Midpalatal implants vs headgear for orthodontic anchorage - a randomized clinical trial: Cephalometric results

OBJECTIVE: To compare the clinical effectiveness of the mid-palatal implant as a method of reinforcing anchorage during orthodontic treatment with that of conventional extra-oral anchorage. DESIGN: A prospective, randomized, clinical trial Setting: Chesterfield and North Derbyshire Royal Hospital NHS Trust and the Charles Clifford Dental Hospital, Sheffield. SUBJECTS AND METHODS: 51 orthodontic patients between the ages of 12 and 39, with a class II division 1 malocclusion and ‘absolute anchorage’ requirements were randomly allocated to either receive a mid-palatal implant or headgear to reinforce orthodontic anchorage. The main outcome of the trial was to compare the mesial movement of the molars and incisors of the two treatment groups between T1 (start) and T2 (end of anchorage reinforcement) as measured from cephalometric radiographs. RESULTS: The reproducibility of the measuring technique was acceptable. There were significant differences between the T1 and T2 measurements within the implant group for the position of the maxillary central incisor (p<0.001), position of the maxillary molar (p=0.009) and position of the mandibular molar (p<0.001). There were significant differences within the headgear group for the position of the mandibular central incisor (p<0.045), position of the maxillary molar (p=<0.001) and position of the mandibular molar (p<0.001). All the skeletal and dental points moved mesially more in the headgear group during treatment than in the implant group. These ranged from an average of 0.5mm more mesial for the mandibular permanent molar to 1.5mm more mesial for the maxillary molar and mandibular base. None of the treatment changes between the implant and headgear groups were statistically significant. CONCLUSIONS: Mid-palatal implants are an acceptable technique for reinforcing anchorage in the orthodontic patient

Midpalatal implants vs headgear for orthodontic anchorage - a randomized clinical trial: Cephalometric results

OBJECTIVE: To compare the clinical effectiveness of the mid-palatal implant as a method of reinforcing anchorage during orthodontic treatment with that of conventional extra-oral anchorage. DESIGN: A prospective, randomized, clinical trial Setting: Chesterfield and North Derbyshire Royal Hospital NHS Trust and the Charles Clifford Dental Hospital, Sheffield. SUBJECTS AND METHODS: 51 orthodontic patients between the ages of 12 and 39, with a class II division 1 malocclusion and ‘absolute anchorage’ requirements were randomly allocated to either receive a mid-palatal implant or headgear to reinforce orthodontic anchorage. The main outcome of the trial was to compare the mesial movement of the molars and incisors of the two treatment groups between T1 (start) and T2 (end of anchorage reinforcement) as measured from cephalometric radiographs. RESULTS: The reproducibility of the measuring technique was acceptable. There were significant differences between the T1 and T2 measurements within the implant group for the position of the maxillary central incisor (p<0.001), position of the maxillary molar (p=0.009) and position of the mandibular molar (p<0.001). There were significant differences within the headgear group for the position of the mandibular central incisor (p<0.045), position of the maxillary molar (p=<0.001) and position of the mandibular molar (p<0.001). All the skeletal and dental points moved mesially more in the headgear group during treatment than in the implant group. These ranged from an average of 0.5mm more mesial for the mandibular permanent molar to 1.5mm more mesial for the maxillary molar and mandibular base. None of the treatment changes between the implant and headgear groups were statistically significant. CONCLUSIONS: Mid-palatal implants are an acceptable technique for reinforcing anchorage in the orthodontic patient

Understanding the genetic complexity of puberty timing across the allele frequency spectrum

Pubertal timing varies considerably and is associated with later health outcomes. We performed multi-ancestry genetic analyses on ~800,000 women, identifying 1,080 signals for age at menarche. Collectively, these explained 11% of trait variance in an independent sample. Women at the top and bottom 1% of polygenic risk exhibited ~11 and ~14-fold higher risks of delayed and precocious puberty, respectively. We identified several genes harboring rare loss-of-function variants in ~200,000 women, including variants in ZNF483, which abolished the impact of polygenic risk. Variant-to-gene mapping approaches and mouse gonadotropin-releasing hormone neuron RNA sequencing implicated 665 genes, including an uncharacterized G-protein-coupled receptor, GPR83, which amplified the signaling of MC3R, a key nutritional sensor. Shared signals with menopause timing at genes involved in DNA damage response suggest that the ovarian reserve might signal centrally to trigger puberty. We also highlight body size-dependent and independent mechanisms that potentially link reproductive timing to later life disease

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

Isatin, regional distribution in rat brain and tissues

Isatin has recently been identified in rat tissues and normal human urine, where it forms the major proportion of the endogenous monoamine oxidase inhibitor, tribulin. In this paper, we show that isatin, measured by gas chromatography/mass spectrometry, has a distinct regional distribution in rat tissues, with highest concentrations in seminal vesicles (1.6 μg/g) and vas deferens (3.4 μg/g). There was also a discontinuous distribution within rat brain, concentrations being highest in the hippocampus (0.13 μg/g)

Isatin: identity with the purified endogenous monoamine oxidase inhibitor tribulin

Purified tribulin, an endogenous monoamine oxidase (MAO) inhibitor, has been identified by direct probe insertion mass spectrometry as the indole-2,3-dione, isatin. A gas chromatographic-mass spectrometric assay for isatin has been developed and used to measure its relatively high concentrations in unpurified human urine, and in rat heart and brain. Isatin is a known compound with a broad range of biological activity; this is the first report of its presence in the animal body. Isatin is a potent inhibitor of MAO, particularly of MAO B (IC50, 3 μM), and also binds to central benzodiazepine receptors (IC50 against clonazepam, 123 μM)

Isatin (indole-2,3-dione) in urine and tissues: detection and determination by gas chromatography—mass spectrometry

A simple procedure based upon capillary column gas chromatography-mass spectrometry (GC—MS) is described for the detection and determination of isatin (indole-2,3-dione) in body fluids and tissues. After addition of 5-methylisatin as internal standard to urine or tissue homogenates, organic extracts are dried and derivatized successively with hydroxylamine hydrochloride and the reagent N-tert.-butyldimethylsilyl-N-methyltrifluoroacetamide (MTBSTFA). The tert.-butyldimethylsilyl derivatives obtained show good GC—MS properties and allow quantification by selected-ion monitoring of m/z 333 (isatin) and m/z 347 (internal standard). Adult and newborn human urine output values lie in the ranges 0.4–3.2 mg/mmol of creatinine (5–30 mg per 24 h) and 0.002–0.518 mg/mmol of creatinine, respectively. There is a discontinuous regional distribution in rat tissues. The GC—MS properties of a number of derivatives formed by successive reaction of isatin with hydroxylamine hydrochloride (or methoxyaminehydrochloride or ethoxyamine hydrochloride) and MTBSTFA, bis(trimethylsilyl)trifluoroacetamide, pentafluoropropionic anhydride or pentafluorobenzyl bromide are also described