Video feedback to update negative self-perceptions in social anxiety disorder: A comparison of internet-delivered vs face-to-face cognitive therapy formats.

BACKGROUND: Video feedback is a technique used in cognitive therapy for social anxiety disorder (CT-SAD) to update patients' negative self-perceptions of how they appear to others. Clients are supported to watch video of themselves engaging in social interactions. While typically undertaken in session with a therapist, this study aimed to investigate the effectiveness of remotely delivered video feedback embedded within an Internet-based cognitive therapy program (iCT-SAD). METHODS: We examined patients' self-perceptions and social anxiety symptoms before and after video feedback in two randomised controlled trials. Study 1 compared 49 iCT-SAD participants with 47 from face-to-face CT-SAD. Study 2 was a replication using data from 38 iCT-SAD participants from Hong Kong. RESULTS: In Study 1, ratings of self-perceptions and social anxiety showed significant reductions following video feedback, in both treatment formats. 92 % of participants in iCT-SAD, and 96 % in CT-SAD thought they looked less anxious compared to their predictions after viewing the videos. The change in self-perception ratings was larger in CT-SAD compared to iCT-SAD, but there was no evidence that the impact of video feedback on social anxiety symptoms around a week later differed between the two treatments. Study 2 replicated the iCT-SAD findings of Study 1. LIMITATIONS: The level of therapist support in iCT-SAD videofeedback varied with clinical need and was not measured. CONCLUSIONS: The findings indicate that video feedback can be delivered effectively online, and that its impact on social anxiety is not significantly different from in-person treatment delivery.

Internet-delivered cognitive therapy for social anxiety disorder in Hong Kong: A randomized controlled trial.

Background: Research is needed to determine the extent to which internet-delivered psychological therapies are effective when delivered in countries and cultures outside of where they were developed. Objective: This waitlist-controlled study evaluated the efficacy of a UK-developed, therapist-guided internet Cognitive Therapy programme for Social Anxiety Disorder (iCT-SAD) when delivered in Hong Kong by local therapists. Methods: Patients were randomized to iCT-SAD (n = 22) or a waitlist control group (n = 22). Assessments took place at weeks 0, 8, and 15 (posttreatment/postwait), with a further 3-month follow-up assessment for the iCT-SAD group. The primary outcome measure was the Liebowitz Social Anxiety Scale (self-report), and posttreatment/postwait diagnostic assessments were completed by independent assessors blind to condition. Trial Registration: ISRCTN11357117. Results: Compared with the waitlist group, iCT-SAD significantly reduced social anxiety symptoms (adjusted difference at posttreatment 55.36, 95%CI 44.32 to 66.39, p < 0.001; d Cohen 2.41). The treatment was also superior to waitlist on all secondary outcome measures. 86% of the iCT-SAD group demonstrated remission from SAD based on the LSAS, compared to 5% of the waitlist group. 73% no longer met diagnostic criteria at posttreatment, compared to 9% of the waitlist group. The gains made by the iCT-SAD group were maintained at three-month follow-up. Conclusions: iCT-SAD showed strong efficacy for the treatment of SAD in Hong Kong. As the clinical outcomes were similar to UK studies, this suggests the dissemination of the treatment into a different cultural setting did not result in a substantial loss of efficacy.

A Parallel Pandemic: Increased Firearm Injuries at Five Northern California Trauma Centers During the COVID-19 Pandemic: An Interrupted Time-series Analysis.

OBJECTIVE: This study aimed to characterize changes in firearm injuries at 5 level 1 trauma centers in Northern California in the 12 months following the start of the COVID-19 pandemic compared with the preceding 4 years, accounting for regional variations and seasonal trends. SUMMARY AND BACKGROUND DATA: Increased firearm injuries have been reported during the early peaks of the COVID-19 pandemic despite shelter-in-place restrictions. However, these data are overwhelmingly from singlecenter studies, during the initial phase of the pandemic prior to lifting of shelter-in-place restrictions, or do not account for seasonal trends. METHODS: An interrupted time-series analysis (ITSA) of all firearm injuries presenting to 5 adult level 1 trauma centers in Northern California was performed (January 2016to February 2021). ITSA modeled the association of the onset of the COVID-19 pandemic (March 2020) with monthly firearm injuries using the ordinary least-squares method, included month indicators to adjust for seasonality, and specified lags of up to 12 months to account for autocorrelation. RESULTS: Prior to the start of COVID-19, firearm injuries averaged (±SD) of 86 (±16) and were decreasing by 0.5/month (P < 0.01). The start of COVID- 19 (March 2020) was associated with an alarming increase of 39 firearm injuries/month (P < 0.01) followed by an ongoing rise of 3.5/mo (P < 0.01). This resulted in an average of 130 (±26) firearm injuries/month during the COVID-19 period and included 8 of the 10 highest monthly firearm injury rates in the past 5 years. CONCLUSIONS: These data highlight an alarming escalation in firearm injuries in the 12 months following the onset of the COVID-19 pandemic in Northern California. Additional studies and resources are needed to better understand and address this parallel public health crisis.

Mortality in hypotensive trauma patients requiring laparotomy is related to degree of hypotension and provides evidence for focused interventions.

BACKGROUND: Mortality in hypotensive patients requiring laparotomy is reported to be 46% and essentially unchanged in 20 years. Resuscitative endovascular balloon occlusion of the aorta (REBOA) has been incorporated into resuscitation protocols in an attempt to decrease mortality, but REBOA can have significant complications and its use in this patient group has not been validated. This study sought to determine the mortality rate for hypotensive patients requiring laparotomy and to evaluate the mortality risk related to the degree of hypotension. Additionally, this study sought to determine if there was a presenting systolic blood pressure (SBP) that was associated with a sharp increase in mortality to target the appropriate patient group most likely to benefit from focused interventions such as REBOA. METHODS: The trauma registry at a level I trauma center was reviewed for patients undergoing emergent laparotomy from January 2007 to June 2020. Data included demographics, mechanism of injury, physiological data, Injury Severity Score, blood products transfused, and outcomes. Group comparisons were based on initial SBP (0 to 50 mm Hg, 60 to 69 mm Hg, 70 to 79 mm Hg, 80 to 89 mm Hg, and ≥90 mm Hg). RESULTS: During the study period, 52 016 trauma patients were treated and 1174 required laparotomy within 90 min of arrival; 424 had an initial SBP of <90 mm Hg. The overall mortality rate was 18%, but mortality increased as SBP decreased (≥90=9%, 80 to 89=20%, 70 to 79=21%, 60 to 69=48%, 0 to 59=66%). Mortality increased sharply with SBP of <70 mm Hg. DISCUSSION: Mortality rate increases with worsening hypotension and increases sharply with an SBP of <70 mm Hg. Further study on focused interventions such as REBOA should target this patient group. LEVEL OF EVIDENCE: Therapeutic/care management, level III.

A Prevention Program for Insomnia in At-risk Adolescents: A Randomized Controlled Study.

OBJECTIVES: To prevent the future development of insomnia in at-risk adolescents. METHODS: A randomized controlled trial comparing 4 weekly insomnia prevention program with a nonactive control group. Subjects were assessed at baseline, postintervention, and 6 and 12 months after intervention. Assessors were blinded to the randomization. Analyses were conducted on the basis of the intention-to-treat principles. RESULTS: A total of 242 adolescents with family history of insomnia and subthreshold insomnia symptoms were randomly assigned to an intervention group (n = 121; mean age = 14.7 ± 1.8; female: 51.2%) or control group (n = 121; mean age = 15.0 ± 1.7; female: 62.0%). There was a lower incidence rate of insomnia disorder (both acute and chronic) in the intervention group compared with the control group (5.8% vs 20.7%; P = .002; number needed to treat = 6.7; hazard ratio = 0.29; 95% confidence interval: 0.12-0.66; P = .003) over the 12-month follow-up. The intervention group had decreased insomnia symptoms (P = .03) and reduced vulnerability to stress-related insomnia (P = .03) at postintervention and throughout the 12-month follow-up. Decreased daytime sleepiness (P = .04), better sleep hygiene practices (P = .02), and increased total sleep time (P = .05) were observed at postintervention. The intervention group also reported fewer depressive symptoms at 12-month follow-up (P = .02) compared with the control group. CONCLUSIONS: A brief cognitive behavioral program is effective in preventing the onset of insomnia and improving the vulnerability factors and functioning outcomes.

Admission base deficit is superior to lactate in identifying shock and resuscitative needs in trauma patients.

BACKGROUND: Base Deficit (BD) and lactate have been used as indicators of shock and resuscitation. This study was done to evaluate the utility of BD and lactate in identifying shock and resuscitative needs in trauma patients. METHODS: A prospective observational study was performed from 3/2014-12/2018. Data included demographics, admission systolic BP, ISS, BD, lactate, blood transfusion, and outcomes. BD and lactate were modeled continuously and categorically and compared. RESULTS: 2271 patients were included. BD and lactate were moderately correlated (r2 = 0.63 p < 0.001). On univariate regression, BD and lactate were associated with transfusion requirement and mortality (p < 0.001), but on multivariate regression, only BD was associated with transfusion requirement and mortality (OR = 1.2, p < 0.001; OR = 1.1, p < 0.001, respectively). BD discriminated better than lactate for hypotension, higher ISS, increased transfusion requirements and mortality. CONCLUSIONS: Admission BD and lactate levels are correlated following injury, but BD is superior to lactate in identifying shock, resuscitative needs and mortality in severely injured trauma patients.

Repeat computed tomography head scan is not indicated in trauma patients taking novel anticoagulation: A multicenter study.

BACKGROUND: The number of trauma patients on prehospital novel oral anticoagulants (NOACs) is increasing. After an initial negative computed tomography of the head (CTH), practice patterns are variable for obtaining repeat CTH to evaluate for delayed intracranial hemorrhage (ICH-d). However, the risks and outcomes of ICH-d for patients on NOACs are unclear. We hypothesized that, for these patients, the incidence of ICH-d is low, similar to that of warfarin, and when it occurs, it does not result in clinically significant worse outcomes. METHODS: Five level 1 trauma centers in Northern California participated in a retrospective review of anticoagulated trauma patients. Patients were included if their initial CTH was negative. Primary outcomes were incidence of ICH-d, neurosurgical intervention, and death. Patient factors associated with the outcome of ICH-d were determined by multivariable regression. RESULTS: From 2016 to 2018, 777 patients met the inclusion criteria (NOAC, n = 346; warfarin, n = 431), 54% of whom received a repeat CTH. Delayed intracranial hemorrhage incidence was 2.3% in the NOAC group and 4% in the warfarin group (p = 0.31). No NOAC patient with ICH-d required neurosurgical intervention or died because of their head injury. Two warfarin patients received neurosurgical intervention, and three died from their head injury. Head Abbreviated Injury Scale ≥3 was associated with increased odds of developing ICH-d (adjusted odds ratio, 32.70; p < 0.01). CONCLUSION: The incidence of ICH-d in patients taking NOAC is low. In this study, patients on NOACs who developed ICH-d after an initial negative CTH did not need neurosurgical intervention or die from their head injury. Repeat CTH in this patient population does not appear necessary. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III.Therapeutic, level IV.

Prospective evaluation of admission cortisol in trauma.

BACKGROUND: A low cortisol level has been shown to occur soon after trauma, and is associated with increased mortality. The purpose of this study was to investigate the impact of low cortisol levels in acute critically ill trauma patients. We hypothesized that patients would require increase vasopressor use, have a greater blood product administration, and increased mortality rate. METHODS: A blinded, prospective observational study was performed at an American College of Surgeons verified Level I trauma center. Adult patients who met trauma activation criteria, received initial treatment at Community Regional Medical Center and were admitted to the intensive care unit were included. Total serum cortisol levels were measured from the initial blood draw in the emergency department. Patients were categorized according to cortisol ≤15 µg/dL (severe low cortisol, SLC), 15.01-25 µg/dL (relative low cortisol, RLC), or >25 µg/dL (normal cortisol, NC) and compared on demographics, injury severity score, initial vital signs, blood product usage, vasopressor requirements, and mortality. RESULTS: Cortisol levels were ordered for 280 patients; 91 were excluded and 189 were included. Penetrating trauma accounted for 19% of injuries and blunt trauma for 81%. 22 patients (12%) had SLC, 83 (44%) had RLC, and 84 (44%) had NC. This study found patients with admission SLC had higher rates of vasopressor requirements, required more units of blood, and had a higher mortality rate than both the RLC and NC groups. CONCLUSION: Low cortisol level can be identified acutely after severe trauma. Trauma patients with SLC had larger blood product requirements, vasopressor use, and increase mortality. Initial cortisol levels are useful in identifying these high-risk patients. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III.

Intercostal Nerve Block with Liposomal Bupivacaine vs Epidural Analgesia for the Treatment of Traumatic Rib Fracture.

BACKGROUND: Rib fractures are common among trauma patients and analgesia remains the cornerstone of treatment. Intercostal nerve blocks provide analgesia but are limited by the duration of the anesthetic. This study compares outcomes of epidural analgesia with intercostal nerve block using liposomal bupivacaine for the treatment of traumatic rib fractures. METHODS: A retrospective chart review was used to identify patients who received either epidural analgesia or intercostal nerve block with liposomal bupivacaine for the treatment of traumatic rib fractures. Patients were matched in a 1:1 ratio on age, Injury Severity Score, and number of rib fractures. Outcomes included intubations, mechanical ventilation days, ICU length of stay (LOS), hospital LOS, and mortality. RESULTS: After matching, 116 patients were included in the study. Patients receiving intercostal nerve blocks with liposomal bupivacaine were less likely to require intubation (3% vs 17%; p = 0.015), had shorter hospital LOS (mean ± SD 8 ± 6 days vs 11 ± 9 days; p = 0.020) and ICU LOS (mean ± SD 2 ± 5 days vs 5 ± 6 days; p = 0.007). There were no differences in ventilator days or mortality. Minor complications occurred in 26% of patients that received an epidural catheter for rib fractures. No complications occurred in the patients receiving intercostal nerve block. CONCLUSIONS: Patients who received intercostal nerve blocks with liposomal bupivacaine required intubation less frequently and had shorter ICU and hospital LOS compared with epidural analgesia patients. These results suggest that intercostal nerve blocks with liposomal bupivacaine might be equal or superior to epidural analgesia.

Changes in splenic capsule with aging; beliefs and reality.

BACKGROUND: Research describing the splenic capsule and its effect on non-operative management of splenic injuries is limited. The aim of this study is to identify the current beliefs about the splenic capsule thickness and investigate changes in the splenic capsule with age. METHODS: Trauma Medical Directors were surveyed on their beliefs regarding splenic capsule thickness changes with age. Thicknesses of cadaveric splenic capsule samples were measured. RESULTS: The majority of trauma medical directors (59%) believe the capsule thickness decreases with age. There were 94 splenic specimens obtained. The splenic capsules of infants were thin and had a uniform layer of elastin fibers. With aging, the capsule becomes thick and develops a collagen layer. CONCLUSION: Most trauma directors believe the splenic capsule thickness decreases with age. However, our results demonstrate that the splenic capsule thickness increases during childhood but remains constant in adulthood.

The impact of obesity on severity of solid organ injury in the adult population at a Level I trauma center.

BACKGROUND: The obese (body mass index, BMI > 30) have been identified as a subgroup of patients in regards to traumatic injuries. A recent study found that high-grade hepatic injuries were more common in obese than non-obese pediatric patients. This study seeks to evaluate whether similar differences exist in the adult population and examine differences in operative versus non-operative management between the obese and non-obese in blunt abdominal trauma. METHODS: Patient with trauma evaluated at an American College of Surgeons verified Level I trauma center from February 2013 to November 2016 were retrospectively reviewed. All patients aged >18 years with blunt mechanism of injury and a BMI listed in the trauma registry were included. Patients were excluded for incomplete data, including BMI or inability to grade hepatic or splenic injury. Data collected included age, gender, BMI, injury severity score, hospital length of stay, procedures on liver or spleen, and mortality. Organ injuries were scored using the American Association for the Surgery of Trauma grading scales, and were determined by either imaging or intraoperative findings. Obesity was classified as BMI > 30 compared with non-obese with BMI < 30. RESULTS: During the study period, 9481 patients were included. There were 322 spleen injuries and 237 liver injuries, with 64 patients sustaining both liver and splenic injuries. No differences existed in the percentage of high-grade hepatic or splenic injuries between the obese and non-obese. Obese patients with liver injuries were more likely to have procedural intervention than non-obese liver injuries and had higher rates of mortality. No differences were found in intervention for splenic injury between obese and non-obese. CONCLUSIONS: Contrary to prior studies on adult and pediatric patients with trauma, this study found no difference between obese and non-obese patients in severity of solid organ injury after blunt abdominal trauma in the adult population. However, there was an increased rate of procedural intervention and mortality for obese patients with liver injuries. LEVEL OF EVIDENCE: 3.

A predictive grading scale for acute cholecystitis.

BACKGROUND: Acute cholecystitis presents in a spectrum of severity, where acute disease may be complicated by severe inflammation, gangrene, and perforation. The goal of this study is to outline an evidence-based grading scale that predicts patient outcomes after laparoscopic cholecystectomy (LC). METHODS: A retrospective review of all patients with a preoperative diagnosis of acute cholecystitis who underwent LC from August 2011 until June 2015 at a tertiary-level hospital was performed. Patients who underwent elective cholecystectomy, incidental cholecystectomy, a planned open cholecystectomy, had gallstone pancreatitis or choledocholithiasis, and those admitted to a non-surgical service were excluded. Severity of disease was obtained from operative and pathology reports, and patients were classified according to the following grading scale:Grade I: symptomatic cholelithiasis.Grade II: acute/chronic cholecystitis.Grade III: gangrenous/necrotizing cholecystitis.Grade IV: gallbladder perforation or abscess.The groups were compared on age, gender, body mass index, severity of gallbladder disease, presence of preoperative systemic inflammatory response syndrome, hospital length of stay, length of operation, complications within 30 days, conversion to open rate, and cost of hospitalization. RESULTS: During the study period, 1252 patients who underwent laparoscopic cholecystectomy were analyzed; 677 met inclusion criteria. The most common grade was grade 2, which was present in 80% of patients, followed by grade 3, which was found in 16% of patients. Grade 4 cholecystitis occurred in 1.2% of patients and grade 1 occurred in 3.2% of patients. There were statistically significant increases in age, presence of preoperative systemic inflammatory response syndrome, hospital length of stay, conversion to open rate, cost of hospitalization, and length of operation with increased cholecystitis grade. CONCLUSIONS: The proposed grading scale is an accurate predictor of duration of operation, conversion to open rate, hospital length of stay, and cost of hospitalization. LEVEL OF EVIDENCE: III. STUDY TYPE: Prognostic.

Internet-Based Cognitive Therapy for Social Anxiety Disorder in Hong Kong: Therapist Training and Dissemination Case Series.

BACKGROUND: Guided internet-based psychological interventions show substantial promise for expanding access to evidence-based mental health care. However, this can only be achieved if results of tightly controlled studies from the treatment developers can also be achieved in other independent settings. This dissemination depends critically on developing efficient and effective ways to train professionals to deliver these interventions. Unfortunately, descriptions of therapist training and its evaluation are often limited or absent within dissemination studies. OBJECTIVE: This study aimed to describe and evaluate a program of therapist training to deliver internet-based Cognitive Therapy for social anxiety disorder (iCT-SAD). As this treatment was developed in the United Kingdom and this study was conducted in Hong Kong with local therapists, an additional objective was to examine the feasibility, acceptability, and initial efficacy of iCT-SAD in this cultural context, based on data from a pilot case series. METHODS: Training in iCT-SAD was provided to 3 therapists and included practice of the face-to-face format of therapy under clinical supervision, training workshops, and treating 6 patients with the iCT-SAD program. Training progress was evaluated using standardized and self-report measures and by reviewing patient outcomes. In addition, feedback from patients and therapists was sought regarding the feasibility and acceptability of the program. RESULTS: The training program was effective at increasing therapists' iCT-SAD knowledge and skills, resulting in levels of competence expected of a specialist Cognitive Behavioral Therapy practitioner. The 6 patients treated by the trainees all completed their treatment and achieved a mean pre- to posttreatment change of 53.8 points (SD 39.5) on the primary patient outcome measure, the Liebowitz Social Anxiety Scale. The within-group effect size (Cohen d) was 2.06 (95% CI 0.66-3.46). There was evidence to suggest that the patients' clinical outcomes were sustained at 3-month follow-up. These clinical results are comparable to those achieved by UK patients treated by the developers of the internet program. Patient and therapist feedback did not identify any major cultural barriers to implementing iCT-SAD in Hong Kong; some modest language suggestions were made to assist understanding. CONCLUSIONS: The therapist training implemented here facilitated the successful dissemination of an effective UK-developed internet intervention to Hong Kong. The treatment appeared feasible and acceptable in this setting and showed highly promising initial efficacy. A randomized controlled trial is now required to examine this more robustly. As therapist training is critical to the successful dissemination of internet interventions, further research to develop, describe, and evaluate therapist training procedures is recommended.

The southwestern surgical congress multi-center trial on suspected common duct stones.

BACKGROUND: Choledocholithiasis is present in up to 15% of cholecystectomy patients. Treatment can be surgical, endoscopic, or via interventional radiology. We hypothesized significant heterogeneity between hospitals exists in the approach to suspected common duct stones. METHODS: A retrospective review of patients that had a preoperative MRCP, endoscopic ultrasound, endoscopic retrograde cholangiopancreatogram (ERCP), or intra-operative cholangiogram was performed. Comparisons were by Wilcoxon-Mann-Whitney tests with significance of p < 0.05 for paired variables and p < 0.017 for multiple comparisons. RESULTS: Twelve participating institutions identified 1263 patients (409 men and 854 women) with a median age of 49 years (IQR: 31-94). Liver function tests (LFT's) were elevated in 939 patients (75%), median bilirubin level 1.75 mg/dl (IQ: 0.8-3.7 mg/dl) and median common duct size 7 mm (IQR 5-10 mm). The most common initial procedure was cholecystectomy with IOC at seven institutions, endoscopy at four and MRCP at one. CONCLUSION: Significant variation exists within the surgical community regarding suspected common duct stones. These results underscore the need for a protocol for common duct stones to minimize multiple, redundant interventions.

Addressing Adolescent Oral Health: A Review.

Oral health is one of the most unmet health care needs of adolescents. Oral disease can have a profound effect on overall health, including pain, missed school, heart disease, and even death. Adolescents have specific needs pertaining to oral health in addition to the usual lifelong issues of caries management, sports injury prevention, and dental referrals. Teen years are a higher risk time for oral piercings, increased sugar intake, nicotine initiation, and orthodontic considerations. Adolescents need a unique approach to motivate them about their oral health issues. This is particularly important because lifelong health habits are created during these formative years, and prevention opportunities for sealants and varnish are only available at this age.

Selectivity switch between FAK and Pyk2: Macrocyclization of FAK inhibitors improves Pyk2 potency.

Herein, we describe the synthesis of Pyk2 inhibitors via macrocyclization of FAK and dual Pyk2-FAK inhibitors. We identified macrocycle 25a as a highly potent Pyk2 inhibitor (IC50=0.7nM), with ∼175-fold improvement in Pyk2 potency as compared to its acyclic counterpart. In many cases, macrocyclization improved Pyk2 potency while weakening FAK potency, thereby improving the Pyk2/FAK selectivity ratio for this structural class of inhibitors. Various macrocyclic linkers were studied in an attempt to optimize Pyk2 selectivity. We observed macrocyclic atropisomerism during the synthesis of 19-membered macrocycles 10a-d, and successfully obtained crystallographic evidence of one atropisomer (10a-AtropB) preferentially bound to Pyk2.

Time is now: venous thromboembolism prophylaxis in blunt splenic injury.

BACKGROUND: The safety and timing of venous thromboembolism (VTE) prophylaxis in patients with blunt splenic injuries is not well known. We hypothesized that early initiation of VTE prophylaxis does not increase failure of nonoperative management or transfusion requirements in these patients. METHODS: A retrospective review of trauma patients with blunt splenic injury was performed. Patients were compared based on initiation and timing of VTE prophylaxis (<24 hours, 24 to 48 hours, 48 to 72 hours, and >72 hours). Patients who received VTE prophylaxis were matched with those who did not. Primary outcomes included were operation or angioembolization. RESULTS: A total of 497 patients (256 received VTE prophylaxis and 241 did not) were included. There was no difference in the number of interventions based on presence of or time to VTE prophylaxis initiation. CONCLUSIONS: Early initiation (<48 hours) of VTE prophylaxis is safe in patients with blunt splenic injuries treated nonoperatively, and may be safe as early as 24 hours.

Cytotoxic and pro-oxidative effects of Imperata cylindrica aerial part ethyl acetate extract in colorectal cancer in vitro.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer. Its global incidence and mortality have been on the rise. Recent strategy of therapies has involved the use of non-steroid anti-inflammatory drugs and cyclooxygenase-selective inhibitors. Aerial parts of Imperata cylindrical L. Raeusch (IMP) have been used as an anti-inflammatory agent in traditional Chinese medicine. HYPOTHESIS: Asarachidonate acid cascadeis often involved in inflammation-related malignancy and IMP is an anti-inflammatory agent, hence it is hypothesized that IMP aerial part ethyl acetate extract exerts cytotoxic effects on colorectal cancer cells in vitro. STUDY DESIGN: The HT-29 adenocarcinoma cell line was used to elucidate its pro-apoptotic activities. Flow cytometry and fluorescent microscopy were performed to assess cell cycle arrest and the accumulation of reactive oxygen species (ROS). The mRNA and hormone levels of arachidonate acid pathways were studied via quantitative reverse transcription PCR (qRT-PCR) and ELISA. RESULTS: The 50% growth inhibitory effect (GI50) of the IMP extract on HT-29 was measured with a value of 14.5 µg/ml. Immuno-blot and caspase-3/7 activity assay showed the pro-apoptotic effect of IMP on the activation of caspase cascade. G2/M arrest was observed via flow cytometry. The ROS activity was modulated by the IMP extraction a concentration-dependent manner in HT-29 cells. The IMP extract increased PGE2 and PGF2α levels qRT-PCR revealed that transcripts of rate-limiting PGE2- and PGF2α-biosynthetic enzymes - COX-1, mPGES1 and AKR1C3 were notably up-regulated. Among the prostanoid receptors, EP1 and FP transcripts were up-regulated while EP4 transcripts decreased. The findings suggest that the proliferative effect of PGE2, which is generally believed to associate with heightened DNA synthesis and cross-talk with MAPK pathways, is likely triggered by the pro-apoptotic or -oxidative effects exerted by IMP extract in HT-29 cells. Concurring with this notion, indomethacin (COX-1/2-inhibitor) was demonstrated to potentiate the cytotoxic effect of IMP extract (GI50 ≦ 10.8 µg/ml). The results show that the cytotoxic effect of IMP extract predominates over the influence of proliferative prostanoids released by challenged colorectal cancer cells, and may present a potential source for development of novel anti-cancer drugs.

Imperatorin exhibits anticancer activities in human colon cancer cells via the caspase cascade.

Despite advances in medical treatments for colon cancer, it remains one of the leading causes of cancer-related mortality among men. Thus, more efficacious treatment strategies for colon cancer are needed. Imperatorin is one of the major ingredients present in the root of Angelica dahurica, and has been used in herbal formulations for the treatment of hypertension and cardiovascular diseases. However, the medical properties of imperatorin remain unclear. In the present study, the anti­proliferative activities of imperatorin were investigated in the HT­29 colon cancer cell line. The results showed that imperatorin significantly inhibited HT­29 colon cancer cell growth with an IC50 value of 78 µM. Imperatorin induced the apoptosis of colon cancer cells through upregulation of p53 and the caspase cascade. Our findings revealed that imperatorin induced cell cycle arrest in the G1 phase. The apoptotic index showed a steady increment when the imperatorin concentration was increased. The results suggest that imperatorin exerts considerable anti­proliferative activities in HT­29 colon cancer cells and highlight the potential of imperatorin as an anticancer agent for colon cancer.

Novel insights into the pathogenicity of epidemic Aeromonas hydrophila ST251 clones from comparative genomics.

Outbreaks in fish of motile Aeromonad septicemia (MAS) caused by Aeromonas hydrophila have caused a great concern worldwide. Here, for the first time, we provide two complete genomes of epidemic A. hydrophila strains isolated in China. To gain an insight into the pathogenicity of epidemic A. hydrophila, we performed comparative genomic analyses of five epidemic strains belonging to sequence type (ST) 251, together with the environmental strain ATCC 7966(T). We found that the known virulence factors, including a type III secretion system, a type VI secretion system and lateral flagella, are not required for the high virulence of the ST251 clonal group. Additionally, our work identifies three utilization pathways for myo-inositol, sialic acid and L-fucose providing clues regarding the factors that underlie the epidemic and virulent nature of ST251 A. hydrophila. Based on the geographical distribution and biological resources of the ST251 clonal group, we conclude that ST251 is a high-risk clonal group of A. hydrophila which may be responsible for the MAS outbreaks in China and the southeastern United States.