Profiling learning strategies of medical students: A person-centered approach.

BACKGROUND: Students within a cohort might employ unique subsets of learning strategies (LS) to study. However, little research has aimed to elucidate subgroup-specific LS usage among medical students. Recent methodological developments, particularly person-centred approaches such as latent profile analysis (LPA), offer ways to identify relevant subgroups with dissimilar patterns of LS use. In this paper, we apply LPA to explore subgroups of medical students during preclinical training in anatomy and examine how these patterns are linked with learning outcomes. METHODS: We analysed the LS used by 689 undergraduate, 1st and 2nd-year medical students across 6 German universities who completed the short version of the Learning Strategies of University Students (LIST-K) questionnaire, and answered questions towards external criteria such as learning resources and performance. We used the thirteen different LS facets of the LIST-K (four cognitive, three metacognitive, three management of internal and three management of external resources) as LPA indicators. RESULTS: Based on LPA, students can be grouped into four distinct learning profiles: Active learners (45% of the cohort), collaborative learners (17%), structured learners (29%) and passive learners (9%). Students in each of those latent profiles combine the 13 LS facets in a unique way to study anatomy. The profiles differ in both, the overall level of LS usage, and unique combinations of LS used for learning. Importantly, we find that the facets of LS show heterogeneous and subgroup-specific correlations with relevant outcome criteria, which partly overlap but mostly diverge from effects observed on the population level. CONCLUSIONS: The effects observed by LPA expand results from variable-centered efforts and challenge the notion that LS operate on a linear continuum. These results highlight the heterogeneity between subgroups of learners and help generate a more nuanced interpretation of learning behaviour. Lastly, our analysis offers practical implications for educators seeking to tailor learning experiences to meet individual student needs.

The K63 deubiquitinase CYLD modulates autism-like behaviors and hippocampal plasticity by regulating autophagy and mTOR signaling.

Nondegradative ubiquitin chains attached to specific targets via Lysine 63 (K63) residues have emerged to play a fundamental role in synaptic function. The K63-specific deubiquitinase CYLD has been widely studied in immune cells and lately also in neurons. To better understand if CYLD plays a role in brain and synapse homeostasis, we analyzed the behavioral profile of CYLD-deficient mice. We found that the loss of CYLD results in major autism-like phenotypes including impaired social communication, increased repetitive behavior, and cognitive dysfunction. Furthermore, the absence of CYLD leads to a reduction in hippocampal network excitability, long-term potentiation, and pyramidal neuron spine numbers. By providing evidence that CYLD can modulate mechanistic target of rapamycin (mTOR) signaling and autophagy at the synapse, we propose that synaptic K63-linked ubiquitination processes could be fundamental in understanding the pathomechanisms underlying autism spectrum disorder.

Micro-computed tomographic analysis of the morphology of maxillary lateral incisors.

OBJECTIVE: This study aimed to investigate the morphology of maxillary lateral incisors (MxLI) using micro-computed tomography (micro-CT). MATERIALS AND METHODS: The root canal configurations (RCC) of maxillary lateral incisors (MxLI) of a mixed Swiss-German population were examined using micro-CT, 3D imaging, and a 4-digit system code indicating the main root canal from coronal to apical thirds and the main foramina number. RESULTS: The most frequently observed RCC of MxLI were 1-1-1/1 (Vertucci I/Ve I, 80.0%), 1-1-2/2 (Ve V, 7.3%), 1-2-1/1 (Ve III, 6.4%), 2-1-1/1 (Ve II, 1.8%), and 1-1-1/2 (1.8%)(n = 110). Three additional RCC were observed less frequently (0.9%). The MxLI showed one physiological foramen in 89.1%, two in 9.1%, and seldom three (1.8%). Most accessory canals were identified in the apical third of a root (20.0%), and no accessory canals in 72.7% of the samples. CONCLUSIONS: Detailed information on the internal morphology of MxLI of a Swiss-German population is given. The most frequently observed RCC of MxLI is 1-1-1/1 (Ve I). However, accessory canals may occur in all apical thirds, and 20% of all teeth investigated showed a challenging RCC for clinical treatment. CLINICAL RELEVANCE: This study offers clinicians comprehensive data on MxLI morphology, emphasizing the significance of understanding varied RCC and accessory canal presence for improving root canal treatment outcomes. Over 25% of teeth exhibited complex RCC or accessory canals, influencing decisions during root canal treatment.

Effect of the antirheumatic medication methotrexate (MTX) on biomechanical compressed human periodontal ligament fibroblasts (hPDLFs).

BACKGROUND: The aim of this study was to investigate the in vitro effect of the antirheumatic drug methotrexate (MTX) on biomechanically compressed human periodontal ligament fibroblasts (hPDLFs), focusing on the expression of interleukin 6 (IL-6), as its upregulation is relevant to orthodontic tooth movement. METHODS: Human PDLFs were subjected to pressure and simultaneously treated with MTX. Cell proliferation, viability and morphology were studied, as was the gene and protein expression of IL-6. RESULTS: Compared with that in untreated fibroblasts, IL-6 mRNA expression in mechanically compressed ligament fibroblasts was increased (two to sixfold; ****p < 0.0001). Under compression, hPDLFs exhibited a significantly more expanded shape with an increase of cell extensions. MTX with and without pressure did not affect IL-6 mRNA expression or the morphology of hPDLFs. CONCLUSION: MTX has no effect on IL-6 expression in compressed ligament fibroblasts.

A comparative study of cyanoacrylate-based tissue adhesive and surgical sutures on marginal flap stability following coronally advanced flap.

INTRODUCTION: The present study evaluated the biomechanical characteristics of cyanoacrylate-based tissue adhesive (TA) compared to surgical sutures in coronally advanced flap (CAF) procedures using an ex-vivo model. MATERIAL AND METHODS: Thirty-six half-pig mandibles were divided into three groups, n=12 each: (I) CAF fixed with sutures (sling and tag suture technique), (II) CAF fixed with TA, and (III) CAF fixed with sutures and TA. At mandibular premolars, gingival recession defects extending 3 mm apical to the cemento-enamel junction (CEJ) were created. CAF procedures were performed using a split-full-split approach, with coronal advancement of the flap to 1 mm above the marked CEJ and stabilization according to the respective groups I-III. Marginal flap stability against pull-of forces (maximum tensile force) was measured with a universal material testing machine until the CEJ became visible. RESULTS: The comparison between groups I-III demonstrated a significantly increased maximum tensile force for the TA (II) compared to the suture group (I) (p<0.001). A significantly increased maximum tensile force was found for the suture and TA (III) compared to the suture group (I) (p<0.001). There was also a significantly increased maximum tensile force in the suture and TA (III) compared to the TA group (II) (p<0.001). CONCLUSION: The results suggest that cyanoacrylate-based TA can increase marginal flap stability compared to sutures in CAF procedures. CLINICAL RELEVANCE: Cyanoacrylate-based TA can be considered a useful and valuable adjunct to conventional suturing techniques in periodontal plastic surgery, especially in cases where high flap stability is required. The results of this ex-vivo study can only be transferred to the clinical situation with limitations. Clinical long-term follow-up data must be generated.

The working angle in low-abrasive air polishing has an influence on gingival damage-an ex vivo porcine model.

OBJECTIVES: To investigate the influence of instrumentation angle during low-abrasive air polishing (LAA) on the oral gingiva using an ex vivo porcine model. MATERIAL AND METHODS: Six tissue samples from each of 14 porcine mandibles were randomly selected and instrumented. Two different LAA powders (glycine 25 µm, tagatose 15 µm) were investigated. An application angle of either 30-60° or 90° was selected. Gingival specimens from different mandibles served as untreated references. Gingival biopsies were examined by scanning electron microscopy and paraffin histology for tissue destruction using a five-level scale. RESULTS: LAA caused significantly less tissue damage at a 90° angle than at a 30-60° angle. This effect was seen in both the glycine-based powder arms (p = 0.002, p = 0.046) and the tagatose-based powder arms (p = 0.003, p = 0.011). However, at identical working angles, the two powders did not show significant differences in terms of gingival erosion (p = 0.79 and p = 0.57; p = 0.91 and p = 0.78, respectively). CONCLUSIONS: LAA may cause less tissue damage at an application angle of 90°. Consequently, it seems advisable to air-polish the soft tissue as perpendicularly as possible. Additionally, glycine and tagatose LAA powders do not seem to differ in concern of soft tissue damage. CLINICAL RELEVANCE: Within the limitations of this ex vivo animal model, this study argues for an application that is as close as possible to the 90° angle intending to minimize soft tissue damage. Manufacturer specifications, however, mainly request applications deviating from the right angle. In order to work in interdental areas using LAA safely, the use of subgingival nozzles might be considered.

Effectiveness and Safety of Over-the-Counter Tooth-Whitening Agents Compared to Hydrogen Peroxide In Vitro.

(1) This study investigated the whitening effect, cytotoxicity and enamel surface alterations induced by different over-the-counter (OTC) bleaching agents in comparison to hydrogen peroxide. (2) Human teeth (n = 60) were randomly assigned into 6 groups (n = 10), stained with coffee solution for 7 d, followed by a whitening period of 7 d with either placebo, bromelain, sodium bicarbonate, sodium chlorite, PAP or hydrogen peroxide. Color measurements were performed with a spectrophotometer. Scanning electron micrographs (SEM) were taken to assess the enamel structure. Cytotoxicity of the tested substances was assessed based on the cell viability of primary human fibroblasts. (3) The application of all whitening gels resulted in a greater color difference of the enamel (ΔE) in comparison to the negative control. Hydrogen peroxide caused the greatest color difference. Bromelain and PAP treatment showed no enamel surface changes, in contrast to hydrogen peroxide treatment, which showed very mild interprismatic dissolution. Bromelain was the only non-cytotoxic agent. (4) The maximum effect achieved by all OTC bleaching agents was the removal of stains, whereas hydrogen peroxide was capable of further whitening the teeth. Bromelain treatment was neither cytotoxic, nor resulted in enamel surface alterations, and its whitening effect was less, yet still effective, compared to hydrogen peroxide.

Functional characterization of a novel TP53RK mutation identified in a family with Galloway-Mowat syndrome.

Galloway-Mowat syndrome (GAMOS) is a very rare condition characterized by early-onset nephrotic syndrome and microcephaly with variable neurologic features. While considerable genetic heterogeneity of GAMOS has been identified, the majority of cases are caused by pathogenic variants in genes encoding the four components of the Kinase, endopeptidase, and other proteins of small size (KEOPS) complex, one of which is TP53RK. Here we describe a 3-year-old male with progressive microcephaly, neurodevelopmental deficits, and glomerular proteinuria. He was found to carry a novel homozygous TP53RK missense variant, c.163C>G (p.Arg55Gly), which was considered as potentially disease-causing. We generated a morpholino tp53rk knockdown model in Xenopus laevis showing that the depletion of endogenous Tp53rk caused abnormal eye and head development. This phenotype could be rescued by the expression of human wildtype TP53RK but not by the c.163C>G mutant nor by another previously described GAMOS-associated mutant c.125G>A (p.Gly42Asp). These findings support the pathogenic role of the novel TP53RK variant.

Regulatory T Cells Contribute to Sexual Dimorphism in Neonatal Hypoxic-Ischemic Brain Injury.

BACKGROUND AND PURPOSE: Neonatal encephalopathy caused by hypoxia-ischemia (HI) is a major cause of death and disability in newborns. Clinical and experimental studies suggest a sexual dimorphism in HI-induced brain injury and therapy responses. A major hallmark of HI pathophysiology is the infiltration of peripheral immune cells into the injured brain. However, the specific role of regulatory T cells (Tregs) in neonatal HI is still unknown. METHODS: Nine-day-old mice were exposed to HI by ligation of the right common carotid artery followed by 1 hour hypoxia (10% oxygen). Using immunohistochemistry, flow cytometry, and microarray analyses, Tregs were investigated in the brain, spleen, and blood 24 hours post HI. The functional role of Tregs was evaluated by acute Treg depletion in depletion of regulatory T cells transgenic mice. Brain injury, neuroinflammatory responses, and vascular injury were analyzed via immunohistochemistry and Western blot 48 hours and 7 days after HI. Functional outcome was assessed 3 days and 5 weeks after HI. RESULTS: Female mice revealed an increased cerebral Treg infiltration, coinciding with elevated chemokine receptor expression. Treg depletion in females aggravated HI-induced brain tissue injury, short-term motor deficits, and long-term deficits in exploratory activity, paralleled by an increased microglia and endothelial activation and leukocyte infiltration. Treg depletion in male mice reduced HI-induced brain injury, short-term motor, and long-term cognitive deficits, associated with reduced vascular injury. Ex vivo isolated female Tregs displayed an increased immunosuppressive activity on effector T cell proliferation and an increased gene enrichment in pathways related to enhanced Treg activity. CONCLUSIONS: Tregs from neonatal female mice provide endogenous neuroprotection, whereas Tregs from male mice increase secondary neurodegeneration. As potential mechanisms, we identified intrinsic transcriptional differences associated with enhanced anti-inflammatory activity of female Tregs. Our study emphasizes the urgent need for sex-stratified clinical and preclinical analyses.

Mutations in PRDM15 Are a Novel Cause of Galloway-Mowat Syndrome.

BACKGROUND: Galloway-Mowat syndrome (GAMOS) is characterized by neurodevelopmental defects and a progressive nephropathy, which typically manifests as steroid-resistant nephrotic syndrome. The prognosis of GAMOS is poor, and the majority of children progress to renal failure. The discovery of monogenic causes of GAMOS has uncovered molecular pathways involved in the pathogenesis of disease. METHODS: Homozygosity mapping, whole-exome sequencing, and linkage analysis were used to identify mutations in four families with a GAMOS-like phenotype, and high-throughput PCR technology was applied to 91 individuals with GAMOS and 816 individuals with isolated nephrotic syndrome. In vitro and in vivo studies determined the functional significance of the mutations identified. RESULTS: Three biallelic variants of the transcriptional regulator PRDM15 were detected in six families with proteinuric kidney disease. Four families with a variant in the protein's zinc-finger (ZNF) domain have additional GAMOS-like features, including brain anomalies, cardiac defects, and skeletal defects. All variants destabilize the PRDM15 protein, and the ZNF variant additionally interferes with transcriptional activation. Morpholino oligonucleotide-mediated knockdown of Prdm15 in Xenopus embryos disrupted pronephric development. Human wild-type PRDM15 RNA rescued the disruption, but the three PRDM15 variants did not. Finally, CRISPR-mediated knockout of PRDM15 in human podocytes led to dysregulation of several renal developmental genes. CONCLUSIONS: Variants in PRDM15 can cause either isolated nephrotic syndrome or a GAMOS-type syndrome on an allelic basis. PRDM15 regulates multiple developmental kidney genes, and is likely to play an essential role in renal development in humans.

Biomechanical evaluation of cyanoacrylate-based tissue adhesive for intraoral wound closure.

OBJECTIVES: The aim of this study was to analyze the biomechanical characteristics of a novel cyanoacrylate-based tissue adhesive (CTA) for soft-tissue closure of the (non-) tooth-bearing alveolar process and around dental implants. MATERIALS AND METHODS: Halves of porcine mandibles (n = 21) were randomly divided into three experimental intraoral wound closure groups (A-C) with three different mucoperiosteal flap types (F1-3, n = 7 each): F1, crestal incision between the last incisor and the canine with a mesial and distal vestibular relief; F2, crestal double-T-shaped incision and dental implant placement between the canine and the first premolar; and F3, trapezoidal incision on the second premolar. F1-3 were respectively closed using (A) monofil non-resorbable sutures, (B) CTA, and (C) a combination of both. Tensile strength (TS) and elasticity (E) measurements were performed for biomechanical analysis. RESULTS: In F1, CTA showed a significantly reduced TS compared to A (p < 0.001) and C (p < 0.01). In F2, an increased TS of C compared to A (p < 0.01) and B (p < 0.001) was found. Here, E was significantly increased in C compared to B (p < 0.02). In F3, TS was significantly decreased in B compared to A (p < 0.01) and C (p < 0.001). The E in group C was significantly increased compared to B (p < 0.01). CONCLUSIONS: Different biomechanical characteristics between CTA and sutures were found. CTA could be a possible alternative to sutures for intraoral wound closure in special conditions. CLINICAL RELEVANCE: A combination of both, suturing and CTA, could be a promising option in critical soft-tissue wounds requiring high functional stability and elasticity.

Variant Arterial Supply of the Descending Colon by the Coeliac Trunk: A Case Report.

Background and Objectives: Knowledge of arterial variations of the intestines is of great importance in visceral surgery and interventional radiology. Materials and Methods: An unusual variation in the blood supply of the descending colon was observed in a Caucasian female body donor. Results: In this case, the left colic artery that regularly derives from the inferior mesenteric artery supplying the descending colon was instead a branch of the common hepatic artery. Conclusions: Here, we describe the very rare case of an aberrant left colic artery arising from the common hepatic artery in a dissection study.

Enhancing Sensitivity of Microflow-Based Bottom-Up Proteomics through Postcolumn Solvent Addition.

The introduction of more sensitive mass spectrometers allows researchers to adapt front-end liquid chromatography (LC) to individual needs for the analysis of complex proteomes. Where absolute sensitivity is not paramount, it is advantageous to switch from a highly sensitive nanoflow-LC setup, the de facto standard platform in mass-spectrometry (MS)-based discovery proteomics, to a more robust, high-throughput-compatible microflow or conventional-flow setup. To enhance the microflow-LC-MS electrospray process of complex proteomic samples, we tested the effects of different solvents, including 2-propanol, methanol, and acetonitrile, pure or as mixture with dimethyl sulfoxide, which were added postcolumn to the eluting sample. Postcolumn addition of organic solvents strongly enhanced the electrospray efficiency in microflow-LC-MS experiments and improved the sensitivity across the entire gradient and for early eluting peptides by up to 10-fold. Postcolumn solvent addition did not negatively affect chromatographic performance and resulted in an overall 28-36% increase in identifications at both the protein and peptide levels. The presented microflow-LC-MS workflow, including postcolumn solvent addition, can be easily adopted on any LC-MS/MS platform.

Biomechanical analysis of the human derived soft tissue graft Epiflex for use in oral soft tissue augmentation.

PURPOSE: This study aimed to investigate the biomechanical properties, cell migration, and revascularization of the acellular dermal matrix Epiflex. As a decellularized, freeze-dried human skin graft, Epiflex has broad applications in medical fields, particularly in implantology and dentistry. Understanding its biomechanical characteristics is crucial for its clinical adoption as a novel soft tissue graft option. METHODS: Epiflex (n = 3) was evaluated in comparison to palatal tissue from body donors (n = 3). Key metrics, such as elongation and tear resistance, were quantified. Both graft types underwent histological analysis and scanning electron microscopy. Additionally, the healing properties of Epiflex were assessed using a Chorioallantoic Membrane (CAM) Assay. RESULTS: Biomechanically, Epiflex (mean = 116.01 N) demonstrated the ability to withstand greater forces (p = 0.013) than human palatal tissue (mean = 12.58 N). When comparing the elongation, no significant difference was measured (ASG mean = 9.93 mm, EF mean = 9.7 mm). Histologically, Epiflex exhibited a loosely connected network of collagen fibers with a dense upper layer. The CAM Assay indicated efficient revascularization. CONCLUSION: Epiflex appears to be a viable option for soft tissue augmentation, particularly appealing to patient groups who avoid all or specific animal-derived products due to ethical or religious reasons.

The classical supraorbital minicraniotomy to approach the areas of origin of anterior skull base meningiomas: Anatomical nuances influencing accessibility, operability, and frontal lobe retraction.

Background: The classical supraorbital minicraniotomy (cSOM) constitutes a minimally invasive alternative for the resection of anterior skull base meningiomas (ASBM). Surgical success depends strongly on optimal patient selection and surgery planning, for which a careful assessment of tumor characteristics, approach trajectory, and bony anterior skull base anatomy is required. Still, morphometrical studies searching for relevant anatomical factors with surgical relevance when intending a cSOM for ASBM resection are lacking. Methods: Bilateral cSOM was done in five formaldehyde-fixed heads toward the areas of origin of ASBM. Morphometrical data with potential relevant surgical implications were analyzed. Results: The more tangential position of the cSOM with respect to the olfactory groove (OG) led to a reduction in surgical freedom (SF) in this area compared to others (P < 0.0001). Frontal lobe retraction (FLR) was also higher when approaching the OG (P < 0.05). Olfactory nerve mobilization was higher when accessing the planum sphenoidale (PS), tuberculum sellae (TS), and anterior clinoid process (ACP) (P < 0.0001). OG depth and the slope of the sphenoid bone between the PS and TS predicted lower SF and higher frontal retraction requirements along the OG and TS, respectively (P < 0.05). In contrast, longer distances to the ACP tip predicted lower SF over this structure (P < 0.01). Conclusion: Although clinical validation is still needed, the present anatomical data suggest that assessing minicraniotomy's position/extension, OG depth, the sphenoid's slope, and distance to ACP-tip might be of particular relevance to predict FLR, maneuverability, and accessibility when considering the cSOM for ASBM resection, thus helping surgeons optimize patient selection and surgical strategy.

Prdm15 acts upstream of Wnt4 signaling in anterior neural development of Xenopus laevis.

Mutations in PRDM15 lead to a syndromic form of holoprosencephaly (HPE) known as the Galloway-Mowat syndrome (GAMOS). While a connection between PRDM15, a zinc finger transcription factor, and WNT/PCP signaling has been established, there is a critical need to delve deeper into their contributions to early development and GAMOS pathogenesis. We used the South African clawed frog Xenopus laevis as the vertebrate model organism and observed that prdm15 was enriched in the tissues and organs affected in GAMOS. Furthermore, we generated a morpholino oligonucleotide-mediated prdm15 knockdown model showing that the depletion of Prdm15 leads to abnormal eye, head, and brain development, effectively recapitulating the anterior neural features in GAMOS. An analysis of the underlying molecular basis revealed a reduced expression of key genes associated with eye, head, and brain development. Notably, this reduction could be rescued by the introduction of wnt4 RNA, particularly during the induction of the respective tissues. Mechanistically, our data demonstrate that Prdm15 acts upstream of both canonical and non-canonical Wnt4 signaling during anterior neural development. Our findings describe severe ocular and anterior neural abnormalities upon Prdm15 depletion and elucidate the role of Prdm15 in canonical and non-canonical Wnt4 signaling.

Fixation and staining methods for macroscopical investigation of the brain.

The proper preservation of human brain tissue is an indispensable requirement for post-mortem investigations. Neuroanatomical teaching, neuropathological examination, neurosurgical training, basic and clinical neuroscientific research are some of the possible downstream applications of brain specimens and, although much apart from one another, proper tissue fixation and preservation is a common denominator to all of them. In this review, the most relevant procedures to fixate brain tissue are described. In situ and immersion fixation approaches have been so far the most widespread ways to deliver the fixatives inside the skull. Although most of them rely on the use of formalin, alternative fixative solutions containing lower amounts of this compound mixed with other preservative agents, have been attempted. The combination of fixation and freezing paved the way for fiber dissection, particularly relevant for the neurosurgical practice and clinical neuroscience. Moreover, special techniques have been developed in neuropathology to tackle extraordinary problems, such as the examination of highly infective specimens, as in the case of the Creutzfeldt-Jakob encephalopathy, or fetal brains. Fixation is a fundamental prerequisite for further staining of brain specimens. Although several staining techniques have been developed for the microscopical investigation of the central nervous system, numerous approaches are also available for staining macroscopic brain specimens. They are mostly relevant for neuroanatomical and neuropathological teaching and can be divided in white and gray matter staining techniques. Altogether, brain fixation and staining techniques are rooted in the origins of neuroscience and continue to arouse interest in both preclinical and clinical neuroscientists also nowadays.

The orobasal organ (of Ackerknecht): A bizarre structure of the mammalian oral cavity.

Vestigial organs are considered to have lost most or all of their functions through evolution. However, these structures can give insights into the phylogenetic history of species. Additionally, vestigial organs can be of clinical importance, since these structures might be confused with pathologies. The orobasal organ of Ackerknecht was discovered by and named after the veterinary anatomist Eberhard Ackerknecht. In 1912, he described morphologically highly variable epithelial invaginations behind the lower medial incisors in different mammalian species. The orobasal organ is considered a rudimentary structure without physiological function, but the evolutionary history of the orobasal organ remains unknown, so far. In this review, we sum up the actual knowledge about the orobasal organ and discuss possible origins of this structure. With this review, we hope to increase awareness of this anatomical structure, and thereby decrease the risk of confusion with a pathological condition like oral cancer.

RDA coupled with deep sequencing detects somatic SVA-retrotranspositions and mosaicism in the human brain.

Cells of the developing human brain are affected by the progressive acquisition of genetic and epigenetic alterations that have been reported to contribute to somatic mosaicism in the adult brain and are increasingly considered a possible cause of neurogenetic disorders. A recent work uncovered that the copy-paste transposable element (TE) LINE-1 (L1) is mobilized during brain development, and thus mobile non-autonomous TEs like AluY and SINE-VNTR-Alu (SVA) families can use L1 activity in trans, leading to de novo insertions that may influence the variability of neural cells at genetic and epigenetic levels. In contrast to SNPs and when considering substitutional sequence evolution, the presence or absence of TEs at orthologous loci represents highly informative clade markers that provide insights into the lineage relationships between neural cells and how the nervous system evolves in health and disease. SVAs, as the 'youngest' class of hominoid-specific retrotransposons preferentially found in gene- and GC-rich regions, are thought to differentially co-regulate nearby genes and exhibit a high mobility in the human germline. Therefore, we determined whether this is reflected in the somatic brain and used a subtractive and kinetic enrichment technique called representational difference analysis (RDA) coupled with deep sequencing to compare different brain regions with respect to de novo SINE-VNTR-Alu insertion patterns. As a result, we detected somatic de novo SVA integrations in all human brain regions analyzed, and the majority of de novo insertions can be attributed to lineages of telencephalon and metencephalon, since most of the examined integrations are unique to different brain regions under scrutiny. The SVA positions were used as presence/absence markers, forming informative sites that allowed us to create a maximum parsimony phylogeny of brain regions. Our results largely recapitulated the generally accepted evo-devo patterns and revealed chromosome-wide rates of de novo SVA reintegration targets and preferences for specific genomic regions, e.g., GC- and TE-rich regions as well as close proximity to genes that tend to fall into neural-specific Gene Ontology pathways. We concluded that de novo SVA insertions occur in the germline and somatic brain cells at similar target regions, suggesting that similar retrotransposition modes are effective in the germline and soma.

Internal Morphology of Mandibular Second Premolars Using Micro-Computed Tomography.

To examine root canal morphology of mandibular second premolars (Mn2P) of a mixed Swiss-German population by means of micro-computed tomography (micro-CT). Root canal configuration (RCC) of 102 Mn2P were investigated using micro-CT unit (µCT 40; SCANCO Medical AG, Brüttisellen, Switzerland) with 3D software imaging (VGStudio Max 2.2; Volume Graphics GmbH, Heidelberg, Germany), described with a four-digit system code indicating the main root canal from coronal to apical thirds and the number of main foramina. A total of 12 different RCCs were detected. 1-1-1/1 (54.9%) was most frequently observed RCC, followed by 1-1-1/2 (14.7%), 1-1-2/2 (10.8%), 1-2-2/2 (4.9%), 1-1-3/3 (3.9%), 1-1-1/3 (2.9%), 2-1-1/1 (2.9%) and less frequently 1-1-2/3, 1-2-1/2, 2-1-2/2, 1-1-2/5, 1-1-1/4 with each 1.0%. No accessory foramina were present in 35.3%, one in 35.3%, two in 21.6%, three and four in 2.9%, and five in 2.0%. In 55.9% Mn2Ps, accessory root canals were present in apical third and 8.8% in middle third of a root. Connecting canals were observed less frequently (6.9%) in apical and 2.9% in the middle third, no accessory/connecting canals in coronal third. Every tenth tooth showed at least or more than three main foramina. Almost two thirds of the sample showed accessory root canals, predominantly in apical third. The mainly single-rooted sample of Mn2Ps showed less frequent morphological diversifications than Mn1Ps.