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Objectives: Using computer-aided design and manufacturing (CAD-CAM) technology in restorative dentistry increased the application of lithium disilicate (LD) materials. The bond strength to core and repairing materials is crucial in the restoration's longevity. This systematic review evaluates the shear bond strength (SBS) of CAD-CAM-LD restorative materials to other materials using different surface treatments., Methods: An electronic literature search was performed through PubMed/Medline, Embase, Web of Science, Scopus, and Google Scholar. Studies were selected based on specific criteria. The risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Quasi-Experimental Studies., Results: Eleven studies were included, primarily investigating composite resin as the repair material. SBS values ranged from 0.82 to 32.96MPa, with the highest values observed for IPS e.max-CAD subjected to silicon carbide polishing, hydrofluoric acid (HF) etching, and silane application. For core materials, the highest SBS was reported for HFtreated IPS e.max-CAD bonded to tribochemically coated titanium and air-abraded zirconia, with SBS values ranging from 5.88 to 34MPa., Conclusions: This review indicates that HF etching combined with silane application is the most effective method for improving bond strength in CAD/CAM-LD restorations. Applying surface treatments to both the core material and CAD/CAM-LD can further enhance bond strength., (Copyright© 2024 Dennis Barber Ltd.)

Breast cancer bone metastases (BMET) are incurable, primarily osteolytic, and occur most commonly in estrogen receptor-α positive (ER+) breast cancer. ER+ human breast cancer BMET modeling in mice has demonstrated an estrogen (E2)-dependent increase in tumor-associated osteolysis and bone-resorbing osteoclasts, independent of estrogenic effects on tumor proliferation or bone turnover, suggesting a possible mechanistic link between tumoral ERα-driven osteolysis and ER+ bone progression. To explore this question, inducible secretion of the osteolytic factor, parathyroid hormone-related protein (PTHrP), was utilized as an in vitro screening bioassay to query the osteolytic potential of estrogen receptor- and signaling pathway-specific ligands in BMET-forming ER+ human breast cancer cells expressing ERα, ERß, and G protein-coupled ER. After identifying genomic ERα signaling, also responsibility for estrogen's proliferative effects, as necessary and sufficient for osteolytic PTHrP secretion, in vivo effects of a genomic-only ER agonist, estetrol (E4), on osteolytic ER+ BMET progression were examined. Surprisingly, while pharmacologic effects of E4 on estrogen-dependent tissues, including bone, were evident, E4 did not support osteolytic BMET progression (vs robust E2 effects), suggesting an important role for nongenomic ER signaling in ER+ metastatic progression at this site. Because bone effects of E4 did not completely recapitulate those of E2, the relative importance of nongenomic ER signaling in tumor vs bone cannot be ascertained here. Nonetheless, these intriguing findings suggest that targeted manipulation of estrogen signaling to mitigate ER+ metastatic progression in bone may require a nuanced approach, considering genomic and nongenomic effects of ER signaling on both sides of the tumor/bone interface., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Aromatase inhibitor-induced arthralgia (AIA) presents a major problem for patients with breast cancer but is poorly understood. This prospective study explored the inflammatory metabolomic changes in the development of AIA. This single-arm, prospective clinical trial enrolled 28 postmenopausal women with early-stage (0-3) ER+ breast cancer starting adjuvant anastrozole. Patients completed the Breast Cancer Prevention Trial (BCPT) Symptom Checklist and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) at 0, 3, and 6 months. The plasma levels of four polyunsaturated fatty acids (PUFAs) and 48 oxylipins were quantified at each timepoint. The subscores for WOMAC-pain and stiffness as well as BCPT-total, hot flash, and musculoskeletal pain significantly increased from baseline to 6 months (all p < 0.05). PUFA and oxylipin levels were stable over time. The baseline levels of 8-HETE were positively associated with worsening BCPT-total, BCPT-hot flash, BCPT-musculoskeletal pain, WOMAC-pain, and WOMAC- stiffness at 6 months (all p < 0.05). Both 9-HOTrE and 13(S)-HOTrE were related to worsening hot flash, and 5-HETE was related to worsening stiffness (all p < 0.05). This is the first study to prospectively characterize oxylipin and PUFA levels in patients with breast cancer starting adjuvant anastrozole. The oxylipin 8-HETE should be investigated further as a potential biomarker for AIA.

Background: Magnetic resonance spectroscopy (MRS) is a non-invasive diagnostic and the neuroimaging method of choice for the noninvasive monitoring of brain metabolism in patients with glioma tumors. 1 H-MRS is a reliable and non-invasive tool used to study glioma. However, the metabolite spectra obtained by 1 H-MRS requires a specific quantification procedure for post-processing. According to our knowledge, no comparisons have yet been made between spectrum analysis software for quantification of gliomas metabolites., Objective: Current study aims to evaluate the difference between this two common software in quantifying cerebral metabolites., Material and Methods: In this analytical study, we evaluate two post-processing software packages, java-based graphical for MR user interface packages (jMRUI) and totally automatic robust quantitation in NMR (TARQUIN) software. 1 H-MRS spectrum from the brain of patients with gliomas tumors was collected for post-processing. AMARES algorithms were conducted to metabolite qualification on jMRUI software, and TARQUIN software were implemented with automated quantification algorithms. The study included a total of 30 subjects. For quantification, subjects were divided into a normal group (n=15) and group of gliomas (n=15)., Results: When calculated by TARQUIN, the mean metabolites ratio was typically lower than by jMRUI. While, the mean ratio of metabolites varied when quantified by jMRUI vs. TARQUIN, both methods apparent clinical associations., Conclusion: TARQUIN and jMRUI are feasible choices for the post-processing of cerebral MRS data obtained from glioma tumors., Competing Interests: None, (Copyright: © Journal of Biomedical Physics and Engineering.)

The World Health Organization (WHO) recently revised its guidelines for rapid diagnosis of drug-resistant tuberculosis (TB). This study aimed to investigate if TB reference diagnostic services are prepared to support these revisions. An online survey was performed among 44 TB National Reference Laboratories (NRLs) in the WHO European Region. Questions addressed the use of WHO-recommended molecular techniques for the diagnosis of drug-resistant TB, the techniques applied to investigate antimicrobial resistance, and questions on quality assurance. Among 35 of 44 (80%) participating NRLs, 29 of 35 (83%) reported using the GeneXpert platform as the initial test to detect Mycobacterium tuberculosis complex and rifampicin resistance. Five laboratories reported using another WHO-recommended, moderate-complexity, automated nucleic acid amplification test for detection of Mycobacterium tuberculosis complex and resistance to rifampicin and isoniazid. Most (32 of 35; 91%) NRLs reported the capacity to test second-line drugs that have been in clinical use for many years (fluoroquinolones, linezolid, and injectable agents). Only 23 of 35 (66%) and 21 of 35 (60%) NRLs reported the capacity to test bedaquiline and clofazimine. Further efforts will be needed to improve the availability of quality-controlled testing against WHO Group A and Group B drugs. Earlier considerations on the scale-up of diagnostic capacities should be enforced as part of future approval processes for new antimycobacterial agents., (Copyright © 2022 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Technical advances in diagnostic techniques have permitted the possibility of multi-disease-based approaches for diagnosis and treatment monitoring of several infectious diseases, including tuberculosis (TB), human immunodeficiency virus (HIV), viral hepatitis and sexually transmitted infections (STI). However, in many countries, diagnosis and monitoring, as well as disease response programs, still operate as vertical systems, potentially causing delay in diagnosis and burden to patients and preventing the optimal use of available resources. With countries facing both human and financial resource constraints, during the COVID-19 pandemic even more than before, it is important that available resources are used as efficiently as possible, potential synergies are leveraged to maximise benefit for patients, continued provision of essential health services is ensured. For the infectious diseases, TB, HIV, hepatitis C (HCV) and STI, sharing devices and integrated services starting with rapid, quality-assured, and complete diagnostic services is beneficial for the continued development of adequate, efficient and effective treatment strategies. Here we explore the current and future potential (as well as some concerns), importance, implications and necessary implementation steps for the use of platforms for multi-disease testing for TB, HIV, HCV, STI and potentially other infectious diseases, including emerging pathogens, using the example of the COVID-19 pandemic.

Aromatase inhibitor-induced arthralgia (AIA) comprises significant, activity-limiting musculoskeletal symptoms, including joint pain, myalgia, and joint stiffness. We conducted a prospective feasibility study in postmenopausal women diagnosed with early-stage (0-3) hormone receptor positive (HR+) breast cancer who were candidates for treatment with adjuvant AI therapy ( n = 16). Tendons of the hands and wrists and the median nerve were imaged using gray-scale and power Doppler ultrasound (US) and US SWE. Arthralgia symptoms were evaluated using the Breast Cancer Prevention Trial (BCPT) Symptom Checklist musculoskeletal subscale (MS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and stiffness subscales. At baseline, there were significant differences in the SW velocities of tendons between dominant and nondominant hands. Increased velocity in 2 of 6 tendons and the median nerve was associated with greater pain at baseline, whereas slower velocity of the extensor digitorum tendon (suggesting decreased stiffness) was associated with a higher WOMAC stiffness score. Increased SW velocity (suggestive of increased stiffness) at baseline in the abductor pollicis longus tendon was associated with a worsening of all three pain and stiffness measures by 6 months. Future studies should evaluate SWE scores related to AIA outcomes in a larger sample size.

Nanotechnology-based photothermal therapy (NPTT) is a new emerging modality of cancer therapy. To have the right prediction and early detection of response to NPTT, it is necessary to get rapid feedback from a tumor treated by NPTT procedure and stay informed of what happens in the tumor site. We performed this study to find if proton magnetic resonance spectroscopy (1H-MRS) can be well responsive to such an imperative requirement. We considered various treatment groups including gold nanoparticles (AuNPs), laser, and the combination of AuNPs and laser (NPTT group). Therapeutic effects on CT26 colon tumor-bearing BALB/c mice were studied by looking at alterations that happened in 1H-MRS signals and tumor size after conducting treatment procedures. In MRS studies, the alterations of choline and lipid concentrations and their ratio were investigated. Having normalized the metabolite peak to water peak, we found a significant decrease in choline concentration post-NPTT (from (1.25 ± 0.05) × 10 -3 to (0.43 ± 0.04) × 10 -3 ), while the level of lipid concentration in the tumor was slightly increased (from (2.91 ± 0.23) × 10 -3 to (3.52 ± 0.31) × 10 -3 ). As a result, the choline/lipid ratio was significantly decreased post-NPTT (from 0.41 ± 0.11 to 0.11 ± 0.02). Such alterations appeared just 1 day after NPTT. Tumor shrinkage in all groups was studied and significant changes were significantly detectable on day 7 post-NPTT procedure. In conclusion, the study of choline/lipid ratio using 1H-MRS may help us estimate what happens in a tumor treated by the NPTT method. Such an in vivo assessment is interestingly feasible as soon as just 1 day post-NPTT. This would undoubtedly help the oncologists make a more precise decision about treatment planning strategies. Monitoring of the choline/lipid ratio by 1 H-MRS can be helpful for prediction and early detection of response to nano-photo-thermal therapy., (© 2021. The Author(s), under exclusive licence to Springer-Verlag London Ltd. part of Springer Nature.)

BACKGROUND: Distinguishing TB relapse from re-infection is important from a clinical perspective to document transmission patterns. We investigated isolates from patients classified as relapse to understand if these were true relapses or re-infections. We also investigated shifts in drug susceptibility patterns to distinguish acquired drug resistance from re-infection with resistant strains. METHODS: Isolates from pulmonary TB patients from 2009 to 2017 were analysed using whole-genome sequencing (WGS). RESULTS: Of 11 patients reported as relapses, WGS results indicated that 4 were true relapses (single nucleotide polymorphism difference ≤5), 3 were re-infections with new strains, 3 were both relapse and re-infection and 1 was a suspected relapse who was later categorised as treatment failure based on sequencing. Of the 9 patients who went from a fully susceptible to a resistant profile, WGS showed that none had acquired drug resistance; 6 were re-infected with new resistant strains, 1 was probably infected by at least two different genotype strains and 2 were phenotypically misclassified. CONCLUSIONS: WGS was shown to distinguish between relapse and re-infection in an unbiased way. The use of WGS minimises the risk of false classification of treatment failure instead of re-infection. Furthermore, our study showed that strains without major genetic differences can cause re-infection.

Orexin receptors expressed in basolateral amygdala (BLA) have been proposed for memory processing and hippocampal plasticity. There are several investigations about the effect of the adrenergic system in BLA on memory enhancement. However, there is no information about the molecular basis of this effect. Adrenergic and orexinergic fibers are found in BLA. In this study, the effects of both adrenergic and orexinergic systems were investigated on the amygdala function. To this end, the selective beta 2 adrenergic agonist (clenbuterol) and orexin receptors' antagonists (OX1R and OX2R, SB-334867-A and TCS-OX2-29, respectively) were administered into the BLA, then the high frequency stimulation (200-Hz) was applied to the perforant pathway and the synaptic plasticity of the dentate granular cells was studied in anaesthetized rats. Clenbuterol injection into the BLA enhanced the population spike (PS) component of LTP in the dentate gyrus (DG), as compared to that observed after dimethyl sulfoxide treatment. In addition, after orexin 1 or 2 receptor antagonists (SB-334867-A and TCS-OX2-29, respectively) injecting into the BLA, the enhancing effect of clenbuterol on PS was reduced. Moreover, the population excitatory post-synaptic potential also decreased in the SB-clenbuterol and TCS- clenbuterol experimental groups. However, the PS amplitude was also decreased in the group treated only by SB or TCS relative to the clenbuterol treated group. The PS amplitude or EPSP slope in the groups treated by both application of orexin receptors' antagonists and clenbuterol was considerably lower relative to the groups treated only by orexin receptors' antagonists. It is concluded that the BLA orexinergic system modulates hippocampal plasticity in relation with the adrenergic system., (Copyright © 2021. Published by Elsevier Inc.)

Background: The median solitary maxillary central incisor syndrome (SMMCI) is a rare malformative syndrome consisting of multiple defects, mainly found on the body midline. It can be correlated to the etiopathological and phenotypic pattern of panhypopituitarism. This case-report describes the rare case of a patient suffering from SMMCI and panhypopituitarism, showing an unusual craniofacial morphology., Case Presentation: From the cephalometric analysis, a skeletal class III was identified (despite the other cases described in literature described as skeletal class II), derived from hypomaxillia and mandibular protrusion. A convex lip profile, with tendency to mandibular hyper-divergency, airway patency, anterior and posterior cross-bite were observed. At the clinical examination, a maxillary cant was evident on the frontal plane that appeared asymmetric, with the prevalence of the third lower part of the face. There were some dysmorphic signs such as: small nose, rectilinear eyelid line and reduced interocular distance., Conclusions: The present clinical case shows how, despite the literature, SMMCI can be associated with a III skeletal class, with maxillary hypoplasia and mandibular protrusion. The interdisciplinary collaboration between dentist and pediatrician is therefore important for the early interception of the malocclusions associated with these syndromes., (© 2021. The Author(s).)

The quest to determine the function of a protein can represent a profound challenge. Although this task is the mandate of countless research groups, a general framework for how it can be approached is conspicuously lacking. Moreover, even expectations for when the function of a protein can be considered to be 'known' are not well defined. In this review, we begin by introducing concepts pertinent to the challenge of protein function assignments. We then propose a framework for inferring a protein's function from four data categories: 'inheritance', 'distribution', 'interactions' and 'phenotypes' (IDIP). We document that the functions of proteins emerge at the intersection of inferences drawn from these data categories and emphasise the benefit of considering them in an evolutionary context. We then apply this approach to the cellular prion protein (PrP C ), well known for its central role in prion diseases, whose function continues to be considered elusive by many investigators. We document that available data converge on the conclusion that the function of the prion protein is to control a critical post-translational modification of the neural cell adhesion molecule in the context of epithelial-to-mesenchymal transition and related plasticity programmes. Finally, we argue that this proposed function of PrP C has already passed the test of time and is concordant with the IDIP framework in a way that other functions considered for this protein fail to achieve. We anticipate that the IDIP framework and the concepts analysed herein will aid the investigation of other proteins whose primary functional assignments have thus far been intractable., (© 2021 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.)

A straightforward method for measuring two aquatic inorganic species of selenium, selenate, Se(VI), and selenite, Se(IV), was developed in this study. Selenium toxicity and bioaccumulation in food chain are strongly dependent on its speciation. Therefore, it is important to measure selenium species as part of any selenium risk assessment practice. In this method, total selenium was first measured using graphite furnace atomic absorption spectrometry, and then, chemical procedures in the literature were used to reduce selenite, Se(IV), to hydrogen selenide (H 2 Se). Total selenium of the same solution was measured again with the analytical instrument after stripping H 2 Se from the solution. The difference of total selenium measured gave Se(IV) concentration. The two main species in natural waters are Se(VI) and Se(IV). Therefore, it can be assumed that after removing Se(IV) from the solution, the remaining total selenium is Se(VI). The two inorganic selenium species of (IV) and (VI) in purified waters and synthetic irrigation waters both spiked with Se(VI) and Se(IV) were determined using this method. Recovery of spiked samples in diluted synthetic irrigation water was 97% for Se(VI) and 99% for Se(IV). Detection limits of the method were 0.32 µg L -1 for Se(VI) and 0.11 µg L -1 for Se(IV). The advantages of the method developed in this study are that it employs a straightforward simple chemical reaction combined with acidification and stripping, requires only one instrument (graphite furnace atomic absorption spectrometry), and does not require extensive sample pretreatment., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

We assessed the impact of COVID-19 on diagnostic services for tuberculosis (TB) by national reference laboratories in the WHO European Region. Of 35 laboratories, 30 reported declines in TB sample numbers, amounting up to > 50% of the pre-COVID-19 volumes. Sixteen reported reagent or consumable shortages. Nineteen reallocated ressources to SARS-CoV-2 testing, resulting in an overall increase in workload, largely without a concomitant increase in personnel (n = 14). This poses a risk to meeting the 2025 milestones of the End TB Strategy.

Background and objectives: The aim of this study is to evaluate mandibular elevator muscles activity and pain on palpation in the early stages of orthodontic treatment with clear aligners using surface electromyography (sEMG). Materials and methods: Surface electromyography (sEMG) activity and pain level on muscle palpation of masseter and anterior temporalis muscles were recorded in a sample of 16 adult subjects (aged 18-32 years; mean 22.5 +/- 3.5 SD) undergoing orthodontic treatment with clear aligners before the treatment (T0), after 1 month of treatment (two clear aligners) (T1), and after 3 months of treatment (T2) (six clear aligners). A chi-square test for nominal data, a Friedman test, and a Wilcoxon-signed rank test as post hoc analysis were applied. Results: No statistically significant differences in muscular pain were observed. At T1, the sEMG activity of masseter muscles at mandibular rest position showed a statistically significant reduction, but after 3 months (T2), the data appeared similar to T0 ( p = 0.03 and p = 0.02). Conclusions: During the treatment with clear aligners, subjects could experience an initial reduction in the masseter basal activity after 1 month of treatment. This effect tends to decrease to baseline levels after 3 months of therapy.

Background: With advances in digital health technologies and proliferation of biomedical data in recent years, applications of machine learning in health care and medicine have gained considerable attention. While inpatient settings are equipped to generate rich clinical data from patients, there is a dearth of actionable information that can be used for pursuing secondary research for specific clinical conditions., Objective: This study focused on applying unsupervised machine learning techniques for traumatic brain injury (TBI), which is the leading cause of death and disability among children and adults aged less than 44 years. Specifically, we present a case study to demonstrate the feasibility and applicability of subspace clustering techniques for extracting patterns from data collected from TBI patients., Methods: Data for this study were obtained from the Progesterone for Traumatic Brain Injury, Experimental Clinical Treatment-Phase III (PROTECT III) trial, which included a cohort of 882 TBI patients. We applied subspace-clustering methods (density-based, cell-based, and clustering-oriented methods) to this data set and compared the performance of the different clustering methods., Results: The analyses showed the following three clusters of laboratory physiological data: (1) international normalized ratio (INR), (2) INR, chloride, and creatinine, and (3) hemoglobin and hematocrit. While all subclustering algorithms had a reasonable accuracy in classifying patients by mortality status, the density-based algorithm had a higher F1 score and coverage., Conclusions: Clustering approaches serve as an important step for phenotype definition and validation in clinical domains such as TBI, where patient and injury heterogeneity are among the major reasons for failure of clinical trials. The results from this study provide a foundation to develop scalable clustering algorithms for further research and validation., (©Sina Ehsani, Chandan K Reddy, Brandon Foreman, Jonathan Ratcliff, Vignesh Subbian. Originally published in JMIR Biomedical Engineering (http://biomedeng.jmir.org), 02.02.2021.)

Background: Photo-thermal therapy (PTT) has been at the center of attention as a new method for cancer treatment in recent years. It is important to predict the response to treatment in the PTT procedure. Using magnetic resonance spectroscopy (MRS) can be considered a novel technique in evaluating changes in metabolites resulted from PTT., Methods: In the present project, we conducted an in vivo study to assess the efficacy of 1 H-MRS as a noninvasive technique to evaluate the response to treatment in the early hours following PTT. The BALB/c mice subcutaneously bearing tumor cells (CT26 cell line) were scanned by 1 H-MRS before and after PTT. Iron oxide-gold core-shell (Fe 3 O 4 @Au) as PTT agent was injected into intra-peritoneal at first and then irradiated by NIR laser. Single-voxel Point RESolved Spectroscopy (PRESS) sequence (TE = 144) was used, and metabolites alternations were evaluated by the non-parametric Wilcoxon test. Besides, Nanoparticle (NP) relaxometry was conducted for negative contrast agents' potentials., Results: MRS choline (Cho) peak dramatically reduced 24 h post-PTT (p = 0.01) and lipid peak as a marker for necrosis of tumor elevated (p = 0.01) just in group 3 (NPs injection + laser irradiation) 24 h after the procedure., Conclusion: 1 H-MRS showed its potential as a method in detecting the changes in metabolites and revealing the outcome accurately. Response to photo-thermal therapy evaluation was achievable only one day after PTT and proved by a 10-day follow-up of the tumor size. Iron oxide-gold core-shell can also be used as a negative contrast agent in MRI images during therapy.

IM: Here we used a demyelination model using an injection of Lysophosphatidylcholine )LPC( in the corpus collosum to examine the myelination activity of differentiated oligodendrocytes derived from Human dental pulp stem cells )hDPDSCs( according to a two step induction protocol., Methods and Materials: The cells were cultured in DMEM-F12 medium containing 1M Retinoic acid and were treated with 5ng/ml platelet-derived growth factor, 10 ng/ml basic fibroblast growth factor for 8-10 days. The differentiation cells were examined via the expression of specific glial markers: Olig2 and O4. Cells were transplanted in to a demylinated rat corpus callosum. The alteration of the demyelination extension as well as remyelination intensity was examined via a specific myelin staining: Luxol Fast Blue and immunohistochemistry., Results: Differentiated oligoprogenitor cells were confirmed via immunofluorescence staining with specific glial markers: Olig2 and O4. Also, the amount of demyelination was decreased and intensity of remyelination showed an increase after an engraftment of differentiated cells. Immunohistochemistry for evaluation of PLP expression proved the mature myelinating oligodendrocytes., Conclusion: hDPSCs can be induced to transdifferentiate into oligoprogenitor cells and respond to the routinely applied regents for glial differentiation of Mesenchymal stem cells. hDPSCs may be a valuable source for cell therapy in neurodegenerative diseases (Fig. 4, Ref. 30). Text in PDF www.elis.sk Keywords: dental pulp stem cells, lysophosphatidylcholine, corpus callosum, oligodendrocyte, differentiation.

Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is caused by drug-induced damage to the axons which is not detected easily due to lack of reliable, clinically applicable modalities. Diffuse tensor imaging (DTI) allows for quantitative measurements of fractional anisotropy (FA) and apparent diffusion coefficient (ADC), which have been shown to detect nerve injury by Magnetic Resonance Imaging (MRI)., Methods: We sought to evaluate if DTI could be used for detection of CIPN in patients with breast cancer treated with a taxane. Patients with h/o exposure to neurotoxic chemotherapy, diabetes, or peripheral neuropathy were excluded. Patients completed pre- and post-chemotherapy MRI of bilateral legs and FACT&GOG-Ntx. Genotyping of single-nucleotide variations (SNVs) was performed to detect known associations with CIPN., Results: We had 14 evaluable patients in this prospective trial. Mean FA values post-chemotherapy were significantly lower than baseline at mid-calf (p < 0.0001) and ankle (p = 0.03). We did not find any significant change in mean ADC values. In patients without symptomatic neuropathy, mean FA values decreased more than symptomatic patients at mid-calf (p < 0.001). Of the 41 genotyped SNVs, only rs8110536 was found to be significantly associated with development of CIPN., Conclusions: Our results show that FA values are indicative of CIPN and differential changes in FA values in symptomatic versus asymptomatic patients highlights its potential to be further studied as a predictive biomarker for CIPN. This is the first study to highlight a non-invasive, imaging based, objective biomarker which, if validated, can be translated into clinic easily.

Background: In recent years, great attention has been paid to the role of herbal medicine in the management of non-alcoholic fatty liver disease (NAFLD). Sumac (Rhus coriaria L.) is a popular herb which contains major bioactive compounds known for a variety of health benefits. This study aimed to assess the effects of sumac powder supplementation on hepatic fibrosis and some metabolic markers in patients with NAFLD., Methods: Eighty-four patients diagnosed with NAFLD were included in this randomized double-blind placebo-controlled clinical trial. They were randomly assigned to receive 2000 mg per day sumac powder (n = 42) or placebo (n = 42) for 12 weeks. Also, both groups received a 500-calories deficit diet plan. Hepatic fibrosis and liver enzymes (ALT and AST) as well as fasting blood sugar (FBS), serum insulin, HbA1c, HOMA-IR (insulin resistance index), QUICKI (insulin sensitivity index), malondialdehyde (MDA), and high sensitivity C-reactive protein (hs-CRP) were measured at baseline and the end of trial., Results: Eighty patients completed the trial. After 12-weeks of intervention, subjects in the sumac group showed a greater decrease in hepatic fibrosis and liver enzymes as well as FBS, serum insulin, HbA1c, HOMA-IR, MDA, and hs-CRP, compared to the placebo (P-value < 0.05); while the QUICKI was significantly higher in the sumac group at the end of intervention., Conclusion: Daily intake of 2000 mg sumac powder along with a low-calorie diet for 12 weeks was beneficial for the management of NAFLD., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The spike glycoprotein of the SARS-CoV-2 virus, which causes COVID-19, has attracted attention for its vaccine potential and binding capacity to host cell surface receptors. Much of this research focus has centered on the ectodomain of the spike protein. The ectodomain is anchored to a transmembrane region, followed by a cytoplasmic tail. Here we report a distant sequence similarity between the cysteine-rich cytoplasmic tail of the coronavirus spike protein and the hepcidin protein that is found in humans and other vertebrates. Hepcidin is thought to be the key regulator of iron metabolism in humans through its inhibition of the iron-exporting protein ferroportin. An implication of this preliminary observation is to suggest a potential route of investigation in the coronavirus research field making use of an already-established literature on the interplay of local and systemic iron regulation, cytokine-mediated inflammatory processes, respiratory infections and the hepcidin protein. The question of possible homology and an evolutionary connection between the viral spike protein and hepcidin is not assessed in this report, but some scenarios for its study are discussed.

Objective: The purpose of this study is to analyze the mandibular condylar volumein a sample of subjects 11-26 years old., Methods: CBCT condylescans from 94 patients (mean age 18.2 ± 4.5 y) acquired with areconstructed layer thickness of 0.5 mm and a 512×512 matrix were examined. Data on condylar volume were compared among three groups with different age ranges: 11-16 years, 17-21years, and 22-26 years. Condylar volumetric measurements were performed with Mimics™ software., Results: A significant increase in condylar volume from puberty to young adulthood was detected ( p  < 0.01). Females showed a higher condylar volume in the 17-21 y group compared with the 11-16 y group. Males showed differences among all three groups., Conclusion: The mandibular condyle growth seems to continue at least until 17-21 years in males but seems to stop before 17 years in females.

The beta-adrenergic receptors of the basolateral amygdala (BLA) are involved in modulating emotional memory formation in the hippocampus. The molecular mechanisms of this involvement are still unclear. In this study, we investigate the effects of the beta-adrenergic receptors of the BLA involvements during the major cellular mechanisms that underlie memory formation in hippocampal sub-regions. Wistar rats were injected with the selective beta receptor agonist, clenbuterol (15 ng/0.5 μl) bilaterally into the BLA. Then, the long-term potentiation (LTP) and the paired-pulse responses were recorded. Control rats were injected by saline at the same volume. Our data indicated that the injection of clenbuterol into the BLA area enhanced the amplitude of the population spike (PS) but not the slope of the excitatory postsynaptic potential (EPSP). In addition, short-term plasticity in the dentate gyrus (DG) region was significantly changed at 500 ms inter-pulse interval. These results suggest that the activation of the beta-adrenergic receptors of the BLA can improve LTP induction, which depends on the short-term plasticity with a mechanism related to the GABAergic transmission. Thus, it can be concluded that the adrenergic system of the BLA engages with long-term and short-term plasticity., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: This pilot study is a prospective controlled clinical trial, designed to evaluate the short-term clinical results (the plaque index) of an educational/motivational program for home oral hygiene, directed to children and adolescents who live in family-homes., Methods: The setting of the project was the province of Milan (Italy), where two family-homes were selected. The study group included 26 children (16 females and 10 males) aged between 7 and 15 years, of Italian nationality, from the family-home communities. The control group included 26 children (15 females and 11 males, aged between 7 and 15 years) of Italian nationality, matched for age and gender distribution with the study group, that were not in a socially disadvantaged condition. Collection of the plaque index (PI) was performed at t0. Then, all basic oral hygiene instructions were given to all children/adolescents and their educators. Education and motivation were repeated in the same way after 4-7 weeks (T1), and after 10-12 weeks (T2). The PI was taken also at T1 and T2., Results: An improvement in the PI was generally found in both groups, but there was no statistically significant difference between the two groups over time. Multivariate analysis of variance (MANOVA) revealed a statistically significant effect of time [F (1, 52) = 90.73, p < 0.001], regardless of the assignment group, in consequence of which the plaque index presented a moderate and significant improvement., Conclusion: The present data confirm the validity of the educational/motivational program to improve oral hygiene in children/adolescents, regardless of the assignment group.

Globally, high rates (and in the WHO European region an increasing prevalence) of co-infection with tuberculosis and HIV and HIV and hepatitis C virus exist. In eastern European and central Asian countries, the tuberculosis, HIV, and viral hepatitis programmes, including diagnostic services, are separate vertical structures. In this Personal View, we consider underlying reasons for the poor integration for these diseases, particularly in the WHO European region, and how to address this with an initial focus on diagnostic services. In part, this low integration has reflected different diagnostic development histories, global funding sources, and sample types used for diagnosis (eg, typically sputum for tuberculosis and blood for HIV and hepatitis C). Cooperation between services improved as patients with tuberculosis needed routine testing for HIV and vice versa, but financial, infection control, and logistical barriers remain. Multidisease diagnostic platforms exist, but to be used optimally, appropriate staff training and sensible understanding of different laboratory and infection control risks needs rapid implementation. Technically these ideas are all feasible. Poor coordination between these vertical systems remains unhelpful. There is a need to increase political and operational integration of diagnostic and treatment services and bring them closer to patients., (Copyright © 2020 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. Published by Elsevier Ltd.. All rights reserved.)

In recent years, extensive evidence has been published about usage of laser in oral lesions. The aim of the present study was to review the effectiveness of laser radiation in the treatment of pediatric oral soft tissue problems. The relevant keywords were searched in EBSCO, Medline (via Ovid), PubMed, Scopus, and Web of Science (WOS) databases. Then, eligible case series and controlled clinical trial studies, which published up to the end of 2018, were extracted and scrutinized. In this study, the age range of ≤ 21 years or the average age of ≤ 21 years was considered as the pediatric group. After limiting the search results, removing duplicate titles and eligibility evaluation, 17 papers were enrolled to the study (seven controlled clinical trials and ten case series). Er:YAG (2940 nm), CO 2 (10,600 nm), Er,Cr:YSGG (2780 nm), and diode (650, 660, and 975 nm) lasers indicated successful clinical results on mucocele excision, frenectomy, gingival incision and re-contouring, and treatment of vascular malformations. In addition, 660-nm diode laser radiation was an effective adjuvant treatment for halitosis and gingivitis induced by multi-bracket appliances. Reduction or absence of pain and bleeding, suitable homeostasis, reduction of operation time, less analgesic consumption, and antibacterial effect were among the advantages of the laser radiation in the studies. Laser as a main or adjuvant tool can have an effective role in surgical and non-surgical treatments of pediatric oral soft tissue problems. Conducting further randomized controlled trial studies on different soft tissue lesions can contribute to drawing better conclusions.

Background: A common strategy in the non-extraction treatment of Class II molar relationship is maxillary molar distalization, which could increase lower face height and cause clockwise mandibular rotation. The aim of this retrospective study was to analyse the effects on vertical dentoskeletal dimension of young adults treated with sequential distalization with orthodontic aligners., Methods: Lateral cephalometric radiographs of 10 subjects (8 females 2 males; mean age 22.7 ± 5.3 years) treated with upper molars sequential distalization with orthodontic aligners (Invisalign, Align Technology, San Josè, California, USA) were analyzed., Results: No statistically significant difference was observed for the primary outcome SN-GoGn between T0 and T1 and it was recorded a mean variation of 0.1 ± 2.0 degrees. Statistically significant differences were found in the linear position of the upper molars (6-PP, 7-PP) the molar class relationship parameter (MR) and the upper incisive inclination (1^PP) with at least p < 0.01., Conclusions: Upper molar distalization with orthodontic aligners guarantee an excellent control of the vertical dimension representing an ideal solution for the treatment of hyperdivergent or openbite subjects. It also allows an excellent control of the incisal torque without loss of anchorage during the orthodontic procedure.

Evidence-based guidance is needed on 1) how tuberculosis (TB) infectiousness evolves in response to effective treatment and 2) how the TB infection risk can be minimised to help countries to implement community-based, outpatient-based care.This document aims to 1) review the available evidence on how quickly TB infectiousness responds to effective treatment (and which factors can lower or boost infectiousness), 2) review policy options on the infectiousness of TB patients relevant to the World Health Organization European Region, 3) define limitations of the available evidence and 4) provide recommendations for further research.The consensus document aims to target all professionals dealing with TB ( e.g TB specialists, pulmonologists, infectious disease specialists, primary healthcare professionals, and other clinical and public health professionals), as well as health staff working in settings where TB infection is prevalent., Competing Interests: Conflict of interest: G.B. Migliori has nothing to disclose. Conflict of interest: E. Nardell has nothing to disclose. Conflict of interest: A. Yedilbayev has nothing to disclose. Conflict of interest: L. D'Ambrosio has nothing to disclose. Conflict of interest: R. Centis has nothing to disclose. Conflict of interest: M. Tadolini has nothing to disclose. Conflict of interest: M. van den Boom has nothing to disclose. Conflict of interest: S. Ehsani has nothing to disclose. Conflict of interest: G. Sotgiu has nothing to disclose. Conflict of interest: M. Dara has nothing to disclose., (The content of this work is copyright of the authors or their employers. Design and branding are Copyright ©ERS 2019.)

Purpose of the Study: The influence of the stomatognathic apparatus on body posture is a continuously discussed topic with contrasting results. The aim of this study is to analyze differences in postural stability between subjects with and without myogenous TMD., Methods: 25 subjects affected by myogenous TMD according with DC/TMD (6 males, 19 females; mean age 31.75±6.68years) and a healthy control group of 19 subjects (4 Males, 15 Females; mean age 27.26±3.85years) were enrolled in the study. Both groups underwent a posturo-stabilometric force platform exam under different mandibular and visual conditions. Sway area and sway velocity of the COP (Center Of foot Pressure) posturo-stabilometric parameters were evaluated and compared applying Mann-U-Whitney statistical test., Results: The sway area and sway velocity parameters resulted statistically significantly higher in the TMD group (sway area p<0.01; sway velocity p<0.05) in mandibular maximum intercuspation and rest positions with eyes open., Conclusions: This study demonstrates a significant difference in body postural stability between subjects with myogenous TMD and healthy controls. In particular, sway area and sway velocity postural parameters are increased in these subjects., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: To describe common genomic tests being used clinically to assess prognosis and guide adjuvant chemotherapy and endocrine therapy decisions for early-stage breast cancer., Methods: Case presentation and review of the literature., Results: Hormone receptor-positive (HR-positive) breast cancers, which express the estrogen and/or progesterone receptor, account for the majority of breast cancers. Endocrine therapy can be highly effective for patients with these HR-positive tumors, and identification of HR-positive breast cancers that do not require the addition of chemotherapy is critical. Clinicopathological features of the breast cancer, including tumor size, nodal involvement, grading, and HR status, are insufficient in predicting the risk for recurrence or the need for chemotherapy. Furthermore, a portion of HR-positive breast cancers have an ongoing risk for late recurrence, and longer durations of endocrine therapy are being used to reduce this risk., Conclusion: There is sufficient evidence for use of genomic testing in early-stage HR-positive breast cancer to aid in chemotherapy recommendations. Further confirmation of genomic assays for prediction of benefit from prolonged endocrine therapy is needed.

Background: Childhood obesity is increasing all over the world. Food insecurity is mentioned as a possible risk factor; however, previous studies have led to inconsistent results in different societies while data are lacking for the Middle East. We aimed to investigate the relationship between food insecurity and general or abdominal obesity in Iranian children in a cross-sectional study., Methods: Anthropometric data including height, weight, and waist circumference were measured by trained nutritionists. General and abdominal obesity were defined based on world health organization (WHO) and Iranian reference curves for age and gender, respectively. Radimer/Cornell food security questionnaire was filled by parents. Data about the physical activity of participants, family socio-economic status, parental obesity and data about perinatal period were also gathered using self-administered questionnaires. Logistic regression was incorporated to investigate the association between food insecurity and obesity in crude and multi-variable adjusted models., Results: A total of 587 children aged 9.30 ± 1.49 years had complete data for analysis. Food insecurity at household level was significantly associated with abdominal obesity (odds ratio (OR) = 1.54; confidence interval (CI):1.01-2.34, p <0.05) and the relationship remained significant after adjusting for all potential confounding variables (OR = 2.02; CI:1.01-4.03, p <0.05). Food insecurity was associated with general obesity neither in crude analysis and multi-variable adjusted models., Conclusions: The slight levels of food insecurity might increase the likelihood of abdominal obesity in Iranian children and macroeconomic policies to improve the food security are necessary. Large-scale prospective studies, particularly in the Middle East, are highly recommended to confirm our results.

Background: Concerning the low population of human endometrial mesenchymal cells within the tissue and their potential application in the clinic and tissue engineering, some researches have been focused on their in vitro expansion., Objective: The aim of this study was to evaluate the effect of leukemia inhibitory factor (LIF) as a proliferative factor on the expansion and proliferation of human endometrial stromal cells., Materials and Methods: In this experimental study, the isolated and cultured human endometrial stromal cells from women at ovulatory phase aged 20-35 years, after fourth passage were divided into control and LIF-treated groups. In the experimental group, the endometrial cells were treated by 10 ng/ml LIF in culture media and the cultured cells without adding LIF considered as control group. Both groups were evaluated and compared for proliferation rate using MTT assay, for CD90 marker by flow cytometric analysis and for the expression of Oct4, Nanog, PCNA and LIFr genes using real-time RT-PCR., Results: The proliferation rate of control and LIF-treated groups were 1.17±0.17 and 1.61±0.06 respectively and there was a significant increase in endometrial stromal cell proliferation following in vitro treatment by LIF compared to control group (p=0.049). The rate of CD90 positive cells was significantly increased in LIF-treated group (98.96±0.37%) compared to control group (94.26±0.08%) (p=0.0498). Also, the expression ratio of all studied genes was significantly increased in the LIF-treated group compared to control group (p=0.0479)., Conclusion: The present study showed that LIF has a great impact on proliferation, survival, and maintenance of pluripotency of human endometrial stromal cells and it could be applicable in cell therapies., Competing Interests: No any conflict of interest for this study.

Numerous genes and molecular pathways are implicated in neurodegenerative proteinopathies, but their inter-relationships are poorly understood. We systematically mapped molecular pathways underlying the toxicity of alpha-synuclein (α-syn), a protein central to Parkinson's disease. Genome-wide screens in yeast identified 332 genes that impact α-syn toxicity. To "humanize" this molecular network, we developed a computational method, TransposeNet. This integrates a Steiner prize-collecting approach with homology assignment through sequence, structure, and interaction topology. TransposeNet linked α-syn to multiple parkinsonism genes and druggable targets through perturbed protein trafficking and ER quality control as well as mRNA metabolism and translation. A calcium signaling hub linked these processes to perturbed mitochondrial quality control and function, metal ion transport, transcriptional regulation, and signal transduction. Parkinsonism gene interaction profiles spatially opposed in the network (ATP13A2/PARK9 and VPS35/PARK17) were highly distinct, and network relationships for specific genes (LRRK2/PARK8, ATXN2, and EIF4G1/PARK18) were confirmed in patient induced pluripotent stem cell (iPSC)-derived neurons. This cross-species platform connected diverse neurodegenerative genes to proteinopathy through specific mechanisms and may facilitate patient stratification for targeted therapy., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction Suppressing both androgens and estrogens may circumvent hormone receptor resistance in breast cancer by reducing androgen receptor stimulation. Selective inhibition of the 17, 20-lyase enzyme by orteronel leads to decreased androgen production in men and would be anticipated to reduce estrogen and androgen production in women. Thus, we conducted a phase 1b study of orteronel in postmenopausal women with hormone-receptor positive (HR+) metastatic breast cancer. Methods The primary objective was to identify the recommended phase 2 dose (R2PD) of orteronel in women; escalation was via standard 3 + 3 design. The initial dose was 300 mg BID and escalated to 400 mg BID. Cycle length was 28 days. Enrolled patients had HR+ metastatic breast cancer and were evaluated every 8 weeks for disease progression. Results Eight heavily pre-treated women enrolled [median age: 57 yo (range 47-73)]. Four received 300 mg BID at dose level 1; 4 received 400 mg BID at dose level 2. No dose limiting toxicities (DLTs) were observed. Adverse events (AE) at least possibly related to orteronel included grade 1-2 nausea (n = 4) and bone pain (n = 3), and grade 1 hypokalemia, hot flashes, myalgia and AST elevation (n = 2). The only grade 3 AE was hypertension (n = 2) with 8 patients receiving 34 cycles of treatment. No objective responses were seen; clinical benefit was seen in 2 patients with stable disease for more than 6 months. Serum estrogens and testosterone were suppressed from baseline on both doses of orteronel. Conclusions Orteronel 400 mg BID is well tolerated in postmenopausal women, and significantly suppresses serum estrogens and testosterone. Clinical benefit was seen among heavily pretreated postmenopausal women with HR+ metastatic breast cancer.

The prion protein (PrP) evolved from the subbranch of ZIP metal ion transporters comprising ZIPs 5, 6 and 10, raising the prospect that the study of these ZIPs may reveal insights relevant for understanding the function of PrP. Building on data which suggested PrP and ZIP6 are critical during epithelial-to-mesenchymal transition (EMT), we investigated ZIP6 in an EMT paradigm using ZIP6 knockout cells, mass spectrometry and bioinformatic methods. Reminiscent of PrP, ZIP6 levels are five-fold upregulated during EMT and the protein forms a complex with NCAM1. ZIP6 also interacts with ZIP10 and the two ZIP transporters exhibit interdependency during their expression. ZIP6 contributes to the integration of NCAM1 in focal adhesion complexes but, unlike cells lacking PrP, ZIP6 deficiency does not abolish polysialylation of NCAM1. Instead, ZIP6 mediates phosphorylation of NCAM1 on a cluster of cytosolic acceptor sites. Substrate consensus motif features and in vitro phosphorylation data point toward GSK3 as the kinase responsible, and interface mapping experiments identified histidine-rich cytoplasmic loops within the ZIP6/ZIP10 heteromer as a novel scaffold for GSK3 binding. Our data suggests that PrP and ZIP6 inherited the ability to interact with NCAM1 from their common ZIP ancestors but have since diverged to control distinct posttranslational modifications of NCAM1.