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Background Migraine is a neurovascular disease with recurrent headache attacks. A polymorphism (rs2651899) of the PRDM16 gene, which is associated with migraine, was identified in recent genome-wide association studies. The potential role of the PRDM16 rs2651899 polymorphism in migraine is still unknown. Therefore, we conducted this systematic review and meta-analysis to examine this issue. Methods We performed a comprehensive literature search of the PubMed, Embase, and Google Scholar databases to identify eligible studies published before October 2018. Individual odds ratio and 95% confidence interval was used to estimate the pooled strength of the association between the PRDM16 rs2651899 polymorphism and common migraine subtypes, including migraine with aura (MA) and migraine without aura (MO). Results Six studies with 2853 cases and 9319 controls that fulfilled the inclusion and exclusion criteria were selected for this meta-analysis. Of the 6 included studies, 4 studies had available data for MWA and another 4 studies had data for MWoA. Overall, significant migraine risks of 1.257, 1.305, and 1.419 were found under allele model (C vs T), dominant model (C/C+T/C vs T/T), and recessive model (C/C vs T/C+T/T), respectively. In the recessive model, significantly increased risks of 1.454 and 1.546 were found for MA and MO, respectively. Conclusion Our major findings suggest that PRDM16 rs2651899 polymorphism is associated with the risk of migraine. Furthermore, we found that PRDM16 rs2651899 polymorphism is significantly related to common migraine subtypes (MA and MO).

Simple Summary Hepatitis virus is a major risk factor for liver cancer. We analyzed possible synergism between momelotinib and sorafenib in hepatitis virus-associated liver cancer. The combined effect of momelotinib and sorafenib both at in vitro and in vivo synergistically sup-presses the proliferation of vHCC cells and effectively reduces the tumor burden. Our results showed that momelotinib effectively suppressed the expression of the IFNGR-JAK-STAT-PARP1 pathway, which results in the downregulation of cancer stem cell genes and enhances the antitumor efficacy of sorafenib by initiating the expression of apoptosis-related genes and inhibiting the DNA repair gene in vHCC cells, thus maximizing its therapeutic potential for patients with HCC. Abstract Background: Hepatitis virus is a major risk factor for liver cancer. The mitochondrial dysfunction IFN gamma-related pathways are activated after virus infection. Jak family-related protein is involved in the downstream of IFN gamma-related pathways. However, the effect of the IFNGR-JAK-STAT pathway acting as functional regulators of their related protein expression on virus infection and hepatocellular carcinoma (HCC) remains unclear. Interestingly, the role of the DNA repair gene (PARP1) in therapy resistant cancers also has not been studied and explored well. In this study, we hypothesized that momelotinib could suppress the progression of HCC by targeting Jak family related and PARP1 DNA repair protein. Based on this observation, we link the relevant targets of the JAK family and the potential applications of targeted therapy inhibitors. Methods: We analyzed possible synergism between momelotinib and sorafenib in hepatitis virus-associated liver cancer. Immunostaining, colony formation assay, cell invasion, migration, and tumorsphere-formation assay were used for drug cytotoxicity, cell viability, and possible molecular mechanism. Result: We first demonstrated that the expression of Jak1 and 2 is significantly upregulated in vHCC than in nvHCC/normal liver tissues. In addition, the gene expression of IFN gamma-related pathways is activated after virus infection. Additionally, we found that momelotinib significantly inhibited the growth of HCC cells and reduces the expression of Jak2, which showed the importance of momelotinib in targeting Jak2 and reducing tumorigenesis in HCC. Meanwhile, momelotinib effectively inhibited the IFNGR-JAK-STAT pathway and reduced the migratory/invasive ability of vHCC cells through down-regulating EMT biomarkers (E-cadherin and vimentin), transcription factor (Slug), and significantly inhibits the DNA damage repair enzyme PARP1. It also induced cell apoptosis of vHCC cells. Furthermore, the combined effect of momelotinib and sorafenib both at in vitro and in vivo synergistically suppresses the proliferation of vHCC cells and effectively reduces the tumor burden. Conclusions: Our results showed that momelotinib effectively suppressed the expression of the IFNGR-JAK-STAT-PARP1 pathway, which results in the downregulation of cancer stem cell genes and enhances the antitumor efficacy of sorafenib by initiating the expression of apoptosis-related genes and inhibiting the DNA repair gene in vHCC cells, thus maximizing its therapeutic potential for patients with HCC.

Traumatic brain injury (TBI) causes major socioeconomic problems worldwide. In the United States, nearly three-quarters of patients with TBI have mild TBI (mTBI). 32% of these patients may develop dizziness. In this study, we analyzed the factor structure of the traditional Chinese version of the DHI and evaluate the differences in DHI factors between dizziness and nondizziness groups. In total, 315 patients with mTBI, comprising 158 with self-reported dizziness and 157 without dizziness, were recruited from three hospitals. The responses for Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Epworth Sleepiness Scale (ESS), and Pittsburgh Sleep Quality Index (PSQI) demonstrated between-group differences. The Chinese DHI had internal validity and had four factors that differed from the English version (3 aspects). The group effects for the physical subscale remained significantly different even after adjustments in the propensity score model. For the Chinese version, two of four factors remained significantly different in the effects between self-reported dizziness and nondizziness groups. The factors of our Chinese DHI differed from those of the original English version of DHI. After adjustments using the propensity score model, the physical subscale demonstrated significant differences between the self-reported dizziness and nondizziness groups. Only two factors from our Chinese DHI were significantly different; moreover, it contained only three physical, five functional, and three emotional items.

Hepatocellular carcinoma (HCC) is one of the most diagnosed malignancies and a leading cause of cancer-related mortality globally. This is exacerbated by its highly aggressive phenotype, and limitation in early diagnosis and effective therapies. The SUMO-activating enzyme subunit 1 (SAE1) is a component of a heterodimeric small ubiquitin-related modifier that plays a vital role in SUMOylation, a post-translational modification involving in cellular events such as regulation of transcription, cell cycle and apoptosis. Reported overexpression of SAE1 in glioma in a stage-dependent manner suggests it has a probable role in cancer initiation and progression. In this study, hypothesizing that SAE1 is implicated in HCC metastatic phenotype and poor prognosis, we analyzed the expression of SAE1 in several cancer databases and to unravel the underlying molecular mechanism of SAE1-associated hepatocarcinogenesis. Here, we demonstrated that SAE1 is over-expressed in HCC samples compared to normal liver tissue, and this observed SAE1 overexpression is stage and grade-dependent and associated with poor survival. The receiver operating characteristic analysis of SAE1 in TCGA&minus, LIHC patients (n = 421) showed an AUC of 0.925, indicating an excellent diagnostic value of SAE1 in HCC. Our protein-protein interaction analysis for SAE1 showed that SAE1 interacted with and activated oncogenes such as PLK1, CCNB1, CDK4 and CDK1, while simultaneously inhibiting tumor suppressors including PDK4, KLF9, FOXO1 and ALDH2. Immunohistochemical staining and clinicopathological correlate analysis of SAE1 in our TMU-SHH HCC cohort (n = 54) further validated the overexpression of SAE1 in cancerous liver tissues compared with &lsquo, normal&rsquo, paracancerous tissue, and high SAE1 expression was strongly correlated with metastasis and disease progression. The oncogenic effect of upregulated SAE1 is associated with dysregulated cancer metabolic signaling. In conclusion, the present study demonstrates that SAE1 is a targetable cancer metabolic biomarker with high potential diagnostic and prognostic implications for patients with HCC.

Rationale: Postpartum ovarian vein thrombophlebitis (POVT) is a rare condition, and it can lead to severe complications and mortality. Here we report a patient who presented with vaginal bleeding and the diagnosis of POVT was confirmed by imaging. Patient concerns: A 38-year-old postpartum woman without remarkable medical history presented with vaginal bleeding and lower abdominal pain. Diagnoses: The diagnosis was confirmed by computed tomography scan marked by a thrombus mass involving the right ovarian vein and inferior vena cava. Interventions: The patient was treated with intravenous antibiotics and low-molecular-weight heparin. Outcomes: The patient recovered smoothly without complications. Lessons: We should pay high attention to the recognition and management of POVT to prevent morbidity and mortality.

Background Triple-negative breast cancer (TNBC) has a more aggressive phenotype and poorer prognosis than hormone receptor (HR+) and human epidermal growth factor receptor (HER2 −) subtypes. Inhibition of cyclin-dependent kinase (CDK)4 and CDK6 was successful in patients with advanced metastatic HR+/HER2− breast cancer, but those with TNBC exhibited low or no response to this therapeutic approach. This study investigated the dual therapeutic targeting of CDK2 and CDK4 by using 4-acetyl-antroquinonol B (4-AAQB) against TNBC cells. Methods We examined the effects of CDK2, CDK4, and CDK6 inhibition through 4-AAQB treatment on TNBC cell lines and established an orthotropic xenograft mouse model to confirm the in vitro results of inhibiting CDK2, CDK4, and CDK6 by 4-AAQB treatment. Results High expression and alteration of CDK2 and CDK4 but not CDK6 significantly correlated with poor overall survival of patients with breast cancer. CDK2 and CDK4 were positively correlated with damage in DNA replication and repair pathways. Docking results indicated that 4-AAQB was bound to CDK2 and CDK4 with high affinity. Treatment of TNBC cells with 4-AAQB suppressed the expression of CDK2 and CDK4 in vitro. Additionally, 4-AAQB induced cell cycle arrest, DNA damage, and apoptosis in TNBC cells. In vivo study results confirmed that the anticancer activity of 4-AAQB suppressed tumor growth through the inhibition of CDK2 and CDK4. Conclusion The expression level of CDK2 and CDK4 and DNA damage response (DDR) signaling are prominent in TNBC cell cycle regulation. Thus, 4-AAQB is a potential agent for targeting CDK2/4 and DDR in TNBC cells.

Resistance to radiotherapy (IR), with consequent disease recurrence, continues to limit the efficacy of contemporary anticancer treatment for patients with hepatocellular carcinoma (HCC), especially in late stage. Despite accruing evidence implicating the PI3K/AKT signaling pathway in cancer-promoting hypoxia, cancerous cell proliferation and radiotherapy-resistance, it remains unclear which molecular constituent of the pathway facilitates adaptation of aggressive HCC cells to tumoral stress signals and drives their evasion of repeated IR-toxicity. This present study investigated the role of PDK1 signaling in IR-resistance, enhanced DNA damage repair and post-IR relapse, characteristic of aggressive HCC cells, while exploring potential PDK1-targetability to improve radiosensitivity. The study employed bioinformatics analyses of gene expression profile and functional protein&ndash, protein interaction, generation of IR-resistant clones, flow cytometry-based ALDH activity and side-population (SP) characterization, siRNA-mediated loss-of-PDK1function, western-blotting, immunohistochemistry and functional assays including cell viability, migration, invasion, clonogenicity and tumorsphere formation assays. We showed that the aberrantly expressed PDK1 characterizes poorly differentiated HCC CVCL_7955, Mahlavu, SK-HEP1 and Hep3B cells, compared to the well-differentiated Huh7 or normal adult liver epithelial THLE-2 cells, and independently activates the PI3K/AKT/mTOR signaling. Molecular ablation of PDK1 function enhanced susceptibility of HCC cells to IR and was associated with deactivated PI3K/AKT/mTOR signaling. Additionally, PDK1-driven IR-resistance positively correlated with activated PI3K signaling, enhanced HCC cell motility and invasiveness, augmented EMT, upregulated stemness markers ALDH1A1, PROM1, SOX2, KLF4 and POU5F1, increased tumorsphere-formation efficiency and suppressed biomarkers of DNA damage&mdash, RAD50, MSH3, MLH3 and ERCC2. Furthermore, the acquired IR-resistant phenotype of Huh7 cells was strongly associated with significantly increased ALDH activity, SP-enrichment, and direct ALDH1-PDK1 interaction. Moreover, BX795-mediated pharmacological inhibition of PDK1 synergistically enhances the radiosensitivity of erstwhile resistant cells, increased Bax/Bcl-2 apoptotic ratio, while suppressing oncogenicity and clonogenicity. We provide preclinical evidence implicating PDK1 as an active driver of IR-resistance by activation of the PI3K/AKT/mTOR signaling, up-modulation of cancer stemness signaling and suppression of DNA damage, thus, projecting PDK1-targeting as a putative enhancer of radiosensitivity and a potential new therapeutic approach for patients with IR-resistant HCC.

Background Emergency intubation in a patient with advanced ankylosing spondylitis (AS) who presents with severe thoracic kyphosis deformity, rigid cervical flexion deformity of the neck, and an inability to achieve the supine position is particularly challenging to emergency physicians. Case Report This study reports on an AS patient presenting with these difficult airway characteristics and acute respiratory failure who was successfully intubated using video laryngoscope-assisted inverse intubation (II) and blind digital intubation (BDI). By using Pentax AirwayScope-assisted inverse intubation, the tracheal tube tip was passed through the glottic opening, but an unexpected resistance occurred during tube advancement, which was overcome by subsequent BDI. By using laryngoscope-assisted II complemented by the BDI technique, the patient was successfully intubated without complications. Why Should an Emergency Physician Be Aware of This? Our case demonstrated that these two emergency airway management techniques are valuable backup methods and complement each other when applied to certain unstable airways, especially when the traditional patient position is not easily accomplished. Unexpected difficulty is not rare during airway management; emergency physicians should always be well prepared both mentally and practically.

Background Falls represent a global health issue among older adults and cause a considerable burden on medical systems. In this study, a fall-risk assessment profile was developed for community-dwelling older adults. Method The data of survey participants aged > 65 years were obtained from three rounds (2005, 2009, and 2013) of the National Health Interview Survey in Taiwan. In total, 8356 older participants were included in this study. Logistic regression analyses were used to determine potential predictors associated with falls. The regression coefficients of the predictors in the final model were translated into scores (by multiplying by 5) and then summed to obtain a total risk-score for falls. A receiver operating characteristic (ROC) curve was used to evaluate the discriminative performance of the risk assessment profile. Result Self-reported falls within 1 year accounted for 19.1% of the total falls. The predictors that were included in the risk profile according to the logistic regression analysis results were as follows: female sex (adjusted odds ratio = 1.57; risk-score = 2), living alone (adjusted odds ratio = 1.56; risk-score = 2), urinary incontinence (adjusted odds ratio = 1.36; risk-score = 2), perceived unhealthiness (adjusted odds ratio = 1.32; risk-score = 1), perceived pain (adjusted odds ratio = 1.51; risk-score = 2), hospital admission in the past year (adjusted odds ratio = 2.42; risk-score = 4), low activity of daily living (ADL) scores (adjusted odds ratio = 1.29; risk-score = 1), and low mobility function scores (adjusted odds ratio = 1.68; risk-score = 3). At a total risk-score cutoff point of 6 (range 0–17), the model predicted falls with a sensitivity and specificity of 75.16 and 52.75%, respectively (area under the ROC curve = 0.70). Conclusion The fall-risk assessment profile comprising eight predictors—female sex, living alone, incontinence, perceived unhealthiness, perceived pain, hospital admission in the past year, low ADL scores, and low mobility function scores—may serve as an assessment tool for identification of older adults with a high risk of falling, and assessment results can be used to facilitate community-based intervention.

Introduction. Unintentional injury remains the leading cause of death in children worldwide. Adequate parental supervision is a crucial strategy for preventing injury. Many factors, such as a large family size, poor socioeconomic status, and the caregiver being a single mother, contribute to unintentional injury in children. In addition, sleep deprivation in caregivers might be associated with injury in children because sleep deprivation causes impaired daytime cognitive function, wake-state instability, and negative moods, thereby impairing caregiver supervision. Therefore, this study determines the association between injury in children and the sleep quality of their primary caregivers. Method. This is a retrospective case–control study on unintentional injury in children aged 0 to 4 years who visited the emergency department (case group) and an age- and sex-matched control group. Sleep quality in caregivers was assessed using the Chinese version of the Pittsburgh Sleep Quality Index (PSQI). Logistic regression was used to evaluate the association between aspects of the PSQI and injury. A propensity score model was used to generate a quasirandomized design. Results. This case-control study recruiting 277 injured and 274 noninjured children was conducted in Taiwan. There was no statistically significant difference in child’s age and primary caregiver’s age between the injured and noninjured groups. The primary outcome, Pittsburgh sleep quality index, was not significantly different between the two groups. The average scores of sleep duration and habitual sleep efficiency in the control group were higher than those in the case group. However, there was no difference between the two groups after adjusting via a propensity score model, including the following potential confounders, child’s age, child’s sex, number of previous injury, caregiver mental status, caregiver’s sex and caregiver’s age, and the number of children living together. Conclusion. Our study was the first to examine the association between injury in children and the sleep quality of their primary caregivers. We observed that no PSQI component significantly affected the risk of injury among children.

Introduction. Emergency decompression is needed in patients with tension pneumothorax, a life-threatening condition. The catheter-based needle thoracostomy was suggested using a 5 cm catheter inserted into the 2nd intercostal space (ICS) and 5th ICS according to the ninth and tenth editions of Advanced Trauma Life Support, respectively. A catheter of suitable length may not be available immediately or the muscle structure of the chest wall may be modified in pneumothorax. Furthermore, alternative sites for needle thoracostomy and reference values of chest wall thickness (CWT) should be explored and warranted. Method. CT scan data and medical data of 650 eligible patients from October 2016 to December 2016 were reviewed. CWT values at four ICSs as well as four variables, namely, age, weight, height, and body mass index (BMI) for both men and women were compared using a nonparametric method, namely, the Wilcoxon signed-rank test. The associations between CWT and the four variables were assessed using the Pearson correlation coefficient. The overall performance of BMI, weight, and height in predicting CWT > 5 cm was evaluated using the receiver-operating characteristic (ROC) curve. Finally, the prediction models were built by using the bootstrap method. Results. Four variables, namely, age, height, weight, and BMI, were compared between the men and women groups. All four variables differed significantly between the two groups, and CWTs at all ICSs, except for the 3rd ICS, differed significantly between the two groups. Among the women, the area under the ROC curve (AUROC) of BMI for predicting CWT > 5 cm at 2nd ICS was larger than the AUROC of weight and height. Among the men, the AUROC of weight for predicting CWT > 5 cm at 2nd ICS was larger than that of BMI and height. The reference value tables were provided for five proposed models for women and men, respectively. Under emergencies, the variable, BMI, or even weight itself, could be used for predicting a failure performance of the needle decompression. For women, CWT at 5th ICS was predicted over 5 cm at BMI over 25.9 kg/m2or weight over 103.1 kg. For men, CWT at 5th ICS was predicted over 5 cm at BMI over 25.5 kg/m2or weight over 157.4 kg. Conclusion. Needle thoracostomy is the preferred first technique for many emergency providers for decompression. Therefore, a reference table for safe needle thoracostomy decompression at four usual sites, namely, 2nd ICS, 3rd CIS, 4th ICS, and 5th ICS, was recommended, which will enable paramedics and emergency specialists to rapidly determine CWT at the appropriate ICSs during emergencies.

Introduction: Dizziness and balance impairment are common symptoms of mild traumatic brain injury (mTBI). Acid-sensing ion channel 3 (ASIC3) is expressed in the vestibular and proprioceptive systems and associated with balance functions. However, whether the genetic variants of ASIC3 are associated with people who suffer dizziness and balance impairment after mTBI remained unknown. Materials and methods: A total of 200 people with mTBI and 109 non-mTBI controls were recruited. Dizziness, balance functions, and the ability to perform daily activities were assessed by Dizziness Handicap Inventory (DHI), and objective balance functions were investigated by the postural stability test. Three diseases-related genetic variants of ASIC3 were determined through polymerase chain reaction and followed by restriction fragment length polymorphism. The Student's t-test and Mann-Whitney U-test were used for normal and abnormal distributed data, respectively. The regression was applied to adjust gender and age. The normality of continuous data was evaluated by Shapiro-Wilk test. Results: In the mTBI people, the rs2288645-A allele carriers exhibited a significantly worse physical domain DHI score (A-allele carriers: 11.39 ± 8.42, non-A carriers: 8.76 ± 7.87, p = 0.03). The rs4148855-GTC deletion carriers an exhibited significantly worse overall postural stability (GTC deletion carriers: 0.53 ± 0.33, non-carriers: 0.46 ± 0.20, p = 0.03). In the controls, rs2288646-A allele carriers were significant worse in the medial-to-lateral postural stability (A-allele carriers: 0.31 ± 0.17, non-A carriers: 0.21 ± 0.10, p = 0.01). Conclusion: The present study demonstrated that ASIC3 genetic variants were associated with certain aspects of balance functions and dizziness questionnaires in people of mTBI and non-mTBI. It provides a possible evidence that ASIC3 could be a new target for the management of the balancing disorders. However, further investigations are warranted to elucidate the underlying mechanisms and clinical significance.

This study demonstrated a training program of the suction-assisted laryngoscopy assisted decontamination (S.A.L.A.D.) technique for emergency medical technician paramedic (EMT-P). The effectiveness of the training program on the improvements of skills and confidence in managing soiled airway was evaluated.In this pilot before-after study, 41 EMT-P participated in a training program which consisted of 1 training course and 3 evaluation scenarios. The training course included lectures, demonstration, and practice and focused on how to perform endotracheal intubation in soiled airway with the S.A.L.A.D technique. The first scenario was performed on standard airway mannequin head with clean airway (control scenario). The second scenario (pre-training scenario) and the third scenario (post-training scenario) were performed in airway with simulated massive vomiting. The post-training scenario was applied immediately after the training course. All trainees were requested to perform endotracheal intubation for 3 times in each scenario. The "pass" of a scenario was defined as more than twice successful intubation in a scenario. The intubation time, count of successful intubation, pass rate, and the confidence in endotracheal intubation were evaluated.The intubation time in the post-training scenario was significantly shorter than that in the pre-training scenario (P = .031). The pass rate of the control, pre-training, and post-training scenario was 100%, 82.9%, and 92.7%, respectively. The proportion of trainees reporting confident or very confident in endotracheal intubation in soiled airway increased from 22.0% to 97.6% after the training program. Kaplan-Meier analysis revealed that the adjusted hazard ratio of successful intubation for post-training versus pre-training scenario was 2.13 (95% confidence interval of 1.57-2.91).The S.A.L.A.D. technique training could efficiently help EMT-P performing endotracheal intubation during massive vomiting simulation.

Background Carbon monoxide (CO) poisoning may result in acute neurological sequelae, cognitive sequelae, and delay neurological sequelae. The administration of hyperbaric oxygen (HBO) to prevent the development of delayed neurological sequelae in CO poisoning have extensively investigated but conflicting results have been reported. We performed a systematic literature review and meta-analysis of randomized controlled trials (RCTs) evaluating HBO treatment and its effect on neuropsychometric dysfunction after CO poisoning. Methods We searched Medline, Embase, Pubmed, and the Cochrane Register of Controlled Trials from inception to December 2017. Eligible studies compared HBO therapy with normobaric oxygen (NBO) in patients with CO poisoning. Results Six studies compared HBO with NBO in CO poisoning patients. Compared with patients treated with NBO, a lower percentage of patients treated with HBO reported headache (16.2% vs 16.5%, relative risk [RR] = 0.83, 95% CI = 0.38-1.80), memory impairment (18.2% vs 23.8%, RR = 0.80, 95% CI = 0.43-1.49), difficulty concentrating (15.0% vs 18.4%, RR = 0.86, 95% CI = 0.55-1.34), and disturbed sleep (14.7% vs 16.2%, RR = 0.91, 95% CI = 0.59-1.39). Two sessions of HBO treatment exhibited no advantage over one session. Conclusions The meta-analysis indicated that compared with CO poisoning patients treated with NBO, HBO treated patients have a lower incidence of neuropsychological sequelae, including headache, memory impairment, difficulty concentrating, disturbed sleep, and delayed neurological sequelae. Taking into consideration the cost-effectiveness of one session of HBO, one session of HBO treatment could be an economical option for patients with CO poisoning with high severity.