Wrist weight-bearing tolerance in healthy adults.

STUDY DESIGN: Cross-sectional. INTRODUCTION: No information is available in the literature regarding the amount of weight-bearing tolerance in a normal human wrist. PURPOSE OF THE STUDY: To establish the normal limits of human wrist weight-bearing tolerance and to determine if gender, age and height are predictors of this weight-bearing tolerance. METHODS: A sample (N = 465) of healthy adults ages 18-64 completed a questionnaire indicating their gender, age range and height. Subjects were instructed in performing a wrist weight-bearing tolerance test using a calibrated analog scale. The amount of pressure that the subject was able to apply to the scale in 3 independent trials was recorded and analyzed. RESULTS: A strong positive correlation was found between average weight- bearing values achieved through the right and left hands for the subjects of this study, r(463)= .97, P < .001. A 2-way analysis of covariance revealed main effects for both gender (20.9, 95% CI [15.7, 26.0] pounds, P < .001) and age (F(4, 454) = 6.143, P < .001, partial η2 = .051). The highest weight-bearing tolerance was observed in males and individuals 25-34 years of age. Multiple regression analysis affirmed that gender, height and age categories of 45-54 and 55 to 64 were all statistically significant predictors of wrist weight-bearing tolerance, P < .01. DISCUSSION: These results establish normal wrist weight-bearing tolerance values and demonstrate that gender, age and height are predictors of this weight-bearing tolerance. CONCLUSION: These results could allow identification of pathologies associated with wrist instability.

Identifying the brain regions associated with acute spasticity in patients diagnosed with an ischemic stroke.

Spasticity is a common impairment found in patients that have been diagnosed with a stroke. Little is known about the pathophysiology of spasticity at the level of the brain. This retrospective study was performed to identify an association between the area of the brain affected by an ischemic stroke and the presence of acute spasticity. Physical and occupational therapy assessments from all patients (n = 441) that had suffered a stroke and were admitted into a local hospital over a 4-year period were screened for inclusion in this study. Subjects that fit the inclusion criteria were grouped according to the presence (n = 42) or absence (n = 129) of acute spasticity by the Modified Ashworth Scale score given during the hospital admission assessment. Magnetic resonance images from 20 subjects in the spasticity group and 52 from the control group were then compared using lesion density plots and voxel-based lesion-symptom mapping. An association of acute spasticity with the gray matter regions of the insula, basal ganglia, and thalamus was found in this study. White matter tracts including the pontine crossing tract, corticospinal tract, internal capsule, corona radiata, external capsule, and the superior fronto-occipital fasciculus were also found to be significantly associated with acute spasticity. This is the first study to describe an association between a region of the brain affected by an infarct and the presence of acute spasticity. Understanding the regions associated with acute spasticity will aid in understanding the pathophysiology of this musculoskeletal impairment at the level of the brain.

Internal threshold of toxicological concern values: enabling route-to-route extrapolation.

The TTC concept uses toxicological data from animal testing to derive generic human exposure threshold values (TTC values), below which the risk of adverse effects on human health is considered to be low. It uses distributions of no-observed-adverse-effect levels (NOAELs) for substances. The 5th percentile value is divided by an uncertainty factor (100) to give a TTC value. As the toxicological data underpinning the TTC concept are from tests with oral exposure, the exposure is to be understood as an external oral exposure. For risk assessment of substances with a low absorption (by the oral route, or through skin), the internal exposure is more relevant than the external exposure. European legislation allows that tests might not be necessary for substances with negligible absorption with low internal exposure. The aim of this work is to derive internal TTC values to allow the TTC concept to be applied to situations of low internal exposure. The external NOAEL of each chemical of three databases (Munro, ELINCS, Food Contact Materials) was multiplied by the bioavailability of the individual chemical. Oral bioavailability was predicted using an in silico prediction tool (ACD Percepta). After applying a reduced uncertainty factor of 25, we derived internal TTC values. For Cramer class I, the internal TTC values are 6.9 µg/kg bw/d (90 % confidence interval: 3.8-11.5 mg/kg bw/d); for Cramer class II/III 0.1 µg/kg bw/d (90 % confidence interval: 0.08-0.14 µg/kg bw/d).

Acquired brain injury self-management programme: a pilot study.

PRIMARY OBJECTIVE: Traditional rehabilitation is not well suited to individuals with chronic mild symptoms following an acquired brain injury. To address this, this study adapted a supported self-management programme (SMP) for this population. The aim of this study was to evaluate the potential effectiveness of this novel SMP. RESEARCH DESIGN: Retrospective case series with repeated measures. METHODS AND PROCEDURES: Fifty-three participants with chronic mild symptoms following an acquired brain injury (primarily mild traumatic brain injury) completed an SMP. The intervention involved eight coaching sessions with each an occupational therapist and psychologist, carried out in the community and based on SMP principles. The Canadian Occupational Performance Measure was administered at baseline, discharge and 3- and 9-month follow-up. This measure yielded scores for performance and satisfaction with daily functioning, covering the domains of self-care, productivity and leisure. MAIN OUTCOMES AND RESULTS: A complete case analysis of programme completers revealed that participants' ratings of their occupational performance and satisfaction improved markedly between baseline and discharge from the SMP. This set of outcome measures remained stable between discharge and the two follow-up points. CONCLUSIONS: This pilot study suggests that SMPs may improve daily functioning in individuals with chronic mild ABI symptoms. More methodologically robust clinical trials are warranted.

Developmental toxicity studies on triclopyr acid, triclopyr butoxyethyl ester and triclopyr triethylamine salt in the rabbit.

Developmental toxicity studies have been conducted in the rabbit on triclopyr acid and its active-ingredient variants, triclopyr triethylamine salt (T-TEA) and triclopyr butoxyethyl ester (T-BEE), which are dissociated or hydrolysed in vivo to triclopyr acid. In this paper, the available developmental toxicity studies on triclopyr acid, T-TEA and T-BEE are summarised and evaluated. For triclopyr acid and T-TEA, there was no evidence of impaired reproductive performance, fetotoxicity, or teratogenicity, even at maternally toxic doses. The no-observed-adverse-effect levels (NOAELs) for developmental toxicity were 75 mg/kg bw per day for triclopyr acid and 100 mg/kg bw per day for T-TEA, equivalent to 72 mg/kg bw per day expressed as triclopyr acid. A study on T-BEE showed increased post-implantation loss and slight increases in skeletal anomalies and variants at the highest dose tested of 100 mg/kg bw per day, a maternally toxic dose. In a follow-up study on T-BEE, focusing on post-implantation loss, no general increase in post-implantation loss was observed, but one animal at 100 mg/kg bw per day with maternal toxicity had complete resorption of implants. The NOAEL for post-implantation loss was 60 mg/kg bw per day, equivalent to 44 mg/kg bw per day expressed as triclopyr acid. It cannot be excluded that T-BEE may be associated with increased post-implantation loss, but it was only seen in association with maternal toxicity. It is concluded that triclopyr acid and its variants are not specifically toxic to the rabbit embryo and fetus, since post-implantation loss only occurred at doses causing maternal toxicity.

Reproductive and developmental evaluations of triclopyr acid, triclopyr butoxyethyl ester and triclopyr triethylamine salt in the rat.

Reproductive and developmental toxicity studies have been conducted in rat and rabbit on triclopyr acid and its active-ingredient variants, triclopyr butoxyethyl ester (T-BEE) and triclopyr triethylamine salt (T-TEA). In this paper the results of a rat two-generation study on triclopyr acid are presented, together with a review of all the reproductive and developmental toxicity data available from the rat studies. In the rat two-generation study, triclopyr acid was administered in the diet, giving doses of 0, 5, 25 or 250 mg/kg bw per day. Parental toxicity, especially maternal toxicity, occurred at 250 mg/kg bw per day with reduced body weight and feed intake, organ weight changes, and kidney toxicity. Slight kidney toxicity was also evident at 25 mg/kg bw per day. Developmental toxicity, in the form of reduced postnatal survival in the F1 and F2 generations and reductions in pre-weaning offspring body weight in both generations, was seen only at a dose causing significant parental toxicity. There were no effects on any other reproductive or developmental parameters at any dose. It is concluded that the developmental toxicity, seen only at the highest dose, was most likely attributable to maternal toxicity. The no-observed-adverse-effect levels were 5 mg/kg bw per day for parental toxicity and 25 mg/kg bw per day for developmental toxicity. From the multigeneration and developmental toxicity studies on triclopyr and its variants, it can also be concluded that triclopyr is not specifically toxic to reproduction and is not selectively toxic to the embryo, fetus or neonate in the rat.

Flumioxazin, a PPO inhibitor: A weight-of-evidence consideration of its mode of action as a developmental toxicant in the rat and its relevance to humans.

Flumioxazin, is a herbicide that has inhibitory activity on protoporphyrinogen oxidase (PPO), a key enzyme in the biosynthetic pathway for heme. Flumioxazin induces anemia and developmental toxicity in rats, including ventricular septal defect and embryofetal death. Studies to elucidate the mode of action (MOA) of flumioxazin as a developmental toxicant and to evaluate its relevance to humans have been undertaken. The MOA in the rat has now been elucidated. The first key event is PPO inhibition, which results in reduced heme synthesis in embryonic erythroblasts. The critical window for this effect is gestational day 12 when almost all erythroblasts are at the polychromatophilic stage, synthesizing heme very actively. Embryonic anemia/hypoxemia is induced and the heart pumps more strongly as a compensatory action during organogenesis, leading to thinning of the ventricular walls and failure of the interventricular septum to build completely and close. Investigations showed that this MOA is specific to rats and has no relevancy to humans. Flumioxazin inhibited PPO in rat hepatocyte mitochondria more strongly than in human. A 3-dimensional molecular simulation revealed that species differences in binding affinity of flumioxazin to PPO, observed previously in vitro, were due to differences in binding free energy. In vitro studies using several types of rat and human cells (erythroblasts derived from erythroleukemia cell lines, cord blood, or pluripotent stem cells), showed that flumioxazin decreased heme synthesis in rat cells but not in human cells, demonstrating a clear, qualitative species difference. Considering all available information, including data from PBPK modelling in rat and human, as well as the fact that anemia is not a symptom in patients with variegate porphyria, a congenital hereditary PPO defect, shows that the sequence of events leading to adverse effects in the rat embryo and fetus are very unlikely to occur in humans.

Risk assessment of carcinogens in food.

Approaches for the risk assessment of carcinogens in food have evolved as scientific knowledge has advanced. Early methods allowed little more than hazard identification and an indication of carcinogenic potency. Evaluation of the modes of action of carcinogens and their broad division into genotoxic and epigenetic (non-genotoxic, non-DNA reactive) carcinogens have played an increasing role in determining the approach followed and provide possibilities for more detailed risk characterisation, including provision of quantitative estimates of risk. Reliance on experimental animal data for the majority of risk assessments and the fact that human exposures to dietary carcinogens are often orders of magnitude below doses used in experimental studies has provided a fertile ground for discussion and diverging views on the most appropriate way to offer risk assessment advice. Approaches used by national and international bodies differ, with some offering numerical estimates of potential risks to human health, while others express considerable reservations about the validity of quantitative approaches requiring extrapolation of dose-response data below the observed range and instead offer qualitative advice. Recognising that qualitative advice alone does not provide risk managers with information on which to prioritise the need for risk management actions, a "margin of exposure" approach for substances that are both genotoxic and carcinogenic has been developed, which is now being used by the World Health Organization and the European Food Safety Authority. This review describes the evolution of risk assessment advice on carcinogens and discusses examples of ways in which carcinogens in food have been assessed in Europe.

Threshold of toxicological concern (TTC) for botanicals - Concentration data analysis of potentially genotoxic constituents to substantiate and extend the TTC approach to botanicals.

This paper evaluates use of the Threshold of Toxicological Concern (TTC) approach to assess safety of botanical preparations that may contain potentially genotoxic constituents, based on estimation of the fraction that may be genotoxic. A database of 107 chemical constituents of botanicals was compiled and their potential for genotoxicity evaluated from published data. Forty-three constituents met the criteria for potential genotoxicity. Concentration data on their occurrence in plants provided 2878 data points; the majority were in the low ppm level (range 0.00001-139,965 ppm, by dry weight). Weibull models of the quantitative distribution data were used to calculate 95th percentile values for chemical concentrations, analysing the dataset according to their presence in botanicals (i) as a single chemical, (ii) as two or more chemicals from the same chemical group, or (iii) as two or more chemicals from different chemical groups. The highest 95th percentile concentration value from these analyses was 1.8%. Using the TTC value of 0.15 µg/person per day for potentially genotoxic substances proposed in 2004, this value of 1.8% was used to derive an adjusted TTC value of 10 µg of plant material on a dry weight basis/person per day for assessment of potentially genotoxic substances in botanicals.

The influence of thresholds on the risk assessment of carcinogens in food.

The risks from exposure to chemical contaminants in food must be scientifically assessed, in order to safeguard the health of consumers. Risk assessment of chemical contaminants that are both genotoxic and carcinogenic presents particular difficulties, since the effects of such substances are normally regarded as being without a threshold. No safe level can therefore be defined, and this has implications for both risk management and risk communication. Risk management of these substances in food has traditionally involved application of the ALARA (As Low as Reasonably Achievable) principle, however ALARA does not enable risk managers to assess the urgency and extent of the risk reduction measures needed. A more refined approach is needed, and several such approaches have been developed. Low-dose linear extrapolation from animal carcinogenicity studies or epidemiological studies to estimate risks for humans at low exposure levels has been applied by a number of regulatory bodies, while more recently the Margin of Exposure (MOE) approach has been applied by both the European Food Safety Authority and the Joint FAO/WHO Expert Committee on Food Additives. A further approach is the Threshold of Toxicological Concern (TTC), which establishes exposure thresholds for chemicals present in food, dependent on structure. Recent experimental evidence that genotoxic responses may be thresholded has significant implications for the risk assessment of chemicals that are both genotoxic and carcinogenic. In relation to existing approaches such as linear extrapolation, MOE and TTC, the existence of a threshold reduces the uncertainties inherent in such methodology and improves confidence in the risk assessment. However, for the foreseeable future, regulatory decisions based on the concept of thresholds for genotoxic carcinogens are likely to be taken case-by-case, based on convincing data on the Mode of Action indicating that the rate limiting variable for the development of cancer lies on a critical pathway that is thresholded.

A Study of Capstone Courses Utilized in United States Doctor of Physical Therapy Program Curricula.

Capstone courses in professional curricula provide opportunities for students to synthesize and integrate clinical and theoretical information from previous coursework. The purpose of this research was to ascertain the number and type of capstone projects utilized by Doctor of Physical Therapy (DPT) programs in the United States. Programs accredited by the Commission on Accreditation in Physical Therapy Education (CAPTE) that published web-accessible curricula were evaluated for the presence of the word capstone in the course title or description. Of the DPT program curricula analyzed (n=204 of 218 possible), 36% designated a capstone course. These capstone courses focused on research (49%), professional development (14%), evidence-based practice (12%), managing complex patients (7%), licensure preparation (4%), clinical education (3%), community service (1%), or a combination or choice between these categories (10%). Consensus regarding capstone courses may serve to promote best practice in entry-level professionals.

Differential diagnosis of a patient referred to physical therapy for dizziness: a case report.

STUDY DESIGN: Case report. BACKGROUND: Dizziness is a common and debilitating condition across the lifespan. Patients with this complaint must be carefully examined to determine the cause of dizziness, rule out the presence of central nervous system dysfunction, and determine the appropriateness of physical therapy intervention. CASE DESCRIPTION: A 90-year-old male was referred to physical therapy six months after the onset of dizziness. A thorough history was taken and examination was performed. Signs consistent with central nervous system dysfunction and peripheral vestibular dysfunction were observed. The patient was treated for the peripheral vestibular disorder and referred back to his physician for further testing. Imaging revealed that the patient had idiopathic normal pressure hydrocephalus. DISCUSSION: This case illustrates the need for physical therapists to perform thorough examinations of patients with a primary complaint of dizziness and properly interpret positive central signs, indicating a potential need for referral to a physician or other healthcare provider when they appear.

Thresholds of Toxicological Concern for cosmetics-related substances: New database, thresholds, and enrichment of chemical space.

A new dataset of cosmetics-related chemicals for the Threshold of Toxicological Concern (TTC) approach has been compiled, comprising 552 chemicals with 219, 40, and 293 chemicals in Cramer Classes I, II, and III, respectively. Data were integrated and curated to create a database of No-/Lowest-Observed-Adverse-Effect Level (NOAEL/LOAEL) values, from which the final COSMOS TTC dataset was developed. Criteria for study inclusion and NOAEL decisions were defined, and rigorous quality control was performed for study details and assignment of Cramer classes. From the final COSMOS TTC dataset, human exposure thresholds of 42 and 7.9 µg/kg-bw/day were derived for Cramer Classes I and III, respectively. The size of Cramer Class II was insufficient for derivation of a TTC value. The COSMOS TTC dataset was then federated with the dataset of Munro and colleagues, previously published in 1996, after updating the latter using the quality control processes for this project. This federated dataset expands the chemical space and provides more robust thresholds. The 966 substances in the federated database comprise 245, 49 and 672 chemicals in Cramer Classes I, II and III, respectively. The corresponding TTC values of 46, 6.2 and 2.3 µg/kg-bw/day are broadly similar to those of the original Munro dataset.

A Non-surgical Intervention for Triangular Fibrocartilage Complex Tears.

BACKGROUND AND PURPOSE: The current literature contains no reports of treatment options other than surgery following failed conservative management of a triangular fibrocartilage complex (TFCC) tear. The purpose of this study is to describe the use of a novel brace as a non-surgical intervention for TFCC tears. METHODS: This paper is a case study of a subject with a magnetic resonance imaging-confirmed TFCC tear. As an alternative to surgery, he consented to wear a novel brace for 12 weeks after conservative management of his injury had failed. His recovery from injury was monitored with a weight-bearing tolerance test and the disabilities of the arm, shoulder and hand (DASH) outcome measure. RESULTS: An increase in weight-bearing tolerance and upper extremity use was evident immediately after donning the brace. After 12 weeks, the subject demonstrated a return to normal weight-bearing tolerance and normal DASH outcome measure scores. These improvements were still evident at a 1-year follow-up appointment. DISCUSSION: Utilizing this novel brace resulted in functional status improvement in a subject with a TFCC tear as demonstrated by significant changes in his DASH outcome measure scores. This case study demonstrates the first non-surgical alternative treatment for a TFCC tear after conservative management has failed. Copyright © 2016 John Wiley & Sons, Ltd.

A gene expression fingerprint of C. elegans embryonic motor neurons.

BACKGROUND: Differential gene expression specifies the highly diverse cell types that constitute the nervous system. With its sequenced genome and simple, well-defined neuroanatomy, the nematode C. elegans is a useful model system in which to correlate gene expression with neuron identity. The UNC-4 transcription factor is expressed in thirteen embryonic motor neurons where it specifies axonal morphology and synaptic function. These cells can be marked with an unc-4::GFP reporter transgene. Here we describe a powerful strategy, Micro-Array Profiling of C. elegans cells (MAPCeL), and confirm that this approach provides a comprehensive gene expression profile of unc-4::GFP motor neurons in vivo. RESULTS: Fluorescence Activated Cell Sorting (FACS) was used to isolate unc-4::GFP neurons from primary cultures of C. elegans embryonic cells. Microarray experiments detected 6,217 unique transcripts of which approximately 1,000 are enriched in unc-4::GFP neurons relative to the average nematode embryonic cell. The reliability of these data was validated by the detection of known cell-specific transcripts and by expression in UNC-4 motor neurons of GFP reporters derived from the enriched data set. In addition to genes involved in neurotransmitter packaging and release, the microarray data include transcripts for receptors to a remarkably wide variety of signaling molecules. The added presence of a robust array of G-protein pathway components is indicative of complex and highly integrated mechanisms for modulating motor neuron activity. Over half of the enriched genes (537) have human homologs, a finding that could reflect substantial overlap with the gene expression repertoire of mammalian motor neurons. CONCLUSION: We have described a microarray-based method, MAPCeL, for profiling gene expression in specific C. elegans motor neurons and provide evidence that this approach can reveal candidate genes for key roles in the differentiation and function of these cells. These methods can now be applied to generate a gene expression map of the C. elegans nervous system.

Diabetes educators: assessment of evolving practice.

A survey evaluating the professional characteristics and practice patterns of diabetes educators was distributed across the United States. The specific survey aims were to assess whether (1) there continues to be a growing trend among US health professionals who consider themselves diabetes educators to obtain certification as certified diabetes educators (CDEs), (2) duties/services associated with diabetes self-management training (DSMT) and medical/medication management differ between diabetes educators who are CDEs versus those who are non-CDEs, and (3) educator practice patterns differ across the major geographic regions of the United States. Of the 507 diabetes educators completing the survey, 83% identified themselves as CDEs. Diabetes educators responding to similar surveys done in 1992 and 1999, 51% and 63%, respectively, identified themselves as CDEs. In this survey, a similar percentage of CDEs and non-CDEs employed DSMT practices of relatively low complexity (eg, general diabetes education) whereas a significantly higher percentage (P < .001) of CDEs employed DSMT practices of relatively high complexity (eg, insulin pump training). Significantly (P < .001) more CDEs provided medical/medication management services compared to non-CDEs. Finally, the practice patterns among CDEs were minimally influenced by region of the country. These results suggest that (1) the trend toward increased certification among diabetes educators has continued, (2) certification is associated with a greater likelihood of delivering complex DSMT services and medical/medication management, and (3) this pattern is consistent across the nation as a whole.

Agricultural chemicals and endocrine-mediated chronic toxicity or carcinogenicity.

This brief review summarizes information on the endocrine effects and mechanisms of action of certain pesticides and considers whether exposure to pesticides with endocrine activity may play a role in human endocrine-related tumors of the breast, testis, prostate, and endometrium. Both animal and human data are considered. If animal data are to be used effectively for predicting human risk, a thorough understanding of comparative endocrinology and the underlying endocrine and pathological mechanisms contained in the animal model is needed. It is concluded that the evidence does not support an association between organochlorine pesticides and breast cancer, while the evidence on other tumor sites is too sparse to draw any conclusions concerning pesticides.

Reliability of the TTC approach: learning from inclusion of pesticide active substances in the supporting database.

Data on pesticide active substances were used to assess the reliability of the Threshold of Toxicological Concern (TTC) approach. Pesticides were chosen as a robust test because of their potential for toxicity. 328 pesticide substances were classified on the basis of their chemical structure, according to the generic scheme proposed by the European Food Safety Authority. 43 carbamates and organophosphates were allocated to the group for neurotoxicity alerts, and 279 substances to Cramer structural Class III. For Class III, the 5th percentile value as calculated from the cumulative distribution curve of the no-observed-effect levels (0.20 mg/kg bw per day), was slightly higher than that determined by Munro (0.15 mg/kg bw per day) from his original database. The difference is explained by the inclusion of carbamates and organophosphates in Munro's Class III. Consideration of the acceptable daily intakes and their underlying toxicity data showed that the TTC approach is conservative for 96.2% of the substances. Overall, this analysis gives added support to the utility of the generic scheme of application of the TTC approach for hazard assessment of substances for which few or no experimental toxicity data are available. A convenient alternative to the Cramer decision tree is proposed.

Homologs of genes expressed in Caenorhabditis elegans GABAergic neurons are also found in the developing mouse forebrain.

BACKGROUND: In an effort to identify genes that specify the mammalian forebrain, we used a comparative approach to identify mouse homologs of transcription factors expressed in developing Caenorhabditis elegans GABAergic neurons. A cell-specific microarray profiling study revealed a set of transcription factors that are highly expressed in embryonic C. elegans GABAergic neurons. RESULTS: Bioinformatic analyses identified mouse protein homologs of these selected transcripts and their expression pattern was mapped in the mouse embryonic forebrain by in situ hybridization. A review of human homologs indicates several of these genes are potential candidates in neurodevelopmental disorders. CONCLUSIONS: Our comparative approach has revealed several novel candidates that may serve as future targets for studies of mammalian forebrain development.