Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities

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The diabetes online community: the importance of forum use in parents of children with type 1 diabetes

Online forums for chronic health conditions emerged as early as 30 yr ago and interest in their study has blossomed. Type 1 diabetes (T1D) forums have grown exponentially since 2005. Therefore, a comprehensive evaluation of these forums is needed. This study assesses the demographics and motivations of parents who use type 1 diabetes forums and the potential impact that forum membership (FM) has on parenting stress and hypoglycemic fear. One hundred and two parents were recruited through online T1D forums and asked to complete qualitative and quantitative measures of their experience with the T1D forums. Results of this study suggest that parents who use T1D forums mirror those who participate in clinic‐based research protocols and are primarily motivated to participate in forums to increase their diabetes knowledge and gain social support. Indeed, parents who use T1D forums report high levels of trust, social support, and perceived knowledge gained. However, FM was positively related to increased self‐reported parenting stress frequency and hypoglycemic fear behaviors. Taken together, the relationships formed within these communities may have a significant impact on the experience of these caregivers. The need for future research and potential implications for physicians, including parent debriefing, are discussed.     

Effects of injury and inflammation on pulpal and periapical nerves

Several studies dealing with the reactions of dental nerve fibers to injury and inflammation are reviewed in this article. The subgroup of dental nerve fibers that contains calcitonin gene-related peptide (CGRP) was examined by immunocytochemistry at various times (1 to 35 days) after one of three degrees of injury: (a) Mild: Four days after making shallow cavities into cervical dentin of first molars of anesthetized adult rats, we found that CGRP fibers had sprouted into the subjacent odontoblast layer and dentin, and then returned to normal by 3 wk. (b) Intermediate: If the cervical cavities were acid etched, we found damage to the odontoblast layer, microabscess formation, and sprouting of CGRP fibers near the abscess, with subsequent formation of reparative dentin and healing. (c) Severe: If the pulp was exposed, a variety of reactions could occur, the most prevalent of which was a severe necrosis leading to development of periapical lesions. Analysis of the progressive stages of pulpal abscess and necrosis showed sprouting CGRP nerve fibers (a) at the retreating interface between abscess and vital pulp; (b) in periapical areas during onset of lesions; and (c) around chronic abscesses in granulomatous periodontal tissues. These studies are discussed in relation to various dental clinical problems such as hypersensitive teeth, episodic toothache, early onset of periapical lesions, dental anesthesia, and possible roles for sensory fibers and neuropeptides in tissue defense and healing.     

Delineation of somatic nerve endings in rat teeth by radioautography of axon-transported protein.

We have shown that there is extensive innervation of cusp pulp and dentin in rat molars. The dental nerves either end freely below the odontoblast layer or form gap junction endings on the odontobast cell body or along its dential process. The nerves are largely absent from response dentin, are found in contact with virtually all other odontoblasts at the tip of the cusps, are less frequent in intercuspal regions, and are absent from root dentin and odontoblast layers. The incisors were completely different from the molars, perhaps because they are continuously erupting teeth. The distribution of nerve endings in rat molars may be representative of that in teeth of other species, but the nerve endings should be mapped radioautographically for each type of tooth before generalizations can be made.     

Morphological variation in the tyrosine receptor kinase A-immunoreactive periodontal ligament epithelium of developing and mature rats

Tyrosine receptor kinase A (trkA) is the high-affinity receptor for nerve growth factor. It has been found in several non-neuronal cell types, indicating biological roles independent of neural function, as well as in the nervous system. An initial study demonstrated that an antibody to the full extracellular domain did not label periodontal ligament epithelium (PLE; also known as epithelial rests of Malassez), but that another antibody which recognises a truncated 41-kDa form of trkA did label PLE. Thus, truncated trkA-immunoreactive (-IR) PLE was further investigated here in developing molars of young rats, and in its mature form in adult rat molars, for its reaction to moderate or deep molar injuries, and for its appearance along the continuously erupting incisors of mature rats. In some of the adult rat molars we also analysed the association of nerve fibres with PLE using antibodies for p75 neurotrophin receptor or peripherin. Rat jaws were fixed with 4% formaldehyde and demineralised, and bound antibody was detected with avidin-biotin-peroxidase and diaminobenzidine or fluorescence procedures. Light microscopy showed great variation in the appearance of trkA-IR PLE and considerable morphological changes during the eruption of molars and incisors. By electron microscopy it was shown that trkA-IR was not uniformly distributed in PLE cells but rather was concentrated in the peripheral zones of each cell cluster. Tooth injury did not influence the form or occurrence of PLE unless there was specific destruction of a ligament region. Qualitative analyses of nerve fibres showed that they only rarely innervated PLE in adult rats, indicating that the truncated receptor has non-neuronal functions in this epithelium. These results suggest that neurotrophin growth factors, acting via truncated trkA receptors, affect the interactions between PLE cells and the periodontal ligament, with fewer PLE interactions with nerves. Furthermore, the expression of these receptors on PLE supports the possibility that these cells are active during tooth development and eruption rather than being merely passive remnants of the degenerating tooth sheath. The similar trkA-IR of PLE and junctional epithelium, as well as their structural association, suggests interactions between these two epithelia.