The Impact of Trans-thoracic Ultrasound on Cardiac Injuries

Objective:

To determine the impact of trans-thoracic ultrasound (TTUS) in patients with chest trauma and potential cardiac injuries and to determine the outcome of patients with cardiac injury detected on TTUS.

Method:

Data were obtained from the Trauma Registry for all patients presenting alive to the University Hospital of the West Indies during the 10-year period commencing January 1, 2001 and who were subjected to a TTUS or emergency thoracotomy for cardiac injuries, or had cardiac injuries at postmortem. In addition to demographics, variables analysed included mechanism and site of injury and outcome.

Results:

Of 405 patients being subjected to a TTUS during the period, 12 (3%) had cardiac injuries. During the same period, 63 patients in the Trauma Registry had proven cardiac injuries. Transthoracic ultrasound was thus conducted on 19% of all patients with cardiac injuries. Three patients had positive TTUS but no cardiac injuries. Of the patients with injuries, the mean age was 30.4 years, 92.1% were male and 65% were as a result of stab wounds, while 22% were as a result of gunshot wounds. The right ventricle was the most common site of injury, accounting for 41% of cases, while the left ventricle, both ventricles and other sites accounted for 27%, 17% and 14%, respectively. Ninety per cent of the group was subjected to emergency thoracotomy; mortality of the entire group was 48%, including one patient who had TTUS.

Conclusions:

This review demonstrates that cardiac injuries remain lethal, diagnosis is largely clinical and TTUS may be over-utilized, having little impact on clinical outcome of patients presenting with this injury.     

Taiwanin C elicits apoptosis in arecoline and 4‐nitroquinoline‐1‐oxide‐induced oral squamous cell carcinoma cells and hinders proliferation via epidermal growth factor receptor/PI3K suppression

Oral Squamous Cell Carcinoma (OSSC) is a major life‐threatening disease with high incidence in the Southeast Asian countries. Chronic exposure to arecoline causes genetic changes in the epithelial cells of the oral mucosa, induces proliferation through activation of the EGF receptor and promotes downstream COX‐2 expression. Taiwanin C, a podophyllotoxin derived from Taiwania cryptomerioides Hayata is known to inhibit COX activity and to hinder PGE2 production in macrophages. In this study a tumor cell line T28 and a non‐tumor cell line N28 derived from mice OSCC models were used to study the effect of Taiwanin C on PGE₂ associated COX‐2 expression and cell cycle regulators. Taiwanin C activated p21 protein expression, down‐regulated cell cycle regulatory proteins, elevated apoptosis and down‐regulated p‐PI3K/p‐Akt survival mechanism in T28 oral cancer cells. Our results therefore emphasize the therapeutic potential of Taiwanin C against arecoline‐induced oral cancer.     

Extensive White Matter Dysfunction in Cognitively Impaired Patients with Secondary-Progressive Multiple Sclerosis

BACKGROUND AND PURPOSE:Cognitive impairment is a common, disabling symptom of MS. We investigated the association between cognitive impairment and WM dysfunction in secondary-progressive multiple sclerosis using DTI.MATERIALS AND METHODS:Cognitive performance was assessed with a standard neuropsychological battery, the Minimal Assessment of Cognitive Function in Multiple Sclerosis. Cognitive impairment was defined as scoring >1.5 standard deviations below healthy controls on ≥2 subtests. Fractional anisotropy maps were compared against cognitive status using tract-based spatial statistics with threshold-free cluster enhancement.RESULTS:Forty-five patients with secondary-progressive multiple sclerosis (median age: 55 years, female/male: 27/18, median Expanded Disability Status Scale Score: 6.5) were prospectively recruited. Cognitively impaired patients (25/45) displayed significantly less normalized global GM and WM volumes (P = .001, P = .024), more normalized T2-weighted and T1-weighted WM lesion volumes (P = .002, P = .006), and lower WM skeleton fractional anisotropy (P < .001) than non-impaired patients. Impaired patients also had significantly lower fractional anisotropy (p_corr < .05) in over 50% of voxels within every major WM tract. The most extensively impinged tracts were the left posterior thalamic radiation (100.0%), corpus callosum (97.8%), and right sagittal stratum (97.5%). No WM voxels had significantly higher fractional anisotropy in patients with cognitive impairment compared with their non-impaired counterparts (p_corr > .05). After the inclusion of confounders in a multivariate logistic regression, only fractional anisotropy remained a significant predictor of cognitive status.CONCLUSIONS:Cognitively impaired patients with secondary-progressive multiple sclerosis exhibited extensive WM dysfunction, though preferential involvement of WM tracts associated with cognition, such as the corpus callosum, was apparent. Multivariate analysis revealed that only WM skeleton fractional anisotropy was a significant predictor of cognitive status.

Cognitive impairment is a prevalent symptom of MS and has been estimated to occur in 43%–65% of patients.¹ Those with secondary-progressive multiple sclerosis (SPMS) exhibit the highest frequency of impairment.² Prior neuroimaging studies have almost exclusively investigated such impairment by assessing discrete cognitive domains, such as information processing speed or working memory, with neuropsychological tests that have established domain specificity. Such an approach is apparent in studies that examined both brain and lesion volumetry^3–6 and WM integrity.^7–11 Domain-specific cognitive tests are powerful tools that can assess the impact of MS pathology on individual cognitive domains and specific neuronal pathways, but cannot investigate cognition as a multidomain entity. Few studies of cognitive impairment in MS have adopted this broader perspective, and patients with MS with multiple domain impairment may exhibit considerably different structural brain damage from their counterparts with single domain impairment.MS has been traditionally viewed as a disease predominantly affecting WM, though only modest associations between T2-weighted hyperintense or T1-weighted hypointense white matter lesion (WML) load and cognitive test performance have been reported.¹² Normal-appearing white matter is being increasingly examined, particularly through DTI techniques.^7–11,13,14 These studies have most frequently used fractional anisotropy (FA) as their primary outcome,^8–11,13,14 whereas mean diffusivity has been investigated to a lesser extent.⁷ Radial diffusivity and axial diffusivity have been examined as secondary outcomes.^11,14 Given the recent emphasis on the role of GM pathology both in the etiology of MS and related cognitive dysfunction, FA was considered in the context of GM volume using multivariate regression.^15–17 Normal-appearing white matter has also been investigated using magnetization transfer ratio.¹⁸Tract-based spatial statistics (TBSS) is being increasingly utilized in DTI studies of MS and cognition.^8,9,11,13 TBSS has improved on traditional voxel-based morphometry by thinning WM to invariant tracts common to all patients.¹⁹ The voxel-based morphometry approach suffers from deficiencies related to spatial alignment and smoothing, which are mitigated by TBSS. Several prior TBSS studies have concluded that cognitive impairment in MS is because of the selective disruption of specific WM tracts associated with cognition, such as the cingulum and corpus callosum (CC).^8,9,11 It should be noted that this spatial specificity has a physiologic basis and is not mediated by the cognitive nature of these tracts. These studies correlated FA values with performance on individual cognitive tests and examined cohorts primarily or solely comprising patients with relapsing-remitting MS (RRMS). DTI outcomes in patients with SPMS with and without cognitive impairment have not been well investigated, yet 65% of patients with RRMS will progress to SPMS.²⁰ While WM injury is initially selective for specific tracts associated with impaired cognition in RRMS, DTI abnormalities are expected to become significantly more widespread and generalized with greater impairment and disease severity progression.We hypothesized that patients with SPMS with impairment spanning multiple cognitive domains should exhibit extensive WM dysfunction not restricted to tracts implicated in cognition, such as the cingulum and CC.     

Moderating Mechanism in the Relationship between Social Isolation and Mental Health among College Students during High-Risk Period of COVID-19 Transmission in Hubei,China

This study explored the effect of perceived social isolation on the mental health of college students during the high-risk period of COVID-19 transmission in Hubei, China and the role of social support from online friends in alleviating this effect. The questionnaire responses of 213 college students from four universities in Hubei were included. Measurement and structural models were constructed using structural equation modeling. The findings revealed that perceived social isolation while under home quarantine was a negative predictor of the mental health of college students in Hubei. Low social support from online friends may lead to a relatively strong relationship between perceived social isolation and mental health in these college students, whereas high social support from online friends may lead to a relatively weak relationship between perceived social isolation and mental health.     

Protocadherin 10 suppresses tumorigenesis and metastasis in colorectal cancer and its genetic loss predicts adverse prognosis

Protocadherin 10 (PCDH10), a novel tumor suppressor gene in human cancers, is located in a common deleted region at chromosome 4q28 in colorectal cancer (CRC). This study aimed to ascertain the genetic loss of PCDH10 and its clinical relevance in CRC and to explore the tumor suppressor function of PCDH10. The genetic deletion of PCDH10 was determined in 171 pairs of primary tumors and corresponding normal mucosae by loss of heterozygosity study. In total, 53 carcinomas were positive for allelic loss of PCDH10. The genetic aberration was significantly associated with tumor progression and distant metastasis (p = 0.021 and p = 0.018, respectively) and was an independent predictor of poor survival for CRC patients (p = 0.005). Expression of PCDH10 gene was silenced or markedly down‐regulated in all of 12 CRC cell lines tested and in 41 of 53 colorectal carcinomas compared with their matched normal mucosae. Ectopic expression of PCDH10 suppressed cancer cell proliferation, anchorage‐independent growth, migration and invasion in vitro. Subcutaneous injection of PCDH10‐expressing CRC cells into SCID mice revealed the reduction of tumor growth compared with that observed in mock‐inoculated mice. Furthermore, through intrasplenic implantation, the re‐expression of PCDH10 in silenced cells restrained liver metastasis and improved survival in SCID mice. In conclusion, PCDH10 is a pivotal tumor suppressor in CRC, and the loss of its function promotes not only tumor progression but also liver metastasis. In addition, the genetic deletion of PCDH10 represents an adverse prognostic marker for the survival of patients with CRC.     

Downregulation of microRNA‐15b by hepatitis B virus X enhances hepatocellular carcinoma proliferation via fucosyltransferase 2‐induced Globo H expression

Globo H, a cancer‐associated carbohydrate antigen, is highly expressed in various types of cancers. However, the role of Globo H in hepatocellular carcinoma (HCC) remains elusive. In our study, we performed glycan microarray analysis of 134 human serum samples to explore anti‐Globo H antibody changes and found that Globo H is upregulated in hepatitis B virus (HBV)‐positive HCC. Similarly, immunohistochemistry showed that Globo H expression was higher in tumors compared to normal tissues. In addition, fucosyltransferase 2 (FUT2), the main synthetic enzyme of Globo H, was also increased in HCC cells overexpressing HBV X protein (HBX). HBX plays an important role in promoting cell proliferation and may be related to increased levels of FUT2 and Globo H. Furthermore, using microRNA profiling, we observed that microRNA‐15b (miR‐15b) was downregulated in patients with HCC and confirmed association of FUT2 expression with expression of its product, Globo H. Therefore, our results suggest that HBX suppressed the expression of miR‐15b, which directly targeted FUT2 and then increased levels of Globo H to enhance HCC cell proliferation. Additionally, proliferation of HBX‐overexpressing HCC cells was significantly inhibited by treatment with Globo H antibody in vitro. In xenograft animal experiments, we found that overexpression of miR‐15b effectively suppressed tumor growth. The newly identified HBX/miR‐15b/FUT2/Globo H axis suggests one possible molecular mechanism of HCC cell proliferation and represents a new potential therapeutic target for HCC treatment.     

Radiosensitization by combining an aurora kinase inhibitor with radiotherapy in hepatocellular carcinoma through cell cycle interruption

Radiotherapy has been integrated into the multimodal treatment of hepatocellular carcinoma (HCC), especially of localized hepatic tumor(s) refractory to conventional treatment. However, tumor control remains unsatisfactory mainly because of insufficient dose, and sublethally irradiated tumor may associate with metastasis. Our aim was to assess the effect of combining a molecularly targeted Aurora kinase inhibitor, VE‐465, with radiotherapy in in vitro and in vivo models of human HCC. Human HCC cell lines (Huh7 and PLC‐5) were used to evaluate the in vitro synergism of combining VE‐465 with irradiation. Flow cytometry analyzed the cell cycle changes, while western blot investigated the protein expressions after the combined treatment. Severe combined immunodeficient (SCID) mice bearing ectopic and orthotopic HCC xenografts were treated with VE‐465 and/or radiotherapy for the in vivo response. VE‐465 significantly enhanced radiation‐induced death in HCC cells by a mechanism involving the enhanced inhibition of histone H3 phosphorylation and interruption of cell cycle change. In SCID, mice bearing ectopic HCC xenografts, pretreatment with VE‐465 (20 mg/kg/day × 9 days) significantly enhanced the tumor‐suppressive effect of radiotherapy (5 Gy/day × 5 days) by 54.0%. A similar combinatorial effect of VE‐465 and radiotherapy was observed in an orthotopic model of Huh7 tumor growth by 17.2%. In the orthotopic Huh7 xenografts, VE‐465 significantly enhanced radiation‐induced tumor growth suppression by a mechanism involving the increased apoptosis. VE‐465 is a potent inhibitor of Aurora kinase with therapeutic value as a radiosensitizer of HCC.     

A new insight into fecal hemoglobin concentration‐dependent predictor for colorectal neoplasia

We sought to assess how much of the variation in incidence of colorectal neoplasia is explained by baseline fecal hemoglobin concentration (FHbC) and also to assess the additional predictive value of conventional risk factors. We enrolled subjects aged 40 years and over who attended screening for colorectal cancer with the fecal immunochemical test (FIT) in Keelung community‐based integrated screening program. The accelerated failure time model was used to train the clinical weights of covariates in the prediction model. Datasets from two external communities were used for external validation. The area under curve (AUC) for the model containing only FHbC was 83.0% (95% CI: 81.5–84.4%), which was considerably greater than the one containing only conventional risk factors (65.8%, 95% CI: 64.2–67.4%). Adding conventional risk factors did not make significant additional contribution (p = 0.62, AUC = 83.5%, 95% CI: 82.1–84.9%) to the predictive model with FHbC only. Males showed a stronger linear dose‐response relationship than females, yielding gender‐specific FHbC predictive models. External validation confirms these results. The high predictive ability supported by a dose‐dependent relationship between baseline FHbC and the risk of developing colorectal neoplasia suggests that FHbC may be useful for identifying cases requiring closer postdiagnosis clinical surveillance as well as being an early indicator of colorectal neoplasia risk in the general population. Our findings may also make contribution to the development of the FHbC‐guided screening policy but its pros and cons in connection with cost and effectiveness of screening should be evaluated before it can be applied to population‐based screening for colorectal cancer.