Search

Objectives During the corona pandemic, dental practices temporarily closed their doors to patients except for emergency treatments. Due to the daily occupational exposure, the risk of SARS-CoV-2 transmission among dentists and their team is presumed to be higher than that in the general population. This study examined this issue among dental teams across Germany. Materials and methods In total, 2784 participants provided usable questionnaires and dry blood samples. Dry blood samples were used to detect IgG antibodies against SARS-CoV-2. The questionnaires were analyzed to investigate demographic data and working conditions during the pandemic. Multivariable logistic mixed-effects models were applied. Results We observed 146 participants with positive SARS-CoV-2 IgG antibodies (5.2%) and 30 subjects with a borderline finding (1.1%). Seventy-four out of the 146 participants with SARS-CoV-2 IgG antibodies did not report a positive SARS-CoV-2 PCR test (50.7%), while 27 participants without SARS-CoV-2 IgG antibodies reported a positive SARS-CoV-2 PCR test (1.1%). Combining the laboratory and self-reported information, the number of participants with a SARS-CoV-2 infection was 179 (6.5%). Though after adjustment for region, mixed-effects models indicated associations of use of rubber dams (OR 1.65; 95% CI: 1.01–2.72) and the number of protective measures (OR 1.16; 95% CI: 1.01–1.34) with increased risk for positive SARS-CoV-2 status, none of those variables was significantly associated with a SARS-CoV-2 status in fully adjusted models. Conclusions The risk of SARS-CoV-2 transmission was not higher among the dental team compared to the general population. Clinical relevance. Following hygienic regulations and infection control measures ensures the safety of the dental team and their patients.

The Study of Health in Pomerania (SHIP), a population-based study from a rural state in northeastern Germany with a relatively poor life expectancy, supplemented its comprehensive examination program in 2008 with whole-body MR imaging at 1.5 T (SHIP-MR). We reviewed more than 100 publications that used the SHIP-MR data and analyzed which sequences already produced fruitful scientific outputs and which manuscripts have been referenced frequently. Upon reviewing the publications about imaging sequences, those that used T1-weighted structured imaging of the brain and a gradient-echo sequence for R2* mapping obtained the highest scientific output; regarding specific body parts examined, most scientific publications focused on MR sequences involving the brain and the (upper) abdomen. We conclude that population-based MR imaging in cohort studies should define more precise goals when allocating imaging time. In addition, quality control measures might include recording the number and impact of published work, preferably on a bi-annual basis and starting 2 years after initiation of the study. Structured teaching courses may enhance the desired output in areas that appear underrepresented.

Objectives In the search for more effective and safe treatment avenues, we investigated cold physical plasma as a new treatment modality for therapy of oral lichen planus (OLP). Material and methods Healthy and diseased human mucosal tissue samples with a size of 3 mm in diameter obtained from OLP patients were subjected to plasma treatment ex vivo or were left untreated. Tissue sections were quantified for immune-infiltration of CD4+ , CD8+ , CD45RA+ , and CD45R0+ T cells. Moreover, the tissues' inflammatory profile was assessed by analyzing 12 different cytokines in the surrounding media. Results A significantly increased infiltrate of CD8+ and CD45-R0+ T cells was detected in OLP tissue samples when compared to healthy tissue. A higher concentration of interleukin (IL) 1β, IL6, IL8, and granulocyte macrophage-colony stimulating factor (GM-CMF) was detected in OLP samples compared to healthy mucosal tissue. For all cytokines and chemokines investigated, 23 out of 24 comparisons showed a decrease in tendency (significant for IL1β, IL2, IL10, and GM-CSF) in response to plasma treatment. In ex vivo-treated tissue, a decrease of T-cell infiltrate in OLP lesions compared with healthy tissue was observed. Conclusion Our findings suggest cold physical plasma can be a promising therapeutic option for OLP that requires further validation in vivo.

Here, we report on six unrelated individuals, all presenting with early-onset global developmental delay, associated with impaired motor, speech and cognitive development, partly with developmental epileptic encephalopathy and physical dysmorphisms. All individuals carry heterozygous missense variants of KCND2, which encodes the voltage-gated potassium (Kv) channel α-subunit Kv4.2. The amino acid substitutions associated with the variants, p.(Glu323Lys) (E323K), p.(Pro403Ala) (P403A), p.(Val404Leu) (V404L) and p.(Val404Met) (V404M), affect sites known to be critical for channel gating. To unravel their likely pathogenicity, recombinant mutant channels were studied in the absence and presence of auxiliary β-subunits under two-electrode voltage clamp in Xenopus oocytes. All channel mutants exhibited slowed and incomplete macroscopic inactivation, and the P403A variant in addition slowed activation. Co-expression of KChIP2 or DPP6 augmented the functional expression of both wild-type and mutant channels; however, the auxiliary β-subunit-mediated gating modifications differed from wild type and among mutants. To simulate the putative setting in the affected individuals, heteromeric Kv4.2 channels (wild type + mutant) were studied as ternary complexes (containing both KChIP2 and DPP6). In the heteromeric ternary configuration, the E323K variant exhibited only marginal functional alterations compared to homomeric wild-type ternary, compatible with mild loss-of-function. By contrast, the P403A, V404L and V404M variants displayed strong gating impairment in the heteromeric ternary configuration, compatible with loss-of-function or gain-of-function. Our results support the etiological involvement of Kv4.2 channel gating impairment in early-onset monogenic global developmental delay. In addition, they suggest that gain-of-function mechanisms associated with a substitution of V404 increase epileptic seizure susceptibility.

Dental restorations and removable dental prostheses have been considered as risk factors for potentially malignant disorders of the oral mucosa. It remains unclear whether amalgam, composite resins, and prosthesis materials can induce potentially malignant disorders.The purpose of this clinical study was to determine the relationship between the presence of amalgam and composite resin restorations, crowns and fixed partial dentures, and removable prostheses in potentially malignant disorders.The data of 6041 participants in the population-based Studies of Health in Pomerania (SHIP) were accessed. Potentially malignant disorders had been clinically diagnosed by calibrated dentists and documented with photographs. Dental treatment was subdivided into restored and replaced teeth. Dental restorations were subclassified as buccal composite resin or amalgam restorations. Prosthetic treatment was subclassified into removable partial or complete prostheses and definitive restorations with crowns and fixed partial dentures.In the maxilla, participants with removable prostheses had a higher incidence of potentially malignant disorders than participants not undergoing treatment with removable prostheses (OR 2.12; 95% CI: 1.08-4.18), but not in the mandible (OR 1.30; 95% CI: 0.67-2.53). The surfaces with composite resin restorations were associated with a slightly higher risk of mucosal lesions than those without the restorations (OR 1.04; 95% CI: 1.01-1.07). No significant association was found between amalgam restorations and mucosal lesions.Participants with removable prostheses have a higher risk of potentially malignant disorders. Composite resin restorations are associated with a higher risk of mucosal lesions, whereas no significant association was found between amalgam restorations and mucosal lesions.

Objective Hereditary spastic paraplegia (HSP) is a highly heterogeneous neurologic disorder characterized by lower-extremity spasticity. Here we set out to determine the genetic basis of an autosomal dominant, pure and infantile onset form of HSP in a cohort of eight patients with a uniform clinical presentation. Methods Trio whole exome sequencing was utilized in five index patients with infantile onset pure HSP to determine the genetic cause of disease. The functional impact of identified genetic variants was verified utilizing bioinformatics and complementary cellular and biochemical assays. Results Distinct heterozygous KPNA3 missense variants were found to segregate with the clinical phenotype in eight patients, in four of them KPNA3 variants have occurred de novo. Mutant Karyopherin-α3 proteins exhibit a variable pattern of altered expression level, subcellular distribution and protein interaction. Interpretation Our genetic findings implicate heterozygous variants in KPNA3 as a novel cause for autosomal dominant, early onset and pure HSP. Mutant Karyopherin-α3 proteins display varying deficits in molecular and cellular functions, thus for the first time implicating dysfunctional nucleocytoplasmic shuttling as a novel pathomechanism causing HSP. This article is protected by copyright. All rights reserved.

Purpose Erupted and impacted third molars have been reported to contribute to systemic inflammation. This study investigated the systemic effect of third molars on serum levels of inflammatory parameters and on inflammatory messenger peptide hormones in a general population sample. Materials and Methods Data of 2,151 participants from the Study of Health in Pomerania were included in this study. Erupted or impacted third molars were assessed with whole-body magnetic resonance imaging at 1.5 T and associated with biomarkers of inflammation, lipid metabolism, glucose metabolism, and peptide hormones by linear regression. Models were adjusted for age, gender, smoking status, education, and type 2 diabetes mellitus. Results Neither erupted nor impacted third molars were associated with high-sensitivity C-reactive protein, white blood cell count, or fibrinogen as markers for systemic inflammation. Participants with erupted third molars had markedly lower serum levels of leptin (β coefficient, −2.47; 95% confidence interval [CI], −4.47 to −0.48), angiopoietin-2 (β coefficient, −135.1; 95% CI, 248.6 to −21.5), and ratio of angiopoietin-2 to tyrosine kinase with immunoglobulin-like loop epidermal growth factor homology domain 2 (β coefficient, −6.57; 95% CI, −13.06 to −00.7) than participants without third molars. No such associations were observed for impacted third molars. Conclusion The present results did not substantiate a relation between third molars and an increase in systemic inflammatory markers. Therefore, dental practitioners should be careful when considering this as the only indication for removal of third molars, especially in medically compromised patients. The results of this study showed that participants with erupted third molars had lower levels of messenger peptide hormones, such as leptin and angiopoetin-2.

AIM We aimed to investigate associations between malocclusions and periodontal disease by comparing it to that of smoking in subjects recruited from the population-based cross-sectional study "Study of Health in Pomerania." MATERIALS AND METHODS Sagittal intermaxillary relationship, variables of malocclusion and socio-demographic parameters of 1,202 dentate subjects, 20-39 years of age, were selected. Probing depth (PD) and attachment loss (AL) were assessed at four sites by tooth in a half-mouth design. Analyses were performed with multilevel models on subject, jaw and tooth level. RESULTS Distal occlusion determined in the canine region, ectopic position of canines, anterior spacing, deep anterior overbite and increased sagittal overjet were associated with AL (p-value

Aims To estimate the association between signs of temporomandibular disorders (TMD) and symptoms of posttraumatic stress disorder (PTSD) in a representative sample from the general population of northeastern Germany. Methods Signs of TMD were assessed with a clinical functional analysis that included palpation of the temporomandibular joints (TMJs) and masticatory muscles. PTSD was assessed with the PTSD module of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, ed 4. The change-in-estimate method for binary logistic regression models was used to determine the final model and control for confounders. Results After the exclusion of subjects without prior traumatic events, the sample for joint pain consisted of 1,673 participants with a median age of 58.9 years (interquartile range 24.8), and the sample for muscle pain consisted of 1,689 participants with a median age of 59.1 years (interquartile range 24.8). Of these samples, 84 participants had pain on palpation of the TMJ, and 42 participants had pain on palpation of the masticatory muscles. Subjects having clinical PTSD (n = 62) had a 2.56-fold increase in joint pain (odds ratio [OR] = 2.56; 95% confidence interval [CI]: 1.14 to 5.71, P = .022) and a 3.86-fold increase (OR = 3.86; 95% CI: 1.51 to 9.85, P = .005) in muscle pain compared to subjects having no clinical PTSD. Conclusion These results should encourage general practitioners and dentists to acknowledge the role of PTSD and traumatic events in the diagnosis and therapy of TMD, especially in a period of international migration and military foreign assignments.

ARGONAUTE-2 and associated miRNAs form the RNA-induced silencing complex (RISC), which targets mRNAs for translational silencing and degradation as part of the RNA interference pathway. Despite the essential nature of this process for cellular function, there is little information on the role of RISC components in human development and organ function. We identify 13 heterozygous mutations in AGO2 in 21 patients affected by disturbances in neurological development. Each of the identified single amino acid mutations result in impaired shRNA-mediated silencing. We observe either impaired RISC formation or increased binding of AGO2 to mRNA targets as mutation specific functional consequences. The latter is supported by decreased phosphorylation of a C-terminal serine cluster involved in mRNA target release, increased formation of dendritic P-bodies in neurons and global transcriptome alterations in patient-derived primary fibroblasts. Our data emphasize the importance of gene expression regulation through the dynamic AGO2-RNA association for human neuronal development., AGO2 binds to miRNAs to repress expression of cognate target mRNAs. Here the authors report that heterozygous AGO2 mutations result in defects in neurological development and impair RNA interference.

Oral cancer mostly develops from oral mucosa regions with morphological alterations transforming malignant. These visible precancerous mucosa lesions are named potentially malignant disorders (PMD). We aimed to analyze the prevalence of PMD and its risk factors for PMD in a population-based sample in Northern Germany.Data of 6078 individuals from the population-based Study of Health in Pomerania (SHIP) was used. PMD were photographically documented and periodontal health was assessed in a standardized procedure.PMD were observed in 54 individuals (0.9%). The most prevalent PMD was homogenous leukoplakia (n = 37) followed by Lichen ruber (n = 9). Smoking (Odds Ratio (OR) 2.70; 95% confidence interval (CI): 1.24-5.87), male sex (OR 3.32; 95%-CI: 1.77-6.21), type 2 diabetes mellitus (OR 2.07; 95%-CI: 1.08-3.98) and body mass index (OR 1.09; CI 1.04-1.14) were significantly associated with PMD, with the corresponding area under the curve (AUC) being 0.696 (CI: 0.655; 0.737).Our results suggest a clinically relevant prevalence of PMD in the population. We identified male sex, type 2 diabetes mellitus, current smoking, and obesity as risk factors. We recommend photographic documentation and intensified training of medical and dental staff to detect and monitor PMD.

Temporomandibular joint disorder (TMD) is a painful functional disorder of the temporomandibular joint, masticatory muscles, and associated musculoskeletal structures of the head and neck. TMD is a type of chronic pain and is widely used as a model for chronic pain. The etiology of TMD pain is multifactorial. Biological, behavioral, environmental, social, emotional, and cognitive factors can contribute to TMD. TMD can manifest with musculoskeletal facial pain complaints and with different forms of jaw dysfunction. Biobehavioral studies suggest an association between TMD pain and coexisting psychopathology, including depression and anxiety. This chapter presents practical clinical recommendations on how to treat patients with symptoms of depression, anxiety, and TMD pain. The authors underline the importance of considering depression and anxiety as risk factors for TMD.

AIM The aim of this study was to clarify the association between impacted or erupted third molars and periodontal pathology, assessed by probing depth (PD) and clinical attachment levels (CAL), in adjacent second molars. MATERIALS AND METHODS Data from the population-based Study of Health in Pomerania (SHIP) was used. This is the first project with whole-body magnetic resonance imaging (WB-MRI) application in a general population setting with dental issues. Calibrated and licensed dentists measured PD and CAL with a periodontal probe. RESULTS In the mandible, individuals with erupted third molars had a 1.45-fold higher odds ratio (CI:1.03; 2.05; p = 0.031) and individuals with impacted third molars had a 2.37-fold higher odds ratio (CI:1.45; 3.85; p

Die Wundheilung zahlt zu den komplexesten biologischen Prozessen im Organismus. Sie lauft in drei aufeinanderfolgenden Stadien ab: der exsudativen, der proliferativen und der reparativen Phase. Zum besseren Verstandnis neuer Therapieansatze ist es erforderlich, die Grundzuge dieser Ablaufe zu kennen. Abhangig von dem Ausmas der Wunde, der Lokalisation, der bakteriellen Besiedlung und dem Wundstadium gilt es, eine geeignete Therapiemodalitat zu finden. Im vorliegenden Beitrag werden die grundlegenden Prinzipien der Wundheilung und der Storfaktoren vermittelt, um die Grundlagen fur die im nachsten Teil zusammengefassten modernen Behandlungsmoglichkeiten zu schaffen.

Notfalle im Mund-Kiefer-Gesichtsbereich begegnen uns im Rettungsdienst und in der Notaufnahme eher selten, sodass das Wissen zu Diagnostik und Therapiemoglichkeiten eher gering ist. Da sich aber die richtige Therapie bereits im Rettungsdienst und in der Notaufnahme durchfuhren bzw. bahnen lassen kann, vermittelt der vorliegende Beitrag die pathophysiologischen Grundlagen zu wichtigen Notfallen und gibt praktische Handlungsempfehlungen, z. B. zum Atemwegsmanagement. Mit dieser Lekture vertiefen Sie Ihr Wissen zu den Themen Mittelgesichtsfrakturen, Verletzungen im Gesichtsbereich, Tumorblutungen bei Mundbodenkarzinomen, Kieferklemme/-sperre, Zahnverletzungen und Besonderheiten bei Reanimationen in Zahnarztpraxen. Zusatzlich werden die Symptome, nach Haufigkeit bei den jeweiligen Notfallen sortiert, vorgestellt und kommentiert.

Aim Oral cancer mostly develops from oral mucosa regions with morphological alterations transforming malignant. These visible precancerous mucosa lesions are named potentially malignant disorders (PMD). We aimed to analyze the prevalence of PMD and its risk factors for PMD in a population-based sample in Northern Germany. Material and Methods Data of 6078 individuals from the population-based Study of Health in Pomerania (SHIP) was used. PMD were photographically documented and periodontal health was assessed in a standardized procedure. Results PMD were observed in 54 individuals (0.9%). The most prevalent PMD was homogenous leukoplakia (n = 37) followed by Lichen ruber (n = 9). Smoking (Odds Ratio (OR) 2.70; 95% confidence interval (CI): 1.24–5.87), male sex (OR 3.32; 95%-CI: 1.77–6.21), type 2 diabetes mellitus (OR 2.07; 95%-CI: 1.08–3.98) and body mass index (OR 1.09; CI 1.04–1.14) were significantly associated with PMD, with the corresponding area under the curve (AUC) being 0.696 (CI: 0.655; 0.737). Conclusion Our results suggest a clinically relevant prevalence of PMD in the population. We identified male sex, type 2 diabetes mellitus, current smoking, and obesity as risk factors. We recommend photographic documentation and intensified training of medical and dental staff to detect and monitor PMD.

Contains fulltext : 182457.pdf (Publisher’s version ) (Open Access) DHX30 is a member of the family of DExH-box helicases, which use ATP hydrolysis to unwind RNA secondary structures. Here we identified six different de novo missense mutations in DHX30 in twelve unrelated individuals affected by global developmental delay (GDD), intellectual disability (ID), severe speech impairment and gait abnormalities. While four mutations are recurrent, two are unique with one affecting the codon of one recurrent mutation. All amino acid changes are located within highly conserved helicase motifs and were found to either impair ATPase activity or RNA recognition in different in vitro assays. Moreover, protein variants exhibit an increased propensity to trigger stress granule (SG) formation resulting in global translation inhibition. Thus, our findings highlight the prominent role of translation control in development and function of the central nervous system and also provide molecular insight into how DHX30 dysfunction might cause a neurodevelopmental disorder.

Objectives To examine the association between third molars and orofacial pain. We hypothesized that impacted third molars are a cause of orofacial pain. Methods Magnetic resonance images of 1808 participants from two population‐based cohorts from Northeastern Germany were analysed to define the status of third molars according to the Pell and Gregory classification. A self‐reported questionnaire and a clinical dental examination were used to detect chronic and acute complaints of orofacial pain, masticatory muscle pain, migraine and other types of headache. Logistic regression models were used to analyse the associations between third molar status and orofacial pain. Results Individuals with impacted third molars in the maxilla had a higher chance of chronic orofacial pain than those with erupted third molars (odds ratio 2.19; 95% CI 1.19‐4.02). No such association was detected for third molars in the lower jaw. Third molars were not associated with masticatory muscle pain, migraine or other types of headache. Conclusions Impacted maxillary third molars might be a cause of chronic orofacial pain. Thus, physicians should consider the eruption/impaction status of third molars in their decision‐making process when treating patients who complain of orofacial pain.

In humans, genetic variants of DLGAP1-4 have been linked with neuropsychiatric conditions, including autism spectrum disorder (ASD). While these findings implicate the encoded postsynaptic proteins, SAPAP1-4, in the etiology of neuropsychiatric conditions, underlying neurobiological mechanisms are unknown. To assess the contribution of SAPAP4 to these disorders, we characterized SAPAP4-deficient mice. Our study reveals that the loss of SAPAP4 triggers profound behavioural abnormalities, including cognitive deficits combined with impaired vocal communication and social interaction, phenotypes reminiscent of ASD in humans. These behavioural alterations of SAPAP4-deficient mice are associated with dramatic changes in synapse morphology, function and plasticity, indicating that SAPAP4 is critical for the development of functional neuronal networks and that mutations in the corresponding human gene, DLGAP4, may cause deficits in social and cognitive functioning relevant to ASD-like neurodevelopmental disorders.

Die Mund-Kiefer-Gesichts(MKG)-Chirurgie entwickelt kontinuierlich ihre Gesundheitstechnologie weiter; dazu gehoren auch Lasergerate und Plasmaquellen. Prozessorientiertes Qualitatsmanagement durch Weiterbildung bei Anwendung neuer Gesundheitstechnologien. Zusammenstellung wichtiger Standards und Anforderungen an Schulungsprogramme in der klinischen Laser- und Plasmamedizin. Das universitare Weiterbildungsstudium Diploma in Aesthetic Laser Medicine (D.A.L.M) fuhrt mit einem 1999 vom Bildungsministerium anerkannten strukturierten, multizentrischen, industrieunabhangigen, wissenschaftsorientierten Studienprogramm zum postgradualen schildfahigen Abschluss. Im prozessorientierten Qualitatsmanagement der asthetisch orientierten Lasermedizin und daruber hinaus in der Plasmamedizin ist das D.A.L.M.-Programm ein wichtiges Instrument.

Shank3 is a multidomain scaffold protein localized to the postsynaptic density of excitatory synapses. Functional studies in vivo and in vitro support the concept that Shank3 is critical for synaptic plasticity and the trans-synaptic coupling between the reliability of presynaptic neurotransmitter release and postsynaptic responsiveness. However, how Shank3 regulates synaptic strength remains unclear. The C terminus of Shank3 contains a sterile alpha motif (SAM) domain that is essential for its postsynaptic localization and also binds zinc, thus raising the possibility that changing zinc levels modulate Shank3 function in dendritic spines. In support of this hypothesis, we find that zinc is a potent regulator of Shank3 activation and dynamics in rat hippocampal neurons. Moreover, we show that zinc modulation of synaptic transmission is Shank3 dependent. Interestingly, an autism spectrum disorder (ASD)-associated variant of Shank3 (Shank3R87C) retains its zinc sensitivity and supports zinc-dependent activation of AMPAR-mediated synaptic transmission. However, elevated zinc was unable to rescue defects in trans-synaptic signaling caused by the R87C mutation, implying that trans-synaptic increases in neurotransmitter release are not necessary for the postsynaptic effects of zinc. Together, these data suggest that Shank3 is a key component of a zinc-sensitive signaling system, regulating synaptic strength that may be impaired in ASD. SIGNIFICANCE STATEMENT Shank3 is a postsynaptic protein associated with neurodevelopmental disorders such as autism and schizophrenia. In this study, we show that Shank3 is a key component of a zinc-sensitive signaling system that regulates excitatory synaptic transmission. Intriguingly, an autism-associated mutation in Shank3 partially impairs this signaling system. Therefore, perturbation of zinc homeostasis may impair, not only synaptic functionality and plasticity, but also may lead to cognitive and behavioral abnormalities seen in patients with psychiatric disorders.

Long-lasting synaptic plasticity is often accompanied by morphological changes as well as formation and/or loss of dendritic spines. Since the spine cytoskeleton mainly consists of actin filaments, morphological changes are primarily controlled by actin binding proteins (ABPs). Inositol-1,4,5-trisphosphate-3-kinase-A (ITPKA) is a neuron-specific, actin bundling protein concentrated at dendritic spines. Here, we demonstrate that ITPKA depletion in mice increases the number of hippocampal spine-synapses while reducing average spine length. By employing actin to ABP ratios similar to those occurring at post synaptic densities, in addition to cross-linking actin filaments, ITPKA strongly inhibits Arp2/3-complex induced actin filament branching by displacing the complex from F-actin. In summary, our data show that in vivo ITPKA negatively regulates formation and/or maintenance of synaptic contacts in the mammalian brain. On the molecular level this effect appears to result from the ITPKA-mediated inhibition of Arp2/3-complex F-actin branching activity.

Background Associations of alexithymia with temporomandibular pain disorders (TMD), facial pain, head pain and migraine have been described, but the role of the different dimensions of alexithymia in pain development remained incompletely understood. Objectives We sought to investigate the associations of alexithymia and its subfactors with signs of TMD and with facial pain, head pain and migraine in the general population. Methods A total of 1494 subjects from the general population completed the Toronto Alexithymia Scale-20 (TAS-20) and underwent a clinical functional examination with palpation of the temporomandibular joint and masticatory muscles. Facial pain, migraine and head pain were defined by questionnaire. A set of logistic regression analyses was applied with adjustment for age, sex, education, number of traumatic events, depressive symptoms and anxiety. Results Alexithymia was associated with TMD joint pain (Odds Ratio 2.63; 95% confidence interval 1.60-4.32 for 61 TAS-20 points vs the median of the TAS-20 score) and with facial pain severity (Odds Ratio 3.22; 95% confidence interval 1.79-5.79). Differential effects of the subfactors were discovered with difficulties in identifying feelings as main predictor for joint, facial, and head pain, and externally oriented thinking (EOT) as U-shaped and strongest predictor for migraine. Conclusion Alexithymia was moderately to strongly associated with signs and symptoms of TMD. These results should encourage dental practioners using the TAS-20 in clinical practice, to screen TMD, facial or head pain patients for alexithymia and could also help treating alexithymic TMD, facial or head pain patients.

This study is a retrospective review of representing clinical follow-up of 12 patients afflicted with advanced squamous cell carcinoma of the head and neck. Herein, we have used novel physical cold atmospheric pressure plasma (CAP) to decontaminate infected cancer ulcerations and evaluated anti-cancer effects. With use of CAP in this cohort, the data suggests: (1) decreased request for pain medication and (2) reduction of typical fetid odor related to (3) reduction of microbial load. In some cases there is (4) superficial partial remission of tumor and even (5) wound healing of infected ulcerations has been observed following CAP exposure. As a result, CAP treatment appears of benefit for select head and neck cancer patients and future work to optimize CAP in the therapeutic armamentarium advances.

With the development of plasma sources generating nonthermal plasmas at atmo- spheric pressure the applications broaden enormously, especially in the medical field. While earlier applications of physical plasma on biological matter focused on inactivation of mi- croorganisms, the latest studies have revealed a modulation of eukaryotic cells by the same type of plasma. The aim of this study was to elucidate molecular mechanisms triggered by non-thermal plasma in human oral mucosa. Ex vivo biopsies were treated directly with the cold atmospheric pressure plasma jet kinpenMED and analyzed for distinctive markers of proliferation, apopto- sis, DNA damage, and differentiation. Moreover, secreted cytokines and growth factors were measured in the supernatant. These results revealed stimulating effects indicated by proliferation consolidated by secretion of VEGF. We also proved that these effects were mediated into deeper layers of the mucosa, without harming the cells on top of the treated samples. DNA damage de- tected as H2A.X-immunoreactivity was nearly constant between all samples. Our study revealed for the first time that human oral mucosa can be modulated by plasma treat - ment. Molecular markers for both cell damage and proliferation helped to identify the mecha- nisms triggered by plasma treatment. Moreover, our results strengthen a safe application of the kinpenMED on human oral tissue. Further studies on diseased skin are being performed in order to proceed towards a safe introduction of plasma medicine into the clinics.

Previous studies have associated depression and temporomandibular joint disorders (TMDs). The temporality, however, remains to be clarified. Most patient studies have selected sub- jects from treatment facilities, whereas in epidemiological studies a clinical examination has not been performed. In this study the 5-year follow-up data of the population-based Study of Health in Pomerania (SHIP) were analyzed. To estimate the effect of symptoms of depression and those of anxiety on the risk of TMD pain, the Composite International Diagnostic-Screener (CID-S) and a clinical functional examination with palpation of the temporomandibular joint and the masticatory muscles were used. After exclusion of subjects having joint pain at baseline, a sample of 3,006 Caucasian par- ticipants with a mean age of 49 years resulted. Of those, 122 participants had signs of TMD joint pain upon palpation. Subjects with symptoms of depression had an increased risk of TMD joint pain upon palpation (rate ratio: 2.1; 95% confidence interval: 1.5-3.0; P < .001). Anxiety symptoms were associ- ated with joint and with muscle pain. The diagnosis, prevention, and therapy of TMD pain should also consider symptoms of depression and those of anxiety, and appropriate therapies if necessary. Perspective: Depressiveand anxietysymptomsshouldbeconsidered asriskfactors for TMD pain.De- pressivesymptomsarespecificforjointpainwhereasanxietysymptomsarespecificformusclepain,find- ings that deserve detailed examination. These findings may support decision-making in treating TMD. a 2012 by the American Pain Society

Previous investigations have confirmed that every fifth dental patient suffers from clinically significant depressive symptoms. However, the putative impact of depressive symptoms on the prosthetic status has not been addressed in these studies. The objective of this study was to investigate the association between depressive symptoms and prosthetic status based on data from the Study of Health in Pomerania (SHIP-0).Data from 2,135 participants aged 30 to 59 years were analyzed. A classification (six classes regarding the number and position of missing teeth per jaw) was used to identify the degree of prosthetic status (no/suboptimal/optimal tooth replacement). The presence of depressive symptoms was assessed with a modified version of von Zerssen's complaints scale. Screening for lifetime diagnoses of mental disorders was performed with the Composite International Diagnostic-Screener (CID-S). Multivariable logistic regressions including several confounders were calculated.A significant protective dose-response effect of depressive symptoms on prosthetic status was found only in men for the lower jaw [0-1 depressive symptoms: odds ratio (OR) = 3.84, 95 % confidence interval (CI, 1.65-8.92), p0.01; 2-3: OR = 2.87 (CI, 1.22-6.74), p0.05; reference, ≥8; adjusted for age, school education, smoking status, household income, marital status, living without a partner, risky alcohol consumption, obesity, diabetes, and physical activity]. There was no such association in women or for the upper jaw. The analyses using the CID-S confirmed these results.In the lower jaw, men with depressive symptoms had a better prosthetic status than men without depressive symptoms suggesting a higher level of concern regarding their personal health.If dentists might have an opportunity to identify men with depressive symptoms they can provide a wide range of treatment options that may enhance patients' self-esteem and contribute to the patient' well-being. Furthermore, depressive symptoms could indicate a discrepancy between self-perception of the dental health and the actual status which influence the dentists' treatment decision making.

The poly(A)-binding protein (PABP), a key component of different ribonucleoprotein complexes, plays a crucial role in the control of mRNA translation rates, stability, and subcellular targeting. In this study we identify RING zinc finger protein Makorin 1 (MKRN1), a bona fide RNA-binding protein, as a binding partner of PABP that interacts with PABP in an RNA-independent manner. In rat brain, a so far uncharacterized short MKRN1 isoform, MKRN1-short, predominates and is detected in forebrain nerve cells. In neuronal dendrites, MKRN1-short co-localizes with PABP in granule-like structures, which are morphological correlates of sites of mRNA metabolism. Moreover, in primary rat neurons MKRN1-short associates with dendritically localized mRNAs. When tethered to a reporter mRNA, MKRN1-short significantly enhances reporter protein synthesis. Furthermore, after induction of synaptic plasticity via electrical stimulation of the perforant path in vivo, MKRN1-short specifically accumulates in the activated dendritic lamina, the middle molecular layer of the hippocampal dentate gyrus. Collectively, these data indicate that in mammalian neurons MKRN1-short interacts with PABP to locally control the translation of dendritic mRNAs at synapses.

The functioning of excitatory synapses in the mammalian brain is governed by macromolecular complexes that are held together by protein-protein, protein-lipid and lipid-lipid interactions. On the presynaptic side, neurotransmitter (NT)-filled synaptic vesicles (SVs) are recruited to specialized

Jacob is a recently identified plasticity-related protein that couples N-methyl-d-aspartate receptor activity to nuclear gene expression. An expression analysis by Northern blot and in situ hybridization shows that Jacob is almost exclusively present in brain, in particular in the cortex and the limbic system. Alternative splicing gives rise to multiple mRNA variants, all of which exhibit a prominent dendritic localization in the hippocampus. Functional analysis in primary hippocampal neurons revealed that a predominant cis-acting dendritic targeting element in the 3'-untranslated region of Jacob mRNAs is responsible for dendritic mRNA localization. In the mouse brain, Jacob transcripts are associated with both the fragile X mental retardation protein, a well described trans-acting factor regulating dendritic mRNA targeting and translation, and the kinesin family member 5C motor complex, which is known to mediate dendritic mRNA transport. Jacob is susceptible to rapid protein degradation in a Ca(2+)- and Calpain-dependent manner, and Calpain-mediated clipping of the myristoylated N terminus of Jacob is required for its nuclear translocation after N-methyl-d-aspartate receptor activation. Our data suggest that local synthesis in dendrites may be necessary to replenish dendritic Jacob pools after truncation of the N-terminal membrane anchor and concomitant translocation of Jacob to the nucleus.

In neurones, a limited number of mRNAs is found in dendrites, including transcripts encoding the microtubule-associated protein 2 (MAP2). Recently, we identified a cis-acting dendritic targeting element (DTE) in MAP2 mRNAs. Here we used the yeast tri-hybrid system to identify potential trans-acting RNA-binding factors of the DTE. A cDNA clone was isolated that encodes a member of a mammalian protein family that is highly homologous to the Drosophila RNA-binding protein Staufen. Mammalian Staufen appears to be expressed in most tissues and brain areas. Two distinct rat brain Staufen isoforms, rStau+I6 and rStau-I6, are encoded by alternatively spliced mRNAs. Both isoforms contain four double-stranded RNA-binding domains (dsRBD). In the larger rStau+I6 isoform, six additional amino acids are inserted in the second dsRBD. Although both isoforms interacted with the MAP2-DTE and various additional RNA fragments in an in vitro north-western assay, rStau-I6 exhibited a stronger signal of bound radioactively labelled RNAs as compared with rStau+I6. Using an antibody directed against mammalian Staufen, the protein was detected in somata and dendrites of neurones of the adult rat hippocampus and cerebral cortex. Ultrastructural studies revealed that in dendrites, rat Staufen accumulates along microtubules. Thus in neurones, rat Staufen may serve to link RNAs to the dendritic microtubular cytoskeleton and may thereby regulate their subcellular localization.

Using peptide affinity purification, we identified an interaction between somatostatin receptors SSTR4 and SSTR1 and PDZ domains 1 and 2 of the postsynaptic proteins postsynaptic density protein of 95kDa (PSD-95) and PSD-93. The existence of the SSTR4/PSD-95 complex was verified by coimmunoprecipitation from transfected cells and solubilized brain membranes. In neurons, dendritically localized SSTR4 partially colocalizes with postsynaptic PSD-95. As functional parameters of the receptor, such as coupling to potassium channels, are not affected by the interaction with PSD-95, the association may serve to localize the receptor to postsynaptic sites.

Summary Background Over the past few decades, new cold plasma sources have been developed that have the great advantage of operating at atmospheric pressure and at temperatures tolerable by biological material. New applications for these have emerged, especially in the field of dermatology. Recently it was demonstrated that cold atmospheric-pressure plasma positively influences healing of chronic wounds. The potential of cold plasma lies in its capacity to reduce bacterial load in the wound while at the same time stimulating skin cells and therefore promoting wound closure. In recent years, there have been great advances in the understanding of the molecular mechanisms triggered by cold plasma involving signalling pathways and gene regulation in cell culture. Aim To investigate cold plasma-induced effects in ex vivo treated human skin biopsies. Methods Human skin tissue was exposed to cold plasma for different lengths of time, and analysed by immunofluorescence with respect to DNA damage, apoptosis, proliferation and differentiation markers. Results After cold plasma treatment, the epidermal integrity and keratin expression pattern remained unchanged. As expected, the results revealed an increase in apoptotic cells after 3 and 5 min of treatment. Strikingly, an induction of proliferating basal keratinocytes was detected after cold plasma exposure for 1 and 3 min. As these are the cells that regenerate the epidermis, this could indeed be beneficial for wound closure. Conclusion We investigated the effect of cold plasma on human skin by detecting molecules for growth and apoptosis, and found that both processes are dependent on treatment time. Therefore, this approach offers promising results for further applications of cold plasma in clinical dermatology.

In eukaryotes, the entwined pathways of RNA transport and local translational regulation are key determinants in the spatio-temporal articulation of gene expression. One of the main advantages of this mechanism over transcriptional control in the nucleus lies in the fact that it endows local sites with independent decision-making authority, a consideration that is of particular relevance in cells with complex cellular architecture such as neurons. Localized RNAs typically contain codes, expressed within cis-acting elements, that specify subcellular targeting. Such codes are recognized by trans-acting factors, adaptors that mediate translocation along cytoskeletal elements by molecular motors. Most transported mRNAs are assumed translationally dormant while en route. In some cell types, especially in neurons, it is considered crucial that translation remains repressed after arrival at the destination site (e.g., a postsynaptic microdomain) until an appropriate activation signal is received. Several candidate mechanisms have been suggested to participate in the local implementation of translational repression and activation, and such mechanisms may target translation at the level of initiation and/or elongation. Recent data indicate that untranslated RNAs may play important roles in the local control of translation.

Staufen is a conserved double-stranded RNA-binding protein required for mRNA localization in Drosophila oocytes and embryos. The mammalian homologues Staufen 1 and Staufen 2 have been implicated in dendritic RNA targeting in neurons. Here we show that in rodent oligodendrocytes, these two proteins are present in two independent sets of RNA granules located at the distal myelinating processes. A third kind of RNA granules lacks Staufen and contains major myelin mRNAs. Myelin Staufen granules associate with microfilaments and microtubules, and their subcellular distribution is affected by polysome-disrupting drugs. Under oxidative stress, both Staufen 1 and Staufen 2 are recruited into stress granules (SGs), which are stress-induced organelles containing transiently silenced messengers. Staufen SGs contain the poly(A)-binding protein (PABP), the RNA-binding proteins HuR and TIAR, and small but not large ribosomal subunits. Staufen recruitment into perinuclear SGs is paralleled by a similar change in the overall localization of polyadenylated RNA. Under the same conditions, the distribution of recently transcribed and exported mRNAs is not affected. Our results indicate that Staufen 1 and Staufen 2 are novel and ubiquitous SG components and suggest that Staufen RNPs are involved in repositioning of most polysomal mRNAs, but not of recently synthesized transcripts, during the stress response. Fil: Thomas, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Martínez Tosar, Leandro Julián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Loschi, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Pasquini, Juana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; Argentina Fil: Correale, Jorge. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Kindler, Stefan. Universitat Hamburg; Alemania Fil: Boccaccio, Graciela Lidia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina

In Drosophila oocytes and neuroblasts, the double-stranded RNA binding protein Staufen assembles into ribonucleoprotein particles, which mediate cytoplasmic mRNA trafficking and translation. Two different mammalian orthologues also appear to reside in distinct RNA-containing particles. To date, relatively little is known about the molecular composition of Staufen-containing ribonucleoprotein complexes. Here, we have used a novel one-step affinity purification protocol to identify components of Staufen 1-containing particles. Whereas the nucleocytoplasmic RNA-binding protein nucleolin is linked to Staufen in an RNA-dependent manner, the association of protein phosphatase 1, the microtubule-dependent motor protein kinesin and several components of the large and small ribosomal subunits with Staufen ribonucleoprotein complexes is RNA-independent. Notably, all these components do not co-purify with a second RNA-binding protein, hnRNPK (heterogeneous ribonucleoprotein K), demonstrating the high specificity of the purification protocol. Furthermore, pull-down and immunoprecipitation experiments suggest a direct interaction between Staufen 1 and the ribosomal protein P0 in vitro as well as in cells. In cell fractionation and sucrose gradient assays, Staufen co-fractionates with intact ribosomes and polysomes, but not with the isolated 40 S ribosomal subunit. Taken together, these findings imply that, in the cytoplasm of mammalian cells, an association with the ribosomal P-stalk protein P0 recruits Staufen 1 into ribosome-containing ribonucleoprotein particles, which also contain kinesin, protein phosphatase 1 and nucleolin.

Providing the basis for local protein synthesis in dendritic microdomains, RNA transport in dendrites is thought to be underlying long-term neuronal plasticity. Dendritic RNA targeting mechanisms can therefore be expected to confer selective advantages in the evolution of complex neural systems. The question thus arises as to when and how dendritically targeted transcripts first acquired their targeting competence. To address this question, the dendritic targeting competence of MAP2 transcripts was examined in chicken, mouse and rat. In one approach, we established the somato-dendritic distribution of MAP2 transcripts in vivo. We found that in contrast to rodent MAP2 mRNAs, which are highly enriched in dendritic regions of the retina, chicken MAP2 transcripts are virtually absent from such areas and are rather confined to neuronal somata. In an independent line of investigation, we determined that a dendritic targeting element (DTE) corresponding to the mammalian MAP2 DTE is not contained in the 3' untranslated region (UTR) of avian MAP2 mRNA. The combined results indicate that in contrast to mammalian MAP2 transcripts, avian MAP2 mRNA is lacking dendritic targeting competence. The data thus suggest that the acquisition of such competence has likely been a relatively recent event in evolution.

The insulin receptor substrate of 53 kDa (IRSp53) is a target of the small GTPase cdc42 which is strongly enriched in the postsynaptic density of excitatory synapses. IRSp53 interacts with the postsynaptic shank1 scaffolding molecule in a cdc42 regulated manner. The functional significance of the cdc42/IRSp53 pathway in postsynaptic sites is however, unclear. Here we identify PSD-95 as a second synaptic interaction partner of IRSp53. Interaction is mediated by a C-terminal PDZ binding motif in IRSp53 and the second PDZ domain of PSD-95. In HEK cells, overexpressed IRSp53 induces filopodia and targets PSD-95 into these processes. Immunoprecipitation and immunocytochemistry experiments demonstrate that the interaction occurs at postsynaptic sites in the brain. By virtue of its PDZ-binding and SH3 domains, IRSp53 is capable of inducing the formation of a triple complex (shank1/IRSp53/PSD-95).

The four members of the family of synapse-associated protein 90/postsynaptic density-95-associated proteins (SAPAP1–4) are adapter proteins of postsynaptic density (PSD). They interact with different synaptic scaffolding proteins, cytoskeletal components, and signalling components, and are therefore considered to assemble functional multiprotein units at synapses. Here, we analyzed the spatiotemporal expression of SAPAP1–SAPAP4 genes in postnatal rat brain by in situ hybridization. All four genes are expressed in many brain areas, leading to overlapping yet distinct mRNA distribution patterns. Moreover, two mRNAs encoding distinct SAPAP3 isoforms exhibit basically identical postnatal expression patterns. In the hippocampus, SAPAP1, SAPAP2, and SAPAP4 transcripts are restricted to cell body zones, whereas SAPAP3 mRNAs are also detected in molecular layers. Thus, SAPAP3 is one of the few PSD components whose local synthesis in dendrites may contribute to an input-specific adaptation of dendritic spine function.

Shank proteins are scaffolding proteins in the postsynaptic density of excitatory synapses in the mammalian brain. In situ hybridization revealed that Shank1/SSTRIP and Shank2/ProSAP1 mRNAs are widely expressed early in postnatal brain development whereas Shank3/ProSAP2 expression increases during postnatal development especially in the cerebellum and thalamus. Shank1 and Shank3 (but not Shank2) mRNAs are present in the molecular layers of the hippocampus, consistent with a dendritic transcript localization. Shank1 and Shank2 transcripts are detectable in the dendritic fields of Purkinje cells, whereas Shank3 mRNA is restricted to cerebellar granule cells. The appearance of dendritic Shank mRNAs in cerebellar Purkinje cells coincides with the onset of dendrite formation. Expression of reporter transcripts in hippocampal neurons identifies a 200-nucleotide dendritic targeting element (DTE) in the Shank1 mRNA. The widespread presence of Shank mRNAs in dendrites suggests a role for local synthesis of Shanks in response to stimuli that induce alterations in synaptic morphology.

In neurones, the somatodendritic microtubule-associated protein 2 regulates the stability of the dendritic cytoskeleton. Its extrasomatic localization appears to be a multicausal mechanism that involves dendritic mRNA trafficking, a process that depends on a dendritic targeting element in the 3′ untranslated region. Two rat MAP2-RNA trans-acting proteins, MARTA1 and MARTA2, exhibit specific high-affinity binding to the dendritic targeting element. We have now affinity-purified MARTA1 from rat brain. Analysis of proteolytic peptides revealed that rat MARTA1 is the orthologue of the human RNA-binding protein KSRP. Rat MARTA1 is a 74-kDa protein that contains four putative RNA-binding domains and is 98% identical to human KSRP. Both purified rat MARTA1 and human KSRP preferentially bind to the dendritic targeting element, but do not strongly interact with other investigated regions of mRNAs encoding microtubule-associated protein 2 and α-tubulin. In rat brain neurones and cultured neurones derived from superior cervical ganglia, MARTA1 is primarily intranuclear, but is also present in the somatodendritic cytoplasm. Thus, MARTA1 may play a role in nucleocytoplasmic mRNA targeting.

MAP2, a dendritically localized microtubule-associated protein (MAP), consists of a pair of high molecular mass (280 kDa) polypeptides, MAP2a and MAP2b, and several low molecular mass (70 kDa) proteins called MAP2c. Although MAP2b and MAP2c have been shown to arise via alternative splicing. It was not clear whether MAP2a is also created by alternative splicing or by posttranslational modification. Using epitope peptide mapping, we have demonstrated that an element specific to MAP2a is situated at its N-terminal end. A cDNA clone from an adult rat brain library was found to contain an additional 246 nucleotides situated at the 5' end of the 9-kb MAP2 mRNA. Antibodies generated against the encoded protein sequence recognize specifically MAP2a in rat brain homogenates. Moreover, although MAP2a, like MAP2b, is found in dendrites and cell bodies, its temporal appearance and cell type-specific distribution in rat brain differs from MAP2b.

In mammalian neurones, homologues of the Drosophila RNA-binding protein Staufen are part of ribonucleoprotein complexes that move bidirectionally along dendritic microtubules and appear to regulate mRNA translocation and translation. In this study, putative components of Staufen granules were identified in a yeast two-hybrid screen of a rat brain cDNA library with a rat Staufen bait. Protein phosphatase-1 was found as an interacting partner. Binding appears to be mediated by a five amino acid residue sequence motif (R-K-V-T-F) in Staufen that is conserved in a number of proteins interacting with the phosphatase. A two amino acid residue mutation within this motif (R-K-V-G-A) disrupted the interaction. A cytoplasmic interaction of both proteins was shown by coimmunoprecipitation of rat Staufen and protein phosphatase-1 from the cytoplasm of transfected cells and rat brain homogenates. In mammalian brain, the phosphatase represents the first described endogenous interaction partner of Staufen. In primary hippocampal neurones, both proteins partially colocalize in somata and neuronal processes. Staufen does not modulate the in vitro protein phosphatase activity. These findings show that protein phosphatase-1 is a native component of Staufen particles. Cellular functions of Staufen may be regulated via phosphorylation or Staufen may recruite the phosphatase into specific ribonucleoprotein complexes.