An International Investigation of Molar Incisor Hypomineralisation (iMIH) and Its Association with Dental Anomalies: Development of a Protocol.

BACKGROUND: Molar incisor hypomineralisation (MIH) is a common disorder of tooth development, which has recently been found to be associated with a higher prevalence of hypodontia. The aim of this international multicentre study is to determine the association between MIH and other developmental anomalies in different populations. METHODS: Investigators were trained and calibrated for the assessment of MIH and dental anomalies and ethical approvals obtained in each participating country. The study aimed to recruit 584 children with MIH and 584 children without MIH. Patients aged 7-16 years who attend specialist clinics will be invited to participate. Children will undergo a clinical examination to determine the presence and severity of MIH, using an established index. The presence of any other anomalies, affecting tooth number, morphology, or position, will be documented. Panoramic radiographs will be assessed for dental anomalies and the presence of third permanent molars. Statistical analysis, using a chi squared test and regression analysis, will be performed to determine any differences in dental anomaly prevalence between the MIH and non-MIH group and to determine any association between dental anomalies and patient characteristics. CONCLUSION: This large-scale study has the potential to improve understanding about MIH with benefits for patient management.

Exploring the Role of Sodium-Glucose Cotransporter as a New Target for Cancer Therapy.

PURPOSE: To evaluate the effects of SGLT2 inhibitors on the proliferation, tumorigenesis, migration, colony formation, apoptosis, selected gene expression pattern, and combination with known chemotherapeutic drugs in different human cancer cell lines. METHODS: The antiproliferative and combined effects of SGLT2 inhibitors were evaluated by MTT assay. Cell migration was assessed using wound-healing and colony formation assays. Apoptosis assay was conducted using annexin V-FITC/ propidium iodide staining. SGLT2 gene expression was determined using real-time PCR. RESULTS: Canagliflozin, dapagliflozin, and ipragliflozin significantly inhibited the growth of different cancer cell lines in a dose and time-dependent manner. IC50 values after 48 hours of treatment with canagliflozin, ipragliflozin, and dapagliflozin ranged from 41.97 µM to 69.49 µM, 63.67 µM to 255.80 µM, and 167.7 µM to 435.70 µM in the examined cancer cell lines, respectively. The combined treatment of SGLT2 with doxorubicin and raloxifene separately resulted in a synergistic effect in Caco-2 and A-549 cell lines. On the other hand, the combination of SGLT2 inhibitors with cisplatin resulted in an antagonistic effect in A-549, Du-145, and Panc-1 cell lines. Canagliflozin and ipragliflozin inhibited cell migration and colony formation ability at IC50 and Sub-IC50 in the examined cancer cell lines. Canagliflozin and ipragliflozin significantly induced apoptosis at IC50 and Double-IC50 in the Du-145 cell line compared to the control. Real-time PCR showed that the treatment with 0.1 IC50 and 0.2 IC50 of both canagliflozin and ipragliflozin resulted in diminished RNA expression of SGLT2, VEGF, and Bcl-2 genes in the Du-145 cell line. CONCLUSION: SGLT2 inhibitors have antiproliferation, anti-tumorigenesis, and anti-migration effects and may induce apoptosis in cancer cells. In addition, treatment with SGLT2 inhibitors resulted in the downregulation of selected genes in the Du-145 cell line.

Durable benefit and change in TCR clonality with nivolumab in a Lynch syndrome-associated glioma.

Germline replication-repair deficient (gRRD) gliomas are exceptional events, and only a few of them have been treated with immune checkpoint inhibitors (ICIs). Contrary to sporadic gliomas, where ICIs have failed to show any objective benefit, the very few patients with gRRD gliomas treated with ICIs to date seem to benefit from programmed-death-1 (PD-1) inhibitors, such as nivolumab or pembrolizumab, either in terms of durable responses or in terms of survival. T-cell immunohistochemistry (IHC) and T-cell receptor (TCR) repertoire using high-throughput next-generation sequencing (NGS) with the Oncomine TCR-Beta-SR assay (Thermo Fisher Scientific) were analyzed in pre- and post-nivolumab tumor biopsies obtained from a patient with a Lynch syndrome-associated glioma due to a germline pathogenic hMLH1 mutation. The aim was to describe changes in the T-cell quantity and clonality after treatment with nivolumab to better understand the role of acquired immunity in gRRD gliomas. The patient showed a slow disease progression and overall survival of 10 months since the start of anti-PD-1 therapy with excellent tolerance. A very scant T-cell infiltrate was observed both at initial diagnosis and after four cycles of nivolumab. The drastic change observed in TCR clonality in the post-nivolumab biopsy may be explained by the highly spatial and temporal heterogeneity of glioblastomas. Despite the durable benefit from nivolumab, the scant T-cell infiltrate possibly explains the lack of objective response to anti-PD-1 therapy. The major change in TCR clonality observed after nivolumab possibly reflects the evolving molecular heterogeneity in a highly pre-treated disease. An in-deep review of the available literature regarding the role of ICIs in both sporadic and gRRD gliomas was conducted.

Corrigendum: Beyond Stereotypes: Analyzing Gender and Cultural Differences in Nonverbal Rapport.

[This corrects the article DOI: 10.3389/fpsyg.2020.599703.].

Beyond Stereotypes: Analyzing Gender and Cultural Differences in Nonverbal Rapport.

The current paper addresses two methodological problems pertinent to the analysis of observer studies in non-verbal rapport and beyond. These problems concern: (1) the production of standardized stimulus materials that allow for unbiased observer ratings and (2) the objective measurement of non-verbal behaviors to identify the dyadic patterns underlying the observer impressions. We suggest motion capture and character animation as possible solutions to these problems and exemplarily apply the novel methodology to the study of gender and cultural differences in non-verbal rapport. We compared a Western, individualistic culture with an egalitarian gender-role conception (Germany) and a collectivistic culture with a more traditional gender role conceptions (Middle East, Gulf States). Motion capture data were collected for five male and five female dyadic interactions in each culture. Character animations based on the motion capture data served as stimuli in the observation study. Female and male observers from both cultures rated the perceived rapport continuously while watching the 1 min sequences and guessed gender and cultural background of the dyads after each clip. Results show that masking of gender and culture in the stimuli was successful, as hit rates for both aspects remained at chance level. Further the results revealed high levels of agreement in the rapport ratings across gender and culture, pointing to universal judgment policies. A 2 × 2 × 2 × 2 ANOVA for gender and culture of stimuli and observers showed that female dyads were rated significantly higher on rapport across the board and that the contrast between female and male dyads was more pronounced in the Arab sample as compared to the German sample. Non-verbal parameters extracted from the motion capture protocols were submitted to a series of algorithms to identify dyadic activity levels and coordination patterns relevant to the perception of rapport. The results are critically discussed with regard to the role of non-verbal coordination as a constituent of rapport.

Nasoethmoidal Intestinal-Type Adenocarcinoma Treated with Cetuximab: Role of Liquid Biopsy and BEAMing in Predicting Response to Anti-Epidermal Growth Factor Receptor Therapy.

Sinonasal intestinal-type adenocarcinomas (SNS-ITAC) are very rare tumors that resemble colorectal cancer in many of their pathological and molecular characteristics. Indeed, in most published series, 10%-14% of SNS-ITAC harbor mutations in KRAS. There is no standard systemic treatment in recurrent or metastatic SNS-ITAC, and there is no evidence of the use of any targeted agent in this entity. We present the case of a recurrent nasoethmoidal ITAC informed as RAS and BRAF wild-type by standard real-time polymerase chain reaction methods and treated with first-line cetuximab and irinotecan without response. Circulating tumor cells coupled to highly sensitive DNA analyses unveiled a mutation in KRAS exon 2 codon 12. Subsequent studies in the primary tumor using BEAMing detected a mutation in the same codon, confirming the KRAS mutated status of the tumor, and possibly explaining the absence of treatment response. This case exemplifies how liquid biopsy can aid in the correct and real-time molecular characterization of tumors even in a rare nonmetastatic cancer of the head and neck. KEY POINTS: Sinonasal intestinal type adenocarcinomas (SNS-ITAC) are rare tumors that commonly develop after a prolonged exposure to organic dusts (wood, leather, etc.), and that resemble colorectal cancer in some of their morphological and molecular characteristics.KRAS mutations have been described in 10%-14% in most series. However, its predictive value for guiding treatment decisions with targeted therapies (i.e., anti-epidermal growth factor receptor [EGFR] therapy) has not been defined.The first case of an SNS-ITAC treated with anti-EGFR therapy (cetuximab) is reported. Analysis of DNA from circulating tumor cells (CTCs) unveiled a mutation in KRAS not detected by standard methods in the primary tumor. However, RAS analysis using BEAMing detected a mutation in the primary tumor in the same codon of KRAS originally detected in CTCs, altogether possibly explaining the lack of treatment response.Liquid biopsy may allow for an accurate molecular diagnosis in rare, organ-confined tumors where few therapeutic options exist. Highly sensitive molecular diagnostics may aid in better characterizing rare entities harboring potentially druggable targets.

Purpura induced by laser hair removal: a case report.

BACKGROUND: Laser hair removal is an effective and safe method for the permanent reduction of unwanted hair. Common side effects include temporary pain, transient erythema, and perifollicular edema. Purpuric eruption is a rare adverse event. CASE PRESENTATION: To the best of our knowledge, this is the second case report of purpura induced by laser hair removal. Our patient is a 50-year-old woman of Arab origin. Her positive reaction to a laser hair removal provocation test helped in the diagnosis; her condition was managed with an orally administered corticosteroid, leading to complete resolution within 5 days. CONCLUSION: Purpura induced by laser hair removal is a self-limiting and unusual side effect; physicians' awareness of such adverse events can help them to avoid unnecessary investigations and provide guidance for better management.

Retroperitoneal ectopic brain: Case report and literature review.

Heterotopic neural tissue (HNT) has been identified in many sites. In our literature review, we have found only two cases of HNT located in the retroperitoneum. As far as we know, cytological features of HNT have not been described. We here report a case of retroperitoneal HNT diagnosed by fine-needle aspiration (FNA) cytology and subsequent resection. Our patient was a male infant born at 26 weeks' gestation. A retroperitoneal solid-cystic lesion measuring 3.8 cm was identified by abdominal ultrasound. FNA was performed and cytology showed highly cellular smears with single cells and masses of fibrillary material. Cells were small with rounded irregular nuclei and variable cytoplasm. Multinucleated cells, cells with neuronal morphology, calcifications, and hemosiderophages could also be seen. The lesion was excised and histology showed fibrillary areas, glial cells, neurons, and ependymal cells. Synaptophysin, GFAP, and EMA were expressed in distinct areas and cell types. No recurrences were observed.

Renal Impairment and Complication After Kidney Transplant at Queen Rania Abdulla Children's Hospital.

OBJECTIVES: Kidney transplant is the treatment of choice for end-stage renal disease, but it is not without complications. We review the medical cause of significant renal impairment and complications that developed after kidney transplant in pediatric patients who required hospital admission and intervention and/or who were followed between 2007 and 2016. MATERIALS AND METHODS: A retrospective noninterventional chart review study was conducted in pediatric patients who received a kidney transplant and/or followed at the nephrology clinic at Queen Rania Abdulla Children's Hospital between 2007 and 2016. RESULTS: In this study, 101 pediatric patients received a total of 103 transplants. Forty-eight patients (47%) experienced deterioration of kidney function out of a total of 53 episodes of complications; 37 of these episodes occurred early (0-6 mo after transplant), and 26 episodes occurred late. The causes of kidney function deterioration were surgical complications, acute tubular necrosis, cell- or antibody-mediated rejection, diabetes mellitus, urinary leak, recurrence of original disease, and chronic allograft nephropathy. Thirteen patients experienced graft loss; 50% of these losses were secondary to noncompliance to immunosuppressant medication treatment after transplant. A total of six patients died; 2 (23%) of these deaths occurred in the first week after transplant, whereas the other 4 patients died over a period of 10 years. CONCLUSIONS: Pediatric kidney transplant is not without complications; however, most of these complications are treatable and reversible. The most serious complications leading to graft loss and death occur early, in the first week after transplant. Improving immunosuppressant compliance after transplant would prevent 50% of graft losses.

Cultures of trust: effects of avatar faces and reputation scores on German and Arab players in an online trust-game.

Reputation systems as well as seller depictions (photos; avatars) have been shown to reduce buyer uncertainty and to foster trust in online trading. With the emergence of globalized e-markets, it remains an urgent question whether these mechanisms, found to be effective for Western cultures, also apply to other cultures. Hypothesizing that members of collectivistic cultures in contrast to those of individualistic cultures would rely more on visual social cues (seller faces) than on factual information (reputation scores), we compared buying decisions of Arab and German participants in an experimental trust game. Photo-realistic avatars were used instead of photos to control facial features and expressions. The results revealed significant main effects for both reputation scores and avatar faces. Moreover, both variables significantly affected the purchase behavior of Arab as well as German buyers, suggesting cross-cultural universals in the processing of trust cues. The results have implications for future cross-cultural studies in e-commerce as well as the design of online markets and shared virtual environments.

Documentation of vancomycin-resistant Staphylococcus aureus (VRSA) among children with atopic dermatitis in the Qassim region, Saudi Arabia.

INTRODUCTION: Staphylococcus aureus is known as a common pathogen in atopic dermatitis. A methicillin-resistant S. aureus strain with reduced susceptibility to vancomycin (VISA/VRSA) is increasing worldwide. The aims of this study were to evaluate the antibiotic-susceptibility pattern of S. aureus isolated from children with atopic dermatitis and to identify the occurrence of resistance to glycopeptide antibiotics. METHODS: Swabs were collected from atopic dermatitis skin lesions of 80 children being treated at dermatology clinics whose ages ranged from 6 months to 15 years in the period from March 2009 to February 2010. Isolates were studied with an antibiogram for an antibiotic-susceptibility test. The selected antibiotics were the usually administered antimicrobials at dermatological clinics in Buraydah (Qassim, Saudi Arabia). Results were determined as minimal inhibitory concentration (MIC) using the Vitek system. RESULTS: Thirty S. aureus isolates showed resistance to streptomycin (100%), benzylpenicillin and ampicillin (96.7%), and oxacillin (90%). S. aureus resistance to trimethoprim/sulfamethoxazole, tigecycline, and vancomycin was 63.3%, 83.3%, and 53.3%, respectively. Resistance to linezolid was less, at 5.7%. CONCLUSIONS: Strains of MRSA with decreasing susceptibility to vancomycin were documented in the Qassim region of Saudi Arabia. Other studies will be required on VISA/VRSA strains concerning phenotypic and genotypic characterization.

The others: universals and cultural specificities in the perception of status and dominance from nonverbal behavior.

The current study analyzes trans-cultural universalities and specificities in the recognition of status roles, dominance perception and social evaluation based on nonverbal cues. Using a novel methodology, which allowed to mask clues to ethnicity and cultural background of the agents, we compared impression of Germans, Americans and Arabs observing computer-animated interactions from the three countries. Only in the German stimulus sample the status roles (employee vs. supervisor) could be recognized above chance level. However we found significant correlations in dominance perception across all countries. Significant correlations were only found for evaluation between German observers and observers from the other two countries. Perceived dominance uniformly predicted the assignment of status-roles in all cultures. Microanalysis of movement behavior further revealed predictive value of specific nonverbal cues for dominance ratings. Results support the hypothesis of universalities in the processing of dominance cues and point to cultural specificities in evaluative responses to nonverbal behavior.

Deciphering the secret code: a new methodology for the cross-cultural analysis of nonverbal behavior.

This article addresses methodological issues in the description and evaluation of nonverbal behavior (NVB) in cross-cultural studies. Videos containing cultural samples of NVB are of little use when analyzing the effects of NVB across cultures. Since video recordings confuse visible behavior with the physical appearances of the actors, they are likely to activate stereotypes derived from hints about an actor's culture and ethnicity that override the effects of the observed NVB. As a solution for this problem, we suggest here a unified computerized method for the transcription and experimental simulation of NVB. This approach makes use of advanced 3-D animation tools to generate detailed protocols of NVB that can be used to generate culture-free stimulus materials using standardized virtual characters.