Oral findings in paediatric patients with severe heart, liver, and kidney failure prior to organ transplantation.

PURPOSE: Organ transplantation is an effective treatment for children with severe heart, liver, and kidney diseases. These patient groups may have more oral and dental diseases than healthy controls. It is important to eliminate oral infection foci before transplantation and to maintain good oral health to avoid potential post-transplant complications. The aim of this study was to describe and compare oral health in Finnish paediatric heart, liver, and kidney transplant recipients prior to organ transplantation. METHODS: Eighty-six children who received a heart (n = 21), liver (n = 19), or kidney (n = 46) transplant in Finland during the years 2014-2018 were included in this study. The inclusion criterion was a pre-transplantation oral examination. Oral hygiene, enamel anomalies, and the number of decayed, missing, and filled teeth (dmft/DMFT) were analyzed retrospectively from medical and dental records and compared between the three patient groups. RESULTS: Children with liver (p = 0.043) or heart (p = 0.047) disease had higher combined primary and permanent dentition dmft/DMFT scores compared to children with kidney disease. A higher combined dmft/DMFT score was associated with poor oral hygiene (p = 0.005). No significant differences in oral hygiene between the patient groups were found. Furthermore, all patient groups had a high prevalence of developmental dental defects. CONCLUSION: Children with liver or heart disease seem to have a higher combined dmft/DMFT score, indicating a higher prevalence of caries compared to children with kidney disease. Prevention of dental caries, along with promoting a good oral hygiene routine and regular check-ups, is suggested in these patient groups.

Effect of childhood physical abuse on social anxiety is mediated via reduced frontal lobe and amygdala-hippocampus complex volume in adult clinical high-risk subjects.

BACKGROUND: Childhood adverse experiences (CAE) are associated with clinical psychiatric disorders and symptoms, and with volumetric abnormalities in the amygdala-hippocampus complex (AmHiC) and frontal lobe (FroL) in adulthood. AIM: To study whether CAE are associated with reduced AmHiC and FroL and whether these structures mediate the effect of CAE on social anxiety and depression. METHOD: In seven European centres, 374 patients with recent onset of psychosis (n = 127), clinical high-risk to psychosis (n = 119) or recent onset of depression (n = 128) were scanned with MRI and their FroL and AmHiC volumes were measured. They all completed self-report scales for assessment of CAE, social anxiety and depression. RESULTS: Of the CAE domains, physical abuse was associated specifically with reduced grey and white matter volumes of FroL and AmHiC in psychotic and high-risk patients. After controlling intracranial volume, PhyAb associated significantly with FroL and its grey matter volume in high-risk patients only. In mediation analyses, the effect of physical abuse on social anxiety was mediated via reduced FroL grey mater volume in high-risk patients. In them, when the effects of AmHiC and depression were controlled, the effect of physical abuse on social anxiety was mediated via FroL grey matter volume reduction. CONCLUSIONS: Childhood physical abuse is associated with reduced frontal lobe and amygdala-hippocampus complex volume in adult subjects with psychotic symptoms. Reduced frontal lobe and amygdala-hippocampus complex volume mediate the effect of physical abuse on social anxiety in high-risk patients. The effect of physical abuse on depression-independent social anxiety is mediated via reduced frontal lobe.

Neurotransmitters behind pain relief with transcranial magnetic stimulation - positron emission tomography evidence for release of endogenous opioids.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) at M1/S1 cortex has been shown to alleviate neuropathic pain. OBJECTIVES: To investigate the possible neurobiological correlates of cortical neurostimulation for the pain relief. METHODS: We studied the effects of M1/S1 rTMS on nociception, brain dopamine D2 and µ-opioid receptors using a randomized, sham-controlled, double-blinded crossover study design and 3D-positron emission tomography (PET). Ten healthy subjects underwent active and sham rTMS treatments to the right M1/S1 cortex with E-field navigated device. Dopamine D2 and µ-receptor availabilities were assessed with PET radiotracers [11 C]raclopride and [11 C]carfentanil after each rTMS treatment. Thermal quantitative sensory testing (QST), contact heat evoked potential (CHEP) and blink reflex (BR) recordings were performed between the PET scans. RESULTS: µ-Opioid receptor availability was lower after active than sham rTMS (P ≤ 0.0001) suggested release of endogenous opioids in the right ventral striatum, medial orbitofrontal, prefrontal and anterior cingulate cortices, and left insula, superior temporal gyrus, dorsolateral prefrontal cortex and precentral gyrus. There were no differences in striatal dopamine D2 receptor availability between active and sham rTMS, consistent with lack of long-lasting measurable dopamine release. Active rTMS potentiated the dopamine-regulated habituation of the BR compared to sham (P = 0.02). Thermal QST and CHEP remained unchanged after active rTMS. CONCLUSIONS: rTMS given to M1/S1 activates the endogenous opioid system in a wide brain network associated with processing of pain and other salient stimuli. Direct enhancement of top-down opioid-mediated inhibition may partly explain the clinical analgesic effects of rTMS. SIGNIFICANCE: Neurobiological correlates of rTMS for the pain relief are unclear. rTMS on M1/S1 with 11 C-carfentanyl-PET activates endogenous opioids. Thermal and heat pain thresholds remain unchanged. rTMS induces top-down opioid-mediated inhibition but not change the sensory discrimination of painful stimuli.

Long-term use of benzodiazepines: Definitions, prevalence and usage patterns - a systematic review of register-based studies.

BACKGROUND: Numerous treatment guidelines recommend that long-term use of benzodiazepines (BZD) should be avoided primarily due to development of tolerance and a risk for BZD dependence. Despite this, long-term BZD use remains a controversial subject in clinical patient care with "for and against" debates. However, there is no explicit understanding of what is meant by long-term BZD use in real world. The aim of this study was to assess different definitions, usage patterns, prevalence and other characteristics of long-term BZD use based on published register-based studies. Synthesis of these characteristics is essential to derive a meaningful definition of long-term BZD. METHODS: Systematic review of register-based studies on long-term BZD use published in 1994-2014. RESULTS: Fourty-one studies met our predetermined inclusion criteria. The length of BZD use defined as "long-term" varied in these studies ranging from one month to several years. The most common definition was six months or longer during a year. The prevalence of long-term BZD use in the general population was estimated to be about 3%. The relative proportion of long-term BZD users (all definitions) in adult BZD users ranged from 6% to 76% (mean 24%; 95% CL 13-36%). The estimates were higher in studies only on the elderly (47%; 95% CL 31-64%). Long-term use involved typically steady treatment with low BZD doses. However, in elderly patients long-term BZD use and exceeding recommended doses was relatively common. Several characteristics associated with long-term use were found. CONCLUSIONS: Long-term BZD use is common and a clinical reality. Uniform definitions for "long-term", which is in line with population-based evidence, is needed to have more comparable results between studies. Our systematic review suggests that duration of BZD treatment over six months, the most common definition for long-term BZD use in the included studies. As also recommended previously, it is a useful starting point for further analyses on disadvantages but also potential advantages associated with long-term BZD use.

Short-term functional outcome and premorbid adjustment in clinical high-risk patients. Results of the EPOS project.

PURPOSE: In patients with schizophrenia, premorbid psychosocial adjustment is an important predictor of functional outcome. We studied functional outcome in young clinical high-risk (CHR) patients and how this was predicted by their childhood to adolescence premorbid adjustment. METHODS: In all, 245 young help-seeking CHR patients were assessed with the Premorbid Adjustment Scale, the Structured Interview for Prodromal Syndromes (SIPS) and the Schizophrenia Proneness Instrument (SPI-A). The SIPS assesses positive, negative, disorganised, general symptoms, and the Global Assessment of Functioning (GAF), the SPI-A self-experienced basic symptoms; they were carried out at baseline, at 9-month and 18-month follow-up. Transitions to psychosis were identified. In the hierarchical linear model, associations between premorbid adjustment, background data, symptoms, transitions to psychosis and GAF scores were analysed. RESULTS: During the 18-month follow-up, GAF scores improved significantly, and the proportion of patients with poor functioning decreased from 74% to 37%. Poor premorbid adjustment, single marital status, poor work status, and symptoms were associated with low baseline GAF scores. Low GAF scores were predicted by poor premorbid adjustment, negative, positive and basic symptoms, and poor baseline work status. The association between premorbid adjustment and follow-up GAF scores remained significant, even when baseline GAF and transition to psychosis were included in the model. CONCLUSION: A great majority of help-seeking CHR patients suffer from deficits in their functioning. In CHR patients, premorbid psychosocial adjustment, baseline positive, negative, basic symptoms and poor working/schooling situation predict poor short-term functional outcome. These aspects should be taken into account when acute intervention and long-term rehabilitation for improving outcome in CHR patients are carried out.

Prediction of psychosis in clinical high-risk patients by the Schizotypal Personality Questionnaire. Results of the EPOS project.

OBJECTIVE: Schizotypal features indicate proneness to psychosis in the general population. It is also possible that they increase transition to psychosis (TTP) among clinical high-risk patients (CHR). Our aim was to investigate whether schizotypal features predict TTP in CHR patients. METHODS: In the EPOS (European Prediction of Psychosis Study) project, 245 young help-seeking CHR patients were prospectively followed for 18 months and their TTP was identified. At baseline, subjects were assessed with the Schizotypal Personality Questionnaire (SPQ). Associations between SPQ items and its subscales with the TTP were analysed in Cox regression analysis. RESULTS: The SPQ subscales and items describing ideas of reference and lack of close interpersonal relationships were found to correlate significantly with TTP. The co-occurrence of these features doubled the risk of TTP. CONCLUSIONS: Presence of ideas of reference and lack of close interpersonal relations increase the risk of full-blown psychosis among CHR patients. This co-occurrence makes the risk of psychosis very high.

Temperament, character and serotonin activity in the human brain: a positron emission tomography study based on a general population cohort.

BACKGROUND: The psychobiological model of personality by Cloninger and colleagues originally hypothesized that interindividual variability in the temperament dimension 'harm avoidance' (HA) is explained by differences in the activity of the brain serotonin system. We assessed brain serotonin transporter (5-HTT) density in vivo with positron emission tomography (PET) in healthy individuals with high or low HA scores using an 'oversampling' study design. Method Subjects consistently in either upper or lower quartiles for the HA trait were selected from a population-based cohort in Finland (n = 2075) with pre-existing Temperament and Character Inventory (TCI) scores. A total of 22 subjects free of psychiatric and somatic disorders were included in the matched high- and low-HA groups. The main outcome measure was regional 5-HTT binding potential (BPND) in high- and low-HA groups estimated with PET and [11C]N,N-dimethyl-2-(2-amino-4-methylphenylthio)benzylamine ([11C]MADAM). In secondary analyses, 5-HTT BPND was correlated with other TCI dimensions. RESULTS: 5-HTT BPND did not differ between high- and low-HA groups in the midbrain or any other brain region. This result remained the same even after adjusting for other relevant TCI dimensions. Higher 5-HTT BPND in the raphe nucleus predicted higher scores in 'self-directedness'. CONCLUSIONS: This study does not support an association between the temperament dimension HA and serotonin transporter density in healthy subjects. However, we found a link between high serotonin transporter density and high 'self-directedness' (ability to adapt and control one's behaviour to fit situations in accord with chosen goals and values). We suggest that biological factors are more important in explaining variability in character than previously thought.

Increased infection risk postliver transplant without pretransplant dental treatment.

OBJECTIVE: Infections cause considerable morbidity after liver transplantation (LT). Acute liver failure is a rapidly progressing life-threatening condition where pretransplant dental evaluation is not always possible. We investigated how missing pretransplant dental treatment in acute or subacute liver failure correlates with post-transplant infectious complications. SUBJECTS AND METHODS: Medical and dental data came from hospital records and infection data from the Finnish LT registry. The follow-up was until February 2011. Of 51 patients (LT during 2000-2006), 16 had and 35 did not have dental treatment pretransplant. RESULTS: Univariate Cox regression analysis demonstrated a 2.46-fold (95% CI 1.06-5.69) infection risk among the patients omitted from dental treatment. After adjustment for either pretransplant factors alone or both pre- and post-transplant factors, the corresponding infection risk increased, respectively, to 8.17-fold (95% CI 2.19-30.6) and 8.54-fold (95% CI 1.82-40.1). This increased risk involved a variety of bacterial, viral, and fungal infections of various sources both < 6 and > 6 months after transplantation. CONCLUSION: High risk of infections was noticed in acute liver failure patients without pretransplant dental treatment, but a more severe medical condition might have influenced the results. We encourage eradication of dental infection foci whenever clinical condition allows.

Observation of the h(c)(1P) Using e+ e- collisions above the DD threshold.

Using 586 pb(-1) of e+ e- collision data at E(c.m.) = 4170 MeV, produced at the Cornell Electron Storage Ring collider and collected with the CLEO-c detector, we observe the process e+ e- → π+ π- h(c)(1P). We measure its cross section to be 15.6±2.3±1.9±3.0 pb, where the third error is due to the external uncertainty on the branching fraction of ψ(2S) → π0 h(c)(1P), which we use for normalization. We also find evidence for e+ e- → ηh(c)(1P) at 4170 MeV at the 3σ level and see hints of a rise in the e+ e- → π+ π- h(c)(1P) cross section at 4260 MeV.

No association between serotonin 5-HT 1A receptors and spirituality among patients with major depressive disorders or healthy volunteers.

An earlier study (Borg et al., Am J Psychiatry 2003) found an inverse correlation between [carbonyl-(11)C]WAY-100635 ligand binding to 5-HT(1A) receptors and scores for self-transcendence, but no other of the six dimensions of the Temperament and Character Inventory, in a group of healthy males. The aim of this study was to investigate if the finding of an inverse correlation between spirituality and 5-HT(1A) could be seen in patients suffering from major depressive disorder or replicated among healthy volunteers. A total of 23 patients with major depressive disorder and 20 healthy volunteers were examined with PET using [carbonyl-(11)C]WAY-100635 as the radioligand. The personality traits were measured using the Finnish version of the Temperament and Character Inventory and correlated with ligand binding (BP). No significant correlations were found between the different Temperament and Character Inventory subscales and BP in any of the studied brain regions (amygdala, anterior cingulate cortex, dorsal raphe nuclei, dorsolateral prefrontal cortex, angular gyrus, inferior, middle, and superior temporal gyri, medial prefrontal cortex orbitofrontal cortex, hippocampus, insular cortex, subgenual anterior cingulate cortex, supramarginal gyrus, ventrolateral prefrontal cortex, and posterior cingulate cortex). These results do not support the idea that the serotonin system forms the biological basis of spiritual experiences among patients suffering from major depressive disorder or among healthy volunteers.

J/psi and psi(2S) Radiative Transitions to eta_{c}.

Using 2.45x10;{7} psi(2S) decays collected with the CLEO-c detector at the Cornell Electron Storage Ring we present the most precise measurements of magnetic dipole transitions in the charmonium system. We measure B(psi(2S)-->gammaeta_{c})=(4.32+/-0.16+/-0.60)x10;{-3}, B(J/psi-->gammaeta_{c})/B(psi(2S)-->gammaeta_{c})=4.59+/-0.23+/-0.64, and B(J/psi-->gammaeta_{c})=(1.98+/-0.09+/-0.30)%. We observe a distortion in the eta_{c} line shape due to the photon-energy dependence of the magnetic dipole transition rate. We find that measurements of the eta_{c} mass are sensitive to the line shape, suggesting an explanation for the discrepancy between measurements of the eta_{c} mass in radiative transitions and other production mechanisms.

Observation of D+ --> etae + nue.

Using a 281 pb-1 data sample collected at the psi(3770) resonance with the CLEO-c detector at the Cornell Electron Storage Ring, we report the first observation of D+ --> etae + nue. We also set upper limits for D+ --> eta'e + nue and D + --> varphie + nue that are about 2 orders of magnitude more restrictive than those obtained by previous experiments.

Observation of chicJ radiative decays to light vector mesons.

Using a total of 2.74 x 10(7) decays of the psi(2S) collected with the CLEO-c detector, we present a study of chi(cJ)-->gammaV, where V=rho(0), omega, phi. The transitions chi(c1)-->gammarho(0 and chi(c1)-->gammaomega are observed with B(chi(c1)-->gammarho(0))=(2.43+/-0.19+/-0.22) x 10(-4) and B(chi(c1)-->gammaomega)=(8.3+/-1.5+/-1.2) x 10(-5). In the chi(c1)-->gammarho(0) transition, the final state meson is dominantly longitudinally polarized. Upper limits on the branching fractions of other chi(cJ) states to light vector mesons are presented.

Determination of the strong phase in D0-->K+pi- using quantum-correlated measurements.

We exploit the quantum coherence between pair-produced D0 and D[over]0 in psi(3770) decays to study charm mixing, which is characterized by the parameters x and y, and to make a first determination of the relative strong phase delta between D0-->K+pi- and D[over]0-->K+pi-. Using 281 pb(-1) of e+e- collision data collected with the CLEO-c detector at Ecm=3.77 GeV, as well as branching fraction input and time-integrated measurements of RM identical with (x2 + y2)/2 and RWS identical with Gamma(D0-->K+pi-)/Gamma(D[over]0-->K+pi-) from other experiments, we find cosdelta=1.03(-0.17)(+0.31)+/-0.06, where the uncertainties are statistical and systematic, respectively. By further including other mixing parameter measurements, we obtain an alternate measurement of cosdelta=1.10+/-0.35+/-0.07, as well as x sindelta=(4.4(-1.8)(+2.7)+/-2.9)x10(-3) and delta=(22(-12-11)(+11+9)) degrees .

Study of the decays D0-->pi{-}e{+}nu{e}, D{0}-->K{-}e{+}nu{e}, D{+}-->pi{0}e{+}nu{e}, and D{+}-->K0e{+}nu{e}.

By using 1.8x10{6} DDpairs, we have measured B(D{0}-->pi{-}e{+}nu{e})=0.299(11)(9)%, B(D{+}-->pi{0}e{+}nu{e})=0.373(22)(13)%, B(D{0}-->K{-}e{+}nu{e})=3.56(3)(9)%, and B(D{+}-->K{0}e{+}nu{e})=8.53(13)(23)% and have studied the q;{2} dependence of the form factors. By combining our results with recent lattice calculations, we obtain |V{cd}|=0.217(9)(4)(23) and |V{cs}|=1.015(10)(11)(106).

Absolute measurement of hadronic branching fractions of the Ds+ meson.

The branching fractions of D(s)(+/-) meson decays serve to normalize many measurements of processes involving charm quarks. Using 298 pb(-1) of e(+)e(-) collisions recorded at a center of mass energy of 4.17 GeV, we determine absolute branching fractions for eight D(s)(+/-) decays with a double tag technique. In particular we determine the branching fraction B(D(s)(+)-->K(-)K(+}pi(+))=(5.50+/-0.23+/-0.16)%, where the uncertainties are statistical and systematic, respectively. We also provide partial branching fractions for kinematic subsets of the K(-)K(+)pi(+) decay mode.

First observation of the decay Ds+-->pn.

Using e+e--->Ds*-Ds+ data collected near the peak Ds production energy, Ecm=4170 MeV, with the CLEO-c detector, we present the first observation of the decay Ds+-->pn. We measure a branching fraction B(Ds+-->pn)=(1.30+/-0.36(-0.16)+0.12)x10(-3). This is the first observation of a charmed meson decaying into a baryon-antibaryon final state.

Obesity and the clinical use of serum GGT activity as a marker of heavy drinking.

OBJECTIVE: Gamma-glutamyl transferase (GGT) is a widely used clinical marker of alcohol abuse. However, although obesity may also elevate serum GGT activities, the effects of overweight on the interpretation of GGT testing have remained poorly defined. MATERIAL AND METHODS: GGT activities from 1147 moderate drinkers and 449 abstainers who were classified according to body mass index (BMI) were compared with those of 208 heavy drinkers admitted for detoxification. RESULTS: GGT upper normal limits, defined based on normal weight abstainers (men 53 U/L; women 45 U/L) were lower than those based on moderate drinkers (men 68 U/L; women 50 U/L). The relative increases in GGT activities in male moderate drinkers with overweight (54%) or obesity (125%) exceeded the corresponding changes found in women (25% and 75%, respectively). The BMI-dependent variation on the sensitivity of GGT for correctly classifying heavy drinkers ranged from 29% to 67%. The rates of false-positive values in the subgroups from low to high BMI varied from 0% to 27%, respectively. CONCLUSIONS: The data indicate that the diagnostic value of serum GGT testing could be improved by using reference data derived from databases of abstainers with normal weight or BMI-based categorization of reference ranges.

Observation of Upsilon(3S)-->tau+tau- and tests of lepton universality in Upsilon decays.

Using data collected with the CLEO III detector at the CESR e+e- collider, we report on a first observation of the decay Upsilon(3S)-->tau+tau-, and precisely measure the ratio of branching fractions of Upsilon(nS), n=1, 2, 3, to tau+tau- and mu+mu- final states, finding agreement with expectations from lepton universality. We derive absolute branching fractions for these decays, and also set a limit on the influence of a low mass CP-odd Higgs boson in the decay of the Upsilon(1S).