Divergence between CBCT and Optical Scans for Soft Tissue Analysis and Cephalometry in Facial Imaging: A cross-sectional study on healthy adults.

BACKGROUND: Facial soft tissue analysis is becoming increasingly emphasized in orthodontic diagnosis and treatment planning. While traditional cephalometry primarily focuses on hard tissues, recent non-invasive imaging techniques offer the potential to comprehensively evaluate three-dimensional (3D) facial soft tissues. The aim of the study was to establish the geometrical 3D and cephalometric divergence between Cone Beam Computed Tomography (CBCT) derived images and scanned soft tissues. Crucial for enhancing orthodontic diagnosis, minimizing patient exposure to ionizing radiation and providing facial cephalometric parameters. MATERIAL AND METHODS: A cross-sectional study was conducted from January 2020 to May 2023. CBCT and 3D facial scans were obtained simultaneously using a specialized imaging system. Reproducible landmark points were selected for both cephalometric and soft tissue analysis. Angular and linear measurements were recorded, and correlations between CT and facial scans were statistically assessed. RESULTS: Comparisons between 10 CBCT-derived and 10 facial scan-based soft tissue representations resulted into 1.8mm mean root median square (RMS). Angular measurements, such as ANB, right gonial angle, and left gonial angle, exhibited a 0.9° of difference with their respective soft tissue variables. In contrast, linear measurements of total anterior facial height showed a lower correlation coefficient, equal to 0.51. The correlation between soft tissues and underlying hard tissues was more pronounced for gonial angles. CONCLUSION: Facial soft tissue analysis using either 3D facial scans or CBCT-derived offers similar results for orthodontic diagnosis and treatment planning. These findings support the use of non-invasive diagnostic tools in orthodontics, although further investigations are needed to comprehensively understand the complexity of hard and soft tissue relationships.

Orthodontic patients and the information found on the web: a cross-sectional study.

BACKGROUND: In recent years, the Web has become a source of medical information for patients, even though the information available online may be incorrect or qualitatively inadequate. Younger generations, immersed in a digital environment since a very tender age, are more likely to get informed online. This study aims to understand the relevance of online information for prospective orthodontic patients and to investigate the effects of digital research on patients' decision-making process, and it also aims to investigate potential generational differences between digital natives and digital immigrants. MATERIALS AND METHODS: An anonymous questionnaire was developed to investigate patients' orthodontic-themed Web searches as well as the effects digital material had on their decision-making process. Before submitting the newly designed survey to patients, it was validated in a pilot study. Univariate analysis was applied to analyze the relationship between the demographic characteristics of respondents and their answers on the use of digital research for the decision-making process. RESULTS: 64.6% of the study population searched the Web for orthodontic information prior to their visit. Google was the most used platform regardless of patients' age. The perceived reliability of online sources varied significantly with age. Men displayed more trusting behavior towards their doctor than women. Prospective patients' satisfaction with affected patients' decision-making processes, and the perceived reliability of online sources of information had repercussions on the doctor-patient relationship. CONCLUSIONS: Orthodontists should be aware that the majority of patients use the Internet as a source for orthodontic information, and that patients who are digital immigrants are more prone to trust the information found online. Patients who perceive the information found on the Web as either useful or reliable don't easily discard it, even if it is inconsistent with the orthodontist's opinion.

Myopalladin knockout mice develop cardiac dilation and show a maladaptive response to mechanical pressure overload.

Myopalladin (MYPN) is a striated muscle-specific immunoglobulin domain-containing protein located in the sarcomeric Z-line and I-band. MYPN gene mutations are causative for dilated (DCM), hypertrophic, and restrictive cardiomyopathy. In a yeast two-hybrid screening, MYPN was found to bind to titin in the Z-line, which was confirmed by microscale thermophoresis. Cardiac analyses of MYPN knockout (MKO) mice showed the development of mild cardiac dilation and systolic dysfunction, associated with decreased myofibrillar isometric tension generation and increased resting tension at longer sarcomere lengths. MKO mice exhibited a normal hypertrophic response to transaortic constriction (TAC), but rapidly developed severe cardiac dilation and systolic dysfunction, associated with fibrosis, increased fetal gene expression, higher intercalated disc fold amplitude, decreased calsequestrin-2 protein levels, and increased desmoplakin and SORBS2 protein levels. Cardiomyocyte analyses showed delayed Ca2+ release and reuptake in unstressed MKO mice as well as reduced Ca2+ spark amplitude post-TAC, suggesting that altered Ca2+ handling may contribute to the development of DCM in MKO mice.

Obsessive-Compulsive Personality Disorder Co-occurring in Individuals with Obsessive-Compulsive Disorder: A Systematic Review and Meta-analysis.

LEARNING OBJECTIVES: After participating in this activity, learners should be better able to:• Assess the rates of co-occurring obsessive-compulsive personality disorder (OCPD) in patients with obsessive-compulsive disorder (OCD)• Identify characteristics related to OCD with co-occurring OCPD. ABSTRACT: The current literature discloses discrepant findings regarding the rates of co-occurring obsessive-compulsive personality disorder (OCPD) in patients with obsessive-compulsive disorder (OCD). In addition, it is not clear which characteristics are related specifically to OCD with co-occurring OCPD. We conducted the first systematic review and meta-analysis of the studies of the prevalence of OCPD in patients with OCD. We also investigated potential moderators of the prevalence, including OCD severity, age of onset of OCD, sex, current age, methodological quality, and publication date of the studies. Electronic databases and gray literature were searched by two independent reviewers. A PRISMA systematic review with a random-effect meta-analysis was conducted. Thirty-four studies were included. A significant mean effect size of 0.25 without publication bias indicated that OCPD was present in 25% of patients with OCD, suggesting that the two conditions are distinct clinical entities. This prevalence was higher than the rates found in the literature for any other personality disorders among OCD patients. OCPD that occurs in the context of OCD was more likely to be present in males and to be characterized by a later age of onset of OCD, older age at assessment, and less severe OCD symptoms. Clinicians should consider these findings when assessing and planning treatment of OCD with co-occurring OCPD.

Synthetic Lethality Screening Identifies FDA-Approved Drugs that Overcome ATP7B-Mediated Tolerance of Tumor Cells to Cisplatin.

Tumor resistance to chemotherapy represents an important challenge in modern oncology. Although platinum (Pt)-based drugs have demonstrated excellent therapeutic potential, their effectiveness in a wide range of tumors is limited by the development of resistance mechanisms. One of these mechanisms includes increased cisplatin sequestration/efflux by the copper-transporting ATPase, ATP7B. However, targeting ATP7B to reduce Pt tolerance in tumors could represent a serious risk because suppression of ATP7B might compromise copper homeostasis, as happens in Wilson disease. To circumvent ATP7B-mediated Pt tolerance we employed a high-throughput screen (HTS) of an FDA/EMA-approved drug library to detect safe therapeutic molecules that promote cisplatin toxicity in the IGROV-CP20 ovarian carcinoma cells, whose resistance significantly relies on ATP7B. Using a synthetic lethality approach, we identified and validated three hits (Tranilast, Telmisartan, and Amphotericin B) that reduced cisplatin resistance. All three drugs induced Pt-mediated DNA damage and inhibited either expression or trafficking of ATP7B in a tumor-specific manner. Global transcriptome analyses showed that Tranilast and Amphotericin B affect expression of genes operating in several pathways that confer tolerance to cisplatin. In the case of Tranilast, these comprised key Pt-transporting proteins, including ATOX1, whose suppression affected ability of ATP7B to traffic in response to cisplatin. In summary, our findings reveal Tranilast, Telmisartan, and Amphotericin B as effective drugs that selectively promote cisplatin toxicity in Pt-resistant ovarian cancer cells and underscore the efficiency of HTS strategy for identification of biosafe compounds, which might be rapidly repurposed to overcome resistance of tumors to Pt-based chemotherapy.

GRASP65 controls Golgi position and structure during G2/M transition by regulating the stability of microtubules.

The mammalian Golgi apparatus is organized in the form of a ribbon-like structure positioned near the centrosome. Despite its multimodular organization, the Golgi complex is characterized by a prominent structural plasticity, which is crucial during essential physiological processes, such as the G2 phase of the cell cycle, during which the Golgi ribbon must be "unlinked" into isolated stacks to allow progression into mitosis. Here we show that the Golgi-associated protein GRASP65, which is well known for its role in Golgi stacking and ribbon formation, is also required for the organization of the microtubule cytoskeleton. GRASP65 is not involved in microtubule nucleation or anchoring. Instead, it is required for the stabilization of newly nucleated microtubules, leading to their acetylation and clustering of Golgi stacks. Ribbon formation and microtubule stabilization are both regulated by JNK/ERK-mediated phosphorylation of S274 of GRASP65, suggesting that this protein can coordinate the Golgi structure with microtubule organization. In agreement with an important role, tubulin acetylation is strongly reduced during the G2 phase of the cell cycle, allowing the separation of the Golgi stacks. Thus, our data reveal a fundamental role of GRASP65 in the integration of different stimuli to modulate Golgi structure and microtubule organization during cell division.

Activation of Autophagy, Observed in Liver Tissues From Patients With Wilson Disease and From ATP7B-Deficient Animals, Protects Hepatocytes From Copper-Induced Apoptosis.

BACKGROUND & AIMS: Wilson disease (WD) is an inherited disorder of copper metabolism that leads to copper accumulation and toxicity in the liver and brain. It is caused by mutations in the adenosine triphosphatase copper transporting ß gene (ATP7B), which encodes a protein that transports copper from hepatocytes into the bile. We studied ATP7B-deficient cells and animals to identify strategies to decrease copper toxicity in patients with WD. METHODS: We used RNA-seq to compare gene expression patterns between wild-type and ATP7B-knockout HepG2 cells exposed to copper. We collected blood and liver tissues from Atp7b-/- and Atp7b+/- (control) rats (LPP) and mice; some mice were given 5 daily injections of an autophagy inhibitor (spautin-1) or vehicle. We obtained liver biopsies from 2 patients with WD in Italy and liver tissues from patients without WD (control). Liver tissues were analyzed by immunohistochemistry, immunofluorescence, cell viability, apoptosis assays, and electron and confocal microscopy. Proteins were knocked down in cell lines using small interfering RNAs. Levels of copper were measured in cell lysates, blood samples, liver homogenates, and subcellular fractions by spectroscopy. RESULTS: After exposure to copper, ATP7B-knockout cells had significant increases in the expression of 103 genes that regulate autophagy (including MAP1LC3A, known as LC3) compared with wild-type cells. Electron and confocal microscopy visualized more autophagic structures in the cytoplasm of ATP7B-knockout cells than wild-type cells after copper exposure. Hepatocytes in liver tissues from patients with WD and from Atp7b-/- mice and rats (but not controls) had multiple autophagosomes. In ATP7B-knockout cells, mammalian target of rapamycin (mTOR) had decreased activity and was dissociated from lysosomes; this resulted in translocation of the mTOR substrate transcription factor EB to the nucleus and activation of autophagy-related genes. In wild-type HepG2 cells (but not ATP7B-knockout cells), exposure to copper and amino acids induced recruitment of mTOR to lysosomes. Pharmacologic inhibitors of autophagy or knockdown of autophagy proteins ATG7 and ATG13 induced and accelerated the death of ATP7B-knockout HepG2 cells compared with wild-type cells. Autophagy protected ATP7B-knockout cells from copper-induced death. CONCLUSION: ATP7B-deficient hepatocytes, such as in those in patients with WD, activate autophagy in response to copper overload to prevent copper-induced apoptosis. Agents designed to activate this autophagic pathway might decrease copper toxicity in patients with WD.

D-Aspartate treatment attenuates myelin damage and stimulates myelin repair.

Glutamate signaling may orchestrate oligodendrocyte precursor cell (OPC) development and myelin regeneration through the activation of glutamate receptors at OPC-neuron synapses. D-Aspartate is a D-amino acid exerting modulatory actions at glutamatergic synapses. Chronic administration of D-Aspartate has been proposed as therapeutic treatment in diseases related to myelin dysfunction and NMDA receptors hypofunction, including schizophrenia and cognitive deficits. Here, we show, by using an in vivo remyelination model, that administration of D-Aspartate during remyelination improved motor coordination, accelerated myelin recovery, and significantly increased the number of small-diameter myelinated axons. Chronically administered during demyelination, D-Aspartate also attenuated myelin loss and inflammation. Interestingly, D-Aspartate exposure stimulated OPC maturation and accelerated developmental myelination in organotypic cerebellar slices. D-Aspartate promoting effects on OPC maturation involved the activation of glutamate transporters, AMPA and NMDA receptors, and the Na+/Ca2+ exchanger NCX3. While blocking NMDA or NCX3 significantly prevented D-Aspartate-induced [Ca2+]i oscillations, blocking AMPA and glutamate transporters prevented both the initial and oscillatory [Ca2+]i response as well as D-Aspartate-induced inward currents in OPC Our findings reveal that D-Aspartate treatment may represent a novel strategy for promoting myelin recovery.

Cadmium effects on the retina of adult Danio rerio.

The aim of this work is to describe the effects of cadmium pollution on the vision of adult zebrafish, Danio rerio. Retinal morpho-cytological alterations were investigated by light and electron microscopy, while the functionality of cadmium-exposed retinae was assessed by re-illumination behavioral tests with white or colored light. Our results demonstrate that cadmium toxicity causes significant degeneration and loss of organization at both macro and microscopic levels. These alterations impair functional responses particularly through an increase in light sensitivity. Metallothioneins were not seen to be up-regulated, while the recovery of visual acuity is due to a regenerative process by Müller cells.