Validation of actigraphy sleep metrics in children aged 8 to 16 years: considerations for device type, placement and algorithms.

BACKGROUND: Actigraphy is often used to measure sleep in pediatric populations, despite little confirmatory evidence of the accuracy of existing sleep/wake algorithms. The aim of this study was to determine the performance of 11 sleep algorithms in relation to overnight polysomnography in children and adolescents. METHODS: One hundred thirty-seven participants aged 8-16 years wore two Actigraph wGT3X-BT (wrist, waist) and three Axivity AX3 (wrist, back, thigh) accelerometers over 24-h. Gold standard measures of sleep were obtained using polysomnography (PSG; Embletta MPRPG, ST + Proxy and TX Proxy) in the home environment, overnight. Epoch by epoch comparisons of the Sadeh (two algorithms), Cole-Kripke (three algorithms), Tudor-Locke (four algorithms), Count-Scaled (CS), and HDCZA algorithms were undertaken. Mean differences from PSG values were calculated for various sleep outcomes. RESULTS: Overall, sensitivities were high (mean ± SD: 91.8%, ± 5.6%) and specificities moderate (63.8% ± 13.8%), with the HDCZA algorithm performing the best overall in terms of specificity (87.5% ± 1.3%) and accuracy (86.4% ± 0.9%). Sleep outcome measures were more accurately measured by devices worn at the wrist than the hip, thigh or lower back, with the exception of sleep efficiency where the reverse was true. The CS algorithm provided consistently accurate measures of sleep onset: the mean (95%CI) difference at the wrist with Axivity was 2 min (-6; -14,) and the offset was 10 min (5, -19). Several algorithms provided accurate measures of sleep quantity at the wrist, showing differences with PSG of just 1-18 min a night for sleep period time and 5-22 min for total sleep time. Accuracy was generally higher for sleep efficiency than for frequency of night wakings or wake after sleep onset. The CS algorithm was more accurate at assessing sleep period time, with narrower 95% limits of agreement compared to the HDCZA (CS:-165 to 172 min; HDCZA: -212 to 250 min). CONCLUSION: Although the performance of existing count-based sleep algorithms varies markedly, wrist-worn devices provide more accurate measures of most sleep measures compared to other sites. Overall, the HDZCA algorithm showed the greatest accuracy, although the most appropriate algorithm depends on the sleep measure of focus.

Organic matter composition and thermal stability influence greenhouse gases production in subtropical peatland under different vegetation types.

Peatlands are a major carbon (C) sink globally. Organic matter quality influence greenhouse gases production. However, little is known about how organic matter from different vegetation types, influences C composition and resultant greenhouse gases production in subtropical peatland. Anoxic incubation experiments were conducted using two types of peats with different botanical origin to assess C composition, CO2 and CH4 production. First peat had cypress dominance and the second knotted spikerush and water lily (spike + lily). Solid-state CPMAS 13C NMR determined C chemical stability, MESTA determined C thermal stability, stable isotopes for C source and gas chromatograph for carbon dioxide (CO2) and methane (CH4). The results indicated dominance of autochthonous C as indicated by δ13C signatures. Low thermal stable C (LTSC) dominated in litter, FL (fermentation layer) and spike + lily sediment, high thermal stable C was dominant in cypress peat. O-alkyl C strongly correlated with LTSC whereas aromatic C correlated negatively with R400 (LTSC:total C ratio). Generally, O-alkyl decreased and alkyl increased along litter-FL-peat continuum. Spike + lily peat exhibited initial stage of decomposition. Indicated by increased alkyl C, aromatic C and aromatic:O-alkyl ratio with increasing peat depth. Also, exhibited 3 times more CH4 and CO2 production compared to cypress peat that dominantly exhibited second stage of decomposition. O-alkyl C exhibited positive relationship with CH4 (P = 0.012, r2 = 0.57) and CO2 (P = 0.047, r2 = 0.41) production whereas R400 related positively with CH4 (P = 0.05, r2 = 0.40). Organic matter thermal and chemical composition varied between the peat types and thermally and chemically labile C influenced CO2 and CH4 production.

Axin2+ PDL Cells Directly Contribute to New Alveolar Bone Formation in Response to Orthodontic Tension Force.

Wnt-ß-catenin signaling plays a key role in orthodontic tooth movement (OTM), a common clinical practice for malocclusion correction. However, its targeted periodontal ligament (PDL) progenitor cells remain largely unclear. In this study, we first showed a synchronized increase in Wnt-ß-catenin levels and Axin2+ PDL progenitor cell numbers during OTM using immunostaining of ß-catenin in wild-type mice and X-gal staining in the Axin2-LacZ knock-in line. Next, we demonstrated time-dependent increases in Axin2+ PDL progenitors and their progeny cell numbers within PDL and alveolar bones during OTM using a one-time tamoxifen-induced Axin2 tracing line (Axin2CreERT2/+; R26RtdTomato/+). Coimmunostaining images displayed both early and late bone markers (such as RUNX2 and DMP1) in the Axin2Lin PDL cells. Conversely, ablation of Axin2+ PDL cells via one-time tamoxifen-induced diphtheria toxin subunit A (DTA) led to a drastic decrease in osteogenic activity (as reflected by alkaline phosphatase) in PDL and alveolar bone. There was also a decrease in new bone mass and a significant reduction in the mineral apposition rate on both the control side (to a moderate degree) and the OTM side (to a severe degree). Thus, we conclude that the Axin2+ PDL cells (the Wnt-targeted key cells) are highly sensitive to orthodontic tension force and play a critical role in OTM-induced PDL expansion and alveolar bone formation. Future drug development targeting the Axin2+ PDL progenitor cells may accelerate alveolar bone formation during orthodontic treatment.

Relationship of arsenic and chromium availability with carbon functional groups, aluminum and iron in Little Washita River Experimental Watershed Reservoirs, Oklahoma, USA.

Sediment from three reservoirs located in the Little Washita River Experimental Watershed (LWREW) in Oklahoma, USA with contrasting dominant land uses were analyzed for total and extractable concentrations of arsenic (As) and chromium (Cr), and the potential ecologic risk to benthic organisms. Extractable As ranged from 0.24 to 1.21 mg kg-1, in the order grazing>cropland>forest and 0.13-0.58 mg kg-1 for extractable Cr, in the order of forest>grazing>cropland. However, only approximately < 1.5% of total As and < 4% of total Cr were extractable. Total As ranged from 16.2 to 141 mg kg-1 and total Cr ranged from 5.06 to 40.1 mg kg-1 both in the order of cropland>grazing>forest. The sediment exhibited an alkaline pH (8.0-8.7). As sorption exhibited a positive relationship with Al (r = 0.9995; P = 0.0001), Fe (r = 0.9829; P = 0.0001), and C (r = 0.4090; P = 0.0017) and Cr correlated positively with Al (r = 0.9676 P = 0.0001), Fe (r = 0.9818; P = 0.0001), and C (r = 0.3368; P = 0.0111). In addition, both As and Cr exhibited positive relationships with carbon (C) functional groups in the order of O-alkyl C> methoxyl C> alkyl C> aromatic C> carboxyl C> phenolic C. The sediment concentration analysis results illustrated that As in all reservoirs exceeded their respective Threshold Effect Level (TEL) and/or Probable Effect Level (PEL) indicating that existing concentrations of metals in these sediments were sufficiently high to cause adverse effects. However, Cr concentrations in all reservoirs evaluated was lower compared to the TEL and PEL.

The cost of baby-led vs. parent-led approaches to introducing complementary foods in New Zealand.

Baby-led approaches to complementary feeding promote intake of family foods rather than infant specific foods, from the start of the complementary feeding period, which advocates suggest should be less expensive. However, this has never been formally examined. We recently completed a 2-year randomised controlled trial comparing baby-led (BLISS) and traditional spoon-feeding (Control) approaches to complementary feeding in 206 infants. Perceived expense was assessed at infant 7, 8, 9 and 12 months of age. The actual cost of intake (food offered, consumed and left over) was calculated from 3-day weighed diet records at 7 and 12 months of age. BLISS was perceived as less expensive than traditional feeding (P = 0.002), but comparisons of actual costs showed only small differences in total daily cost for food offered (NZ$0.20 and NZ$0.10 at 7 and 12 months, respectively), consumed (NZ$0.30, NZ$0.20) or left over (NZ$0.10, NZ$0.20). Baby-led approaches are not cheaper for families than traditional spoon-feeding.

Do differences in compositional time use explain ethnic variation in the prevalence of obesity in children? Analyses using 24-hour accelerometry.

BACKGROUND/OBJECTIVES: Whether variation in sleep and physical activity explain marked ethnic and socioeconomic disparities in childhood obesity is unclear. As time spent in one behaviour influences time spent in other behaviours across the 24-hour day, compositional analyses are essential. The aims of this study were to determine how ethnicity and socioeconomic status influence compositional time use in children, and whether differences in compositional time use explain variation in body mass index (BMI) z-score and obesity prevalence across ethnic groups. METHODS: In all, 690 children (58% European, 20% Maori, 13% Pacific, 9% Asian; 66% low-medium deprivation and 34% high deprivation) aged 6-10 years wore an ActiGraph accelerometer 24-hours a day for 5 days yielding data on sedentary time, sleep, light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA). Height and weight were measured using standard techniques and BMI z-scores calculated. Twenty-four hour movement data were transformed into isometric log-ratio co-ordinates for multivariable regression analysis and effect sizes were back-transformed. RESULTS: European children spent more time asleep (predicted difference in minutes, 95% CI: 16.1, 7.4-24.9) and in MVPA (6.6 min, 2.4-10.4), and less time sedentary (-10.2 min, -19.8 to -0.6) and in LPA (-12.2 min, -21.0 to -3.5) than non-European children. Overall, 10% more sleep was associated with a larger difference in BMI z-score (adjusted difference, 95% CI: -0.13, -0.25 to -0.01) than 10% more MVPA (-0.06, -0.09 to -0.03). Compositional time use explained 35% of the increased risk of obesity in Pacific compared with European children after adjustment for age, sex, deprivation and diet, but only 9% in Maori and 24% in Asian children. CONCLUSIONS: Ethnic differences in compositional time use explain a relatively small proportion of the ethnic differences in obesity prevalence that exist in children.

Sleep and pre-bedtime activities in New Zealand adolescents: differences by ethnicity.

AIM: To describe the screen and nonscreen activities adolescents engage in one hour before bedtime and associations with sleep quantity and quality, including differences by ethnic group. DESIGN: Cross-sectional survey. PARTICIPANTS: 4,192 adolescents aged 13-17 years (52% boys); 71% NZ European, 13% Maori, 8% Asian, 6% Pacific, and 2% other ethnic groups. MEASURES: Participants completed questions about sleep timing, quality (Pittsburgh Sleep Quality Index), and chronotype (Morningness-Eveningness Scale for Children). Seventeen questions captured pre-bedtime activities. RESULTS: Overall, 39% slept less than the recommended hour of sleep (<8 h) and 57% reported poor sleep quality. Asian teenagers reported shorter sleep duration than New Zealand (NZ) Europeans (-45 min [95% CI: -58 to -32]) primarily from later bedtimes (1 hour), with higher odds of long sleep latency, but less disturbed sleep and a more "eveningness" chronotype. Bedtimes were later in Maori and Pacific adolescents (15 and 41 min, respectively) than NZ Europeans. Most screen activities were negatively associated with sleep quantity and quality. For nonscreen activities, snacking and drinking caffeinated beverages and alcohol were significantly associated with shorter sleep (-8, -28, and -20 min, respectively), whereas interacting with family and friends and exercise/sports before bed were associated with longer sleep (P < 0.001). Time with family, exercise, schoolwork, and household chores were all associated with better sleep quality (P < 0.001). Ethnic differences were apparent for several pre-bedtime activities. DISCUSSION: Ethnic differences related to subjective sleep parameters exist in NZ adolescents. Observed variations in sleep patterns and presleep activities suggest that sleep health messages should be tailored for different ethnic groups.

Correction: Mitochondrial oxodicarboxylate carrier deficiency is associated with mitochondrial DNA depletion and spinal muscular atrophy-like disease.

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A case-comparison study of pregnant women with mitochondrial disease - what to expect?

OBJECTIVE: Mitochondrial disease is a disorder of energy metabolism that affects 1 in 4300 adults in the UK. Pregnancy is associated with physiological demands that have implications for energy metabolism. We were interested to know how pregnancy was affected in women with mitochondrial disease, particularly those with the most common pathogenic mutation m.3243A>G. DESIGN: Retrospective case-comparison study. POPULATION/SETTING: Sixty-seven women with genetically confirmed mitochondrial disease from the UK Mitochondrial Diseases Cohort and 69 unaffected women participated. METHODS: Participants answered questionnaires regarding each of their pregnancies. Patients were divided into two groups according to genetic mutation, with those harbouring m.3243A>G comprising a single group. MAIN OUTCOME MEASURES: Pregnancy-related complications, mode of delivery, gestational age and birthweight of newborns. RESULTS: Of 139 live births in the comparison group, 62 were in the m.3243A>G group and 87 were in the 'all other mutations' group. Pregnancies of women with the m.3243A>G mutation had significantly more gestational diabetes (odds ratio [OR] = 8.2, 95% CI 1.3-50.1), breathing difficulties (OR = 7.8, 95% CI 1.0-59.1) and hypertension (OR = 8.2, 95% CI 3.1-21.5) than the comparison group. Only half of the pregnancies in the m.3243A>G group had normal vaginal delivery, with emergency caesarean section accounting for 24.2% of deliveries. Babies were born significantly earlier to mothers harbouring m.3243A>G with 53.3% of them preterm (<37 weeks). These babies were also more likely to require resuscitation and admission. CONCLUSION: Women who carried the m.3243A>G mutation appeared to be at higher risk of complications during pregnancies, caesarean section and preterm delivery than the unaffected women or those with other forms of mitochondrial disease. TWEETABLE ABSTRACT: Pregnant women with mitochondrial disease - m.3243A>G mutation - are at greatly increased risk of complications and preterm delivery.

Self-monitoring has no adverse effect on disordered eating in adults seeking treatment for obesity.

OBJECTIVES: Although monitoring is considered a key component of effective behaviour change, the development of apps has allowed consumers to constantly evaluate their own diet, with little examination of what this might mean for eating behaviour. The aim of this study was to investigate whether self-monitoring of diet using the app MyFitnessPal or daily self-weighing increases the reported occurrence of eating disorders in adults with overweight/obesity following a weight loss programme. METHODS: Two hundred fifty adults with body mass index ≥ 27 kg/m2 received diet and exercise advice and were randomized to one of four monitoring strategies (daily self-weighing, MyFitnessPal, brief monthly consults or self-monitoring hunger) or control for 12 months. The Eating Disorder Examination Questionnaire 6.0 was used to assess eating disorder symptoms and behaviours for the previous 28 d at 0 and 12 months. RESULTS: There were no significant differences in the global Eating Disorder Examination Questionnaire score or the subscales between those in the four monitoring groups and the control at 12 months (all p ≥ 0.164), nor were there differences in binge eating, self-induced vomiting, laxative misuse or excessive exercise at 12 months (p ≥ 0.202). The overall prevalence of one or more episodes of binge eating was 53.6% at baseline and 50.6% at 12 months, with no change over time (p = 0.662). CONCLUSIONS: There was no evidence that self-monitoring, including using diet apps like MyFitnessPal or daily self-weighing, increases the reported occurrence of eating disorder behaviours in adults with overweight/obesity who are trying to lose weight.

Parental reactions to weight screening in young children: a randomized controlled trial.

BACKGROUND: Parental inability to recognize child overweight and physician reluctance to instigate discussion prevents behaviour change. OBJECTIVE: To evaluate parental acceptance of child overweight status following screening. METHODS: Interviewers used motivational interviewing or best practice care to discuss overweight status of 271 young children (BMI ≥ 85th ) with parents using simple traffic-light BMI charts. Follow-up sessions two weeks later (n = 251, 93%) were coded qualitatively to assess parental reactions to the information (overweight diagnosis) and how it was presented (feedback condition). RESULTS: Eight-two percent of parents rated the charts positively with few (8-10%) feeling judged. Motivational interviewing parents viewed feedback as more empathetic (relative risk, 95% CI: 4.07, 1.64-10.09), but more uncomfortable (12.2, 1.48-100.1) than best practice care parents. Overall, 65.2% of parents accepted their child was overweight, 22.1% were ambivalent and 12.7% rejected the information. Although motivational interviewing parents were less likely to accept it (OR, 95% CI: 0.49, 0.37-0.64) and more likely to be ambivalent (2.01, 1.17-3.47), the most important predictor of acceptance was a positive experience of feedback (P < 0.001). CONCLUSIONS: Simple traffic-light charts facilitate discussion of child overweight status with parents. Style of feedback is less relevant than ensuring a positive experience for parents to increase acceptance of the weight information.

Biallelic mutations in mitochondrial tryptophanyl-tRNA synthetase cause Levodopa-responsive infantile-onset Parkinsonism.

Mitochondrial aminoacyl-tRNA synthetases (mtARSs) are essential, ubiquitously expressed enzymes that covalently attach amino acids to their corresponding tRNA molecules during translation of mitochondrial genes. Deleterious variants in the mtARS genes cause a diverse array of phenotypes, many of which involve the nervous system. Moreover, distinct mutations in mtARSs often cause different clinical manifestations. Recently, the gene encoding mitochondrial tryptophanyl tRNA synthetase (WARS2) was reported to cause 2 different neurological phenotypes, a form of autosomal recessive intellectual disability and a syndrome of severe infantile-onset leukoencephalopathy. Here, we report the case of a 17-year-old boy with compound heterozygous mutations in WARS2 (p.Trp13Gly, p.Ser228Trp) who presented with infantile-onset, Levodopa-responsive Parkinsonism at the age of 2 years. Analysis of patient-derived dermal fibroblasts revealed decreased steady-state WARS2 protein and normal OXPHOS content. Muscle mitochondrial studies suggested mitochondrial proliferation without obvious respiratory chain deficiencies at the age of 9 years. This case expands the phenotypic spectrum of WARS2 deficiency and emphasizes the importance of mitochondrial protein synthesis in the pathogenesis of Parkinsonism.

Improving rates of overweight, obesity and extreme obesity in New Zealand 4-year-old children in 2010-2016.

BACKGROUND: Prevalence of childhood obesity is high in developed countries, and there is a growing concern regarding increasing socio-economic disparities. OBJECTIVES: To assess trends in the prevalence of overweight, obesity and extreme obesity among New Zealand 4-year olds, and whether these differ by socio-economic and ethnic groupings. METHODS: A national screening programme, the B4 School Check, collected height and weight data for 75-92% of New Zealand 4-year-old children (n = 317 298) between July 2010 and June 2016. Children at, or above, the 85th, 95th and 99.7th percentile for age and sex adjusted body mass index (according to World Health Organization standards) were classified as overweight, obese and extremely obese, respectively. Prevalence rates across 6 years (2010/11 to 2015/16) were examined by sex, across quintiles of socio-economic deprivation, and by ethnicity. RESULTS: The prevalence of overweight, obesity and extreme obesity decreased by 2.2 [95% CI, 1.8-2.5], 2.0 [1.8-2.2] and 0.6 [0.4-0.6] percentage points, respectively, between 2010/2011 and 2015/2016. The downward trends in overweight, obesity and extreme obesity in the population persisted after adjustment for sex, ethnicity, deprivation and urban/rural residence. Downward trends were also observed across sex, ethnicity and deprivation groups. CONCLUSIONS: The prevalence of obesity appears to be declining in 4-year-old children in New Zealand across all socio-economic and ethnic groups.

Potential phosphorus eutrophication mitigation strategy: Biochar carbon composition, thermal stability and pH influence phosphorus sorption.

Phosphorus (P) eutrophication is a major pollution problem globally, with unprecedented amount of P emanating from agricultural sources. But little is known about the optimization of soil-biochar P sorption capacity. The study objective was to determine how biochar feedstocks and pyrolysis conditions influences carbon (C) thermal stability, C composition and pH and in turn influence the phosphorus sorption optimization. Biochar was produced from switchgrass, kudzu and Chinese tallow at 200, 300, 400, 500, 550, 650,750 °C. Carbon thermal stability was determined by multi-element scanning thermal analysis (MESTA), C composition was determined using solid state 13C NMR. Phosphorus sorption was determined using a mixture of 10% biochar and 90% sandy soil after incubation. Results indicate increased P sorption (P < 0.0001) and decreased P availability (P < 0.0001) with increasing biochar pyrolysis temperature. However, optimum P sorption was feedstock specific with switchgrass indicating P desorption between 200 and 550 °C. Phosphorus sorption was in the order of kudzu > switchgrass > Chinese tallow. Total C, C thermal stability, aromatic C and alkalinity increased with elevated pyrolysis temperature. Biochar alkalinity favored P sorption. There was a positive relationship between high thermal stable C and P sorption for Kudzu (r = 0.62; P = 0.0346) and Chinese tallow (r = 0.73; P = 0.0138). In conclusion, biochar has potential for P eutrophication mitigation, however, optimum biochar pyrolysis temperature for P sorption is feedstock specific and in some cases might be out of 300-500 °C temperature range commonly used for agronomic application. High thermal stable C dominated by aromatic C and alkaline pH seem to favor P sorption.

The effect of increasing risk and challenge in the school playground on physical activity and weight in children: a cluster randomised controlled trial (PLAY).

BACKGROUND: To investigate whether changing the play environment in primary schools to one that includes greater risk and challenge increases physical activity and reduces body mass index (BMI). SUBJECTS/METHODS: A 2-year cluster randomised controlled trial was undertaken in 16 New Zealand schools (years 1-8). Intervention schools (n=8) redesigned their play environments to encourage imaginative and independent free play by increasing opportunities for risk and challenge (for example, rough-and-tumble play), reducing rules and adding new playground components (for example, loose parts). Control schools (n=8) were asked to not change their play environment. A qualified playworker rated all school play environments at baseline and 1 year. Primary outcomes were moderate-to-vigorous physical activity (7-day accelerometry) and BMI z-score, collected in 840 children at baseline, 1 and 2 years. Data were analysed using generalised estimating equations. RESULTS: Multiple changes were made to the school play environments resulting in a significant difference in overall play evaluation score between intervention and control schools of 4.50 (95% confidence interval: 1.82 to 7.18, P=0.005), which represents a substantial improvement from baseline values of 19.0 (s.d. 3.2). Overall, schools liked the intervention and reported many benefits, including increased physical activity. However, these beliefs did not translate into significant differences in objectively measured physical activity, either as counts per minute (for example, 35 (-51 to 120) during lunch break) or as minutes of moderate-to-vigorous physical activity (0.4, -1.1 to 2.0). Similarly, no significant differences were observed for BMI, BMI z-score or waist circumference at 1 or 2 years (all P>0.321). CONCLUSIONS: Altering the school play environment to one that promoted greater risk and challenge for children did not increase physical activity, nor subsequently alter body weight. Although schools embraced the concept of adding risk and challenge in the playground, our findings suggest that children may have been involved in different, rather than additional activities.

Adherence to hunger training using blood glucose monitoring: a feasibility study.

BACKGROUND: "Hunger training", which aims to teach people to eat only when blood glucose is below a set target, appears promising as a weight loss strategy. As the ability of participants to adhere to the rigorous protocol has been insufficiently described, we sought to determine the feasibility of hunger training, in terms of retention in the study, adherence to measuring blood glucose, and eating only when blood glucose concentrations are below a set level of 4.7 mmol/L. METHOD: We undertook a two-week feasibility study, utilising an adaptive design approach where the specific blood glucose cut-off was the adaptive feature. A blood glucose cut-off of 4.7 mmol/L (protocol A) was used for the first 20 participants. A priori we decided that if interim analysis revealed that this cut-off did not meet our feasibility criteria, the remaining ten participants would use an individualised cut-off based on their fasting glucose concentrations (protocol B). RESULTS: Retention of the participants in the study was 97 % (28/29 participants), achieving our criterion of 85 %. Participants measured their blood glucose before 94 % (95 % CI 91, 98) of eating occasions (criterion 80 %). However, participants following protocol A, which used a standard blood glucose cut-off of 4.7 mmol/L, were only able to adhere to eating when blood glucose was below the prescribed level 66 % of the time, below our within-person criterion of 75 %. By contrast, those participants following protocol B (individualised cut-off) adhered to the eating protocol 84 % of the time, a significant (p = 0.010) improvement over protocol A. CONCLUSION: Hunger training appears to be a feasible method, at least in the short-term, when an individualised fasting blood glucose is used to indicate that a meal can begin.

Characterization of short root anomaly in a Mexican cohort--hereditary idiopathic root malformation.

OBJECTIVE: The purpose of this study was to systematically characterize individuals with short root anomaly (SRA) without any history of orthodontic treatment. The long-term objective of the study was to improve diagnosis and treatment planning and determine risk factors for developing SRA. SETTING AND SAMPLE POPULATION: Twenty-seven patients including two families and 16 unrelated individuals from (9-48 years) reported to orthodontic and/or dental practitioners within the USA. MATERIALS AND METHODS: Digital panoramic and periapical films were analyzed to document pattern and frequency of SRA-affected teeth. Crown-to-root (CR) ratios of the affected teeth were used to characterize the extent of malformation. Pedigree analysis by inspection was completed for one family to determine pattern of inheritance. RESULTS: Twenty-six of the twenty-seven individuals were of Latino descent, and one was of Filipino descent. Hard tissues including enamel, dentin, pulp chambers and canals, and surrounding soft tissues were normal. We found that 25 of 27 individuals had localized SRA and two Latino individuals had generalized SRA. Teeth were affected bilaterally with maxillary central incisors (~63%) and mandibular second premolars most commonly involved (~33%). Affected teeth had a distinct, similar radiographic appearance; in the generalized cases, there was a more severe affection with larger (~twice) CR ratios. Ninety-four percent of affected individuals did not show a significant difference in the CR ratios at different ages. Pedigree analysis suggests an autosomal dominant inheritance pattern in one family. CONCLUSION: This is the first report to show that SRA occurs more frequently in Latino individuals and has a predilection for anterior teeth. The occurrence of SRA in two families further confirms a hereditary component and supports a distinct nosology and nomenclature, hereditary idiopathic root malformation (HIRM) and warrants further investigation.

Diquat causes caspase-independent cell death in SH-SY5Y cells by production of ROS independently of mitochondria.

Evidence indicates that Parkinson's disease (PD), in addition to having a genetic aetiology, has an environmental component that contributes to disease onset and progression. The exact nature of any environmental agent contributing to PD is unknown in most cases. Given its similarity to paraquat, an agrochemical removed from registration in the EU for its suspected potential to cause PD, we have investigated the in vitro capacity of the related herbicide Diquat to cause PD-like cell death. Diquat showed greater toxicity towards SH-SY5Y neuroblastoma cells and human midbrain neural cells than paraquat and also MPTP, which was independent of dopamine transporter-mediated uptake. Diquat caused cell death independently of caspase activation, potentially via RIP1 kinase, with only a minor contribution from apoptosis, which was accompanied by enhanced reactive oxygen species production in the absence of major inhibition of complex I of the mitochondrial respiratory chain. No changes in α-synuclein expression were observed following 24-h or 4-week exposure. Diquat may, therefore, kill neural tissue by programmed necrosis rather than apoptosis, reflecting the pathological changes seen following high-level exposure, although its ability to promote PD is unclear.

A novel de novo STXBP1 mutation is associated with mitochondrial complex I deficiency and late-onset juvenile-onset parkinsonism.

Mutations in STXBP1 have recently been identified as a cause of infantile epileptic encephalopathy. The underlying mechanism of the disorder remains unclear and, recently, several case reports have described broad and progressive neurological phenotypes in addition to early-onset epilepsy. Herein, we describe a patient with early-onset epilepsy who subsequently developed a progressive neurological phenotype including parkinsonism in her early teens. A de novo mutation in STXBP1 (c.416C>T, p.(Pro139Leu)) was detected with exome sequencing together with profound impairment of complex I of the mitochondrial respiratory chain on muscle biopsy. These findings implicate a secondary impairment of mitochondrial function in the progressive nature of the disease phenotype.