Panikattacken sind mit einer Lebenszeitprävalenz von ungefähr 15% ein relativ häufiges Phänomen im Gegensatz zu einer vollen Panikstörung, die eine Prävalenz von 2,3–3% aufweist. In der vorliegenden epidemiologischen Untersuchung (n = 481) einer bundesweiten repräsentativen Stichprobe wurde geprüft, ob früh (vor dem 25. Lebensjahr) und spat auftretende Panikattacken sich hinsichtlich Symptomatik, Verlaufs- und Komorbiditätsmustern unterscheiden. Neben einer erhöhten Angstsymptomatik, insbesondere bezüglich respiratorischer Beschwerden und der Angst zu sterben, zeigte sich bei Panikattacken mit spätem Beginn ein erhöhtes Risiko für Multimorbidität. Auch entwickelten sich bei dieser Gruppe komorbide Bedingungen schneller. Dagegen waren Panikattacken mit frühem Beginn und einem erhöhten Risiko für Agoraphobie sowie phobische Störungen verbunden. Die Ergebnisse werden im Hinblick auf pathogenetische Mechanismen und Implikationen für die Planung therapeutischer Interventionen diskutiert.

The group A beta-haemolytic streptococcus is known to be the aetiologic agent in acute rheumatic fever, but the exact pathogenesis remains obscure. A review of the histopathology of the Aschoff body suggests that the cardiac pathology is a granulomatous hypersensitivity reaction. However the streptococcus has not been found in the lesions, and the agent responsible for the granuloma has not yet been identified. Circulating immune complexes have previously been measured in some children with acute rheumatic fever. The normal or raised complement components measured by some workers in acute rheumatic fever suggests that the immune complexes may not be complement fixing. Considering that the usual assays for measuring immune complexes depend on complement fixation, the failure of the immune complexes to fix complement might produce false negative results. A physical, non-complement fixing assay (polyethylene glycol precipitation - PEG), was therefore used to measure circulating immune complexes. Results were expressed as total IgG precipitated (g/L), or as a percentage of serum IgG. Immune complexes were also measured by two complement dependent assays, a Clq binding assay (ClqBA), and conglutinin binding assay (CBA). Complexes were assayed in 15 children with acute rheumatic carditis (ARC), 11 with non-active, chronic rheumatic heart disease (CRHD), 13 with acute poststreptococcal glomerulonephritis (APSGN), and 15 normal children and adults (NORMAL). Total haemolytic complement, complement components as well as the complement breakdown product C3d, were measured.

A cross-sectional study of risk factors for coronary heart disease (CHD) in a random sample of 976 coloured people revealed a population greatly at risk of CHD. The major reversible risk factors were very common: 57% of men and 41% of women smoked, 17,2% of men and 18,4% of women were hypertensive (>160/95 mm Hg or receiving medication), and 17,4% of men and 16,2% of women had a total serum cholesterol value above 6,5 mmol/litre. The high cut-off points used to identify the above prevalence rate do not reflect the total population at risk. At lower but real levels of risk 94,6% of men and 89,8% of women carried some degree of CHD risk factors was found.

Hoarding disorder is a relatively new diagnosis in the DSM-5, only just included in the most recent edition. The disorder has piqued the interest of many in the community, in part because of the hit TV show called “Hoarders.” Although there is interest, there continues to be relatively few research studies into the causes, treatment, and management of this disorder specifically in adolescences. Yet, in the research that has been published, it often sites the disorder first appearing in adolescents. This paper will discuss the following elements of adolescent hoarding disorder: The potential etiology and risk factors noted in the literature, the DSM-5 criteria for the diagnosis of hoarding disorder, and the characteristic signs and symptoms found in the adolescent presentation, as well as treatment. Finally, it will also include recommendations for healthcare professionals for early screening and treatment.

Objective: To determine the prevalence and odds ratios for cleft lip and/or palate (CL/P) among infants prenatally exposed to opioids with or without neonatal opioid withdrawal syndrome (NOWS). Design: This study represents an exploratory, retrospective cohort study design of newborn medical health records from 2011 to 2016. Setting: Records were drawn from a regional health system located in South Central Appalachia. Population and Study Sample: The original population yielded 3 cohorts of infants: (1) infants with opioid exposure (OE) but not requiring pharmacological intervention (OE; N = 168); (2) infants with NOWS requiring pharmacological intervention (N = 294); and (3) infants with no opioid exposure (NOE; N = 16 090), the primary comparison group. Main Outcome: Infants in the NOWS and OE groups showed significantly increased prevalence and odds ratios for CL/P when compared to those in the NOE group. Results: Prevalence rates per 1000 live births for infants with OE (35.71) and infants with NOWS (6.80) were significantly higher than those for infants with NOE (1.37). Comparison of infants with OE to the NOE group revealed significantly increased odds for CL/P, isolated cleft palate (CP), cleft lip (CL), and cleft lip and palate (CLP) (27.05, 41.81, 19.26, 19.37, respectively; all Ps <.008). The odds ratios for infants with NOWS compared to the NOE group were significantly higher for CL/P and CP (5.00 and 10.98, respectively; Ps <.03) but not for CL and CLP. Conclusion: The results provide additional evidence that prenatal OE should be considered among the critical environmental risk factors that can contribute to CL/P.

No description available.

No description available.

Despite evidence of an association between prenatal acetaminophen exposure and attention deficit hyperactivity disorder (ADHD) in offspring, the causal role of prenatal acetaminophen exposure in child ADHD remains unclear owing to limitations of prior studies. Prior studies have relied on maternal self-report, failed to quantify acetaminophen dose, and lacked mechanistic insight. Chapter 1 formally introduces this topic and provides background information summarizing the high prevalence of ADHD, widespread use of acetaminophen during pregnancy, and potential molecular mechanisms through which the drug may harm fetal development. In Chapter 2, we examined the association between prenatal acetaminophen exposure measured in meconium and ADHD in children aged 6 to 7 years, along with the potential for mediation by functional brain connectivity. Data came from a prospective birth cohort study from the Centre Hospitalier Université de Sherbrooke in Sherbrooke, Québec, Canada. We included 393 eligible children, of whom 345 had meconium samples collected at delivery and information on ADHD diagnosis. Mothers were enrolled from September 25, 2007, to September 10, 2009, at their first prenatal care visit or delivery. Acetaminophen levels were measured in meconium, and physician diagnosis of ADHD was determined at follow-up when children were aged 6 to 7 years or from medical records. Additionally, when children were aged 9 to 11 years, resting-state brain connectivity was assessed with magnetic resonance imaging, and attention problems and hyperactivity were assessed with the Behavioral Assessment System for Children Parent Report Scale. Associations between meconium acetaminophen levels and outcomes were estimated with linear and logistic regressions weighted on the inverse probability of treatment to account for potential confounders. Causal mediation analysis was used to test for mediation of the association between prenatal acetaminophen exposure and hyperactivity by resting-state brain connectivity. Among the 345 children included in the analysis (177 boys [51.3%]; mean [SD] age, 6.58 [0.54] years), acetaminophen was detected in 199 meconium samples (57.7%), and ADHD was diagnosed in 33 children (9.6%). Compared with no acetaminophen, detection of acetaminophen in meconium was associated with increased odds of ADHD (odds ratio [OR], 2.43; 95%CI, 1.41-4.21). A dose-response association was detected; each doubling of exposure increased the odds of ADHD by 10% (OR, 1.10; 95%CI, 1.02-1.19). Children with acetaminophen detected in meconium showed increased negative connectivity between frontoparietal and default mode network nodes to clusters in the sensorimotor cortices, which mediated an indirect effect on increased child hyperactivity (14%; 95%CI, 1%-26%). In Chapter 3, we used data from the same Canadian birth cohort to examine whether prenatal acetaminophen exposure is associated with adverse birth outcomes and/or pregnancy complications, and if birth outcomes may mediate the association of prenatal acetaminophen with child ADHD. This study included 393 children for whom acetaminophen was measured in meconium at delivery. We tested associations of prenatal acetaminophen with birthweight, preterm birth, gestational age, small and large for gestational age, gestational diabetes, preeclampsia, and high blood pressure. Using causal mediation analyses, we assessed whether birth outcomes mediated the association of prenatal acetaminophen with ADHD. We imputed missing data via multiple imputation and used inverse probability weighting to account for confounding and selection bias. Prenatal acetaminophen exposure was associated with decreased birthweight by 136 g (β = −136; 95% CI [−229, −43]), 20% increased weekly hazard of delivery (hazard ratio = 1.20; 95% CI [1.00, 1.43]), and over 60% decreased odds of being born large for gestational age (odds ratio = 0.38; 95% CI [0.20, 0.75]). Prenatal acetaminophen was not associated with small for gestational age, preterm birth, or any pregnancy complications. Causal mediation effects were non-significant for all birth outcomes in both unadjusted and adjusted models, indicating no evidence that birth outcomes linked prenatal acetaminophen exposure with child ADHD. In Chapter 4, we examined the effects of developmental acetaminophen exposure on mouse behavior and frontal cortex gene expression. Although prior studies have investigated neurodevelopmental effects of prenatal acetaminophen exposure in rodents, the results of these studies are not always in agreement. Additionally, no mouse studies of prenatal acetaminophen exposure have investigated offspring attention deficits in behavior tasks specifically designed to measure attention, and no prior rodent studies have utilized ‘omics’ technologies for an untargeted exploration of potential mechanisms. We randomly assigned pregnant mice (starting embryonic day 4-10) to receive acetaminophen (150 mg/kg/day) or vehicle control through postnatal day 14. We employed a battery of behavior tests for 111 mouse offspring, including pup ultrasonic vocalizations, elevated plus maze, open field test, CatWalk, pre-pulse inhibition, and 5-choice serial reaction time task. Frontal cortex was collected at birth from 24 pups for RNA-sequencing. Developmental acetaminophen treatment resulted in increased pup vocalizations after separation from the litter, as well as decreased ambulation and vertical rearings in the open field task among male but not female offspring. Acetaminophen treatment was also associated with altered frontal cortex gene expression relating to glutathione and cytochrome p450 metabolism, DNA damage, and the endocrine and immune systems. Together with the multitude of other cohort studies showing adverse neurodevelopment associated with prenatal acetaminophen exposure, this work suggests caution should be used in administering acetaminophen during pregnancy. In humans, we found that prenatal acetaminophen exposure was associated with child ADHD, altered resting-state brain connectivity, and adverse birth outcomes. Furthermore, our results suggest altered brain connectivity as a potential underlying mechanism linking prenatal acetaminophen use with child hyperactivity. While adverse birth outcomes such as preterm birth and reduced birthweight are known to be associated with ADHD, we found no evidence for mediation by birth outcomes of the association between prenatal acetaminophen exposure and ADHD. In mice, we found that developmental acetaminophen treatment resulted in elevated anxiety-like behaviors in male offspring, as well as gene expression changes in the frontal cortex. Future studies are needed to explore whether the altered molecular pathways revealed by RNA-sequencing directly link acetaminophen exposure with offspring behavior changes.

Early life adversity (ELA) produces long lasting developmental changes to the postnatal brain, increasing predisposition to a number of physical and psychiatric disorders. The mechanisms through which ELA is able to create lasting detrimental changes to neuronal development remains unclear. This thesis tested the hypothesis that increases in fear generalization, a common symptom in psychiatric disorders, follows ELA exposure in age dependent and sexually dimorphic ways in alignment with the findings of clinical studies. The effects of ELA often impact fear circuitry and we confirmed, using electrophysiology and tissue imaging, that 5-HT circuitry from the median raphe nucleus (MRN), integral to fear response, was impaired following ELA. Using a transgenic mouse model that allows for modulation of serotonergic release, we showed that circumventing serotonergic pathways disrupted by ELA and increasing whole brain 5-HT release was enough to rescue hippocampal dependent fear responses and fear generalization. Involvement of the hippocampus in ELA effects, particularly the ventral dentate gyrus (vDG), in fear overgeneralization was confirmed as hyperactivity in thevDG following exposure to novel contexts was rescued by increased 5-HT release. In addition to ELA-induced hyperactivity of the vDG, known to potentiate stress susceptibility, I demonstrated that ELA resulted in an increase in passive coping strategies, HPA axis dysfunction and elevated stress hormone release. These effects were seen predominantly in adult females and rescued in those with increased 5-HT release. Together these data suggest that increased predisposition to psychiatric disorders following ELA exposure involves the disruption of fear circuitry regulated by 5-HT activity. Identifying the underlying circuits altered by ELA not only provides insight about disrupted postnatal brain development, but also increases our knowledge of the timeline, trajectory and factors affecting healthy postnatal brain development.

Objective: To conduct a literature review of published studies of buccally impacted maxillary canines, which presents the etiology, characteristics, and prevalence of these teeth.    Material and method: The search covered three different electronic databases (PubMed, Scopus, and Cochrane Library). The inclusion criteria were studies on maxillary canines ectopia, specifically patients with either a unilateral or bilateral diagnosis of buccally displaced maxillary canines; studies on children and adolescents under 18 years; however, most focus on children aged 9-11 years, and only fulltext articles published in English or Swedish were accepted. In addition, different study designs were included, for example, reviews, retrospective, and biometric studies. Two reviewers independently evaluated selected full-text articles, and any disagreements were resolved by consensus. Results: The applied search terms identified 319 articles in the different databases, out of the 319 yielded articles, 163 were excluded as duplicates. The remaining 183 studies were screened in abstract form by all three reviewers. Out of them, only 11 studies on buccally displaced/impacted canines met the inclusion criteria and were prescribed as eligible studies for full-text analysis. There was a wide variation in the objectives of these 11 studies, though all of them included at least one of the studies' investigations requirements: etiology, characteristics, or prevalence. The results from the final analysis were presented in a preset protocol.  Conclusion: This literature review disclosed that few studies have investigated and presented buccally impaction of the canines. Additional investigations are warranted. / Syfte: Att genomföra en litteraturöversikt av publicerade studier om buckalt retinerade överkäkshörntänder. Litteraturöversikten avser etiologin, egenskaperna och prevalensen av dessa tillstånd.   Material och metod: Sökningen omfattade tre olika sökdatabaser (PubMed, Scopus och Cochrane Library). Inklusionskriterierna för vår studie var, ektopiska överkäkshörntänder, patienter med antingen ett unilateralt eller bilateralt tillstånd av buckalt retinerade hörntänder. Studierna som inkluderades handlade om barn och ungdomar under 18 år, dock sträckte sig fokuset mestadels mellan åldrarna 9-11 år. Enbart artiklar i fulltext användes och dessa var publicerade på engelska och svenska. Diverse studietyper inkluderades, exempelvis översikts-, retrospektiva och biometriska studier. Slutligen, utvärderades utvalda fulltextartiklar av två enskilda granskare. Oenighet mellan granskarna som uppstod diskuterades fram till en uppnådd konsensus. Resultat: De tillämpade söktermerna identifierade 319 artiklar från tre olika databaser. Av 319 artiklar exkluderades 163 som dubbletter. Återstående 183 artiklar genomgick en titel-abstract granskning och detta genomfördes av alla tre granskare. Det återstod endast 11 studier avseende buckalt retinerade överkäkshörntänder som omfattade inklusionskriterierna och skulle läsas i fulltext. Artiklarnas syfte var varierande. Texterna i urvalet, inkluderade minst en av studiens frågeställningar: etiologi, karakteristiska egenskaper eller prevalens. Analysens slutliga resultat presenteras i ett protokoll. Slutsats: Denna litteraturöversikt indikerar att få studier har studerat buckalt retinerade hörntänder. Därmed tycks att ytterligare forskning behövs.