comparing the risk of CS among women with (1) subfertility without IT, (2) non-invasive IT (OI, IUI) or (3) invasive IT (IVF)-each relative to (4) spontaneous conception (SC). MAIN OUTCOME MEASURES: CS rate according to one of four modes of conception, overall and stratified by each of the TGCS groups. RESULTS: Relative to SC (26.9%), the risk of CS increased in those with subfertility without IT (RR 1.17, 95% CI 1.16-1.18), non-invasive IT (RR 1.21, 95% CI 1.18-1.24) and invasive IT (RR 1.39, 95% CI 1.36-1.42). Within each Robson group, similar patterns of RRs were seen, but with markedly differing rates. For example, in Group 1 (nulliparous, singleton, cephalic at ≥37 weeks, with spontaneous labour), the respective rates were 15.0, 19.4, 18.7 and 21.9%; in Group 2 (nulliparous, singleton, cephalic at ≥37 weeks, without spontaneous labour), the rates were 35.9, 44.4, 43.2 and 54.1%; and in Group 8 (multiple pregnancy), they were 55.9, 67.5, 65.0 and 69.3%, respectively. CONCLUSIONS: CS is relatively more common in women with subfertility and those receiving IT, an effect that persists across Robson groups. TWEETABLE ABSTRACT: Caesarean delivery is more common in women with infertility independent of demographics and prenatal conditions.

Nurse-delivered focused echocardiography to determine intravascular volume status in a deployed maritime critical care unit.

Focused echocardiography is increasingly used by clinicians to guide fluid resuscitation. The UK Defence Medical Services (DMS) have adopted focused echocardiography as a tool to guide flow assessment and resuscitation in deployed critical care. We aimed to explore whether two focused echo techniques, namely Inferior Vena Cava (IVC) and Left Ventricular Outflow Tract Velocity Time integer (LVOT VTi) respiratory variability could be taught to a group of critical care nurses without previous exposure to ultrasound imaging. After a five-week program of training, validation was carried out on healthy volunteers. The mentor, an accredited focused echo trainer, and six nurses performed a total of forty-eight scans on eleven volunteers. The mentor and students acquired subcostal long axis views of the IVC and apical five chamber views using a high frequency linear ultrasound probe. Mean values from three measurements were obtained for IVC diameter and LVOT VTi. Minimum and maximum values were recorded for both variables across a full respiratory cycle. Echo images were saved and at least two images for each student were reviewed offline by an accredited echo-training supervisor. In all cases students were able to obtain adequate echo windows. There was good correlation between values recorded by the mentor and students for both IVC diameter (r = 0.90, p < 0.001) and LVOT VTi (r = 0.77, p < 0.001). Bland Altman analysis showed good correlation with minimal bias for VTi measurements. There was some increase in bias for IVC measurements below 1.2 cm. In summary, we found that these skills for assessing intravascular volume status could be acquired in a relatively short time by specialist nurses without previous experience, and that results were comparable to those produced by an experienced practitioner.

A dose-escalation study of indisulam in combination with capecitabine (Xeloda) in patients with solid tumours.

This dose escalation study was designed to determine the recommended dose of the multi-targeted cell cycle inhibitor indisulam in combination with capecitabine in patients with solid tumours and to evaluate the pharmacokinetics of the combination. Thirty-five patients were treated with indisulam on day 1 of each 21-day cycle. Capecitabine was administered two times daily (BID) on days 1-14. Plasma concentrations of indisulam, capecitabine and its three metabolites were determined for pharmacokinetic analysis. The main dose-limiting toxicity was myelosuppression. Hand/foot syndrome and stomatitis were the major non-haematological toxicities. The recommended dose was initially established at indisulam 700 mg m(-2) and capecitabine 1250 mg m(-2) BID. However, during cycle 2 the recommended dose was poorly tolerated in three patients. A dose of indisulam 500 mg m(-2) and capecitabine 1250 mg m(-2) BID proved to be safe at cycle 1 and 2 in nine additional patients. Indisulam pharmacokinetics during cycle 1 were consistent with pharmacokinetic data from phase I mono-therapy studies. However, exposure to indisulam was remarkably increased at cycle 2 due to a drug-drug interaction between capecitabine and indisulam. Partial response was confirmed in two patients, one with colon carcinoma and the other with pancreatic carcinoma. Seventeen patients had stable disease. Indisulam (700 mg m(-2)) in combination with capecitabine (1250 mg m(-2) BID) was well tolerated during the first cycle. A dose of indisulam 500 mg m(-2) and capecitabine 1250 mg m(-2) BID was considered safe in multiple treatment cycles. The higher incidence of toxicities observed during cycle 2 can be explained by a time-dependent pharmacokinetic drug-drug interaction.

Psychological well-being of mothers of youth with fragile X syndrome: syndrome specificity and within-syndrome variability.

BACKGROUND: Research on parental well-being has focused largely on Down syndrome and autism; however, fragile X syndrome is likely to pose different challenges for parents compared with these other diagnostic conditions. Moreover, there is considerable variability among youth with fragile X syndrome; for example, 25% to 33% of affected youth meet criteria for a co-morbid diagnosis of autism. It is likely that parents of youth with fragile X syndrome will experience different degrees and patterns of stress, depending on whether their offspring do or do not have a co-morbid diagnosis of autism. In the present study, we compared mothers of three groups of young males on measures of psychological well-being and stress: those with fragile X syndrome and a co-morbid diagnosis of autism; those with fragile X syndrome alone; and those with Down syndrome. METHOD: The sample consisted of mothers of adolescent and young adult males with fragile X syndrome and co-morbid autism (n=9), fragile X syndrome alone (n=19), and Down syndrome (n=19). We screened all youth for autism using the Autism Behavior Checklist, which was completed by mothers, fathers and teachers, and the youth who scored above the suggested cut-off were evaluated by a licensed psychologist to determine autism status. The three groups of youth did not differ in chronological age (16.4, 15.8 and 16.0 years, respectively) or non-verbal mental age (3.8, 3.9 and 3.8 years, respectively). Several self-report measures were completed by mothers. These measures assessed current mental health status (e.g. the Center for Epidemiological Studies Depression Scale), perceptions of their son's and family's functioning (e.g. the Positive Affect Index, which measures closeness felt by the mother to her son and also reciprocated closeness felt by the son towards the mother, as perceived by the mother), and approach to coping with their son's disability [e.g. the Multidimensional Coping Inventory (COPE), which measures emotion-focused and problem-solving focused coping]. RESULTS: The results suggest that fragile X syndrome creates more challenges to maternal psychological well-being than Down syndrome, and that the combination of fragile X syndrome and autism can be particularly challenging. Differences among groups, however, were manifested mainly as concerns about the affected son and about relationships within the family rather than as lower levels of mental health. Thus, mothers of sons with fragile X syndrome, regardless of the son's autism status, reported more pessimism about the son's future and more conflict within the family than mothers of sons with Down syndrome. Additionally, mothers of sons with fragile X syndrome and co-morbid autism reported lower levels of reciprocated closeness than the other two groups of mothers. CONCLUSION: We consider possible causes of these maternal differences, the implications for clinical practice, needs for future research, and the importance of understanding child and contextual factors as well as the dynamics leading to these differences.

Cognitive, language and social-cognitive skills of individuals with fragile X syndrome with and without autism.

BACKGROUND: It is not known whether those with co-morbid fragile X syndrome (FXS) and autism represent a distinct subtype of FXS; whether the especially severe cognitive delays seen in studies of young children with co-morbid FXS and autism compared with those with only FXS continue into adolescence and young adulthood; and whether autism in those with FXS is 'true autism', i.e. reflects the same underlying problems as idiopathic autism. METHOD: We compared the non-verbal IQ of adolescents and young adults with co-morbid FXS and autism (n = 10) with those with only FXS (n = 44). We then created a subsample of those with FXS only, matched on non-verbal IQ, mental age and gender (n = 21) to the subsample of those with co-morbid FXS and autism. We compared the two groups on measures of expressive language, receptive language (lexical, grammatical morphology and syntactic patterns), and a theory of mind task. RESULTS: Those with co-morbid FXS and autism had lower non-verbal IQs than those with only FXS. The participants with co-morbid FXS and autism did not perform as well as the cognitive ability- and gender-matched participants with only FXS on the three measures of receptive language or the theory of mind task; there were no differences on the expressive language measure. CONCLUSIONS: Our findings support the notion that those with co-morbid FXS and autism represent a distinct subtype of FXS, with more impairment in receptive language and theory of mind even when controlling for their lower non-verbal IQ relative to those with only FXS. The greater cognitive impairments observed in those with co-morbid FXS and autism continues into adolescence and young adulthood; and the autism seen in those with FXS appears to be the same as idiopathic autism.

Long-term safety and efficacy of repositioning dislocated plate haptic intraocular lenses in the ciliary sulcus.

PURPOSE: To report safety and efficacy outcomes of repositioning posterior dislocated plate haptic lenses (PHLs) in the ciliary sulcus (CS). DESIGN: Retrospective interventional case series. METHODS: Fifteen consecutive eyes with dislocated PHL repositioned in the CS were reviewed retrospectively. Pars plana vitrectomy was required in 12 of 15 cases. The main outcome variables were initial and final best-corrected visual acuity (BCVA) and length of follow-up. RESULTS: All lenses remained centered for an average of 48.7 months (range 4 to 99 months) of follow-up with no recurrent dislocation, cystoid macular edema, chronic iritis, or iris chaffing. Initial and final BCVA of 20/40 or better was attained in 93.3% (14 of 15) and 66.7% (10 of 15) of eyes, respectively. Decline of final BCVA was attributable to secondary eye diseases and not related to repositioning. CONCLUSIONS: Our study reports dislocated PHL may be managed safely and effectively by placement in the CS with long-term stability under certain clinical scenarios.

Culture plate temperature and delayed incubation effect on bacterial recovery.

PURPOSE: To discover if initial culturing conditions (plate temperature and time delay to incubation) adversely influence the recovery of organisms associated with bacterial keratitis. METHODS: The rate of temperature equilibration of culture plates taken from a refrigerator and placed in an incubator and left on the desk was evaluated with a digital thermometer. A standard inoculum for each of five organisms (S. aureus, S. pneumoniae, P. aeruginosa, E. aerogenes, K. oxytoca) isolated from human bacterial keratitis was spread evenly on blood agar plates at refrigerator (Tcold; 4 degrees C), room (Troom; 24 degrees C), and incubator (Twarm; 37 degrees C) temperatures. The plates were then kept at room temperature for 0, 1, 3, 5, and 8 hours before overnight incubation at 37 degrees C (S. pneumoniae under microaerophilic conditions), and the number of colony-forming units was counted. RESULTS: Cold plates took at least 15 minutes in an incubator to attain room temperature, and up to an hour when left on the desk. Increased organism recovery was found comparing both Twarm and Troom plates (6.2 to 24.8% and 7.0 to 14.7%, respectively, P<0.001) to Tcold plates for all organisms except S. pneumoniae (P=0.057). Comparing Twarm plates to Troom plates demonstrated an increased recovery (P<0.001) for S. aureus. Delayed incubation resulted in decreased recovery for S. pneumoniae (P<0.001). CONCLUSIONS: Culture plates should preferably be warmed at least to room temperature before inoculation, as well as promptly incubated to increase bacterial recovery from cases of septic keratitis.

Accelerated escape from GH autonegative feedback in midpuberty in males: evidence for time-delimited GH-induced somatostatinergic outflow in adolescent boys.

A single injected pulse of GH inhibits the time-delayed secretion of GH in the adult by way of central mechanisms that drive somatostatin and repress GHRH outflow. The marked amplification of spontaneous GH pulse amplitude in puberty poses an autoregulatory paradox. We postulated that this disparity might reflect unique relief of GH-induced autonegative feedback during this window of development. The present study contrasts GH autonegative feedback in: 1) normal prepubertal boys (PP) (n = 6; Tanner genital stage I, chronologically aged 8 yr, 9 months to 10 yr, 1 month; median bone age 8.5 yr); 2) longitudinally identified midpubertal boys (MP) (n = 6; Tanner genital stages III/IV, aged 12 yr, 6 months to 15 yr, 6 months; median bone age 15 yr); and 3) healthy young men (YM) (n = 6, aged 18-24 yr; bone age >18 yr). Subjects each underwent four randomly ordered tandem peptide infusions on separate mornings while fasting: i.e. 1) saline/saline infused iv bolus at 0830 h and 1030 h; 2) saline/GHRH (0.3 microg/kg i.v. bolus) at the foregoing times; 3) recombinant human (rh) GH (3 microg/kg as a 6-min square-wave i.v. pulse)/saline; and 4) rhGH and GHRH. To monitor GH autofeedback effects, blood samples were obtained every 10 min for 5.5 h beginning at 0800 h (30 min before GH or saline infusion). Serum GH concentrations were quantitated by ultrasensitive chemiluminometry (threshold 0.005 microg/liter). On the day of successive saline/saline infusion, MP boys maintained higher serum concentrations of: 1) GH ( microg/liter), 2.2 +/- 0.25, compared with PP (0.61 +/- 0.10) or YM (0.88 +/- 0.36) (P = 0.011); 2) IGF-I ( micro g/liter), 493 +/- 49 vs. PP (134 +/- 16) and YM (242 +/- 22) (P < 0.001); 3) T (ng/dl), 524 +/- 58 vs. PP (<20) (P < 0.001); and 4) E2 (pg/ml),19 +/- 3 vs. PP (< 10) (P = 0.030) (mean +/- SEM). Consecutive saline/GHRH infusion elicited comparable peak (absolute maximal) serum GH concentrations (micrograms per liter) in the three study groups, i.e. 18 +/- 5.0 (PP), 9.6 +/- 1.7 (MP), and 14 +/- 5.3 (YM) (each P < 0.01 vs. saline; P = NS cohort effect). Injection of rhGH attenuated subsequent GHRH-stimulated peak serum GH concentrations (micrograms per liter) to 7.8 +/- 1.9 (PP), 5.8 +/- 1.2 (MP), and 4.8 +/- 1.1 (YM) (each P < 0.01 vs. saline; P = NS pubertal effect). GH autofeedback reduced non-GHRH-stimulated (basal) serum GH concentrations by 0.74 +/- 0.28 (PP), 5.7 +/- 1.7 (MP) and 1.4 +/- 0.27 (YM) fold, compared with saline (P = 0.016 for MP vs. PP or YM). In addition to greater fractional autoinhibition, MP boys exhibited markedly accentuated postnadir escape (4.6-fold steeper slope) of suppressed GH concentrations (P < 0.001 vs. PP or YM). Linear regression analysis of data from all 18 subjects revealed that the fasting IGF-I concentration negatively predicted fold-autoinhibition of GHRH-stimulated peak GH release (r = -0.847, P = 0.006) and positively forecast fold-autoinhibition of basal GH release (r = +0.869, P < 0.001). In contrast, the kinetics of rhGH did not differ among the three study cohorts. In summary, boys in midpuberty manifest equivalent responsiveness to exogenous GHRH-stimulated GH secretion; heightened susceptibility to rhGH-induced fractional inhibition of endogenous secretagogue-driven GH release, compared with the prepubertal or adult male; and accelerated recovery of GH output after acute autonegative feedback. This novel tripartite mechanism could engender recurrent high-amplitude GH secretory bursts that mark sex hormone-dependent activation of the human somatotropic axis.

The insulin-like growth factor system in kidney diseases.

The insulin-like growth factor system is intimately involved in renal development, growth, function and the pathophysiology of several disease states. Exogenous IGF-I increases GFR and RPF, perhaps mediated by nitric oxide (NO). In chronic renal failure, IGF-I, the binding proteins and their fragments decrease bioavailability. After transplantation, the levels of bioactive IGF-I increase likely due to better nutrition and increased clearance of the binding proteins and their fragments. In the nephritic syndrome, a similar mechanism may be active, in that the binding proteins and their fragments may inhibit IGF-I action.

Phase I study in advanced cancer patients of a diversified prime-and-boost vaccination protocol using recombinant vaccinia virus and recombinant nonreplicating avipox virus to elicit anti-carcinoembryonic antigen immune responses.

PURPOSE: This trial sought to determine, for the first time, the validity in human vaccinations of using two different recombinant vaccines in diversified prime-and-boost regimens to enhance T-cell responses to a tumor antigen. PATIENTS AND METHODS: Eighteen patients with advanced tumors expressing carcinoembryonic antigen (CEA) were randomized to receive either recombinant vaccinia (rV)-CEA followed by three avipox-CEA vaccinations, or avipox-CEA (three times) followed by one rV-CEA vaccination. Subsequent vaccinations in both cohorts were with avipox-CEA. Immunologic monitoring was performed using a CEA peptide and the enzyme-linked immunospot assay for interferon gamma production. RESULTS: rV-CEA followed by avipox-CEA was superior to the reverse order in the generation of CEA-specific T-cell responses. Further increases in CEA-specific T-cell precursors were seen when local granulocyte-macrophage colony-stimulating factor (GM-CSF) and low-dose interleukin (IL)-2 were given with subsequent vaccinations. The treatment was extremely well tolerated. Limited clinical activity was seen using vaccines alone in this patient population. Antibody production against CEA was also observed in some of the treated patients. CONCLUSION: rV-CEA was more effective in its role as a primer of the immune system; avipox-CEA could be given up to eight times with continued increases in CEA T-cell precursors. Future trials should use rV-CEA first followed by avipox-CEA. Vaccines specific to CEA are able to generate CEA-specific T-cell responses in patients without significant toxicity. T-cell responses using vaccines alone may be inadequate to generate significant anticancer objective responses in patients with advanced disease. Cytokines such as GM-CSF and IL-2 may play a key role in generating such responses.

Phase I study in cancer patients of a replication-defective avipox recombinant vaccine that expresses human carcinoembryonic antigen.

PURPOSE: A phase I clinical trial in patients with advanced carcinoma was conducted, using a replication-defective avipox vaccine containing the gene for the human carcinoembryonic antigen (CEA). The canarypox vector, designated ALVAC, has the ability to infect human cells but cannot replicate. PATIENTS AND METHODS: The recombinant vaccine, designated ALVAC-CEA, was administered intramuscularly three times at 28-day intervals. Each cohort of six patients received three doses of either 2.5 x 10(5), 2.5 x 10(6), or 2.5 x 10(7) plaque-forming units of vaccine. RESULTS: The vaccine was well tolerated at all dose levels and no significant toxicity was attributed to the treatment. No objective antitumor response was observed during the trial in patients with measurable disease. Studies were conducted to assess whether ALVAC-CEA had the ability to induce cytolytic T-lymphocyte (CTL) responses in patients with advanced cancer. Peripheral blood mononuclear cells (PBMCs) from patients with the MHC class I A2 allele were obtained before vaccine administration and 1 month after the third vaccination. Peripheral blood mononuclear cells were incubated with the CEA immunodominant CTL epitope carcinoembryonic antigen peptide-1 and interleukin 2 and quantitated using CTL precursor frequency analysis. In seven of nine patients evaluated, statistically significant increases in CTL precursors specific for CEA were observed in PBMCs after vaccination, compared with before vaccination. CONCLUSION: These studies constitute the first phase I trial of an avipox recombinant in cancer patients. The recombinant vaccine ALVAC-CEA seems to be safe and has been demonstrated to elicit CEA-specific CTL responses. These studies thus form the basis for the further clinical exploration of the ALVAC-CEA recombinant vaccine in phase I/II studies in protocols designed to enhance the generation of human T-cell responses to CEA.

Functional analysis of the DNA-stimulated ATPase domain of yeast SWI2/SNF2.

The yeast SWI2/SNF2 polypeptide is a subunit of the SWI/SNF protein complex that is required for many transcriptional activators to function in a chromatin context. SWI2 is believed to be the founding member of a new subfamily of DNA-stimulated ATPases/DNA helicases that includes proteins that function in DNA repair (RAD5, RAD16, ERCC6), recombination (RAD54), transcription (MOT1, ISWI, brm, BRG1, hBRM) and cell cycle control (STH1). We have created a set of 16 mutations within the SWI2 ATPase domain and have analyzed the functional consequences of these mutations in vivo. We have identified residues within each of the seven ATPase motifs that are required for SWI2 function. We have also identified crucial residues that are interspersed between the known ATPase motifs. In contrast, we identify other highly conserved residues that appear to be dispensable for SWI2 function. We also find that single amino acid changes in ATPase motifs IV and VI lead to a dominant negative phenotype. None of the 12 SWI2 mutations that disrupt SWI2 activity in vivo alter the assembly of the SWI/SNF complex. These studies provide an invaluable framework for biochemical analysis of the SWI2 ATPase and for functional analysis of other SWI2 family members.

Biochemical modulation in the treatment of advanced cancer: a study of combined leucovorin, fluorouracil, and iododeoxyuridine.

Multiple studies have shown that leucovorin-fluorouracil regimens are modestly superior to fluorouracil alone in the treatment of advanced colorectal cancer. Laboratory data suggest that iododeoxyuridine could further enhance the efficacy of leucovorin-fluorouracil regimens. This report describes the Phase I clinical evaluation of a leucovorin-fluorouracil-iododeoxyuridine chemotherapy regimen. Twenty-four patients received treatment with leucovorin (500 mg/m2), fluorouracil (500 mg/m2), and iododeoxyuridine (escalating doses) on days 1 and 8 of a 21-day cycle. The maximum tolerated dose of iododeoxyuridine was 1200 mg/m2, with a recommended Phase II dose of 1000 mg/m2. Myelosuppression (leukopenia) was dose limiting; other commonly observed treatment toxicities were nausea/vomiting, mucositis, and hyperlacrimation. Although the 1200 mg/m2 dose was tolerated during the initial few cycles of therapy, chronic administration could not be maintained secondary to dose-limiting neutropenia. Since neutropenia was dose limiting, in a follow-up study, 10 patients received a modified regimen (treatment on days 1 and 6 instead of days 1 and 8) with the addition of granulocyte colony-stimulating factor (days 8-19). The addition of granulocyte colony-stimulating factor, however, did not permit further escalation of the iododeoxyuridine dose. Three partial responses and six minor responses were observed. Phase II studies of this regimen are ongoing in advanced colorectal and advanced pancreatic cancer to determine response rates in these diseases.

In vitro comparison of parameters affecting the fixation strength of sagittal split osteotomies.

PURPOSE: The goal of this study was to determine how different parameters affect the bending strength of human cadaver mandibles that have undergone a sagittal split osteotomy. MATERIALS AND METHODS: The effects of screw material (titanium [Ti] vs polylactic acid/polyglycolic acid [PLA/PGA]), screw configuration (linear vs inverted L-shape), screw diameter (2.0 mm vs 2.7 mm), material into which screws were inserted (human mandible, bovine rib, synthetic polymer), and loading rate (1.0 mm/min vs 10.0 mm/min) were quantified. Also, biomechanical principles were used to model shear stress and displacement. Variable lever arms, screw material, screw diameter, screw configuration, distance between screws, and bone properties were all evaluated in this model. RESULTS: Accounting for variable mandible geometries and differentiating between deflections (and shear stresses) due to bending and due to torsion, in vitro mechanical testing revealed that there was a statistically significant difference in total shear stress at 3 mm of deflection depending on screw material (Ti > PLA/PGA), screw diameter, and material into which screws are inserted (mandibles > ribs = synthetic polymer). There was no significant difference in total shear stress depending on screw configuration or strain rate. CONCLUSION: Total shear stress and deflections are important and more viable parameters than load to assess parameters of clinical importance in osteotomy or fracture fixation.

Osteogenic protein-1 (OP-1) expression and processing in Chinese hamster ovary cells: isolation of a soluble complex containing the mature and pro-domains of OP-1.

We have characterized the expression and processing of Osteogenic Protein-1 (hOP-1), a bone morphogenic protein of the TGF-beta family, in Chinese hamster ovary cells. The hOP-1 is initially synthesized as a monomeric 50 kDa pro-protein that is dimerized, glycosylated, and then proteolytically cleaved at the Arg-Xaa-Xaa-Arg maturation site in an acidic cellular compartment before secretion into the medium. Of the four potential N-linked glycosylation sites two are used, one in the mature domain and one in the pro-domain. Gel permeation chromatography of secreted hOP-1 in physiological buffers yields an apparent molecular weight of 110-120 k, indicating that after proteolytic processing the two pro-domains remain non-covalently associated with the disulfide linked mature dimer in a complex termed soluble hOP-1. Purified soluble hOP-1 is significantly more soluble in physiological buffers than the purified mature OP-1.

Life change stress factors in hospitalized otolaryngologic patients.

In this present era of specialty medicine and surgery, the physician should not lose sight of the total patient as he practices within the narrow limits of his specialty. Since there is evidence that stress created by life change factors may be associated with the onset of illness, we investigated life change factors in 100 patients hospitalized on an otolaryngology-head and neck surgery service to determine whether their stress scores were significantly higher than those of a nonhospitalized population of similar age and sociocultural background. The Social Readjustment Rating Scale (SRRS) was used to measure life change units (LCU) in the experimental and control groups. Nonparametric statistics used to analyze the data showed that at the .01 level of confidence hospitalized patients had stress scores significantly higher than those of the control group. We conclude that a clustering of life changes may have a significant impact on a patient's disease history. Awareness of LCU levels could be useful in detecting a patient's vulnerability to disease, and may therefore be useful in a preventive medicine approach to understanding and treating the total patient.