Grading Acanthosis Nigricans Using a Smartphone and Color Analysis: A Novel Noninvasive Method to Screen for Impaired Glucose Tolerance and Type 2 Diabetes.

Objective: The objective of this study was to develop ANcam, a novel method for identifying acanthosis nigricans (AN) using a smartphone camera and computer-aided color analysis for noninvasive screening of people with impaired glucose tolerance (IGT). Research Design and Methods: Adult and juvenile participants with or without diagnosed type 2 diabetes were recruited in Trinidad and Tobago. After obtaining informed consent, participants' history, demographics, anthropometrics, and A1C were collected and recorded. Three subject matter experts independently graded pictures of the posterior neck and upper back using the ANcam smartphone application and Burke methods. A correlation matrix investigated 25 color channels for association with hyperpigmentation, and the diagnostic thresholds were determined with a receiver operating characteristic curve analysis. Results: For the 227 participants with captured images and A1C values, the cyan/magenta/yellow/black (CMYK) model color channel CMYK_K was best correlated with IGT at an A1C cutoff of 5.7% (39 mmol/mol) (R = 0.45, P <0.001). With high predictive accuracy (area under the curve = 0.854), the cutoff of 7.67 CMYK_K units was chosen, with a sensitivity of 81.1% and a specificity of 70.3%. ANcam had low interrater variance (F = 1.99, P = 0.137) compared with Burke grading (F = 105.71, P <0.001). ANcam detected hyperpigmentation on the neck at double the self-reported frequency. Elevated BMI was 2.9 (95% CI 1.9-4.3) times more likely, elevated blood pressure was 1.7 (95% CI 1.2-2.4) times more likely, and greater waist-to-hip ratio was 2.3 (95% CI 1.4-3.6) times more likely with AN present. Conclusion: ANcam offers a sensitive, reproducible, and user-friendly IGT screening tool to any smartphone user that performs well with most skin tones and lighting conditions.

Incidence of Vitamin D Deficiency in Foot and Ankle Arthrodesis Nonunions.

Background Vitamin D has been found to be crucial in musculoskeletal health. The role of vitamin D levels in orthopedic patients has become a growing area of interest given its negative impact on fracture healing which can contribute to the development of nonunion following surgery. We sought to investigate the incidence of hypovitaminosis D in a cohort of patients who experienced a nonunion following a foot and ankle arthrodesis procedure. Methodology Patients who underwent a major elective foot and ankle arthrodesis procedure and developed a nonunion were given the opportunity to obtain serum vitamin D levels. All vitamin D levels were reported from percutaneous venous blood samples and compared to our institution's range of accepted normal values (25-80 ng/mL). Results A total of 13 patients who developed a nonunion agreed to have a vitamin D level obtained, and 11 of 13 patients had a low vitamin D level (average = 14.6 ng/mL, range = 9-24 ng/mL). Five patients underwent revision arthrodesis after normalization of vitamin D levels, and four out of five patients went on to successful union. Conclusions Hypovitaminosis D may be a modifiable risk factor for nonunion following a major foot and ankle arthrodesis procedure. Orthopedic surgeons should consider vitamin D screening and supplementation in patients undergoing elective arthrodesis procedures.

Resilience Improves Patient-Reported Outcomes After Orthopaedic Trauma.

OBJECTIVES: To analyze the relationship between patient resilience and patient-reported outcomes after orthopaedic trauma. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Single Level 1 Trauma Center. PATIENT SELECTION CRITERIA: Patients were selected based on completion of the Patient-Reported Outcomes Measurement Information System (PROMIS) and Brief Resilience Scale (BRS) surveys 6 months after undergoing operative fracture fixation following orthopaedic trauma. Patients were excluded if they did not complete all PROMIS and BRS surveys. OUTCOME MEASURES AND COMPARISONS: Resilience, measured by the BRS, was analyzed for its effect on patient-reported outcomes, measured by PROMIS Global Physical Health, Physical Function, Pain Interference, Global Mental Health, Depression, and Anxiety. Variables collected were demographics (age, gender, race, body mass index), injury severity score, and postoperative complications (nonunion, infection). All variables were analyzed with univariate for effect on all PROMIS scores. Variables with significance were included in multivariate analysis. Patients were then separated into high resilience (BRS >4.3) and low resilience (BRS <3.0) groups for additional analysis. RESULTS: A total of 99 patients were included in the analysis. Most patients were male (53%) with an average age of 47 years. Postoperative BRS scores significantly correlated with PROMIS Global Physical Health, Pain Interference, Physical Function, Global Mental Health, Depression, and Anxiety ( P ≤ 0.001 for all scores) at 6 months after injury on both univariate and multivariate analyses. The high resilience group had significantly higher PROMIS Global Physical Health, Physical Function, and Global Mental Health scores and significantly lower PROMIS Pain Interference, Depression, and Anxiety scores ( P ≤ 0.001 for all scores). CONCLUSIONS: Resilience in orthopaedic trauma has a positive association with patient outcomes at 6 months postoperatively. Patients with higher resilience report higher scores in all PROMIS categories regardless of injury severity. Future studies directed at increasing resilience may improve outcomes in patients who experience orthopaedic trauma. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Depression and comorbid obstructive sleep apnea: Association between positive airway pressure adherence, occurrence of self-harm events, healthcare resource utilization, and costs.

OBJECTIVE: Previous studies have shown that treatment of obstructive sleep apnea (OSA) with positive airway pressure (PAP) therapy in patients with depression may improve depression symptoms and response to antidepressant therapy. We investigated the association between PAP therapy adherence, self-harm events, healthcare resource utilization (HCRU), and costs over 2 years in a national sample of patients with pre-existing depression and newly diagnosed comorbid OSA. METHODS: Administrative claims data were linked to objective PAP therapy usage. Inverse probability treatment weighting was used to compare outcomes over 2 years across PAP adherence levels. The predicted numbers of emergency room (ER) visits and hospitalizations by adherence level were assessed using risk-adjusted generalized linear models. RESULTS: 37,459 patients were included. Relative to non-adherent patients, consistently adherent patients had fewer self-harm events (0.04 vs 0.05, p < 0.001) after 1 year, and significantly (all p < 0.001) fewer ER visits (0.66 vs 0.86) and all-cause hospitalizations (0.13 vs 0.17), and lower total ($11,847 vs $11,955), inpatient hospitalization ($1634 vs $2274), and ER visit ($760 vs $1006) costs per patient in the second year of PAP therapy. Consistently adherent patients showed lower risk for hospitalizations and ER visits. LIMITATIONS: Using observational claims data, we were unable to assess clinical characteristics including sleep, sleepiness, and daytime symptoms, or important social determinants of health. We were limited in assessing care received outside of the included health plans. CONCLUSION: Consistent adherence to PAP therapy over 2 years was associated with improved HCRU outcomes for patients with pre-existing depression newly diagnosed with comorbid OSA.

Incidence of thyroid disease in patients with forefoot deformity.

BACKGROUND: Hallux valgus and lesser toe deformities are common foot disorders with substantial functional consequences. While the exact etiologies are multi-factorial, it is unknown if certain endocrine abnormalities, such as thyroid dysfunction, may be associated with these pathologies. The current study sought to investigate the prevalence of thyroid disease in patients with hallux valgus or lesser toe deformities. METHODS: Every new patient who presented to our institution's foot and ankle clinic during a three-month time period was given a survey to determine the presence of a known thyroid disorder. The diagnosis for each visit was then recorded. Additionally, a national, publicly available database was queried for patients diagnosed with thyroid disease and concomitant hallux valgus or specific forefoot pathology. Odds ratios for the presence of thyroid dysfunction were then calculated for each patient group. RESULTS: Three-hundred and fifty initial visit patient surveys were collected, and 74 (21.1%) patients had a known diagnosis of thyroid disease. The most common diagnoses were primary hypothyroidism (n = 61, 17.4%), secondary hypothyroidism (n = 6, 1.7%), thyroiditis (n = 4, 1.1%), and hyperthyroidism (n = 3, 0.9%). Thyroid disease was present in 16 of 26 patients (61.5%) with a diagnosis of hallux valgus (OR 7.3, CI[3.16-16.99], p < 0.0001). Lesser toe deformities, including hammertoes, mallet toes, bunionettes and crossover toes, were also significantly associated with thyroid disease (OR 5.45, CI[1.83-16.26], p < 0.002). The national database revealed 905,924 patients with a diagnosis of a specific forefoot deformity, and 321,656 of these patients (35.5%) had a concomitant diagnosis of a thyroid condition (OR 2.11, CI[2.10-2.12], p < 0.0001). CONCLUSIONS: The current study suggests a significant association between forefoot pathology and thyroid dysfunction, especially hallux valgus and lesser toe deformities. Increased understanding of these correlations may offer an important opportunity in population health management, both in diagnosis and treatment. While further studies with long-term outcomes are necessary, the early diagnosis of thyroid disease may provide an opportunity to predict and potentially alter the course of forefoot pathology.

Global DNA Methylation and Histone Posttranslational Modifications in Human and Nonhuman Primate Brain in Association with Prenatal Alcohol Exposure.

BACKGROUND: Based upon experimental animal studies, the neurodevelopmental abnormalities associated with prenatal alcohol exposure (PNAE)/fetal alcohol spectrum disorder (FASD) have been attributed, at least in part, to epigenetic modifications. However, there are no direct analyses of human brain tissue. METHODS: Immunohistochemical detection of global epigenetic markers was performed on temporal lobe samples of autopsied fetuses and infants with documented PNAE. They were compared to age-, sex-, and postmortem delay-matched control cases (18 pairs; 20 to 70.5 weeks postconception). Temporal lobe tissue from a macaque monkey model of PNAE was also studied (5.7 to 6 months of age). We used antibodies targeting 4 DNA cytosine, 4 histone methylation, and 6 histone acetylation modifications and assigned scores based upon the semiquantitatively graded intensity and proportion of positively labeled nuclei in the ventricular and subventricular zones, ependyma, temporal cortex, temporal white matter, dentate gyrus (DG), and CA1 pyramidal layer. RESULTS: Temporal changes were identified for almost all marks according to the state of maturation in the human brain. In the DG (and 3 other brain regions), a statistically significant increase in H3K9ac was associated with PNAE. Statistically significant decreases were seen among 5mC, H3K4me3, H3K9ac, H3K27ac, H4K12ac, and H4K16ac in select regions. In the macaques, H3K36me3 decreased in the DG, and the ependyma showed decreases in 5fC and H3K36me3. CONCLUSIONS: In human brain, global intranuclear epigenetic modifications are brain region and maturation state-specific. These exploratory results support the general hypothesis that PNAE is associated with a global decrease in DNA methylation, a global decrease in histone methylation, and a global increase in histone acetylation. Although the human and monkey subjects are not directly comparable in terms of brain maturation, considering the rapid temporal changes in global epigenetic modifications during brain development, interspecies comparisons may be extremely difficult.

Long-term follow-up of total shoulder replacement surgery with inset glenoid implants for arthritis with deficient bone.

BACKGROUND: Total shoulder replacement surgery has been a successful treatment for patients with shoulder arthritis. However, long-term results are limited by complications such as glenoid loosening, wear, and instability. Also, glenoid bone deficiency limits available treatment options and outcomes. Successful short-term outcomes have been reported previously using inset glenoid implants for deficient arthritic bone, but long-term outcomes have not been reported using this technique. METHODS: A retrospective analysis was performed on 21 of 24 consecutive patients treated with inset glenoid implants for severe glenohumeral joint arthritis with bone deficiency with prospectively collected data. Inclusion criteria were patients with shoulder arthritis and severe glenoid bone deficiency, defined by perpendicular glenoid vault depth less than 15 mm. No bone grafts were used. All patients were evaluated preoperatively and after surgery with physical examination, radiographic studies, and outcome measures. There were 10 males and 11 females, 17 cases with osteoarthritis and 4 with inflammatory arthritis, and 5 patients with rotator cuff tears (3 full thickness and 2 partial tears). Mean age was 68 years. RESULTS: There were no surgical complications. At a mean follow-up of 8.7 years, there were statistically significant improvements (P < .001) in visual analog pain scores (7.7 to 0.1), American Shoulder and Elbow Surgeons outcome scores (23 to 95), and range of motion. There were no loose glenoids. No patients required any revision surgery. CONCLUSIONS: This study documents the long-term efficacy and safety of total shoulder replacement surgery with inset glenoid implants used to reconstruct deficient, arthritic glenoid bone.

Association between menthol-flavoured cigarette smoking and flavoured little cigar and cigarillo use among African-American, Hispanic, and white young and middle-aged adult smokers.

OBJECTIVES: Flavour additives in cigarettes and little cigars and cigarillos (LCCs), which influence smokers' risk perceptions, may reinforce dual flavoured tobacco use. We examined the association among mentholated cigarette use, risk perceptions for flavour additives in LCCs and flavoured LCC smoking behaviour. METHODS: Data from a national probability sample of 964 young and middle-aged adult current cigarette smokers were analysed. Multinomial logistic regression models examined the relationship among mentholated cigarette smoking, risk perceptions and current flavoured LCC use for the analytic sample and gender and race/ethnicity. RESULTS: Daily menthol cigarette smokers, compared to occasional, non-menthol smokers, had increased odds of flavoured LCC smoking (OR=1.75, 95% CI 1.02 to 2.98). This relationship was found for males, blacks/African-Americans and Hispanics/Latinos (p<0.05). Positive perceptions of menthol-flavoured additives in LCCs was associated with increased odds of flavoured LCC use among the analytic sample, males and blacks/African-Americans (p<0.05). Positive perceptions for clove-flavoured, spice-flavoured and alcohol-flavoured additives were also associated with flavoured LCC use among the analytic sample (p<0.05). CONCLUSIONS: Use of menthol-flavoured cigarettes and positive perceptions about menthol-flavoured and other flavour additives in LCCs may contribute to dual use with flavoured LCCs among adult cigarette smokers, specifically those from vulnerable populations.

Suppression of the GTPase-activating protein RGS10 increases Rheb-GTP and mTOR signaling in ovarian cancer cells.

The regulator of G protein signaling 10 (RGS10) protein is a GTPase activating protein that accelerates the hydrolysis of GTP and therefore canonically inactivates G proteins, ultimately terminating signaling. Rheb is a small GTPase protein that shuttles between its GDP- and GTP-bound forms to activate mTOR. Since RGS10 suppression augments ovarian cancer cell viability, we sought to elucidate the molecular mechanism. Following RGS10 suppression in serum-free conditions, phosphorylation of mTOR, the eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), p70S6K and S6 Ribosomal Protein appear. Furthermore, suppressing RGS10 increases activated Rheb, suggesting RGS10 antagonizes mTOR signaling via the small G-protein. The effects of RGS10 suppression are enhanced after stimulating cells with the growth factor, lysophosphatidic acid, and reduced with mTOR inhibitors, temsirolimus and INK-128. Suppression of RGS10 leads to an increase in cell proliferation, even in the presence of etoposide. In summary, the RGS10 suppression increases Rheb-GTP and mTOR signaling in ovarian cancer cells. Our results suggest that RGS10 could serve in a novel, and previously unknown, role by accelerating the hydrolysis of GTP from Rheb in ovarian cancer cells.

Vinyl sulfone analogs of lysophosphatidylcholine irreversibly inhibit autotaxin and prevent angiogenesis in melanoma.

Autotaxin (ATX) is an enzyme discovered in the conditioned medium of cultured melanoma cells and identified as a protein that strongly stimulates motility. This unique ectonucleotide pyrophosphatase and phosphodiesterase facilitates the removal of a choline headgroup from lysophosphatidylcholine (LPC) to yield lysophosphatidic acid (LPA), which is a potent lipid stimulator of tumorigenesis. Thus, ATX has received renewed attention because it has a prominent role in malignant progression with significant translational potential. Specifically, we sought to develop active site-targeted irreversible inhibitors as anti-cancer agents. Herein we describe the synthesis and biological activity of an LPC-mimetic electrophilic affinity label that targets the active site of ATX, which has a critical threonine residue that acts as a nucleophile in the lysophospholipase D reaction to liberate choline. We synthesized a set of quaternary ammonium derivative-containing vinyl sulfone analogs of LPC that function as irreversible inhibitors of ATX and inactivate the enzyme. The analogs were tested in cell viability assays using multiple cancer cell lines. The IC50 values ranged from 6.74 to 0.39 µM, consistent with a Ki of 3.50 µM for inhibition of ATX by the C16H33 vinyl sulfone analog CVS-16 (10b). A phenyl vinyl sulfone control compound, PVS-16, lacking the choline-like quaternary ammonium mimicking head group moiety, had little effect on cell viability and did not inhibit ATX. Most importantly, CVS-16 (10b) significantly inhibited melanoma progression in an in vivo tumor model by preventing angiogenesis. Taken together, this suggests that CVS-16 (10b) is a potent and irreversible ATX inhibitor with significant biological activity both in vitro and in vivo.

The Src homology 3 binding domain is required for lysophosphatidic acid 3 receptor-mediated cellular viability in melanoma cells.

The LPA3 receptor is a G protein-coupled receptor that binds extracellular lysophosphatidic acid and mediates intracellular signaling cascades. Although we previously reported that receptor inhibition using siRNA or chemical inhibition obliterates the viability of melanoma cells, the mechanism was unclear. Herein we hypothesized that amino acids comprising the Src homology 3 (SH3) ligand binding motif, R/K-X-X-V/P-X-X-P or (216)-KTNVLSP-(222), within the third intracellular loop of LPA3 were critical in mediating this outcome. Therefore, we performed site-directed mutagenesis of the lysine, valine and proline, replacing these amino acids with alanines, and evaluated the changes in viability, proliferation, ERK1/2 signaling and calcium in response to lysophosphatidic acid. Our results show that enforced LPA3 expression in SK-MEL-2 cells enhanced their resiliency by allowing these cells to oppose any loss of viability during growth in serum-free medium for up to 96 h, in contrast to parental SK-MEL-2 cells, which show a significant decline in viability. Similarly, site-directed alanine substitutions of valine and proline, V219A/P222A or 2aa-SK-MEL-2 cells, did not significantly alter viability, but adding a further alanine to replace the lysine, K216A/V219A/P222A or 3aa-SK-MEL-2 cells, obliterated this function. In addition, an inhibitor of the LPA3 receptor had no impact on the parental SK-MEL-2, 2aa-SK-MEL-2 or 3aa-SK-MEL-2 cells, but significantly reduced viability among wt-LPA3-SK-MEL-2 cells. Taken together, the data suggest that the SH3 ligand binding domain of LPA3 is required to mediate viability in melanoma cells.

Cost of fetal alcohol spectrum disorder diagnosis in Canada.

BACKGROUND: Fetal Alcohol Spectrum Disorder (FASD) is underdiagnosed in Canada. The diagnosis of FASD is not simple and currently, the recommendation is that a comprehensive, multidisciplinary assessment of the individual be done. The purpose of this study was to estimate the annual cost of FASD diagnosis on Canadian society. METHODS: The diagnostic process breakdown was based on recommendations from the Fetal Alcohol Spectrum Disorder Canadian Guidelines for Diagnosis. The per person cost of diagnosis was calculated based on the number of hours (estimated based on expert opinion) required by each specialist involved in the diagnostic process. The average rate per hour for each respective specialist was estimated based on hourly costs across Canada. Based on the existing clinical capacity of all FASD multidisciplinary clinics in Canada, obtained from the 2005 and 2011 surveys conducted by the Canada Northwest FASD Research Network, the number of FASD cases diagnosed per year in Canada was estimated. The per person cost of FASD diagnosis was then applied to the number of cases diagnosed per year in Canada in order to calculated the overall annual cost. RESULTS: Using the most conservative approach, it was estimated that an FASD evaluation requires 32 to 47 hours for one individual to be screened, referred, admitted, and diagnosed with an FASD diagnosis, which results in a total cost of $3,110 to $4,570 per person. The total cost of FASD diagnostic services in Canada ranges from $3.6 to $5.2 million (lower estimate), up to $5.0 to $7.3 million (upper estimate) per year. DISCUSSION: As a result of using the most conservative approach, the cost of FASD diagnostic services presented in the current study is most likely underestimated. The reasons for this likelihood and the limitations of the study are discussed.

Development of a conceptual model of health-related quality of life for systemic lupus erythematosus from the patient's perspective.

AIMS: The aim of this study was to evaluate the impact of systemic lupus erythematosus (SLE) on the lives of patients in order to inform the development of a conceptual model. METHODS: Twenty-two participants with SLE (defined as meeting four of the 11 ACR criteria) were recruited for this study. Semi-structured, in-person interviews were conducted with each participant, exploring the symptoms experienced and the impact on the patient's life. Thematic analysis of interview transcripts was conducted in ATLAS.ti software to identify areas of impact and explore the interrelationships between concepts to inform the development of a conceptual model. RESULTS: Almost all participants were female (95%); the sample was diverse in terms of age (mean age of 45.5 years; age range of 20-60 years), ethnicity (59% black/African American) and disease duration. Commonly reported symptoms were pain, fatigue/tiredness and skin problems. Qualitative analysis revealed seven themes relating to the impact of SLE symptoms on patient's Health Related Quality of Life (HRQL): emotions, social, family and leisure activities, daily activities, cognition, appearance, employment activities and independence. The interrelationships between symptoms, impacts and symptom triggers are illustrated in a conceptual model. CONCLUSIONS: The conceptual model illustrates the wide-reaching impact of SLE symptoms on a patient's HRQL, and the potential broad impact of a treatment that improves SLE symptoms.

The Canadian guidelines and the interdisciplinary clinical capacity of Canada to diagnose fetal alcohol spectrum disorder.

BACKGROUND: In 2005, the CMAJ published the Fetal alcohol spectrum disorder: Canadian guidelines for diagnosis. The intent of this publication was to encourage a more consistent interdisciplinary team approach and diagnostic procedure for FASD diagnoses. That same year, the Canada Northwest FASD Research Network (CanFASD Northwest) determined the locations and capacity for interdisciplinary FASD diagnosis across Canada. Six years later, we wondered how successfully these Guidelines had been in bringing consistency to FASD clinical work. METHOD: All clinical programs in Canada that routinely performed FASD evaluations were identified through membership in either our Network Action Team on FASD Diagnosis, professional meetings, organizational memberships, websites, programs lists available from Provincial or Federal offices or by word of mouth. Surveys were sent to all of the programs identified. RESULTS: A total of 55 clinics had been identified in seven provinces and one territory in 2005 that did FASD multidisciplinary diagnostics. In 2011 only 44 clinics were identified in six provinces and one territory using the same methodology. Survey responses were completed by 89% of these 44 clinics identified in 2011. The Guidelines were well known to all programs and actively referred to by most. Only 46% of respondents had a full staff of professionals on site for diagnosis, however 90% did use the team approach in determining final FASD diagnosis, while 79% used the team to help in developing a treatment plan. Among the clinics reporting, 74% of them used the new diagnostic schema proposed in the Guidelines and another 12% report using both the Guidelines and another system for diagnosis. INTERPRETATION: The Guidelines have become well known to the medical community. They have contributed to increased consistency in approach and in diagnosis. The variations in clinical ability to fully staff themselves, and the 20% decline in clinic numbers suggest important funding gaps. Many provinces and territories still have no local interdisciplinary programs for FASD diagnosis, and the need across Canada is still many times greater than what is currently available.

Developing effective, culturally appropriate avenues to FASD diagnosis and prevention in northern Canada.

This article describes 2 research initiatives that are being undertaken by members of the Canada Northwest FASD Research Network, involving collaborations between researchers, clinicians, service providers and community members in the Canadian North. Improving both the diagnosis and prevention of FASD requires evidence-based approaches to clinical and social service delivery that are capable of accounting for the unique contours of the geographic, regional and cultural diversities in which women become pregnant and in which families live. Although FASD has been a priority for communities and governments in northern Canada, research capacity has not been available to support the development of the context-specific knowledge needed to inform policy and practice in this region. Moreover, there have not been adequate mechanisms for transferring practice-based knowledge from the Canadian North to researchers and service providers in the South, who might make use of this knowledge to inform their own practice. Herein, we highlight the ways in which reciprocal knowledge exchange involving CanFASD Northwest researchers at academic health science centres and diverse stakeholder groups is supporting multi-directional capacity building in FASD diagnosis and prevention.

Normal distribution of palpebral fissure lengths in Canadian school age children.

BACKGROUND: Fetal alcohol syndrome (FAS) includes the facial dysmorphic feature of short palpebral fissures (PFs) and short PFs are a key physical marker for identifying children with FAS and some other rarer conditions. There is concern that normative data on PFs now available may not reflect all racial/ethnic groups and might be inaccurate in general. OBJECTIVES: To accomplish a large population based study that would accurately determine normative PF values across the full diversity of the Canadian school age population. METHODS: A normative sample of school age children was identified in Vancouver, British Columbia and Winnipeg, Manitoba to reflect the diversity of racial and national groups in Canada. The sample included students in grades 2, 4, 6, 8, and 10 from 17 schools in Vancouver and 31 schools in Winnipeg. Schools were selected based on racial diversity obtained from data from the 2001 Statistics Canada census. 1064 students in Vancouver and 1033 students in Winnipeg were photographed in a standardized way. Photographs were analyzed using a computerized method. RESULTS: Analysis demonstrated that PFs do grow with age and there is a slight but meaningful difference between boys and girls in each age group. It is possible to define Canadian standards without reference to racial or ethnic origin. CONCLUSION: Mean results with norms and standard deviations are presented in figures for clinical use and are clinically smaller than those found in the most commonly used reference book.

Dual control of cytosolic metals by lysosomal transporters in lobster hepatopancreas.

This study describes the membrane transport mechanisms used by lobster (Homarus americanus) hepatopancreatic epithelial lysosomes to accumulate and sequester heavy metals from the cytosol, and thereby aid in the regulation of these ions entering the animal from dietary constituents. The present investigation extends previous work describing lysosomal metal uptake by cation exchange with protons and suggests that a second, parallel, lysosomal transport process involving metal-thiol conjugates may work in conjunction with the cation antiporter to control cytoplasmic metal concentrations. Transport of (65)Zn(2+) by lysosomal membrane vesicles (LMV) incubated in 1 mmol l(-1) glutathione (GSH) was not significantly different from metal transport in the absence of the tripeptide. However, preloading LMV with 1 mmol l(-1) alpha-ketoglutarate (AKG), and then incubating in a medium containing 1 mmol l(-1) GSH, more than doubled metal uptake, compared with vesicles equilibrated with chloride or possessing an outwardly directed chloride gradient. Kinetic analysis of lysosomal (65)Zn(2+) influx as a function of zinc concentration, in vesicles containing 1 mmol l(-1) AKG and incubated in 1 mmol l(-1) GSH, revealed the presence of a sigmoidal, low affinity, high capacity carrier process transporting the metal into the organelle. These data indicated the possible presence of an organic anion exchanger in lobster lysosomal membranes. Western blot analysis of LMV with a rabbit anti-rat OAT1 antibody showed the presence of an orthologous OAT1-like protein (approximate molecular mass of 80 kDa) signal from these membranes. These results, and those published previously, suggest the occurrence of two metal transporters on hepatopancreatic membranes, a high affinity, low capacity cation antiporter and a low affinity, high capacity organic anion exchanger. Together these two systems have the potential to regulate cytoplasmic metals over a wide concentration range.

Development of Canadian screening tools for fetal alcohol spectrum disorder.

BACKGROUND: Fetal alcohol spectrum disorder (FASD) is the most common cause of neurobehavioural handicap in North America. Screening for FASD may facilitate diagnosis and hence management of these children. We present a variety of screening tools for the identification of children at risk for FASD. METHODS: We critically reviewed and evaluated published and practiced methods for their potential of screening suspected cases, their epidemiological characteristics (sensitivity, specificity, positive and negative predictive values) [Phase I], as well as their feasibility [Phase II]. RESULTS: The following five tools were selected for the FASD screening toolkit: screening fatty acid ethyl esters in neonatal meconium, the modified Child Behaviour Checklist, Medicine Wheel tool, Asante Centre Probation Officer Tool, and maternal history of drinking and drug use. CONCLUSIONS: The toolkit for FASD screening aims at screening different populations, from the newborns to youth and at-risk mothers. It is anticipated that the toolkit will facilitate diagnosis of FASD.

Building clinical capacity for fetal alcohol spectrum disorder diagnoses in western and northern Canada.

BACKGROUND: Fetal alcohol syndrome and fetal alcohol spectrum disorder are common problems. In response to this problem the Canada Northwest FASD Research Network was established in 2005 by the Canada Northwest FASD Ministerial Partnership. This study was conducted to determine the FASD clinical activity in Canada Northwest. METHODS: The Network identified all clinical programs via Internet sites, provincial postings and professional word of mouth references that purported to do FASD assessments regularly using a multidisciplinary assessment team. Each of these programs was sent a questionnaire asking about clinical capacity, aggregate diagnostic results, team composition, time of clinical assessment and cost of assessment. RESULTS: Of the 27 programs identified to receive the questionnaire 15 programs responded. These programs were determined to have evaluated about 85% of the patients evaluated by all the programs. The total 7 jurisdictional capacity for FASD diagnosis was 816 evaluations in 2005 and projected to be 975 in 2006. Selection methods for appointing patients for assessment seemed excellent as 23% of those assessed were found to have FAS or pFAS and another 44% had other forms of FASD. The most common professionals to participate in the team evaluations were Paediatricians, Clinical Psychologists, Speech and Language Pathologists and Occupational Therapists. INTERPRETATION: Clinics are developing in western and northern Canada to diagnose patients with FASD. Comparing the experiences of these clinics can help to determine the continued need to increase diagnostic capacity, standardize diagnostic approaches to assure consistency of approach and diagnosis across the sites and appropriately staff and fund the programs. Key words: FASD; diagnosis; Canada; clinics.