The chemopreventive isothiocyanate sulforaphane reduces anoikis resistance and anchorage-independent growth in non-small cell human lung cancer cells.

The capacity of cancer cells to resist detachment-induced apoptosis, i.e. anoikis, as well as anchorage-independent growth are crucial prerequisites for tumor metastasis. Therefore, agents interfering these properties may provide novel anti-metastatic strategies. Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, is known as a potent chemopreventive agent, but its effect on anoikis resistance has not been investigated. In this study, two non-small cell lung cancer (NSCLC) cell lines, A549 and CL1-5 cells, were treated with SFN under either suspension or adhesion conditions. SFN exhibited more potent cytotoxicity against suspending rather than adherent cancer cells. The selective cytotoxicity was due to the induction of anoikis, as evident by chromatin condensation, Annexin V binding, and activation of the mitochondrial apoptotic pathway. SFN also inhibited NSCLC cell to form spherical colonies, suggesting that anchorage-independent growth was prevented by SFN. Consistently, SFN treatment led to inactivation of FAK and Akt, down-regulation of ß-catenin, and up-regulation of the cyclin-dependent kinase inhibitor p21. Because A549 cells with wild-type p53 are more sensitive to SFN than p53-mutant CL1-5 cells, p53 dependency of SFN responses were determined in p53-knockdown A549 cells. Knockdown of p53 attenuated the ability of SNF to inhibit anoikis resistance and sphere formation in A549 cancer cells, suggesting that the presence of p53 in NSCLC cancer cells is involved in the sensitivity to SFN. These results provide new insight into mechanisms underlying the chemopreventive ability of SFN and suggest a potential benefit of SFN to interfere with tumor metastasis.

Characteristics and outcomes of "Do Not Resuscitate" patients admitted to the emergency department-Intensive care unit.

BACKGROUND: Appropriate utilization of intensive care unit (ICU) beds are essential. Patients with critical illness who have do not resuscitate (DNR) have a reduced priority of intensive care. However, the possibility of recovery/survival is ambiguous and multifactorial. OBJECTIVE: To deliberate the characteristics and outcomes of critical illness in patients with prior DNR who were admitted to the emergency department (ED)-ICU. METHOD: This was a retrospective cohort study conducted between April 2015 and November 2015 in a university-based hospital. Non-traumatic patients with DNR admitted to ED-ICU from ED were included. RESULTS: Seventy-eight non-trauma patients with prior DNR status were included in the final analysis. 51.3% (40/78) patients were male with median age 83 (IQR: 75-89) years. The median APACHE II score was 24.5 (IQR: 20-30). 50% (39/78) of the DNR patients survived to discharge. Patients who survived to discharge had lower APACHE II score (23 (IQR: 20-28) vs. 28 (18-38), p = 0.028). There was no significant difference in age, gender, and Charlson index. ROC curves were constructed, generating a cut-off of the APACHE II score at 29.5 for determining survival to discharge (AUC = 0.644, p = 0.028). In multivariate Cox proportional model, APACHE II score above 29.5 was an independent predictor for mortality. (Hazard ratio = 2.46; 95% confidence interval: 1.04-5.83, p = 0.042). CONCLUSION: Our study found that 50% of patients with prior DNR on ICU admission survived to discharge, indicating that aggressive care is not definitely futile. Further prospective studies are required to evaluate the cost-effectiveness and patients' and/or families' satisfaction of the ICU admission of DNR patients.

Red blood cell distribution width is associated with mortality in elderly patients with sepsis.

INTRODUCTION: RDW is a prognostic biomarker and associated with mortality in cardiovascular disease, stroke and metabolic syndrome. For elderly patients, malnutrition and multiple comorbidities exist, which could affect the discrimination ability of RDW in sepsis. The main purpose of our study was to evaluate the prognostic value of RDW in sepsis among elderly patients. METHODS: This was a retrospective cohort study conducted in emergency department intensive care units (ED-ICU) between April 2015 and November 2015. Elderly patients (≥65years old) who were admitted to the ED-ICU with a diagnosis of severe sepsis and/or septic shock were included. The demographic data, biochemistry data, qSOFA, and APACHE II score were compared between survivors and nonsurvivors. RESULTS: A total of 117 patients was included with mean age 81.5±8.3years old. The mean APACHE II score was 21.9±7.1. In the multivariate Cox proportional hazards model, RDW level was an independent variable for mortality (hazard ratio: 1.18 [1.03-1.35] for each 1% increase in RDW, p=0.019), after adjusting for CCI, any diagnosed malignancy, and eGFR. The AUC of RDW in predicting mortality was 0.63 (95% confidence interval [CI]: 0.52-0.74, p=0.025). In subgroup analysis, for qSOFA <2, nonsurvivors had higher RDW levels than survivors (17.0±3.3 vs. 15.3±1.4%, p=0.044). CONCLUSIONS: In our study, RDW was an independent predictor of in-hospital mortality in elderly patients with sepsis. For qSOFA scores <2, higher RDW levels were associated with poor prognosis. RDW could be a potential parameter used alongside the clinical prediction rules.

Identifying the Risk Factor and Prevention of Limb Ischemia in Extracorporeal Membrane Oxygenation with Femoral Artery Cannulation.

OBJECTIVE: Application of extracorporeal membrane oxygenation (ECMO) for life support has been widely used in various fields of resuscitation. When the common femoral artery (CFA) is used during cannulation for ECMO support in adults, it is often complicated by limb ischemia. Placement of distal perfusion catheter (DPC) can reduce the incidence of limb ischemia and increases the likelihood of limb preservation, but selection criteria is uncertain. METHODS: This is a retrospective study. Data was reviewed for patients in one medical center who were supported by venoarterial extracorporeal membrane oxygenation (VA-ECMO) via CFA cannulation percutaneously between January 2008 and June 2014. Two groups were divided into no-ischemia and ischemic limb. Age, sex, height, weight, body surface area (BSA), cannula size, femoral artery diameter, comorbidity, acute physiology and chronic health evaluation (APACHE) II score, vasoactive-inotropic score (VIS) and mortality rate were analyzed. Doppler was used by measuring the distal pulsation in the dorsalis pedis and posterior tibial artery to select the patients. A DPC was prophylactically inserted percutaneously into the superficial femoral artery for antegrade flow to the extremity in the patients who met selection criteria. RESULTS: 139 (43.6%) patients were included in the study and limb ischemia occurred in 46 (33%) of 139. There was a significant difference between the no-ischemia group and the ischemia group in age (55.5 ± 14.2 versus 63.2 ± 13.2; P < .001), common femoral artery diameter (0.82 ± 0.14 versus 0.63 ± 0.17; P < .001 ), known peripheral artery occlusive disease (9% versus 24%; P < .001) and VIS (12.1 ± 8.1 versus 15.8 ± 10.1; P < .001). Mortality rate was higher in the ischemia group (46% versus 26% ; P < .001). 11 patients who met the selection criteria had a DPC prophylactically inserted and no ischemia limb occurred. CONCLUSION: Smaller common femoral artery diameter (≤6.3 cm); known peripheral arterial occlusive disease; higher VIS (≥15.8); absence of distal pulsation pre-cannulation or immediately after post-cannulation or 4 hrs later have higher risk of limb ischemia when CFA cannulation is used for VA-ECMO. Due to this, the mortality and morbidity rate increases when limb ischemia occurs. A DPC should be prophylactically inserted in high-risk patients who meet selection criteria.

Periarrest Modified Early Warning Score (MEWS) predicts the outcome of in-hospital cardiac arrest.

BACKGROUND/PURPOSE: The Modified Early Warning Score (MEWS) reflects the physiological changes of cardiac arrest and has been used in identifying patient deterioration. Physiological reserve capacity is an important outcome predictor, but is seldom reported due to recording limitations in cardiac arrest patients. The aim of the study was to evaluate whether periarrest MEWS could be a further prognostic factor in in-hospital cardiac arrest. METHODS: This was a retrospective cohort study of nontrauma adult patients who had experienced in-hospital cardiac arrest during emergency department stays at an urban, 2600-bed tertiary medical center in Taiwan from February 2011 to July 2013. Data regarding patients' characteristics, Charlson Comorbidity Score, MEWS score before events, mode of arrest, and outcome details were extracted following the Utstein guidelines for uniform reporting of cardiac arrest. RESULTS: During the 30-month period, 234 patients suffered in-hospital cardiac arrest during emergency department stays, and 99 patients with periarrest MEWS were included in the final analysis. The MEWS at triage did not differ significantly between survival-to-discharge and mortality groups (3.42 ± 2.2 vs. 4.02 ± 2.65, p = 0.811). Periarrest MEWS was lower in the survival-to-discharge group (4.41 ± 2.28 vs. 5.82 ± 2.84, p = 0.053). In multivariate logistic regression analysis, periarrest MEWS was an independent predictors for survival to discharge. A rise in periarrest MEWS reduced the chance of survival to discharge by 0.77-fold (95% confidence interval: 0.60-0.97, p = 0.028). CONCLUSION: The simplest MEWS system not only can be used as a prevention measure, but the periarrest MEWS could also be considered as an independent predictor of mortality after in-hospital cardiac arrest.

Balance function and sensory integration after mild traumatic brain injury.

OBJECTIVE: This study examined the disparities in balance functions and sensory integration in patients with mild traumatic brain injuries (mTBIs) and healthy controls. PARTICIPANTS: One hundred and seven patients with mTBI and 107 age- and sex-matched controls were recruaited for this study. PRIMARY MEASURES: Symptoms of dizziness, balance functions and the ability to perform daily activities were assessed using the dizziness handicap inventory (DHI). This study also performed the postural-stability test and a modified clinical test of sensory integration by using the Biodex Stability System (BBS). RESULTS: DHI scores (functional, emotional, physical and total self-reported scores) were substantially increased in patients following an mTBI compared with the scores of the controls (p < 0.000). The postural-stability test indices (anterior-posterior) (p = 0.045) and the sensory-integration test index (eyes-open-firm-surface index) (p = 0.006) were substantially lower in patients with mTBI than in the controls. However, indices of two other postural-stability test indices (overall and medial-lateral) and three other sensory-integration tests indices (eyes-closed-firm-surface, eyes-open-foam-surface and eyes-closed-foam-surface) measured for the mTBI group did not differ from those of the control group. CONCLUSION: Activities of daily living, balance in postural stability and sensory integration were strongly impaired in patients with mTBI.

Eradication of Helicobacter pylori for prevention of ulcer recurrence after simple closure of perforated peptic ulcer: a meta-analysis of randomized controlled trials.

BACKGROUND: Eradication of Helicobacter pylori has become part of the standard therapy for peptic ulcer. However, the role of H pylori eradication in perforation of peptic ulcers remains controversial. It is unclear whether eradication of the bacterium confers prolonged ulcer remission after simple repair of perforated peptic ulcer. METHODS: A systematic review and meta-analysis of randomized controlled trials was performed to evaluate the effects of H pylori eradication on prevention of ulcer recurrence after simple closure of perforated peptic ulcers. The primary outcome to evaluate these effects was the incidence of postoperative ulcers; the secondary outcome was the rate of H pylori elimination. RESULTS: The meta-analysis included five randomized controlled trials and 401 patients. A high prevalence of H pylori infection occurred in patients with perforated peptic ulcers. Eradication of H pylori significantly reduced the incidence of ulcer recurrence at 8 wk (risk ratio 2.97; 95% confidence interval: 1.06-8.29) and 1 y (risk ratio 1.49; 95% confidence interval: 1.10-2.03) postoperation. The rate of H pylori eradication was significantly higher in the treatment group than in the nontreatment group. CONCLUSIONS: Eradication therapy should be provided to patients with H pylori infection after simple closure of perforated gastroduodenal ulcers.

Aristolochic acid-induced accumulation of methylglyoxal and Nε-(carboxymethyl)lysine: an important and novel pathway in the pathogenic mechanism for aristolochic acid nephropathy.

Aristolochic acid, found in the Aristolochia species, causes aristolochic acid nephropathy (AAN) and can develop into renal failure. Methylglyoxal (MGO) is a highly cytotoxic compound generated from the metabolic process of glucose or fatty acids. It binds to proteins and forms N(ε)-(carboxymethyl)lysine (CML), which contributes to aging and diabetes mellitus complications. However, no relevant literature explores the relationship of MGO and CML with AAN. By injecting AA (10mg/kg BW) into C3H/He mice for 5 consecutive days, we successfully developed an AAN model and observed tubular atrophy with decreased renal function. Creatinine clearance also decreased from 10.32 ± 0.79 ml/min/kg to 2.19 ± 0.29 ml/min/kg (p<0.01). The concentration of MGO in kidney homogenates increased 12 × compared to the control group (from 18.23 ± 8.05 µg/mg of protein to 231.16 ± 17.57 µg/mg of protein, p<0.01), and CML was observed in the renal tubules of the mice by immunohistochemistry. Furthermore, compared to the control group, GSH levels decreased by 0.32 × (from 2.46 ± 0.41 µM/µg of protein to 0.78 ± 0.15 µM/µg of protein, p<0.01), whereas intra-renal antioxidant capacity decreased by 0.54×(from 6.82 ± 0.97 U to 3.71 ± 0.25 U; unit is equivalent to µM Trolox/mg of protein, p<0.01). In this study, we found that serious kidney damage induced by AA is related to an increase and accumulation of MGO and CML.

Bruns-Cushing nystagmus due to hypertensive unilateral paramedian pontine base infarction.

Bruns-Cushing nystagmus is unusually rare and is known to be related with cerebellopontine angle tumor. A 32-year-old male patient came to our emergency department 3 times because of dizziness, right upper limb ataxia, hypertension, and Bruns-Cushing nystagmus. Magnetic resonance imaging demonstrated left paramedian pontine infarction. In conclusion, Bruns-Cushing nystagmus not only indicates a cerebellopontine angle tumor but may also be associated with pontine infarction.

Worsening of Dizziness Impairment Is Associated with Bone Marrow Kinase on Chromosome X Level in Patients after Mild Traumatic Brain Injury.

Over 2 million people suffer from mild traumatic brain injury (mTBI) each year. Predicting symptoms of mTBI and the characterization of those symptoms has been challenging. Biomarkers that correlate clinical symptoms to disease outcome are desired to improve understanding of the disease and optimize patient care. Bone marrow kinase on chromosome X (BMX), a member of the TEC family of nonreceptor tyrosine kinases, is up-regulated after traumatic neural injury in a rat model of mTBI. The aim of this investigation was to determine whether BMX serum concentrations can effectively be used to predict outcomes after mTBI in a clinical setting. A total of 63 patients with mTBI (Glasgow Coma Score [GCS] between 13 and 15) were included. Blood samples taken at the time of hospital admission were analyzed for BMX. Data collected included demographic and clinical variables. Outcomes were assessed using the Dizziness Handicap Inventory (DHI) questionnaire at baseline and 6 weeks postinjury. The participant was asssigned to the case group if the subject's complaints of dizziness became worse at the sixth week assessment; otherwise, the participant was assigned to the control group. A receiver operating characteristic curve was constructed to explore BMX level. Significant associations were found between serum levels of BMX and dizziness. Areas under the curve for prediction of change in DHI postinjury were 0.76 for total score, 0.69 for physical score, 0.65 for emotional score, and 0.66 for functional score. Specificities were between 0.69 and 0.77 for total score and emotional score, respectively. Therefore, BMX demonstrates potential as a candidate serum biomarker of exacerbating dizziness post-mTBI.

Initial serum glucose level and white blood cell predict ventricular arrhythmia after first acute myocardial infarction.

OBJECTIVE: The aims of this study are to analyze the factors that predispose the occurrence of ventricular arrhythmia (VA) in young patients with a first acute myocardial infarction (AMI) in the emergency department (ED) and to establish predictive implications. METHODS: This is a 10-year retrospective cohort study. Patients who were older than 18 years and younger than 45 years with a first attack of AMI were recruited from the ED of 3 university teaching hospitals from January 1, 1998, to December 31, 2007. RESULTS: Five hundred young patients (472 men and 28 women) who met the inclusion criteria were enrolled. Within these patients, the incidence of life-threatening VA with first attack of AMI was 8% (n = 40). They were categorized into 2 groups: VA attack (n = 40) and non-VA attack (n = 460). In univariable analyses, acute anterolateral ST-segment elevation myocardial infarction (65% vs 47.8%; P = .04), elevate white blood cell (WBC) count (16.4 +/- 3.4 vs 11.5 +/- 3.1 x 10(3)/mm(3); P < .01), and initial serum glucose level (202.6 +/- 90.9 vs 151.9 +/- 64.7 mg/dL; P < .01) were significantly increased in the VA group. Multiple logistic regression model identified WBC count and initial serum glucose level as the significant independent variables in the prediction of VA attack for young patients with first attack of AMI. The receiver operating characteristic area for WBC count and serum glucose level in predicting the risk of VA occurring after AMI was 0.869 and 0.756, respectively. CONCLUSION: Initial serum glucose level and WBC may be used as valuable predictors for VA attack in young patients with first AMI.

A pilot study of citizens' opinions on the Incident Command System in Taiwan.

Local residents may have different views on disaster-response modes depending on their cultural and socioeconomic background. The purpose of this study was to examine Taiwan residents' opinions on the Incident Command System (ICS). We performed a structured survey through face-to-face interviews in mudslide-affected communities. Quantitative analysis showed that the residents exhibited a clear preference for the ICS core-principle attributes of 'integrated communications', 'transfer of command' and 'modular organisation'. By contrast, the residents tended towards a non-ICS approach for 'incident action plan' and 'manageable span of control'. Qualitative analysis revealed an uncertain attitude towards 'transfer of command' and 'incident action plan'. Community acceptance is important in the promotion of the ICS. A better understanding of residents' preferences should be acquired through a broader community survey, allowing us to understand perspectives on the ICS among different societies and facilitate implementation of the ICS at the basic community level.

Congenital midline nasal mass: cases series and review of the literature.

Encephalocele, glioma and dermoid cyst are the most common midline nasal masses. Given their potential for intracranial extension, prompt treatment is necessary to prevent complications. Herein, we present two cases of midline nasal masses. A comparison was made to delineate the differences between their clinical courses, treatments and outcomes. Case 1 was a baby girl with respiratory distress beginning at birth. Nasal glioma without definite intracranial extension was present. The mass was completely excised with the aid of a video-assisted endoscope without complications. At follow-up two years after surgery, no recurrence was noted. Case 2 was a two-year-old boy with a midline nasal dermoid cyst. Extirpation of the lesion through a vertical-dorsal approach was performed. He was discharged three days after surgery with a satisfactory aesthetic result.

Cryptanshinone Inhibits the Glycolysis and Inhibits Cell Migration Through PKM2/ß-Catenin Axis in Breast Cancer.

BACKGROUND: Breast cancer is one of the most prevalent gynecologic malignancies worldwide. Despite the high sensitivity in response to chemotherapy, drug resistance occurred frequently in clinical treatment. Cryptotanshinone (CTS) is a herbal medicine and has been identified as an anti-inflammatory and anti-oxidative drug. METHODS: In vitro assays, including the cell proliferation assay, colony formation assay, Western blot analysis, transwell migration/invasion assays, and cell scratch assay were used to explore the biological activities and working mechanism of CTS. Breast cancer cells were also transfected with PKM2 expressing vectors to define the molecular mechanisms involved in CTS-mediated anti-tumor activity. RESULTS: We found that CTS shows anti-proliferative effects and decreases the clonogenic ability of breast cancer cells. We also found that CTS inhibited the migration and invasion activity of MCF-7 and MDA-MB-231 cells by different analyzed methods. CTS also downregulated the levels of glycolysis-related proteins, such as PKM2, LDHA, and HK2. In addition, overexpression of PKM2 recovered CTS-mediated suppression of cell proliferation, colony formation, and cell mobility of breast cancer cells. We also found PKM2 was significantly overexpressed in tumor tissues and invasive ductal breast carcinoma compared to normal tissues and patients with high PKM2 expression had worse overall survival and metastasis-free survival outcomes. CONCLUSION: CTS inhibited the proliferation, migration, and invasion of breast cancer cells. The involved mechanism may refer to the downregulation of the PKM2/ß-catenin axis.

TGF-beta inhibits IL-1beta-activated PAR-2 expression through multiple pathways in human primary synovial cells.

To investigate the mechanism how Transforming growth factor-beta(TGF-beta) represses Interleukin-1beta (IL-1beta)-induced Proteinase-Activated Receptor-2 (PAR-2) expression in human primary synovial cells (hPSCs). Human chondrocytes and hPSCs isolated from cartilages and synovium of Osteoarthritis (OA) patients were cultured with 10% fetal bovine serum media or serum free media before treatment with IL-1beta, TGF-beta1, or Connective tissue growth factor (CTGF). The expression of PAR-2 was detected using reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting. Collagen zymography was performed to assess the activity of Matrix metalloproteinases-13 (MMP-13). It was demonstrated that IL-1beta induces PAR-2 expression via p38 pathway in hPSCs. This induction can be repressed by TGF-beta and was observed to persist for at least 48 hrs, suggesting that TGF-beta inhibits PAR-2 expression through multiple pathways. First of all, TGF-beta was able to inhibit PAR-2 activity by inhibiting IL-1beta-induced p38 signal transduction and secondly the inhibition was also indirectly due to MMP-13 inactivation. Finally, TGF-beta was able to induce CTGF, and in turn CTGF represses PAR-2 expression by inhibiting IL-1beta-induced phospho-p38 level. TGF-beta could prevent OA from progression with the anabolic ability to induce CTGF production to maintain extracellular matrix (ECM) integrity and to down regulate PAR-2 expression, and the anti-catabolic ability to induce Tissue inhibitors of metalloproteinase-3 (TIMP-3) production to inhibit MMPs leading to avoid PAR-2 over-expression. Because IL-1beta-induced PAR-2 expressed in hPSCs might play a significantly important role in early phase of OA, PAR-2 repression by exogenous TGF-beta or other agents might be an ideal therapeutic target to prevent OA from progression.

How risky is caring for emergency patients at risk of malpractice litigation: a population based epidemiological study of Taiwan's experiences.

BACKGROUND: Emergency medicine has generally been considered a high risk specialty. The purpose of this study is to assess the risk of being sued in the district courts for caring emergency room (ER) patients from the perspective of epidemiology. METHODS: This research was designed to be a retrospective population based cohort study. We intended to find out the incidence of litigations arising from ER patients and that of birth inpatients in Taiwan, and computed their relative risks. The inclusion criterion was set to be incidents transpired in the time period of 1998 to 2002. The study materials included the reimbursement claim dataset of the National Health Insurance from 1998 to 2002, and the district court decision database of the Judicial Yuan from 1999 to 2006. RESULTS: The average annual incidence rate of becoming a plaintiff for ER patients is 0.86 per million, and for birth patients is 33.5 per million. There is a statistically significant difference between birth patients and ER patients. The relative risk comparing ER patients against birth inpatients is 0.03. CONCLUSION: The findings of this population based study indicate that the patient population emergency physicians are facing in Taiwan have relatively lower risks of developing litigation in comparison with the patients that come to give birth. Due to the large volume of ER patients, malpractice still pose a major threat in the emergency department, and misdiagnosis remains the major complaint of plaintiffs in subsequent litigations.

Correction: Increased long-term risk of major adverse cardiovascular events in patients with carbon monoxide poisoning: A population-based study in Taiwan.

[This corrects the article DOI: 10.1371/journal.pone.0176465.].

Incidences of Hypothyroidism Associated With Surgical Procedures for Thyroid Disorders: A Nationwide Population-Based Study.

Background and Aim: Limited information available about different types of thyroid surgeries with risk for postoperative hypothyroidism. This study aimed to investigate the risk of developing early and late-onset postoperative hypothyroidism in patients with thyroid disorders. Methods: We used a large cohort data from the Taiwan National Health Insurance Research Data Base (NHIRDB) and identified 9,693 (9, 348) patients from January 1998 to December 2010, admitted for thyroid disorder surgeries. We used the surgical procedures time as the index date. Our observational retrospective cohort study excluded the subjects diagnosed with hypoparathyroidism and hypothyroidism before any surgeries. We analyzed the data using the Cox regression model to calculate the hazard ratio. Result: Postoperative hypothyroidism associated with bilateral-total (HR, 4.27; 95% CI, 3.32-5.50), one-side total and another subtotal (HR, 3.16; 95% CI, 2.59-3.86), bilateral-subtotal (HR, 1.65; 95% CI, 1.37-1.98), and unilateral-total (HR, 1.17; 95% CI, 0.95-1.44) surgical procedures. The time intervals for thyroid disorders were 320 cases developed postoperative hypoparathyroidism in eight weeks, 480 cases the second month, and 1000 cases in the first year after surgery. Conclusion: Findings suggest that thyroidectomy was associated with transient postoperative hypothyroidism in thyroid disorder patients. The bilateral-total surgical procedure was strongly associated with temporary postoperative hypothyroidism.

Collagen 1A1 (COL1A1) Is a Reliable Biomarker and Putative Therapeutic Target for Hepatocellular Carcinogenesis and Metastasis.

Increasing evidence shows that hepatocellular carcinoma (HCC) is a principal cause of cancer-related mortality globally, especially among Asian and African populations. Collagen type I α1 (COL1A1) is the major component of type I collagen. While aberrant expression of COL1A1 and COL1A2 is implicated in numerous cancers, the differential role of COL1A1 in malignant, premalignant and normal tissues remains unclear, and its clinical significance in HCC has not been elucidated. In this study, using bioinformatics analysis of publicly-available HCC microarray data from Gene Expression Omnibus (GEO) and RNAseq data from The Cancer Genome Atlas (TCGA) database, we determined that COL1A1 is significantly upregulated in HCC tumor tissues in comparison to normal tissues. Our analysis also revealed that COL1A1 confers survival advantage and enhanced oncogenicity on HCC cells. Interestingly, the siRNA-mediated silencing of COL1A1 expression (siCOLIA1) suppressed HCC cells clonogenicity, motility, invasiveness and tumorsphere formation. Concomitantly, siCOL1A1 abrogated Slug-dependent epithelial-to-mesenchymal transition (EMT) and HCC stemness gene-signature, by attenuating expression of stemness markers SOX2, OCT4 and CD133. The present study provides some mechanistic insight into COL1A1 activity in HCC and highlights its putative role as an important diagnostic biomarker and potential therapeutic target in early development and metastasis of HCC.

Psychometric Evaluation of Anxiety, Depression, and Sleep Quality after a Mild Traumatic Brain Injury: A Longitudinal Study.

Introduction. Over 1 million mild traumatic brain injury (mTBI) cases are reported annually worldwide and may result in cognitive, physical, and emotional deterioration; depression; anxiety; and sleep problems. However, studies on long-term mTBI effects are limited. This study included 440 patients, and regular follow-ups of psychological assessments were performed for 2 years. Four questionnaires, including the Pittsburgh sleep quality index (PSQI), Epworth sleepiness scale (ESS), Beck's anxiety inventory (BAI), and Beck's depression inventory (BDI), were used to evaluate sleep problems, daytime sleepiness, anxiety, and depression, respectively. Results show that BAI and BDI scores considerably improved at the 6th-week, 1st-year, and 2nd-year follow-ups compared to baseline, yet these remained significantly different. In addition, anxiety and depression were prominent symptoms in a select subgroup of patients with poor initial evaluations, which improved over the 2 years. However, the ESS and PSQI scores fluctuated only mildly over the same time span. In conclusion, the mTBI patients showed a gradual improvement of anxiety and depression over the 2 years following injury. While anxiety and depression levels for mTBI patients in general did not return to premorbid status, improvements were observed. Sleep disorders persisted and were consistent with initial levels of distress.