Diagnostic value of water swallow test for dysphagia in patients with head and neck cancer: A systematic review and meta-analysis.

The diagnostic efficacy of the water swallow test (WST) is relatively robust for patients with neurogenic dysphagia; however, its diagnostic performance in identifying dysphagia among patients with HNC varies across studies. Our study aims to assess the diagnostic value of the WST for detecting dysphagia in patients with HNC. Systematic retrieval of studies on the use of WST for screening dysphagia in patients with HNC from databases up to August 1, 2023. Quality assessment of the included studies was performed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Calculate the pooled sensitivity, specificity, positive likelihood ratio (LR), negative LR, diagnostic odds ratio (DOR), and area under the receiver operating characteristic curve (AUC) to evaluate the screening ability of WST for dysphagia. A total of seven articles, encompassing eight study groups, were included, involving the analysis of 691 patients. The meta-analysis results demonstrate that the WST has a combined sensitivity, specificity, positive LR, negative LR, DOR, and AUC for diagnosing dysphagia in patients with HNC of 0.82 (95% CI [0.64, 0.92]), 0.79 (95% CI [0.70, 0.86]), 4.00 (95% CI [2.51, 6.36]), 0.22 (95% CI [0.10, 0.50]), 17.94 (95% CI [5.56, 57.92]), and 0.86 (95% CI [0.83, 0.89]), respectively. Significant heterogeneity was observed among the included studies. Meta-regression analysis showed that the pooled sensitivity of tumor sites and treatment was closely related, while the pooled specificity of treatment and version was closely related. The subgroup analysis showed that the WST's pooled sensitivity for diagnosing dysphagia in patients with nasopharyngeal cancer was 0.40 (95% CI [0.26, 0.56]), with an AUC of 0.50, lower than in other HNC sites. The WST performed better in surgical patients than in those undergoing radiotherapy (RT) or chemoradiotherapy (CRT), with lower sensitivity, specificity, and AUC values of 0.49 (95% CI [0.36, 0.61]), 0.66 (95% CI [0.59, 0.72]), and 0.64, respectively, for RT or CRT patients. The modified WST version showed different specificity values of 0.82 (95% CI [0.75, 0.87]), compared to the regular version of 0.68 (95% CI [0.61, 0.74]). Additionally, Deek's test indicated the absence of publication bias in this study (p = 0.32). The WST demonstrates favorable sensitivity and specificity in detecting dysphagia among patients with HNC. However, the diagnostic value may vary depending on factors such as tumor sites, treatment, and the specific version of the WST used.

[Research Progress of Indocyanine Green Fluorescence Laparoscopic Technique in Clinical Application].

Indocyanine green (ICG) is the most commonly used near-infrared fluorescent (NIRF) dye in clinical practice, and its mediated near-infrared fluorescence imaging technology is gradually applied in clinical practice. It has shown great potential in invasive surgery (MIS) and is expected to become the standard technology for surgical diagnosis and treatment of diseases. The clinical application of ICG fluorescence laparoscopy is reviewed here.

High level of winter warming aggravates soil carbon, nitrogen loss and changes greenhouse gas emission characteristics in seasonal freeze-thaw farmland soil.

Changes in the soil environment caused by winter warming is affecting the carbon and nitrogen cycles of seasonal freeze-thaw farmland soil. A field experiment was conducted in a seasonal freeze-thaw farmland soil of northeast China to investigate the effects caused from different levels of warming (W1 + 1.77 °C, W2 + 0.69 °C and C + 0 °C) on soil carbon and nitrogen dynamics, microbial biomass and greenhouse gases fluxes. During the early and middle winter, the contents of all kinds of soil carbon and nitrogen (Ammonium, nitrate, total nitrogen, dissolved organic carbon, readily oxidizable organic carbon and soil organic carbon) tended to increase with the increase of warming level, while during the late winter, their contents under different temperature treatments roughly present trend of W2 ≥C > W1. Except for the late thawing period, warming increased the contents of soil microbial biomass carbon and nitrogen, during the late thawing period, with the increase of warming level, MBC and MBN decreased significantly. Warming would stimulate the release of greenhouse gases from soil. But due to the differences of soil environmental conditions in each period and soil nutrient dynamics under different treatments, which made the effects of different levels of warming on soil GHGs fluxes in different periods are different. Our study suggested that low-level warming improved the availability of soil carbon and nitrogen, increased the contents of microbial biomass and greenhouse gas emissions. However, although high-level winter warming showed a similar phenomenon in the early and middle winter to the low-level warming, during the late winter, high-level warming increased soil nutrients loss and broke the seasonal coupling relationship between crop nutrient acquisition and soil microbial nutrient supply, and even led to the adaptation of soil CO2 release to it. This is of great significance for exploring the carbon and nitrogen cycle mechanisms of global terrestrial ecosystem.

Preoperative computed tomography-based tumoral radiomic features prediction for overall survival in resectable non-small cell lung cancer.

Objectives: The purpose of this study was to evaluate whether preoperative radiomics features could meliorate risk stratification for the overall survival (OS) of non-small cell lung cancer (NSCLC) patients. Methods: After rigorous screening, the 208 NSCLC patients without any pre-operative adjuvant therapy were eventually enrolled. We segmented the 3D volume of interest (VOI) based on malignant lesion of computed tomography (CT) imaging and extracted 1542 radiomics features. Interclass correlation coefficients (ICC) and LASSO Cox regression analysis were utilized to perform feature selection and radiomics model building. In the model evaluation phase, we carried out stratified analysis, receiver operating characteristic (ROC) curve, concordance index (C-index), and decision curve analysis (DCA). In addition, integrating the clinicopathological trait and radiomics score, we developed a nomogram to predict the OS at 1 year, 2 years, and 3 years, respectively. Results: Six radiomics features, including gradient_glcm_InverseVariance, logarithm_firstorder_Median, logarithm_firstorder_RobustMeanAbsoluteDeviation, square_gldm_LargeDependenceEmphasis, wavelet_HLL_firstorder_Kurtosis, and wavelet_LLL_firstorder_Maximum, were selected to construct the radiomics signature, whose areas under the curve (AUCs) for 3-year prediction reached 0.857 in the training set (n=146) and 0.871 in the testing set (n=62). The results of multivariate analysis revealed that the radiomics score, radiological sign, and N stage were independent prognostic factors in NSCLC. Moreover, compared with clinical factors and the separate radiomics model, the established nomogram exhibited a better performance in predicting 3-year OS. Conclusions: Our radiomics model may provide a promising non-invasive approach for preoperative risk stratification and personalized postoperative surveillance for resectable NSCLC patients.

A Bimetallic Metal-Organic-Framework-Based Biomimetic Nanoplatform Enhances Anti-Leukemia Immunity via Synchronizing DNA Demethylation and RNA Hypermethylation.

Epigenetic-alterations-mediated antigenicity reducing in leukemic blasts (LBs) is one of the critical mechanisms of immune escape and resistance to T-cell-based immunotherapy. Herein, a bimetallic metal-organic framework (MOF)-based biomimetic nanoplatform (termed as AFMMB) that consists of a DNA hypomethylating agent, a leukemia stem cell (LSC) membrane, and pro-autophagic peptide is fabricated. These AFMMB particles selectively target not only LBs but also LSCs due to the homing effect and immune compatibility of the LSC membrane, and induce autophagy by binding to the Golgi-apparatus-associated protein. The autophagy-triggered dissolution of AFMMB releases active components, resulting in the restoration of the stimulator of interferon genes pathway by inhibiting DNA methylation, upregulation of major histocompatibility complex class-I molecules, and induction of RNA-methylation-mediated decay of programmed cell death protein ligand transcripts. These dual epigenetic changes eventually enhance T-cell-mediated immune response due to increased antigenicity of leukemic cells. AFMMB also can suppress growth and metastases of solid tumor, which was suggestive of a pan-cancer effect. These findings demonstrate that AFMMB may serve as a promising new nanoplatform for dual epigenetic therapy against cancer and warrants clinical validation.

WRKY29 transcription factor regulates ethylene biosynthesis and response in arabidopsis.

The gaseous phytohormone ethylene participates in a lot of physiological processes in plants. 1-aminocyclopropane-1-carboxylic acid (ACC) synthase (ACS, EC 4.4.1.14) and the ACC oxidase (ACO, EC 1.14.17.4) are key enzymes in ethylene biosynthesis. However, how ACSs and ACOs are regulated at the transcriptional level is largely unknown. In the present study, we showed that an Arabidopsis (Arabidopsis thaliana) WRKY-type transcription factor (TF), WRKY29 positively regulated the expression of ACS5, ACS6, ACS8, ACS11 and ACO5 genes and thus promoted basal ethylene production. WRKY29 protein was localized in nuclei and was a transcriptional activator. Overexpression of WRKY29 caused pleiotropic effect on plant growth, development and showed obvious response even without ACC treatment. Inducible overexpression of WRKY29 also reduced primary root elongation and lateral root growth. A triple response assay of overexpression and mutant seedlings of WRKY29 showed that overexpression seedlings had shorter hypocotyls than the transgenic GFP (Green Fluorescence Protein) control, while mutants had no difference from wild-type. A qRT-PCR assay demonstrated that expression of multiple ACSs and ACO5 was up-regulated in WRKY29 overexpression plants. A transactivation assay through dual luciferase reporter system confirmed the regulation of promoters of ACS5, ACS6, ACS8, ACS11 and ACO5 by WRKY29. Both in vivo chromatin immunoprecipitation (ChIP)- quantitative PCR and in vitro electrophoretic mobility shift assay (EMSA) revealed that WRKY29 directly bound to the promoter regions of its target genes. Taken together, these results suggest that WRKY29 is a novel TF positively regulating ethylene production by modulating the expression of ACS and ACO genes.

Cyclodextrin-Functionalized Gold Nanorods Loaded with Meclofenamic Acid for Improving N6-Methyladenosine-Mediated Second Near-Infrared Photothermal Immunotherapy.

Cancer immunotherapy has achieved considerable clinical progress in recent years on account of its potential to treat metastatic tumors and inhibit recurrence. However, low patient response rates and dose-limiting toxicity are the major limitations of immunotherapy. Nanoparticle-based photothermal immunotherapy can amplify antitumor immune responses, although poor tumor penetration depth of near-infrared radiation (NIR) and the immunosuppressive tumor microenvironment significantly dampen its effects. We designed a nanoplatform based on gold nanorods for NIR-II-mediated photothermal therapy (PTT) combined with N6-methyladenosine (m6A) demethylase inhibition to achieve enhanced photothermal immunotherapy against prostate cancer. The GNRs were assembled layer by layer with polystyrenesulfonate as the interconnecting layer and then coated with a cationic polymer of γ-cyclodextrin (CD)-cross-linked low-molecular-weight polyethylenimine that was conjugated to an 8-mer peptide targeting the prostate tumor-specific gastrin-releasing peptide receptor. The m6A RNA demethylase inhibitor meclofenamic acid (MA) was then loaded into the CD cavity through hydrophobic interactions. GNR-CDP8MA specifically targeted the prostate tumor cells and selectively accumulated at the tumor site in vivo. In addition, GNR-CDP8MA almost completely ablated prostate cancer cell-derived tumors upon 1208 nm laser irradiation. Mechanistically, NIR-II triggered the release of MA from GNR-CDP8MA, which increased global mRNA m6A methylation and decreased the stability of PDL1 transcripts. Furthermore, GNR-CDP8MA-mediated PTT-induced immunogenic cell death in the primary tumor and consequently enhanced antitumor immunity by activating the antigen-presenting dendritic cells and tumor-specific effector T cells in the metastatic tumors. This study offers insights into synergistic m6A RNA methylation and PTT as an effective strategy for cancer immunotherapy.

The effects of hepatic ischemia/reperfusion injury on postoperative cognitive function in aged rats.

Introduction: Hepatic ischemia/reperfusion injury (I/R) is a significant source of morbidity and mortality after liver surgery. The aim of this study was to investigate the effect of hepatic I/R injury on the hippocampus in rats with postoperative cognitive dysfunction (POCD). Material and methods: Adult male Sprague-Dawley rats (n = 160, age: 20-25 months, weight: 300-350 g) received I/R surgery with ischemia for 20 min, 30 min, and 40 min in different groups. Behavior tests of the Morris water maze (MWM) test and the passive avoidance test were applied. Population spike (PS) of pyramidal cells, nuclear factor κB (NF-κB) and protein kinase γ (PKCγ) in the hippocampus were observed. Results: Within 10 days after surgery, in aged rats with varying impaired cognitive function, spike size and spike latency period were reduced, level of PKCγ was decreased and an increased level of NF-κB was observed in the I/R group, especially in the I/R group with ischemia for 40 min. The parameters showed no significant difference in rats in the I/R group compared with the sham group at the 18th day after surgery. Conclusions: Hepatic I/R injury has a negative impact on the postoperative cognitive function in aged rats, leading to hippocampus changes with PS abnormity and level changes of NF-κB, PKCγ. However, this cognitive deficit improved over time.

Low-frequency electroacupuncture improves disordered hepatic energy metabolism in insulin-resistant Zucker diabetic fatty rats via the AMPK/mTORC1/p70S6K signaling pathway.

BACKGROUND AND AIM: Disordered hepatic energy metabolism is found in obese rats with insulin resistance (IR). There are insufficient experimental studies of electroacupuncture (EA) for IR and type 2 diabetes mellitus (T2DM). The aim of this study was to probe the effect of EA on disordered hepatic energy metabolism and the adenosine monophosphate (AMP)-activated protein kinase (AMPK)/mammalian target of rapamycin complex 1 (mTORC1)/ribosomal protein S6 kinase, 70-kDa (p70S6K) signaling pathway. METHODS: Zucker Diabetic Fatty (ZDF) rats were randomly divided into three groups: EA group receiving EA treatment; Pi group receiving pioglitazone gavage; and ZF group remaining untreated (n = 8 per group). Inbred non-insulin-resistant Zucker lean rats formed an (untreated) healthy control group (ZL, n = 8). Fasting plasma glucose (FPG), fasting insulin (FINS), C-peptide, C-reactive protein (CRP) and homeostatic model assessment of insulin resistance (HOMA-IR) indices were measured. Hematoxylin-eosin (H&E) staining was used to investigate the liver morphologically. The mitochondrial structure of hepatocytes was observed by transmission electron microscopy (TEM). Western blotting was adopted to determine protein expression of insulin receptor substrate 1 (IRS-1), mTOR, mTORC1, AMPK, tuberous sclerosis 2 (TSC2) and p70S6K, and their phosphorylation. RT-PCR was used to quantify IRS-1, mTOR, mTORC1, AMPK and p70S6K mRNA levels. RESULTS: Compared with the ZF group, FPG, FINS, C-peptide, CRP and HOMA-IR levels were significantly reduced in the EA group (p < 0.05, p < 0.01). Evaluation of histopathology showed improvement in liver appearances following EA. Phosphorylation levels of AMPK, mTOR and TSC2 decreased, and IRS-1 and p70S6K increased, in hepatocytes of the ZF group, while these negative effects appeared to be alleviated by EA. CONCLUSIONS: EA can effectively ameliorate IR and regulate energy metabolism in the ZDF rat model. AMPK/mTORC1/p70S6K and related molecules may represent a potential mechanism of action underlying these effects.

Dexmedetomidine alleviates hepatic ischaemia-reperfusion injury via the PI3K/AKT/Nrf2-NLRP3 pathway.

Hepatic ischaemia-reperfusion (I/R) injury constitutes a tough difficulty in liver surgery. Dexmedetomidine (Dex) plays a protective role in I/R injury. This study investigated protective mechanism of Dex in hepatic I/R injury. The human hepatocyte line L02 received hypoxia/reoxygenation (H/R) treatment to stimulate cell model of hepatic I/R. The levels of pyroptosis proteins and inflammatory factors were detected. Functional rescue experiments were performed to confirm the effects of miR-494 and JUND on hepatic I/R injury. The levels of JUND, PI3K/p-PI3K, AKT/p-AKT, Nrf2, and NLRP3 activation were detected. The rat model of hepatic I/R injury was established to confirm the effect of Dex in vivo. Dex reduced pyroptosis and inflammation in H/R cells. Dex increased miR-494 expression, and miR-494 targeted JUND. miR-494 inhibition or JUND upregulation reversed the protective effect of Dex. Dex repressed NLRP3 inflammasome by activating the PI3K/AKT/Nrf2 pathway. In vivo experiments confirmed the protective effect of Dex on hepatic I/R injury. Overall, Dex repressed NLRP3 inflammasome and alleviated hepatic I/R injury via the miR-494/JUND/PI3K/AKT/Nrf2 axis.

iHear: Canadian medical student based hearing assessment program for grade school children using a tablet audiometer.

PURPOSE: To evaluate the progress and challenges of a hearing screening program as well as review the incidence of pediatric hearing loss in grade school children participating in this program. METHODS: Medical students from the University of Ottawa established iHear, a grade school hearing assessment program that uses novel tablet audiometry. Over 3 years, children in grades 1 and 2 were assessed and those found to have abnormal results on iHear assessment were then referred to audiology for formal testing, and to otolaryngology if needed. RESULTS: From 2014 to 2017, 753 children aged 5-9 years old were assessed for hearing loss. Mean age of participants was 6.7 years, 51.9% of whom were female. Of the children assessed, 86 (11.4%) had abnormal results and 6 (0.8%) had inconsistent results, necessitating 92 referrals for assessment by a professional audiologist. Of the 65 participants who completed secondary audiologic assessment, 54 (83.1%) were normal and 11 (16.9%) had a definitive hearing loss or abnormal tympanometry. A total of 32 children were lost to follow-up. A total of 118 medical students were involved in the iHear program. CONCLUSIONS: Hearing loss in grade school populations continues to go undetected across Canada. Programs such as iHear demonstrate that gaps in the provision of hearing assessment can be filled effectively by medical students equipped with tablet audiometry. Medical student exposure to audiology and otolaryngology increased through the iHear program.

Nalbuphine and dexmedetomidine as adjuvants to ropivacaine in ultrasound-guided erector spinae plane block for video-assisted thoracoscopic lobectomy surgery: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Adjuvants to local anesthetics, such as nalbuphine and dexmedetomidine, can be used to improve the quality and duration of peripheral nerve block effects. Dexmedetomidine has been successfully used as an adjuvant of erector spinae plane block (ESPB) with ropivacaine in video-assisted thoracoscopic lobectomy surgeries (VATLS). This study aimed to compare the effects of nalbuphine and dexmedetomidine used as adjuvants to ropivacaine for ESPB in VATLS. METHODS: A total of 102 patients undergoing VATLS with ESPB were enrolled and randomized into 3 groups, each of which received a different adjuvant to ropivacaine. The visual analogue scale score, onset and duration of sensory block, use of patient-controlled analgesia (PCA), rate of rescue analgesia, duration of postoperative hospitalization, incidence of postoperative nausea and vomiting, and chronic pain were measured and observed. RESULTS: The visual analogue scale score, total PCA use, rate of rescue analgesia, and postoperative chronic pain in the ropivacaine with dexmedetomidine (RD), and ropivacaine with nalbuphine (RN) groups were lower than those in the ropivacaine (RC) group (P < .05). The duration of sensory block was longer and the first use of PCA occurred later in the RD and RN groups than they did in the RC group (P < .05). CONCLUSIONS: As an adjuvant to ropivacaine in ESPB, nalbuphine and dexmedetomidine are comparable in terms of the associated analgesia, sensory block duration, need for rescue analgesia, and incidence of chronic pain in patients after VATLS.

Distinct subtypes of proprioceptive dorsal root ganglion neurons regulate adaptive proprioception in mice.

Proprioceptive neurons (PNs) are essential for the proper execution of all our movements by providing muscle sensory feedback to the central motor network. Here, using deep single cell RNAseq of adult PNs coupled with virus and genetic tracings, we molecularly identify three main types of PNs (Ia, Ib and II) and find that they segregate into eight distinct subgroups. Our data unveil a highly sophisticated organization of PNs into discrete sensory input channels with distinct spatial distribution, innervation patterns and molecular profiles. Altogether, these features contribute to finely regulate proprioception during complex motor behavior. Moreover, while Ib- and II-PN subtypes are specified around birth, Ia-PN subtypes diversify later in life along with increased motor activity. We also show Ia-PNs plasticity following exercise training, suggesting Ia-PNs are important players in adaptive proprioceptive function in adult mice.

Single cell RNA sequencing identifies early diversity of sensory neurons forming via bi-potential intermediates.

Somatic sensation is defined by the existence of a diversity of primary sensory neurons with unique biological features and response profiles to external and internal stimuli. However, there is no coherent picture about how this diversity of cell states is transcriptionally generated. Here, we use deep single cell analysis to resolve fate splits and molecular biasing processes during sensory neurogenesis in mice. Our results identify a complex series of successive and specific transcriptional changes in post-mitotic neurons that delineate hierarchical regulatory states leading to the generation of the main sensory neuron classes. In addition, our analysis identifies previously undetected early gene modules expressed long before fate determination although being clearly associated with defined sensory subtypes. Overall, the early diversity of sensory neurons is generated through successive bi-potential intermediates in which synchronization of relevant gene modules and concurrent repression of competing fate programs precede cell fate stabilization and final commitment.

Yes­associated protein protects and rescues SH­SY5Y cells from ketamine­induced apoptosis.

Ketamine is a widely used intravenous anesthetic; however, basic and clinical studies have demonstrated that prolonged exposure can cause irreversible injury to the immature human brain. Yes­associated protein (YAP) is the main effector of the Hippo signaling pathway, which serves an important role in regulating tissue homeostasis and organ size during development. However, whether YAP mediates ketamine­induced apoptosis is not completely understood. Based on the functions of YAP during apoptosis resistance and cell self­renewal regulation, the present study hypothesized that YAP serves a role during ketamine­induced apoptosis. An in vitro model was utilized to investigate the effects of ketamine on neurotoxicity and to further investigate the role of YAP in ketamine­induced apoptosis using techniques including CCK­8 assay, flow cytometry and western blotting. The present study assessed the effects of YAP overexpression and knockdown on the expression of typical apoptotic markers in SH­SY5Y cells. Ketamine induced apoptosis in a dose­dependent manner, which was regulated by YAP. Following YAP overexpression, ketamine­treated SH­SY5Y cells displayed increased activity and viability, whereas expression levels of the apoptotic markers were decreased compared with the negative control group. By contrast, ketamine­induced apoptosis was enhanced following YAP knockdown. Collectively, the results of the present study indicated that YAP may serve an important role during ketamine­induced neurotoxicity, and alterations to YAP signaling may counteract ketamine­induced apoptosis. The neuroprotective effect of YAP activation may serve as a novel pharmacological target for the treatment of ketamine­induced neurotoxicity via neurogenesis normalization.

Diagnosis and management of septal deviation and nasal valve collapse - a survey of Canadian otolaryngologists.

BACKGROUND: Management of nasal valve collapse (NVC) in patients with a septal deviation can be challenging. Our objective was to determine the opinions of Canadian Otolaryngologists regarding the diagnosis and management of nasal obstruction in patients with septal deviation and NVC. METHODS: A twenty-question survey was developed for the purpose of our study. Questions were divided into the following areas: diagnosis, management and prognosis. We included all otolaryngologists who were members of the Canadian Society of Otolaryngology. RESULTS: The response rate to our survey was 18%. The most commonly identified cause of a failed septoplasty was incomplete septoplasty (41.9%), followed by nasal valve collapse (25.6%). The Cottle manoeuvre (62.8%) and visual inspection (39.5%) were noted to be the most important diagnostic tools for external and internal NVC respectively. However, physicians often rely on a variable number of different examinations when making a diagnosis of nasal valve collapse. When evaluating which patients with a septal deviation also required nasal valve surgery, 27.9% of responders believed the current physical examination methods provided a high accuracy, while 55.8% indicated moderate accuracy and 16.3% indicated low accuracy. Compared to other subspecialties in Otolaryngology, Facial Plastic and Reconstruction Surgeons noted higher septoplasty failure rates in patients with co-morbid NVC. CONCLUSIONS: NVC is an important concern for otolaryngologists performing septoplasty. Although most physicians believe that the physical exam provides a moderate effectiveness when predicting who requires a functional rhinoplasty, diagnostic methods used for NVC is varied and inconsistent.

Muscle-selective RUNX3 dependence of sensorimotor circuit development.

The control of all our motor outputs requires constant monitoring by proprioceptive sensory neurons (PSNs) that convey continuous muscle sensory inputs to the spinal motor network. Yet the molecular programs that control the establishment of this sensorimotor circuit remain largely unknown. The transcription factor RUNX3 is essential for the early steps of PSNs differentiation, making it difficult to study its role during later aspects of PSNs specification. Here, we conditionally inactivate Runx3 in PSNs after peripheral innervation and identify that RUNX3 is necessary for maintenance of cell identity of only a subgroup of PSNs, without discernable cell death. RUNX3 also controls the sensorimotor connection between PSNs and motor neurons at limb level, with muscle-by-muscle variable sensitivities to the loss of Runx3 that correlate with levels of RUNX3 in PSNs. Finally, we find that muscles and neurotrophin 3 signaling are necessary for maintenance of RUNX3 expression in PSNs. Hence, a transcriptional regulator that is crucial for specifying a generic PSN type identity after neurogenesis is later regulated by target muscle-derived signals to contribute to the specialized aspects of the sensorimotor connection selectivity.

A cell fitness selection model for neuronal survival during development.

Developmental cell death plays an important role in the construction of functional neural circuits. In vertebrates, the canonical view proposes a selection of the surviving neurons through stochastic competition for target-derived neurotrophic signals, implying an equal potential for neurons to compete. Here we show an alternative cell fitness selection of neurons that is defined by a specific neuronal heterogeneity code. Proprioceptive sensory neurons that will undergo cell death and those that will survive exhibit different molecular signatures that are regulated by retinoic acid and transcription factors, and are independent of the target and neurotrophins. These molecular features are genetically encoded, representing two distinct subgroups of neurons with contrasted functional maturation states and survival outcome. Thus, in this model, a heterogeneous code of intrinsic cell fitness in neighboring neurons provides differential competitive advantage resulting in the selection of cells with higher capacity to survive and functionally integrate into neural networks.

An aggressive central giant cell granuloma in a pediatric patient: case report and review of literature.

BACKGROUND: Central giant cell granulomas are benign tumours of the mandible, presenting in children and young adults. Divided into non- and aggressive subtypes, the aggressive subtype is relatively rare and can occasionally progress rapidly, resulting in significant morbidity. CASE PRESENTATION: We present a case of an aggressive central giant cell granuloma (CGCG) in a six year-old female. The lesion originated in the right mandibular ramus and progressed rapidly to involve the condyle. Diagnosis was made using a combination of imaging and pathology. A timely en bloc resection of the hemi-mandible was performed with placement of a reconstructive titanium plate and condylar prosthesis. CONCLUSION: Our case demonstrates the importance of considering CGCG in the differential diagnosis of rapidly progressive mandibular lesions in the pediatric population. Prompt diagnosis and management can greatly improve long-term outcomes.

18F-fluoromisonidazole positron emission tomography may be applicable in the evaluation of colorectal cancer liver metastasis.

BACKGROUND: Positron emission tomography (PET) imaging is a non-invasive functional imaging method used to reflect tumor spatial information, and to provide biological characteristics of tumor progression. The aim of this study was to focus on the application of 18F-fluoromisonidazole (FMISO) PET quantitative parameter of maximum standardized uptake value (SUVmax) ratio to detect the liver metastatic potential of human colorectal cancer (CRC) in mice. METHODS: Colorectal liver metastases (CRLM) xenograft models were established by injecting tumor cells (LoVo, HT29 and HCT116) into spleen of mice, tumor-bearing xenograft models were established by subcutaneously injecting tumor cells in the right left flank of mice. Wound healing assays were performed to examine the ability of cell migration in vitro. 18F-FMISO uptake in CRC cell lines was measured by cellular uptake assay. 18F-FMISO-based micro-PET imaging of CRLM and tumor-bearing mice was performed and quantified by tumor-to-liver SUVmax ratio. The correlation between the 18F-FMISO SUVmax ratio, liver metastases number, hypoxia-induced factor 1α (HIF-1α) and serum starvation-induced glucose transporter 1 (GLUT-1) was evaluated using Pearson correlation analysis. RESULTS: Compared with HT29 and HCT116, LoVo-CRLM mice had significantly higher liver metastases ratio and shorter median survival time. LoVo cells exhibited stronger migration capacity and higher radiotracer uptake compared with HT29 and HCT116 in in vitro. Moreover, 18F-FMISO SUVmax ratio was significantly higher in both LoVo-CRLM model and LoVo-bearing tumor model compared to models established using HT29 and HCT116. In addition, Pearson correlation analysis revealed a significant correlation between 18F-FMISO SUVmax ratio of CRLM mice and number of liver metastases larger than 0.5 cm, as well as between 18F-FMISO SUVmax ratio and HIF-1α or GLUT-1 expression in tumor-bearing tissues. CONCLUSIONS: 18F-FMISO parameter of SUVmax ratio may provide useful tumor biological information in mice with CRLM, thus allowing for better prediction of CRLM and yielding useful radioactive markers for predicting liver metastasis potential in CRC.