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.

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.

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.

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.

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.

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.

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.

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.

Variants of the Anterior Subtemporal Approach to the Gasserian Ganglion and Related Structures: An Anatomical Study With Relevant Implications for Keyhole Surgery.

BACKGROUND: The advantages and limitations of different craniotomy positions and approach trajectories to the gasserian ganglion (GG) and related structures using an anterior subtemporal approach have not been studied systematically. Knowledge of these features is of importance when planning keyhole anterior subtemporal (kAST) approaches to the GG to optimize access and minimize risks. METHODS: Eight formalin-fixed heads were used bilaterally to assess temporal lobe retraction (TLR), trigeminal exposure, and relevant anatomical aspects of extra- and transdural classic anterior subtemporal (CLAST) approaches compared with slightly dorsally and ventrally allocated corridors. RESULTS: TLR to the GG and foramen ovale was found to be lower via the CLAST approach (P < 0.001). Using the ventral variant, TLR to access the foramen rotundum was minimized (P < 0.001). The overall TLR was maximal using the dorsal variant (P < 0.001) owing to interposition of the arcuate eminence. An extradural CLAST approach required wide exposure of the greater petrosal nerve (GPN) and middle meningeal artery (MMA) sacrifice. Both maneuvers were spared using a transdural approach. Using CLAST, medial dissection >39 mm can enter the Parkinson triangle, jeopardizing the intracavernous internal carotid artery. The ventral variant enabled access to the anterior portion of the GG and foramen ovale without the need for MMA sacrifice or GPN dissection. CONCLUSIONS: The CLAST approach provides high versatility to approach the trigeminal plexus, minimizing TLR. However, an extradural approach jeopardizes the GPN and requires MMA sacrifice. The risk of cavernous sinus violation exists when progressing medially beyond 4 cm. The ventral variant has some advantages to access the ventral structures and avoid MMA and GPN manipulation. In contrast, the usefulness of the dorsal variant is rather limited owing to the greater TLR required.

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.

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.

The chemicals between us-First results of the cluster analyses on anatomy embalming procedures in the German-speaking countries.

Hands-on courses utilizing preserved human tissues for educational training offer an important pathway to acquire basic anatomical knowledge. Owing to the reevaluation of formaldehyde limits by the European Commission, a joint approach was chosen by the German-speaking anatomies in Europe (Germany, Austria, Switzerland) to find commonalities among embalming protocols and infrastructure. A survey comprising 537 items was circulated to all anatomies in German-speaking Europe. Clusters were established for "ethanol"-, formaldehyde-based ("FA"), and "other" embalming procedures, depending on the chemicals considered the most relevant for each protocol. The logistical framework, volumes of chemicals, and infrastructure were found to be highly diverse between the groups and protocols. Formaldehyde quantities deployed per annum were three-fold higher in the "FA" (223 L/a) compared to the "ethanol" (71.0 L/a) group, but not for "other" (97.8 L/a), though the volumes injected per body were similar. "FA" was strongly related to table-borne air ventilation and total fixative volumes ≤1000 L. "Ethanol" was strongly related to total fixative volumes >1000 L, ceiling- and floor-borne air ventilation, and explosion-proof facilities. Air ventilation was found to be installed symmetrically in the mortuary and dissection facilities. Certain predictors exist for the interplay between the embalming used in a given infrastructure and technical measures. The here-established cluster analysis may serve as decision supportive tool when considering altering embalming protocols or establishing joint protocols between institutions, following a best practice approach to cater toward best-suited tissue characteristics for educational purposes, while simultaneously addressing future demands on exposure limits.

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.

A morphometric analysis of the circumolivary fiber bundle of the human brainstem.

The circumolivary fiber bundle (CFB) is considered to be an anatomical variation, which can be found on the surface of the human medulla oblongata. The macroscopical fiber bundle runs downwards from either the anterior median fissure, the pyramid, or both, around the inferior pole of the olive and turns upwards to reach the restiform body of the inferior cerebellar peduncle. Multiple fiber systems feed the constitution of the CFB (collateral corticospinal fibers, fibers connecting to the reticular formation, anterior external arcuate fibers). With this examination we provide a systematic analysis of the frequency of occurrence (6.14%), size, and laterality of the CFB. Including all three fiber bundle parts (descending part, genu, and ascending part), the left-sided sizes were increased. Likewise, the appearance of an unilateral left-sided CFB could be detected in more than 60% of our cases. Our morphometrical analysis currently covers the largest sample of investigated brainstem sides (n = 489) so far. This investigation should widen the perspective on how anatomists, neuroradiologists, and neurosurgeons expect the anterolateral surface of the human medulla oblongata.

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.

Photon-Counting Detector CT Virtual Monoengergetic Images for Cochlear Implant Visualization-A Head to Head Comparison to Energy-Integrating Detector CT.

Cochlear implants (CIs) are the primary treatment method in patients with profound sensorineural hearing loss. Interpretation of postoperative imaging with conventional energy-integrating detector computed tomography (EID-CT) following CI surgery remains challenging due to metal artifacts. Still, the photon-counting detector (PCD-CT) is a new emerging technology with the potential to eliminate these problems. This study evaluated the performance of virtual monoenergetic (VME) EID-CT images versus PCD-CT in CI imaging. In this cadaveric study, two temporal bone specimens with implanted CIs were scanned with EID-CT and PCD-CT. The images were assessed according to the visibility of interelectrode wire, size of electrode contact, and diameter of halo artifacts. The visibility of interelectrode wire sections was significantly higher when reviewing PCD-CT images. The difference in diameter measurements for electrode contacts between the two CT scanner modalities showed that the PCD-CT technology generally led to significantly larger diameter readings. The larger measurements were closer to the manufacturer's specifications for the CI electrode. The size of halo artifacts surrounding the electrode contacts did not differ significantly between the two imaging modalities. PCT-CT imaging is a promising technology for CI imaging with improved spatial resolution and better visibility of small structures than conventional EID-CT.

TMBIM5 loss of function alters mitochondrial matrix ion homeostasis and causes a skeletal myopathy.

Ion fluxes across the inner mitochondrial membrane control mitochondrial volume, energy production, and apoptosis. TMBIM5, a highly conserved protein with homology to putative pH-dependent ion channels, is involved in the maintenance of mitochondrial cristae architecture, ATP production, and apoptosis. Here, we demonstrate that overexpressed TMBIM5 can mediate mitochondrial calcium uptake. Under steady-state conditions, loss of TMBIM5 results in increased potassium and reduced proton levels in the mitochondrial matrix caused by attenuated exchange of these ions. To identify the in vivo consequences of TMBIM5 dysfunction, we generated mice carrying a mutation in the channel pore. These mutant mice display increased embryonic or perinatal lethality and a skeletal myopathy which strongly correlates with tissue-specific disruption of cristae architecture, early opening of the mitochondrial permeability transition pore, reduced calcium uptake capability, and mitochondrial swelling. Our results demonstrate that TMBIM5 is an essential and important part of the mitochondrial ion transport system machinery with particular importance for embryonic development and muscle function.

Role of Pre-Operative Brain Imaging in Patients with NSCLC Stage I: A Retrospective, Multicenter Analysis.

Background: Lung cancer is the worldwide leading oncological cause of death in both genders combined and accounts for around 40-50% of brain metastases in general. In early-stage lung cancer, the incidence of brain metastases is around 3%. Since the early detection of asymptomatic cerebral metastases is of prognostic value, the aim of this study was to analyze the incidence of brain metastases in early-stage lung cancer and identify possible risk factors. Methods: We conducted a retrospective multicentric analysis of patients with Stage I (based on T and N stage only) Non-Small Cell Lung Cancer (NSCLC) who had received preoperative cerebral imaging in the form of contrast-enhanced CT or MRI. Patients with a history of NSCLC, synchronous malignancy, or neurological symptoms were excluded from the study. Analyzed variables were gender, age, tumor histology, cerebral imaging findings, smoking history, and tumor size. Results were expressed as mean with standard deviation or median with range. Results: In total, 577 patients were included in our study. Eight (1.4%) patients were found to have brain metastases in preoperative brain imaging. Tumor histology was adenocarcinoma in all eight cases. Patients were treated with radiotherapy (five), surgical resection (two), or both (one) prior to thoracic surgical treatment. Other than tumor histology, no statistically significant characteristics were found to be predictive of brain metastases. Conclusion: Given the low incidence of brain metastases in patients with clinical Stage I NSCLC, brain imaging in this cohort could be avoided.