Chronic stridor in a toddler after ingestion of a discharged button battery: a case report.

BACKGROUND: Button battery (BB) ingestions (BBI) are increasingly prevalent in children and constitute a significant, potentially life-threatening health hazard, and thus a pediatric emergency. Ingested BBs are usually charged and can cause severe symptom within 2 h. Discharged BBs ingestion is very rare and protracted symptom trajectories complicate diagnosis. Timely imaging is all the more important. Discharged BBs pose specific hazards, such as impaction, and necessitate additional interventions. CASE PRESENTATION: We present the case of a previously healthy 19-month-old girl who was admitted to our pediatric university clinic in Germany for assessment of a three-month history of intermittent, mainly inspiratory stridor, snoring and feeding problems (swallowing, crying at the sight of food). The child's physical examination and vital signs were normal. Common infectious causes, such as bronchitis, were ruled out by normal lab results including normal infection parameters, negative serology for common respiratory viruses, and normal blood gas analysis, the absence of fever or pathological auscultation findings. The patient's history contained no evidence of an ingestion or aspiration event, no other red flags (e.g., traveling, contact to TBC). Considering this and with bronchoscopy being the gold standard for foreign body (FB) detection, an x-ray was initially deferred. A diagnostic bronchoscopy, performed to check for airway pathologies, revealed normal mucosal and anatomic findings, but a non-pulsatile bulge in the trachea. Subsequent esophagoscopy showed an undefined FB, lodged in the upper third of the otherwise intact esophagus. The FB was identified as a BB by a chest X-ray. Retrieval of the battery proved extremely difficult due to its wedged position and prolonged ingestion and required a two-stage procedure with consultation of Ear Nose Throat colleagues. Recurring stenosis and regurgitation required one-time esophageal bougienage during follow-up examinations. Since then, the child has been asymptomatic in the biannual endoscopic controls and is thriving satisfactorily. CONCLUSION: This case describes the rare and unusual case of a long-term ingested, discharged BB. It underscores the need for heightened vigilance among healthcare providers regarding the potential hazards posed by discharged BBIs in otherwise healthy children with newly, unexplained stridor and feeding problems. This case emphasizes the critical role of early diagnostic imaging and interdisciplinary interventions in ensuring timely management and preventing long-term complications associated even to discharged BBs.

The antitumor effects of herbal medicine Triphala on oral cancer by inactivating PI3K/Akt signaling pathway: based on the network pharmacology, molecular docking, in vitro and in vivo experimental validation.

BACKGROUND: This research aimed to investigate the anti-tumor effects and underlying genetic mechanisms of herbal medicine Triphala (TRP) in oral squamous cell carcinoma (OSCC). METHODS: The target genes of Triphala (TRP) in oral squamous cell carcinoma (OSCC) were identified, and subsequent functional enrichment analysis was conducted to determine the enriched signaling pathways. Based on these genes, a protein-protein interaction network was constructed to identify the top 10 genes with the highest degree. Genes deregulated in OSCC tumor samples were identified to be hub genes among the top 10 genes. In vitro experiments were performed to investigate the influence of TRP extracts on the cell metabolic activity, migration, invasion, apoptosis, and proliferation of two OSCC cell lines (CAL-27 and SCC-9). The functional rescue assay was conducted to investigate the effect of applying the inhibitor and activator of an enriched pathway on the phenotypes of cancer cells. In addition, the zebrafish xenograft tumor model was established to investigate the influence of TRP extracts on tumor growth and metastasis in vivo. RESULTS: The target genes of TRP in OSCC were prominently enriched in the PI3K-Akt signaling pathway, with the identification of five hub genes (JUN, EGFR, ESR1, RELA, and AKT1). TRP extracts significantly inhibited cell metabolic activity, migration, invasion, and proliferation and promoted cell apoptosis in OSCC cells. Notably, the application of TRP extracts exhibited the capacity to downregulate mRNA and phosphorylated protein levels of AKT1 and ESR1, while concomitantly inducing upregulation of mRNA and phosphorylated protein levels in the remaining three hub genes (EGFR, JUN, and RELA). The functional rescue assay demonstrated that the co-administration of TRP and the PI3K activator 740Y-P effectively reversed the impact of TRP on the phenotypes of OSCC cells. Conversely, the combination of TRP and the PI3K inhibitor LY294002 further enhanced the effect of TRP on the phenotypes of OSCC cells. Remarkably, treatment with TRP in zebrafish xenograft models demonstrated a significant reduction in both tumor growth and metastatic spread. CONCLUSIONS: Triphala exerted significant inhibitory effects on cell metabolic activity, migration, invasion, and proliferation in OSCC cell lines, accompanied by the induction of apoptosis, which was mediated through the inactivation of the PI3K/Akt pathway.

Identifying crosstalk genetic biomarkers linking a neurodegenerative disease, Parkinson's disease, and periodontitis using integrated bioinformatics analyses.

Objective: To identify the genetic linkage mechanisms underlying Parkinson's disease (PD) and periodontitis, and explore the role of immunology in the crosstalk between both these diseases. Methods: The gene expression omnibus (GEO) datasets associated with whole blood tissue of PD patients and gingival tissue of periodontitis patients were obtained. Then, differential expression analysis was performed to identify the differentially expressed genes (DEGs) deregulated in both diseases, which were defined as crosstalk genes. Inflammatory response-related genes (IRRGs) were downloaded from the MSigDB database and used for dividing case samples of both diseases into different clusters using k-means cluster analysis. Feature selection was performed using the LASSO model. Thus, the hub crosstalk genes were identified. Next, the crosstalk IRRGs were selected and Pearson correlation coefficient analysis was applied to investigate the correlation between hub crosstalk genes and hub IRRGs. Additionally, immune infiltration analysis was performed to examine the enrichment of immune cells in both diseases. The correlation between hub crosstalk genes and highly enriched immune cells was also investigated. Results: Overall, 37 crosstalk genes were found to be overlapping between the PD-associated DEGs and periodontitis-associated DEGs. Using clustering analysis, the most optimal clustering effects were obtained for periodontitis and PD when k = 2 and k = 3, respectively. Using the LASSO feature selection, five hub crosstalk genes, namely, FMNL1, MANSC1, PLAUR, RNASE6, and TCIRG1, were identified. In periodontitis, MANSC1 was negatively correlated and the other four hub crosstalk genes (FMNL1, PLAUR, RNASE6, and TCIRG1) were positively correlated with five hub IRRGs, namely, AQP9, C5AR1, CD14, CSF3R, and PLAUR. In PD, all five hub crosstalk genes were positively correlated with all five hub IRRGs. Additionally, RNASE6 was highly correlated with myeloid-derived suppressor cells (MDSCs) in periodontitis, and MANSC1 was highly correlated with plasmacytoid dendritic cells in PD. Conclusion: Five genes (i.e., FMNL1, MANSC1, PLAUR, RNASE6, and TCIRG1) were identified as crosstalk biomarkers linking PD and periodontitis. The significant correlation between these crosstalk genes and immune cells strongly suggests the involvement of immunology in linking both diseases.

Single-Cell Transcriptome Analysis Reveals Different Immune Signatures in HPV- and HPV + Driven Human Head and Neck Squamous Cell Carcinoma.

Background: Head and neck squamous cell carcinoma (HNSCC) is a significant health problem and related to poor long-term outcomes, indicating more research to be done to deeply understand the underlying pathways. Objective: This current study aimed in the assessment of the viral- (especially human papilloma virus [HPV]) and carcinogen-driven head and neck squamous cell carcinoma (HNSCC) microenvironment based on single-cell sequencing analysis. Methods: Data were downloaded from GEO database (GSE139324), including 131224 cells from 18 HP- HNSCC patients and 8 HPV+ HNSCC patients. Following data normalization, all highly variable genes in single cells were identified, and batch correction was applied. Differentially expressed genes were identified using Wilcoxon rank sum test. A gene enrichment analysis was performed in each cell cluster using KEGG analysis. Single-cell pseudotime trajectories were constructed with MONOCLE (version 2.6.4). Cell-cell interactions were analyzed with CellChat R package. Additionally, cell-cell communication patterns in key signal pathways were compared in different tissue groups. A hidden Markov model (HMM) was used to predict gene expression states (on or off) throughout pseudotime. Five-year overall survival outcomes were compared in both HPV+ and HPV- subsets. Results: 20,978 high-quality individual cells passed quality control. RNA-seq data were used from 522 HNSCC primary tumor samples. 1,137 differentially expressed genes between HPV+ and HPV- HNSCC patients were investigated. 96 differentially expressed genes were associated with overall survival and highly enriched in B cell associated biological process. Cell composition differed between types of samples. MHC-I, MHC-II, and MIF signaling pathways were found to be most relevant. Within these pathways, some cells were either signal receiver or signal sender, depending on sample type, respectively. Six genes were obtained, AREG and TGFBI (upregulation), CD27, CXCR3, MS4A1, and CD19 (downregulation), whose expression and HPV types were highly associated with worse overall survival. AREG and TGFBI were pDC marker genes, CXCR3 and CD27 were significantly expressed in T cell-related cells, while MS4A1 and CD19 were mainly expressed in B naïve cells. Conclusions: This study revealed dynamic changes in cell percentage and heterogeneity of cell subtypes of HNSCC. AREG, TGFBI, CD27, CXCR3, MS4A1, and CD19 were associated with worse overall survival in HPV-related HNSCC. Especially B-cell related pathways were revealed as particularly relevant in HPV-related HNSCC. These findings are a basis for the development of biomarkers and therapeutic targets in respective patients.

Decision-Making in the Pediatric Emergency Department-A Survey of Guidance Strategies among Residents.

(1) Introduction: Working in an emergency department requires fast and straightforward decisions. Therefore, decision guidance represents an essential tool for successful patient-centered care. Beyond the residents' own knowledge and experience, printed books have been the primary source of information in the past. The aim of this study was to discover which strategies current residents use the most and to identify alternative quick reference strategies in the digital age. (2) Materials and Methods: This study analyzed the responses of a short questionnaire directed at 41 residents in a single pediatric emergency department (32 pediatric and 9 pediatric surgery residents) over a period of one month. (3) Results: Thirty-three (80.5%) residents answered the entire questionnaire. Strikingly, responses indicated that printed books are still pivotal in guiding decision-making. In addition, the acquisition of information via computers or smartphones plays an increasing role. However, the opinion and council of the attending physician is still of great value to the residents and is not to be underestimated. Overall, most of the residents would prefer to have access to a specially designed smartphone application. (4) Conclusions: Certainty and validity are essential in decision-making in a pediatric emergency department. Although printed books and attending physicians are still considered as reliable sources of information, internet-based information plays an increasing role. In order to provide the best up-to-date and most recent information, a validated and consistently updated smartphone application could be a useful option.

Shared Molecular Mechanisms between Atherosclerosis and Periodontitis by Analyzing the Transcriptomic Alterations of Peripheral Blood Monocytes.

OBJECTIVE: This study investigated the nature of shared transcriptomic alterations in PBMs from periodontitis and atherosclerosis to unravel molecular mechanisms underpinning their association. METHODS: Gene expression data from PBMs from patients with periodontitis and those with atherosclerosis were each downloaded from the GEO database. Differentially expressed genes (DEGs) in periodontitis and atherosclerosis were identified through differential gene expression analysis. The disease-related known genes related to periodontitis and atherosclerosis each were downloaded from the DisGeNET database. A Venn diagram was constructed to identify crosstalk genes from four categories: DEGs expressed in periodontitis, periodontitis-related known genes, DEGs expressed in atherosclerosis, and atherosclerosis-related known genes. A weighted gene coexpression network analysis (WGCNA) was performed to identify significant coexpression modules, and then, coexpressed gene interaction networks belonging to each significant module were constructed to identify the core crosstalk genes. RESULTS: Functional enrichment analysis of significant modules obtained by WGCNA analysis showed that several pathways might play the critical crosstalk role in linking both diseases, including bacterial invasion of epithelial cells, platelet activation, and Mitogen-Activated Protein Kinases (MAPK) signaling. By constructing the gene interaction network of significant modules, the core crosstalk genes in each module were identified and included: for GSE23746 dataset, RASGRP2 in the blue module and VAMP7 and SNX3 in the green module, as well as HMGB1 and SUMO1 in the turquoise module were identified; for GSE61490 dataset, SEC61G, PSMB2, SELPLG, and FIBP in the turquoise module were identified. CONCLUSION: Exploration of available transcriptomic datasets revealed core crosstalk genes (RASGRP2, VAMP7, SNX3, HMGB1, SUMO1, SEC61G, PSMB2, SELPLG, and FIBP) and significant pathways (bacterial invasion of epithelial cells, platelet activation, and MAPK signaling) as top candidate molecular linkage mechanisms between atherosclerosis and periodontitis.

Shared Genetic and Epigenetic Mechanisms between the Osteogenic Differentiation of Dental Pulp Stem Cells and Bone Marrow Stem Cells.

OBJECTIVE: To identify the shared genetic and epigenetic mechanisms between the osteogenic differentiation of dental pulp stem cells (DPSC) and bone marrow stem cells (BMSC). MATERIALS AND METHODS: The profiling datasets of miRNA expression in the osteogenic differentiation of mesenchymal stem cells from the dental pulp (DPSC) and bone marrow (BMSC) were searched in the Gene Expression Omnibus (GEO) database. The differential expression analysis was performed to identify differentially expressed miRNAs (DEmiRNAs) dysregulated in DPSC and BMSC osteodifferentiation. The target genes of the DEmiRNAs that were dysregulated in DPSC and BMSC osteodifferentiation were identified, followed by the identification of the signaling pathways and biological processes (BPs) of these target genes. Accordingly, the DEmiRNA-transcription factor (TFs) network and the DEmiRNAs-small molecular drug network involved in the DPSC and BMSC osteodifferentiation were constructed. RESULTS: 16 dysregulated DEmiRNAs were found to be overlapped in the DPSC and BMSC osteodifferentiation, including 8 DEmiRNAs with a common expression pattern (8 upregulated DEmiRNAs (miR-101-3p, miR-143-3p, miR-145-3p/5p, miR-19a-3p, miR-34c-5p, miR-3607-3p, miR-378e, miR-671-3p, and miR-671-5p) and 1 downregulated DEmiRNA (miR-671-3p/5p)), as well as 8 DEmiRNAs with a different expression pattern (i.e., miR-1273g-3p, miR-146a-5p, miR-146b-5p, miR-337-3p, miR-382-3p, miR-4508, miR-4516, and miR-6087). Several signaling pathways (TNF, mTOR, Hippo, neutrophin, and pathways regulating pluripotency of stem cells), transcription factors (RUNX1, FOXA1, HIF1A, and MYC), and small molecule drugs (curcumin, docosahexaenoic acid (DHA), vitamin D3, arsenic trioxide, 5-fluorouracil (5-FU), and naringin) were identified as common regulators of both the DPSC and BMSC osteodifferentiation. CONCLUSION: Common genetic and epigenetic mechanisms are involved in the osteodifferentiation of DPSCs and BMSCs.

The Middle Part of the Plucked Hair Follicle Outer Root Sheath Is Identified as an Area Rich in Lineage-Specific Stem Cell Markers.

Hair follicle outer root sheath (ORS) is a putative source of stem cells with therapeutic capacity. ORS contains several multipotent stem cell populations, primarily in the distal compartment of the bulge region. However, the bulge is routinely obtained using invasive isolation methods, which require human scalp tissue ex vivo. Non-invasive sampling has been standardized by means of the plucking procedure, enabling to reproducibly obtain the mid-ORS part. The mid-ORS shows potential for giving rise to multiple stem cell populations in vitro. To demonstrate the phenotypic features of distal, middle, and proximal ORS parts, gene and protein expression profiles were studied in physically separated portions. The mid-part of the ORS showed a comparable or higher NGFR, nestin/NES, CD34, CD73, CD44, CD133, CK5, PAX3, MITF, and PMEL expression on both protein and gene levels, when compared to the distal ORS part. Distinct subpopulations of cells exhibiting small and round morphology were characterized with flow cytometry as simultaneously expressing CD73/CD271, CD49f/CD105, nestin, and not CK10. Potentially, these distinct subpopulations can give rise to cultured neuroectodermal and mesenchymal stem cell populations in vitro. In conclusion, the mid part of the ORS holds the potential for yielding multiple stem cells, in particular mesenchymal stem cells.

Identification of miRNAs as the Crosstalk in the Interaction between Neural Stem/Progenitor Cells and Endothelial Cells.

AIM: This study is aimed at identifying genetic and epigenetic crosstalk molecules and their target drugs involved in the interaction between neural stem/progenitor cells (NSPCs) and endothelial cells (ECs). MATERIALS AND METHODS: Datasets pertaining to reciprocal mRNA and noncoding RNA changes induced by the interaction between NSPCs and ECs were obtained from the GEO database. Differential expression analysis (DEA) was applied to identify NSPC-induced EC alterations by comparing the expression profiles between monoculture of ECs and ECs grown in EC/NSPC cocultures. DEA was also utilized to identify EC-induced NSPC alterations by comparing the expression profiles between monoculture of NSPCs and NSPCs grown in EC/NSPC cocultures. The DEGs and DEmiRNAs shared by NSPC-induced EC alterations and EC-induced NSPC alterations were then identified. Furthermore, miRNA crosstalk analysis and functional enrichment analysis were performed, and the relationship between DEmiRNAs and small molecular drug targets/environment chemical compounds was investigated. RESULTS: One dataset (GSE29759) was included and analyzed in this study. Six genes (i.e., MMP14, TIMP3, LOXL1, CCK, SMAD6, and HSPA2), three miRNAs (i.e., miR-210, miR-230a, and miR-23b), and three pathways (i.e., Akt, ERK1/2, and BMPs) were identified as crosstalk molecules. Six small molecular drugs (i.e., deptropine, fluphenazine, lycorine, quinostatin, resveratrol, and thiamazole) and seven environmental chemical compounds (i.e., folic acid, dexamethasone, choline, doxorubicin, thalidomide, bisphenol A, and titanium dioxide) were identified to be potential target drugs of the identified DEmiRNAs. CONCLUSION: To conclude, three miRNAs (i.e., miR-210, miR-230a, and miR-23b) were identified to be crosstalks linking the interaction between ECs and NSPCs by implicating in both angiogenesis and neurogenesis. These crosstalk molecules might provide a basis for devising novel strategies for fabricating neurovascular models in stem cell tissue engineering.

Digital avulsion injuries: epidemiology and factors influencing finger preservation.

INTRODUCTION: The surgical treatment of ring avulsion injuries is still challenging. This study provides data concerning epidemiology and factors influencing finger survival rate. We wanted to answer the question whether microsurgical advancement and a high level of surgical expertise nowadays may improve the outcome. PATIENTS AND METHODS: Between 11/2007 and 06/2016 95 ring avulsions were treated (classified according to Kay). Complete documentation was available from 87 patients (25 female). The mean age was 34 (4-82) years. Intact perfusion (Kay I) was preoperatively seen in 20 fingers while 67 were avascular (Kay II-IV). RESULTS: In 89%, the ring finger was injured during mainly private accidents. Primary amputation was performed in 38 Kay II-IV injuries. Revascularization was applied to 29 fingers while 8 of them (28%) primarily failed. After initially successful revascularization/replantation of 21 fingers, 6 had to be amputated secondarily (success rate: 52%). There was no significant correlation between affected finger and rate of finger preservation. Climbing over a fence as trauma mechanism significantly correlated with lower finger preservation rates and higher incidence of Kay IV injuries. CONCLUSION: Despite microsurgical advances and high levels of surgical expertise the finger survival rate after ring avulsion injuries still seems to be mostly influenced by the extend of intrinsic damage.

Brain-derived neurotrophic factor serum concentrations in acute depressive patients increase during lithium augmentation of antidepressants.

In recent years, lithium has proved an effective augmentation strategy of antidepressants in both acute and treatment-resistant depression. Neuroprotective and procognitive effects of lithium have been evidenced. Brain-derived neurotrophic factor (BDNF) has been shown to play a key role in the pathophysiology of several neurological and psychiatric disorders. The BDNF hypothesis of depression postulates that a loss of BDNF is directly involved in the pathophysiology of depression, and its restoration may underlie the therapeutic efficacy of antidepressant treatments. Brain-derived neurotrophic factor serum concentrations were measured in a total of 83 acutely depressed patients before and after 4 weeks of lithium augmentation. A significant BDNF increase has been found during treatment (F2,81 = 5.04, P < 0.05). Brain-derived neurotrophic factor concentrations at baseline correlated negatively with relative Hamilton Depression Scale change after treatment with lithium (n = 83; r = -0.23; P < 0.05). This is the first study showing that lithium augmentation of an antidepressant strategy can increase BDNF serum concentrations. Our study replicates previous findings showing that serum BDNF levels in patients with depressive episodes increase during effective antidepressant treatment. Further studies are needed to separate specific effects of different antidepressants on BDNF concentration and address potential BDNF downstream mechanisms.

Ablative targeting of fatty-tissue using a high-powered diode laser.

BACKGROUND AND OBJECTIVE: Concerning current clinical practice, laser-assisted lipoplasty is still secondary to other procedures. In order to evaluate effects of thermal interaction with fatty-tissue, a near infrared diode laser was examined under reproducible conditions. METHODS: Based on optical spectroscopy of fatty-tissue, a high-powered diode laser (lambda = 940 nm) was used to irradiate n = 59 fat samples of fresh corpses in non-contact mode. Thermal effects were histologically evaluated by computer based metric measurements. Calculated values included ablation rate (AR) and the ratio of cavity diameter to diameter of collateral damage (CCD(ratio)). Pearson's correlation and analysis of covariance (ANCOVA) were used for statistical evaluation. P values of less than 0.05 were considered to indicate statistical significance. RESULTS: Regarding the conditions examined, irradiances from 250 to 400 W/cm(2) revealed both increased ablation capacities and decreased collateral damages. An average irradiance of 370+/-0 W/cm(2) shows an average CCD(ratio) of 2:1 and an average AR of 9.98+/-7.65 mm(3)/second. CONCLUSION: Near infrared high-powered diode laser energy proved to be eligible for tissue protective ablation of fat in vitro. Further studies are necessary to improve efficiency and safety of this procedure.