Cognitive flexibility and performance in children and adolescents with threshold and sub-threshold bipolar disorder

Greater understanding of cognitive function in children and adolescents with bipolar disorder (BD) is of critical importance to improve our ability to design targeted treatments to help with real-world impairment, including academic performance. We sought to evaluate cognitive performance among children with either BD type I, II, or “not otherwise specified” (NOS) participating in multi-site Course and Outcome of Bipolar Youth study compared to typically developing controls (TDC) without psycho-pathology. In particular, we sought to test the hypothesis that BD-I and BD-II youths with full threshold episodes of mania or hypomania would have cognitive deficits, including in reversal learning, vs. those BD-NOS participants with sub-threshold episodes and TDCs. N = 175 participants (BD-I = 81, BD-II = 11, BD-NOS = 28, TDC = 55) completed Cambridge Neuropsychological Automated Testing Battery (CANTAB) tasks. A priori analyses of the simple reversal stage of the CANTAB intra-/extra-dimensional shift task showed that aggregated BD-I/II participants required significantly more trials to complete the task than either BD-NOS participants with sub-syndromal manic/hypomanic symptoms or than TDCs. BD participants across sub-types had impairments in sustained attention and information processing for emotionally valenced words. Our results align with prior findings showing that BD-I/II youths with distinct episodes have specific alterations in reversal learning. More broadly, our study suggests that further work is necessary to see the interaction between neurocognitive performance and longitudinal illness course. Additional work is required to identify the neural underpinnings of these differences as targets for potential novel treatments, such as cognitive remediation

Nicotinic Receptor Alpha7 Expression during Tooth Morphogenesis Reveals Functional Pleiotropy

The expression of nicotinic acetylcholine receptor (nAChR) subtype, alpha7, was investigated in the developing teeth of mice that were modified through homologous recombination to express a bi-cistronic IRES-driven tau-enhanced green fluorescent protein (GFP); alpha7GFP) or IRES-Cre (alpha7Cre). The expression of alpha7GFP was detected first in cells of the condensing mesenchyme at embryonic (E) day E13.5 where it intensifies through E14.5. This expression ends abruptly at E15.5, but was again observed in ameloblasts of incisors at E16.5 or molar ameloblasts by E17.5–E18.5. This expression remains detectable until molar enamel deposition is completed or throughout life as in the constantly erupting mouse incisors. The expression of alpha7GFP also identifies all stages of innervation of the tooth organ. Ablation of the alpha7-cell lineage using a conditional alpha7Cre×ROSA26-LoxP(diphtheria toxin A) strategy substantially reduced the mesenchyme and this corresponded with excessive epithelium overgrowth consistent with an instructive role by these cells during ectoderm patterning. However, alpha7knock-out (KO) mice exhibited normal tooth size and shape indicating that under normal conditions alpha7 expression is dispensable to this process. The function of ameloblasts in alpha7KO mice is altered relative to controls. High resolution micro-computed tomography analysis of adult mandibular incisors revealed enamel volume of the alpha7KO was significantly reduced and the organization of enamel rods was altered relative to controls. These results demonstrate distinct and varied spatiotemporal expression of alpha7 during tooth development, and they suggest that dysfunction of this receptor would have diverse impacts upon the adult organ

Controversies concerning the diagnosis and treatment of bipolar disorder in children

This commentary grows out of an interdisciplinary workshop focused on controversies surrounding the diagnosis and treatment of bipolar disorder (BP) in children. Although debate about the occurrence and frequency of BP in children is more than 50 years old, it increased in the mid 1990s when researchers adapted the DSM account of bipolar symptoms to diagnose children. We offer a brief history of the debate from the mid 90s through the present, ending with current efforts to distinguish between a small number of children whose behaviors closely fit DSM criteria for BP, and a significantly larger number of children who have been receiving a BP diagnosis but whose behaviors do not closely fit those criteria. We agree with one emerging approach, which gives part or all of that larger number of children a new diagnosis called Severe Mood Dysregulation or Temper Dysregulation Disorder with Dysphoria

The International Society for Bipolar Disorders Task Force report on pediatric bipolar disorder: Knowledge to date and directions for future research

Objectives: Over the past two decades, there has been tremendous growth in research regarding bipolar disorder (BD) among children and adolescents (ie, pediatric BD [PBD]). The primary purpose of this article is to distill the extant literature, dispel myths or exaggerated assertions in the field, and disseminate clinically relevant findings. Methods: An international group of experts completed a selective review of the literature, emphasizing areas of consensus, identifying limitations and gaps in the literature, and highlighting future directions to mitigate these gaps. Results: Substantial, and increasingly international, research has accumulated regarding the phenomenology, differential diagnosis, course, treatment, and neurobiology of PBD. Prior division around the role of irritability and of screening tools in diagnosis has largely abated. Gold-standard pharmacologic trials inform treatment of manic

Hammaspulpan biologiaa

Tiivistelmä Karieksen aiheuttamat komplikaatiot, hampaan voimakas kuluminen tai muu ulkoinen ärsytys voivat johtaa hammasytimen eli pulpan oireiseen tai oireettomaan inflammaatioon, jota seuraa pulpakudoksen osittainen tai etenevä hajoaminen ja kuolio. Sairaan pulpan asianmukaisella hoidolla pyritään säilyttämään hampaan vitaliteetti joko täydellisesti tai osittain, ja tällaista hoitoa voidaan siten pitää ”ehkäisevänä endodontiana”. Dentiini-pulpakompleksin fysiologian ja patologian ymmärtäminen on oikean diagnoosin ja näin ollen oikean hoidon edellytys. Tässä katsauksessa kuvataan terveen pulpan perusrakenne ja fysiologia. Lisäksi käydään läpi tulehdusreaktioiden käynnistymisen ja etenemisen periaatteita pulpakavumissa ja juurikanavissa, jotka ovat tulehdusprosessin kannalta joustamaton ympäristö. Tämän ohella käsitellään kivun ja hypersensitiivisyyden mekanismeja sekä keinoja, joilla dentiini-pulpakompleksi voi reagoida toistuvaan tai persistoivaan, kipua aiheuttavaan ärsytykseen. Pulpan tulehduksen hoitomuodot voivat vaihdella karieksen ekskavoinnista ja kaviteetin sulkemisesta sekä osittaisesta tai täydellisestä pulpotomiasta aina endodonttiseen hoitoon, ja niitä pohditaan tarkemmin tämän teeman muissa artikkeleissa, jotka käsittelevät diagnostiikkaa, vitaalin pulpan hoitoa ja kiireellistä hoitoa.Abstract Pulp Biology Pulpal complications of caries, extensive wear or other external irritations may result in symptomatic or asymptomatic inflammation, followed by partial or progressing pulp tissue degradation and necrosis. Appropriate treatment of diseased pulp may aim to preserve the vitality of the pulp, either completely or partially, and can thus be regarded as “preventive endodontics”. Understanding of the physiology and pathology of dentin-pulp complex is a prerequisite for the proper diagnosis and is thus the correct choice of treatment. This review describes the basic structure and physiology of a healthy dental pulp and the principles of the initiation and progression of inflammatory reactions in the low-compliance environment of the pulp chamber and root canals. The mechanisms of the pain and hypersensitivity, as well as the means that the dentin-pulp complex may react to a repeated or persistent pain-producing irritation, are also discussed. The chosen treatment modalities may vary from caries excavation and cavity sealing, partial or complete pulpotomy to an endodontic treatment, and will be discussed in detail in other articles in this issue dealing with the diagnostics, vital pulp therapies and emergency treatments

Human dental pulp stromal cell conditioned medium alters endothelial cell behavior

Abstract Background Angiogenesis is of utmost importance for tissue regeneration and repair. Human dental pulp stromal cells (hDPSCs) possess angiogenic potential, as they secrete paracrine factors that may alter the host microenvironment. However, more insight into how hDPSCs guide endothelial cells (ECs) in a paracrine fashion is yet to be obtained. Therefore, the current study aimed to investigate the effect(s) of conditioned medium derived from hDPSCs (hDPSC-CM) on EC behavior in vitro. Methods hDPSCs were harvested from third molars scheduled for surgical removal under informed consent. The angiogenic profile of hDPSC-CM was identified using human angiogenesis antibody array and enzyme-linked immunosorbent assay (ELISA). Using real-time reverse transcription-polymerase chain reaction (RT-PCR) and ELISA, the mRNA and protein expression level of specific angiogenic biomarkers was determined in human umbilical vein endothelial cells (HUVECs) exposed to hDPSC-CM. The effect of hDPSC-CM on HUVEC attachment, proliferation and migration was evaluated by crystal violet staining, MTT, transwell migration along with real-time cell monitoring assays (xCELLigence; ACEA Biosciences, Inc.). A Matrigel assay was included to examine the influence of hDPSC-CM on HUVEC network formation. Endothelial growth medium (EGM-2) and EGM-2 supplemented with hDPSC-CM served as experimental groups, whereas endothelial basal medium (EBM-2) was set as negative control. Results A wide range of proangiogenic and antiangiogenic factors, including vascular endothelial growth factor, tissue inhibitor of metalloproteinase protein 1, plasminogen activator inhibitor (serpin E1), urokinase plasminogen activator and stromal cell-derived factor 1, was abundantly detected in hDPSC-CM by protein profiling array and ELISA. hDPSC-CM significantly accelerated the adhesion phases, from sedimentation to attachment and spreading, the proliferation rate and migration of HUVECs as shown in both endpoint assays and real-time cell analysis recordings. Furthermore, Matrigel assay demonstrated that hDPSC-CM stimulated tubulogenesis, affecting angiogenic parameters such as the number of nodes, meshes and total tube length. Conclusions The sustained proangiogenic and promaturation effects of hDPSC-CM shown in this in vitro study strongly suggest that the trophic factors released by hDPSCs are able to trigger pronounced angiogenic responses, even beyond EGM-2 considered as an optimal culture condition for ECs