A pilot study of nocturnal temporalis muscle activity in TMD diagnostic groups of women.

Temporomandibular disorder (TMD) incidences are believed to be related to parafunctional behaviours like teeth clenching. This pilot study aimed to (i) develop an automated clench-detection algorithm, and (ii) apply the algorithm to test for differences in nocturnal clenching in women with and without TMD. Subjects gave informed consent to participate. Adult women were categorised using Diagnostic Criteria for TMD according to presence/absence (+/-) of both TM joint disc placement (DD) and chronic pain (P) into two groups (+DD+P, -DD-P) with 12 subjects each. Surface temporalis electromyography was recorded during oral tasks performed by subjects at two laboratory sessions. The data were used to characterise muscle activity per N of bite force (µV/N) for each subject, develop the clench-detection algorithm and test its accuracy. Ambulatory surface temporalis electromyography was self-recorded by each subject over three nights and analysed using the algorithm and bite force (N) versus muscle activity µV/N calibrations. Bonferroni-adjusted homoscedastic t-tests assessed for significant between-group differences in clenching (P < 0·05). Sensitivity, specificity and accuracy of algorithm-detected laboratory clenches were all ≥96%. During self-recordings 95% of clenches had durations of <4 s and peak forces of <10 N in both groups. Mean clench durations were significantly longer (P = 0·042) in +DD+P (1·9 ± 0·8 s) than -DD-P subjects (1·4 ± 0·4 s). Mean temporalis duty factors (%clench time/total recording time) were significantly larger (P = 0·041) in +DD+P (0·47 ± 0·34%) than -DD-P (0·26 ±0·22%) subjects. Nocturnal temporalis muscle activities detected by a validated algorithm were longer per clench and recording time in +DD+P compared to -DD-P women.

A Novel Eigenvector-based Method to Detect Mild Alzheimer's Disease Using Event-Related Potentials.

Event-related potentials (ERPs) are a physiological measure of cognitive function that have shown diagnostic and prognostic utility in Alzheimer's disease (AD). In this study, we used a novel eigenvector-based technique to better understand brain electrophysiological differences between subjects with mild AD and healthy controls (HC). Using ERPs from 75 subjects with mild AD and 95 HC, we first calculated cognitive task eigenvectors within each subject from three conditions and then calculated second-order eigenvector components to compare the AD group to the HC group. A MANOVA of the three second-level components discriminated between AD and HC multivariately (Wilks' lambda=.4297, p<0.0001, R2 = .5703), and also on each of the three components univariately (all 3 p-values<0.0001). The eigenvector-based technique used in this study accurately discriminated between the mild AD group and HC. As such, this analysis method adds to our understanding of the differences in ERP signal between AD and HC, and could provide a sensitive biomarker for diagnosis and monitoring of AD progression.

Parent-reported distress in children under 3 years old during preventive medical and dental care.

PURPOSE: This study examined factors related to young children's distress during preventive oral health visits. Additionally, associations between parent-reported child behaviour during the dental visit and during previous medical visits were tested. METHODS: One hundred twenty-two children under 3 years of age enrolled in a government insurance programme for low-income children were seen for examination, prophylaxis, and fluoride application at a university-based dental clinic. Child distress was rated by parents on a numerical rating scale. RESULTS: The average age of children enrolled was 23.5 ± 7.3 months. The majority (55.7 %) were judged to have little or no distress pre-examination. Mild or no distress during the examination was reported for 42.6 % of the children and severe distress was reported for 39.4 %. Intensity of distress during the examination was not associated with the child's age, gender, dental health, or previous experience with dental care. Distress was also unrelated to the caregiver's education level or own dental health. Intensity of distress was associated with the child's pre-dental examination distress and distress during prior medical examinations and injections. CONCLUSIONS: Dental professionals can better anticipate child distress by assessing children before a dental examination and enquiring about previous medical experiences. Strategies to prepare parents and alleviate distress may help children cope with the preventive dental visit.

Cardiopulmonary exercise testing prior to myeloablative allo-SCT: a feasibility study.

The feasibility of symptom-limited cardiopulmonary exercise testing (CPET) prior to allo-SCT was assessed in addition to the prognostic value of CPET-derived measures. CPET was performed prospectively on 21 patients with hematologic malignancies, with assessments of peak (for example, peak oxygen consumption, VO2peak) and submaximal (for example, ventilatory threshold (VT)) measures of cardiopulmonary function. No serious adverse events were observed during CPET procedures, with 95% of patients achieving criteria for a peak test. Mean VO2peak was 24.7±6.4 mL kg(-1 )min(-1) (range: 10.9-35.5), equivalent to 29%±17% below that of age-matched healthy controls. All patients proceeded with the conditioning regimen followed by allo-SCT. Median follow-up was 25 months. During this period, 11 (52.4%) patients died (n=6, relapsed disease; n=5, non-relapse mortality (NRM)); 9 patients (43%) developed pulmonary toxicity. In univariate analyses, both peak and submaximal markers of cardiopulmonary function were predictors of OS, pulmonary toxicity and NRM. For OS, the HR for VO2peak and VT were 0.89 (95% CI, 0.8-0.99, P=0.04) and 0.84 (95% CI, 0.71-0.98, P=0.03), respectively. In conclusion, CPET is safe and feasible prior to allo-SCT. Patients have marked impairments in cardiopulmonary function prior to allo-SCT. CPET-derived metrics may complement conventional measures to improve risk stratification.

Oblique lateral radiographs and bitewings; estimation of organ doses in head and neck region with Monte Carlo calculations.

OBJECTIVES: When bitewing radiographs are not possible (e.g. patients with special needs), oblique lateral radiographs may offer an alternative. The aims of this study were to assess the impact of horizontal projection angulation, focus-to-skin distance, exposure time and age of the patient on the equivalent radiation dose of several organs in the head and neck region by means of personal computer X-ray Monte Carlo (PCXMC) calculations and to assess the dose obtained from conventional bitewing radiographs. METHODS: PCXMC v. 2.0 software (STUK(®), Helsinki, Finland) was used to estimate the equivalent radiation doses and the total effective dose. Three exposure times, five age categories, two focus-to-skin distances and eight horizontal geometric angulations were assumed. The organs involved were the thyroid gland, oesophagus, salivary glands, bone marrow, oral mucosa, skull, cervical spine and skin. A similar calculation was also performed for bitewings taken with a rectangular collimator. Results and conclusion Bitewings taken with rectangular collimation decrease the radiation burden of the patient to 50%, compared with circular collimation. In the oblique lateral radiographs, focus-to-skin distance, patient's age and beam collimation had a significant impact on the equivalent doses measured in this study. Exposure time had a significant impact on the equivalent doses of the salivary glands, oral mucosa, skull and skin. Horizontal angulations had a significant impact on the equivalent doses of the thyroid gland, bone marrow, oral mucosa, skull and cervical spine. The total effective radiation dose was significantly influenced by all parameters investigated in this study.

Novel use of topical dapsone 5% gel for erythema elevatum diutinum: safer and effective.

We present a case of an otherwise healthy 81-year-old gentleman with multiple asymptomatic, erythematous, indurated papules and plaques, ranging in size from 0.5 to 1.5 cm, involving the dorsal, lateral, and palmar surfaces of the fingers bilaterally. A clinical suspicion of erythema elevatum diutinum (EED) led to initial treatment with topical dapsone 5% gel (ACZONE; Allergan Inc, Irvine, CA). Lesional biopsy demonstrated a dense perivascular infiltration of polymorphonuclear leukocytes and chronic inflammatory cells with perivascular fibrin deposition. Focal neutrophilic infiltration of superficial dermal blood vessel walls was present, suggesting a leukocytoclastic vasculitis. Stains for bacteria and fungi were negative. Clinicopathologic findings were consistent with EED, and in the interim, improvement with topical dapsone 5% gel was noted. Addition of oral dapsone led to complete resolution of the lesions. We present this case to illustrate the subtle, indolent clinical presentation of EED and demonstrate the uncomplicated use of topical dapsone 5% gel for rapid improvement and subsequent successful treatment of localized disease.

Challenges, concerns and common problems: physiological consequences of spinal cord injury and microgravity.

INTRODUCTION: Similarities between the clinical presentation of individuals living with spinal cord injury (SCI) and astronauts are remarkable, and may be of great interest to clinicians and scientists alike. OBJECTIVES: The primary purpose of this review is to outline the manner in which cardiovascular, musculoskeletal, renal, immune and sensory motor systems are affected by microgravity and SCI. METHODS: A comprehensive review of the literature was conducted (using PubMed) to evaluate the hallmark symptoms seen after spaceflight and SCI. This literature was then examined critically to determine symptoms common to both populations. RESULTS: Both SCI and prolonged microgravity exposure are associated with marked deteriorations in various physiological functions. Atrophy in muscle and bone, cardiovascular disturbances, and alterations in renal, immune and sensory motor systems are conditions commonly observed not only in individuals with SCI, but also in those who experience prolonged gravity unloading. CONCLUSION: The preponderance of data indicates that similar physiological changes occur in both SCI and prolonged space flight. These findings have important implications for future research in SCI and prolonged space flight.

Transcobalamin II receptor polymorphisms are associated with increased risk for neural tube defects.

OBJECTIVE: Women who have low cobalamin (vitamin B(12)) levels are at increased risk for having children with neural tube defects (NTDs). The transcobalamin II receptor (TCblR) mediates uptake of cobalamin into cells. Inherited variants in the TCblR gene as NTD risk factors were evaluated. METHODS: Case-control and family-based tests of association were used to screen common variation in TCblR as genetic risk factors for NTDs in a large Irish group. A confirmatory group of NTD triads was used to test positive findings. RESULTS: 2 tightly linked variants associated with NTDs in a recessive model were found: TCblR rs2336573 (G220R; p(corr)=0.0080, corrected for multiple hypothesis testing) and TCblR rs9426 (p(corr)=0.0279). These variants were also associated with NTDs in a family-based test before multiple test correction (log-linear analysis of a recessive model: rs2336573 (G220R; RR=6.59, p=0.0037) and rs9426 (RR=6.71, p=0.0035)). A copy number variant distal to TCblR and two previously unreported exonic insertion-deletion polymorphisms were described. CONCLUSIONS: TCblR rs2336573 (G220R) and TCblR rs9426 represent a significant risk factor in NTD cases in the Irish population. The homozygous risk genotype was not detected in nearly 1000 controls, indicating that this NTD risk factor may be of low frequency and high penetrance. 9 other variants are in perfect linkage disequilibrium with the associated single nucleotide polymorphisms. Additional work is required to identify the disease-causing variant. Our data suggest that variation in TCblR plays a role in NTD risk and that these variants may modulate cobalamin metabolism.

Postgraduate Symposium: The MTHFR C677T polymorphism, B-vitamins and blood pressure.

High blood pressure (BP) and elevated homocysteine are reported as independent risk factors for CVD and stroke in particular. The main genetic determinant of homocysteine concentrations is homozygosity (TT genotype) for the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene, typically found in approximately 10% of Western populations. The B-vitamins folate, vitamin B12 and vitamin B6 are the main nutritional determinants of homocysteine, with riboflavin more recently identified as a potent modulator specifically in individuals with the TT genotype. Although observational studies have reported associations between homocysteine and BP, B-vitamin intervention studies have shown little or no BP response despite decreases in homocysteine. Such studies, however, have not considered the MTHFR C677T polymorphism, which has been shown to be associated with BP. It has been shown for the first time that riboflavin is an important determinant of BP specifically in individuals with the TT genotype. Research generally suggests that 24 h ambulatory BP monitoring provides a more accurate measure of BP than casual measurements and its use in future studies may also provide important insights into the relationship between the MTHFR polymorphism and BP. Further research is also required to investigate the association between specific B-vitamins and BP in individuals with different MTHFR genotypes in order to confirm whether any genetic predisposition to hypertension is correctable by B-vitamin intervention. The present review will investigate the evidence linking the MTHFR C677T polymorphism to BP and the potential modulating role of B-vitamins.

Heart rate variability responses to a psychologically challenging scuba dive.

AIM: Given the controversy regarding cardiovascular responses and heart rate variability (HRV) in underwater conditions, the authors assessed the combined effect of psychological stress and scuba diving on cardiac autonomic modulation measured through HRV during and following a diving mission. METHODS: Ten healthy adults (three females; seven males; Body Mass Index [BMI] 23.7 + or - 2.1; age 26.4 + or - 2.9) performed a 20-minute dive in a neutral buoyancy water tank (27 degrees C) at a depth of five meters. The dive scenario involved repairing components of a scientific instrument using a high fidelity task mock-up. Data for HRV (three from the time domain and three from the frequency domain) were obtained for 20 minutes prior to (PRE), during (DIVE), and for 20 minutes following (POST) the dive sortie. RESULTS: Heart rate in DIVE was increased when compared to PRE and POST (74 + or - 10 vs. 108 + or - 16 vs. 72 + or - 8 beats x min(-1), respectively). The time domain measure pNN50 (37.3 + or - 16.9 vs. 14.1 + or - 10.1 vs. 22.0 + or - 12.2%, respectively), and the R-R interval (0.72 + or - 0.26 vs. 0.59 + or - 0.11, vs. 0.86 + or - 0.24, respectively) showed a significant decrease in DIVE compared to PRE and POST, while no changes were detected in the frequency domain indices between measurements. During POST, the square root of the mean of squared differences between successive intervals returned to PRE levels, but pNN50 values remained decreased at DIVE levels. CONCLUSIONS: These findings suggest a decrease in parasympathetic indices during a psychologically challenging scuba dive and a delay in vagal reactivation during the 20-minute period following the dive.

Complex interactions with several arms of the complement system dictate innate and humoral immunity to adenoviral vectors.

The complement system is known to play critical roles in pathogen identification, initiation of innate immune responses and facilitation of adaptive immune responses. Several studies have suggested that recombinant adenoviruses (rAds) interact with proteins of the complement system within minutes of administration. In this study, we assessed the roles of the alternative (Factor B), classical (C1q and C4) and common (C3) arms of the complement system in the innate and humoral response to systemic rAd administration using mice genetically deficient for each of these functions. Although most plasma cytokines and chemokines induced by Ads appeared to be elicited in a C3-dependent manner, we found that rAd-induced thrombocytopenia was dependent on Factor B and C3, implicating the alternative pathway as responsible for this response. Alteration of the complement-dependent transcriptome response after rAd-induced liver gene expression was also found to be Factor B- and C3-dependent. Ad interactions with the classical and alternative arms of the complement system can also be redundant, as many complement-dependent, Ad-induced innate immune responses appeared to be primarily C3-dependent. We also identified a C3 dependence of Ad-mediated induction of the nuclear factor-kappaB (NF-kappaB) activation pathway. Finally, we confirmed that humoral immune responses to the vector capsid, and the transgene it encodes, are also complement-dependent.

Folate and clefts of the lip and palate--a U.K.-based case-control study: Part II: Biochemical and genetic analysis.

OBJECTIVE: To investigate associations between nonsyndromic oral clefts and biochemical measures of folate status and the MTHFR C677T variant in the United Kingdom, where there has been no folic acid fortification program. METHOD: Dietary details were obtained from the mothers of 112 cases of cleft lip with or without cleft palate (CL+/-P), 78 cleft palate only (CP) cases, and 248 unaffected infants. Infant and parental MTHFR C677T genotype was determined. Red blood cell (RBC) and serum folate and homocysteine levels were assessed in 12-month postpartum blood samples from a subset of mothers. The data were analyzed by logistic and log-linear regression methods. RESULTS: There was an inverse association between CL+/-P and maternal MTHFR CT (odds ratio [OR] = 0.5, 95% confidence interval [CI] = 0.31-0.95) and TT (OR = 0.6, 95% CI = 0.21-1.50) genotypes, with similar risk estimates for CP. There was no clear association with infant MTHFR genotype. Higher levels of maternal postpartum RBC and serum folate were associated with a lower risk for CL+/-P and an increased risk for CP. Higher levels of serum homocysteine were associated with a slightly increased risk for both CL+/-P and CP. CONCLUSION: While the inverse relation between the mother's having the MTHFR C677T variant and both CL+/-P and CP suggests perturbation of maternal folate metabolism is of etiological importance, contrasting relations between maternal postpartum levels of RBC and serum folate by type of cleft are difficult to explain.

The effects of functional electrical stimulation leg cycle ergometry training on arterial compliance in individuals with spinal cord injury.

STUDY DESIGN: A prospective intervention of functional electrical stimulation leg cycle ergometry (FES-LCE) of four women with spinal cord injury (SCI). OBJECTIVE: To evaluate the effect of FES-LCE training on arterial compliance in individuals with chronic SCI of traumatic origin. SETTING: Tertiary rehabilitation center in Canada. METHODS: Large and small artery compliance were measured at the radial artery before and after a 3-month training program using FES-LCE. RESULTS: There was no significant change in large artery compliance after FES-LCE (16.0+/-4.2 to 16.8+/-6.1 ml mm Hg(-1) x 10, P=NS). There was a marked (63%) increase in small artery compliance after the FES training program (4.2+/-1.8 to 6.9+/-3.2 ml mm Hg(-1) x 100, P<0.05). CONCLUSION: It appears that FES-LCE is effective in improving small artery compliance in females with SCI.

Intensive rotational grazing assists control of gastrointestinal nematodosis of sheep in a cool temperate environment with summer-dominant rainfall.

While rotational grazing methods have an accepted role in the management of gastrointestinal nematodosis (GIN) of small ruminants in humid tropical regions, their efficacy and application in cool temperate regions is more controversial. This study evaluated GIN over 2 years in three classes of fine wool Merino sheep (lambs, hoggets and ewes) under three different sheep management systems in a cool tableland environment near Armidale NSW Australia (950m altitude, 30 degrees 31'S, 151 degrees 39'E). The management systems were High input (HI) with high fertiliser inputs, a target of 100% sown pasture, high stocking rate (13.4 dry sheep equivalents/ha) and relatively long grazing periods; Typical (TYP) New England management system with moderate fertiliser inputs and stocking rate (9.3DSE/ha) and relatively long grazing periods; and Intensive rotational grazing (IRG) with moderate fertiliser inputs and stocking rate (8.8DSE/ha) but very short (mean 5 days) grazing periods and long (mean 103 days) rest periods. Twenty sheep of each class in each management treatment were sampled monthly for faecal worm egg counts (WEC, followed by larval differentiation), and body weights with a blood sample taken for haematology every second month. The proportion of sheep with WEC above zero did not differ between management systems but the magnitude of WEC did, with sheep under IRG displaying lower mean WEC than those on the other treatments (IRG: 326, HI: 594, TYP: 536, eggs/g P<0.0001). This was despite a significantly longer mean interval between anthelmintic treatments (IRG: 144 days, HI: 77 days, TYP: 78 days, P<0.0001). The IRG management system also influenced the composition of the infections with sheep on this treatment having a significantly lower proportion of Haemonchus contortus in their faecal cultures (IRG: 59.7%, HI: 79.4%, TYP: 80.9%, P<0.05) and a significantly higher proportion of Trichostrongylus spp. Sheep on the IRG treatment also had a significantly higher haematocrit (HCT) than those on the other management systems. Despite the lower WEC and higher HCT, sheep under IRG also had significantly lower bodyweights and fleece weights overall, although this was only evident in sheep raised to adulthood prior to the experiment, not those raised during the 2-year experimental period. The results demonstrate that IRG systems with short grazing periods and long rest periods between grazing events can assist with control of GIN in cool temperate climates where H. contortus is the dominant parasite.

Wild-type adenoviruses from groups A-F evoke unique innate immune responses, of which HAd3 and SAd23 are partially complement dependent.

Alternative human and non-human Ad serotype vectors are currently studied for gene therapy and/or vaccine applications to capitalize upon their likely ability to avoid pre-existing immunity to HAd5. However, relatively little attention has been given to the nature and scope of innate immune responses generated by alternative Ad serotypes. In this study, we characterized several innate immune responses after intravenous administration of wild-type Ad serotypes HAd31, HAd3, HAd5, HAd37, SAd23 and HAd41, representing groups A-F, respectively. Notably, biodistribution studies revealed significant differences between the serotypes, with high levels of HAd3 genomes found in the liver and lung, and HAd37 genomes found in the spleen after systemic administration. Relative to similar treatments with other Ad serotypes, HAd3 and SAd23 induced altered innate immune responses, illustrated by induction of higher levels of cellular gene transcription in several tissues, and higher plasma levels of cytokines and chemokines. We also investigated whether complement interactions have a role in HAd3- and SAd23-induced responses. We confirmed complement dependent gene transcription, plasma cytokine/chemokine responses, and liver toxicities incurred after administration of HAd3 and SAd23. This study highlights the potential benefits and/or limitations to the proposed use of alternative Ad serotypes for gene therapy or vaccine applications.

Vitamin B12 and folate deficiency in later life.

OBJECTIVES: to examine the prevalence of vitamin B12 deficiency and folate deficiency in later life in representative samples of the elderly population in the United Kingdom. DESIGN: a population-based cross-sectional analysis of 3,511 people aged 65 years or older from three studies was used to estimate the age-specific prevalence of vitamin B12 deficiency and of folate deficiency. Vitamin B12 deficiency is conventionally diagnosed if serum vitamin B12 < 150 pmol/l ('low vitamin B12'). We defined 'metabolically significant vitamin B12 deficiency' as vitamin B12 < 200 pmol/l and blood total homocysteine >20 micro mol/l. Folate deficiency, which usually refers to serum folate <5 nmol/l, was defined as 'metabolically significant' if serum folate was <7 nmol/l and homocysteine >20 micro mol/l. RESULTS: the prevalence of vitamin B12 deficiency, whether defined as low vitamin B12 or metabolically significant vitamin B12 deficiency increased with age in all three studies, from about 1 in 20 among people aged 65-74 years to 1 in 10 or even greater among people aged 75 years or greater. The prevalence of folate deficiency also increased with age, and was similar to that for vitamin B12 deficiencies, but only about 10% of people with low vitamin B12 levels also had low folate levels. CONCLUSION: the high prevalence of vitamin B12 and folate deficiency observed in older people indicates a particular need for vigilance for deficiency of these vitamins. Reliable detection and treatment of vitamin deficiency could reduce the risk of deficiency-related disability in old age.

Folate, vitamin B12 and birth defects.

While the evidence that folic acid/folate can prevent most cases of NTDs if taken periconceptually, the position is less clear with respect to OFCs. Some studies indicate a positive protection while others are negative. There are also conflicting reports as to whether or not the C677T variant of MTHFR increases risk. This is to be contrasted with NTDs where it clearly does.

Low-dose folic acid lowers plasma homocysteine levels in women of child-bearing age.

BACKGROUND: Ongoing clinical trials are investigating whether lowering plasma homocysteine reduces the risk of vascular disease. If so, food fortification with folic acid will be the likely result, and sub-optimal amounts are likely to be preferred, for safety reasons. Dose-finding studies are needed before the outcomes of these trials, to establish the benefits and risks of folic acid consumption over the widest intake range likely to be encountered. AIM: To find the lowest dose of folic acid that effectively reduces plasma homocysteine in premenopausal women. DESIGN: Double-blind, randomized placebo-controlled trial. METHODS: Women of child-bearing age (n=95) were randomly allocated to 0, 100, 200, or 400 microg/day of folic acid. Red-cell folate and plasma homocysteine were measured at baseline and after 10 weeks supplementation. RESULTS: Median red cell folate levels increased significantly in the 200 microg(p=0.0001) and 400 microg(p=0.0001) groups; but not in the placebo (0 microg) (p=0.25) or the 100 microg (p=0.5) groups. Only the 200 microg and the 400 microg groups had significant decreases in plasma homocysteine, (p=0.04 and p=0.0008, respectively). However, when subjects whose initial plasma homocysteine was <8 micromol/l (already optimally low) were removed from the analysis, there were significant plasma homocysteine decreases in all three treatment groups, but not the placebo group. DISCUSSION: In this sub-population, low doses of folic acid significantly lower plasma homocysteine. This could be achieved safely by fortification.