Connectivity-based neuromarker for children's inhibitory control ability and its relevance to body mass index.

Preserving a normal body mass index (BMI) is crucial for the healthy growth and development of children. As a core aspect of executive functions, inhibitory control plays a pivotal role in maintaining a normal BMI, which is key to preventing issues of childhood obesity. By studying individual variations in inhibitory control performance and its associated connectivity-based neuromarker in a sample of primary school students (N = 64; 9-12 yr), we aimed to unravel the pathway through which inhibitory control impacts children's BMI. Utilizing resting-state functional MRI scans and a connectivity-based psychometric prediction framework, we found that enhanced inhibitory control abilities were primarily associated with increased functional connectivity in brain structures vital to executive functions, such as the superior frontal lobule, superior parietal lobule, and posterior cingulate cortex. Conversely, inhibitory control abilities displayed a negative relationship with functional connectivity originating from reward-related brain structures, such as the orbital frontal and ventral medial prefrontal lobes. Furthermore, we revealed that both inhibitory control and its corresponding neuromarker can moderate the association between food-related delayed gratification and BMI in children. However, only the neuromarker of inhibitory control maintained its moderating effect on children's future BMI, as determined in the follow-up after one year. Overall, our findings shed light on the potential mechanisms of how inhibitory control in children impacts BMI, highlighting the utility of the connectivity-based neuromarker of inhibitory control in the context of childhood obesity.

Enhancing Triplet-Triplet Annihilation Upconversion: From Molecular Design to Present Applications.

Photon upconversion, the process of converting low-energy photons into high-energy ones, has been widely applied for solar energy conversion, photoredox catalysis, and various biological applications such as background-free bioimaging, cancer therapy, and optogenetics. Upconversion materials that are based on triplet-triplet annihilation (TTA) are of particular interest due to their low excitation power requirements (e.g., ambient sunlight) and easily tunable excitation and emission wavelengths. Despite advances that have been made with respect to TTA upconversion (TTA-UC) in the past decade, several challenges remain for near-infrared light-activatable triplet-triplet annihilation upconversion (NIR TTA-UC). These challenges include low upconversion quantum yield, small anti-Stokes shift, and incompatibility with oxygen, the latter of which seriously limits the practical applications of NIR TTA-UC.This Account will summarize the recent research endeavors to address the above-mentioned challenges and the recent new applications. The first part of this Account highlights recent strategies of molecular design to modulate the excited states of photosensitizers and annihilators, two key factors to determine TTA-UC performance. Novel molecular engineering strategies such as the resonance energy transfer method, dimerization of dye units, and the helix twist molecular structure have been proposed to tune the excited states of photosensitizers. The obtained photosensitizers exhibited enhanced absorption of deep tissue penetrable near-infrared (NIR) light, produced a triplet excited state with elevated energy level and prolonged lifetime, and promoted intersystem crossing, leading to an upgraded TTA-UC system with significantly expanded anti-Stokes shift. With respect to the annihilator, the perylene derivatives were systematically explored, and their attached aromatic groups were found to be the key to adjusting the energy levels of both the triplet and singlet excited states. The resultant optimal TTA-UC system exhibits the highest recorded efficiency among NIR TTA-UC systems.Moreover, to resolve the oxygen-induced TTA-UC quenching, enzymatic reactions were recently introduced. More specifically, the glucose oxidase-catalyzed glucose oxidation reaction showed the ability to rapidly consume oxygen to turn on the TTA-UC luminescence in an aqueous solution. The resultant TTA-UC nanoparticle was able to detect glucose and an enzyme related to glucose metabolism in a highly specific, sensitive, and background-free manner. Further, the upconverted singlet excited state of the annihilator was directly utilized as the catalyst or the excited substrate. For example, the modification of annihilators and drug molecules with photolabile linkages can realize the long wavelength light-induced photolysis. Compared to direct short-wavelength-driven photolysis, this sensitized TTA photolysis (TTAP) exhibits superior reaction yield and lower photodamage, which are important in the release of drugs for tumor treatment in vivo. Moreover, the improved upconversion efficiency can enable the successful coupling of NIR TTA-UC with a visible light absorbing photocatalyst for NIR-driven photoredox catalysis. Compared to direct visible-light photocatalysis, TTA-UC mediated NIR photoredox catalysis showed superior product yield especially in large scale reaction systems owing to the deep penetration power of NIR light. More interestingly, among a few promising technology applications, three-dimensional (3D) printing based on photopolymerization can operate with faster speed and energy-input several orders of magnitude lower when the two-photon polymerization is replaced with TTA-UC mediated polymerization. We believe this Account will spur interest in the further development and application of TTA-UC in the areas of energy, chemistry, material science, and biology.

AAST multicenter prospective analysis of prehospital tourniquet use for extremity trauma.

BACKGROUND: Tourniquet use for extremity hemorrhage control has seen a recent increase in civilian usage. Previous retrospective studies demonstrated that tourniquets improve outcomes for major extremity trauma (MET). No prospective study has been conducted to date. The objective of this study was to evaluate outcomes in MET patients with prehospital tourniquet use. We hypothesized that prehospital tourniquet use in MET decreases the incidence of patients arriving to the trauma center in shock. METHODS: Data were collected prospectively for adult patients with MET at 26 Level I and 3 Level II trauma centers from 2015 to 2020. Limbs with tourniquets applied in the prehospital setting were included in the tourniquet group and limbs without prehospital tourniquets were enrolled in the control group. RESULTS: A total of 1,392 injured limbs were enrolled with 1,130 tourniquets, including 962 prehospital tourniquets. The control group consisted of 262 limbs without prehospital tourniquets and 88 with tourniquets placed upon hospital arrival. Prehospital improvised tourniquets were placed in 42 patients. Tourniquets effectively controlled bleeding in 87.7% of limbs. Tourniquet and control groups were similarly matched for demographics, Injury Severity Score, and prehospital vital signs (p > 0.05). Despite higher limb injury severity, patients in the tourniquet group were less likely to arrive in shock compared with the control group (13.0% vs. 17.4%, p = 0.04). The incidence of limb complications was not significantly higher in the tourniquet group (p > 0.05). CONCLUSION: This study is the first prospective analysis of prehospital tourniquet use for civilian extremity trauma. Prehospital tourniquet application was associated with decreased incidence of arrival in shock without increasing limb complications. We found widespread tourniquet use, high effectiveness, and a low number of improvised tourniquets. This study provides further evidence that tourniquets are being widely and safely adopted to improve outcomes in civilians with MET. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

[Retracted] MicroRNA­874 inhibits growth, induces apoptosis and reverses chemoresistance in colorectal cancer by targeting X­linked inhibitor of apoptosis protein.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the western blotting data shown in Fig. 5D were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published on Oncology Reports 36: 542­550, 2016; DOI: 10.3892/or.2016.4810].

LncRNA LUADT1 is Upregulated in Mantle Cell Lymphoma and Modulates TRIM11 by Sponging miR-24-3p to Inhibit Cell Apoptosis.

The microRNA MiR-24-3p suppresses cancer progression by targeting TRIM11. The long noncoding RNA LUADT1 has been reported to promote lung adenocarcinoma proliferation. We found LUADT1 may form base pairing with miR-24-3p. This study aimed to explore the interactions among LUADT1, miR-24-3p, and TRIM11 in mantle cell lymphoma (MCL). Our study recruited 40 MCL patients and 40 healthy volunteers. Tumor tissues were collected from 40 newly diagnosed MCL patients and embedded in paraffin wax. B lymphocytes were isolated from all tissue samples by using CD19+ magnetic beads and DETACHaBEAD CD19. Human MCL cell line Grante-519 and JeKo-1 were transfected with LUADT1 and TRIM11 expression vectors, microRNA mimics or inhibitors. Then, quantitative polymerase chain reaction and Western blot were used to detect the level of relative messenger RNA and protein expression, respectively. Flow cytometry was performed to detect the apoptosis rate. LUADT1 and miR-24-3p were upregulated while TRIM11 was downregulated in MCL both in tissues and cell lines compared with hyperplastic lymphadenitis and peripheral lymphocyte cells. Bioinformatics analysis showed that LUADT1 may bind miR-24-3p, which can target TRIM11. Correlation analysis showed that LUADT1 was not significantly correlated with miR-24-3p. However, it was positively and significantly correlated with TRIM11. In MCL cells, LUADT1 overexpression led to upregulated TRIM11, whereas miR-24-3p overexpression led to downregulated TRIM11. Cell apoptosis analysis showed that LU-ADT1, miR-24-3p inhibitor and TRIM11 overexpression led to decreased apoptotic rate of MCL cells, whereas miR-24-3p overexpression led to an increased apoptotic rate of MCL cells. In addition, miR-24-3p overexpression attenuated the effects of LUADT1 overexpression. Therefore, LUADT1 was upregulated in MCL and could modulate TRIM11 by sponging miR-24-3p to inhibit cancer cell apoptosis.

Relationship between elevated microRNAs and growth factors levels in the vitreous of patients with proliferative diabetic retinopathy.

AIM: The aim of this study was to identify differentially expressed microRNAs (miRNAs) in the vitreous of patients with proliferative diabetic retinopathy (PDR) and correlate some of them with growth factors. METHODS: Vitreous samples were collected from 5 PDR eyes and 5 control eyes, and then miRNAs were assayed with next-generation sequencing (NGS). Three differentially expressed miRNAs were validated in vitreous of another cohort using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). RESULTS: Transforming growth factor ß (TGF-ß) and vascular endothelial growth factor (VEGF) signaling pathway were excavated out through bioinformatic analysis of deregulated miRNAs. The expression of hsa-miR-24-3p, hsa-miR-197-3p and hsa-miR-3184-3p, VEGF-A and TGF-ß were confirmed to be significantly higher in the vitreous of PDR eyes than controls(P < 0.05). Furthermore, Pearson's correlation analysis showed significantly positive correlations between these elevated miRNAs and growth factors (P < 0.05). CONCLUSIONS: Elevated vitreous levels of hsa-miR-24-3p, hsa-miR-197-3p, hsa-miR-3184-3p in PDR patients may play roles in pathophysiology of PDR, the target mRNAs of which significantly enriched in VEGF and TGF-ß signaling pathways. Positive correlations between elevated vitreous levels of the three miRNAs and VEGF-A, TGF-ß in PDR patients could provide a novel research direction for PDR.

Impacts of different administration modes of dexmedetomidine with 0.5% ropivacaine on intercostal nerve block.

BACKGROUND: To investigate the effectiveness and rationality of different administration modes of dexmedetomidine with 0.5% ropivacaine on intercostal nerve block. METHODS: In total, 150 patients aged from 20-45 years with a body mass index (BMI): 18.5-23.9 kg/m2, met the criteria from the American Society of Anesthesiologists (ASA) class: I-II, and underwent lumpectomy in our center were equally randomized into three groups using a table of random numbers. Group D1: perineural administration of dexmedetomidine 0.5 µg/kg + intercostal nerve block with 0.5% ropivacaine; group D2: intravenous infusion of dexmedetomidine0.5 µg/kg + intercostal nerve block with 0.5% ropivacaine; and group R: intercostal nerve block with 0.5% ropivacaine. The Numerical Rating Scale (NRS) of pain and the Ramsay Sedation Scale were used for assessing pain and sedation levels 4, 8, 12, and 24 hours after the operation. The total duration of analgesia, total requirement of rescue analgesia, and adverse reactions were recorded. RESULTS: The NRS scores in groups D1 and D2 were significantly lower than that in group R, 8 hours after the operation (both P<0.05), and the NRS score in group D1 was significantly lower than in group D2 12 hours after the operation (P<0.05). The Ramsay scores showed no significant differences among all three groups at all time points after surgery. The duration of analgesia in group D1 was significantly longer than in group D2 (P<0.05). No rescue analgesia was needed in all three groups, and no adverse reactions such as dizziness, dry mouth, nausea, vomiting, and respiratory depression were reported. CONCLUSIONS: The combinations of dexmedetomidine with ropivacaine for intercostal nerve blocking can prolong the duration of analgesia after lumpectomy; however, the duration of analgesia is longer via the perineural route than via the intravenous route.

Ultrasonographic inferior vena cava diameter response to trauma resuscitation after 1 hour predicts 24-hour fluid requirement.

BACKGROUND: Identification of occult hypovolemia in trauma patients is difficult. We hypothesized that in acute trauma patients, the response of ultrasound-measured minimum inferior vena cava diameter (IVCDMIN), IVC Collapsibility Index (IVCCI), minimum internal jugular diameter (IJVDMIN) or IJV Collapsibility Index (IJVCI) after up to 1 hour of fluid resuscitation would predict 24-hour resuscitation intravenous fluid requirements (24FR). METHODS: An NTI-funded, American Association for the Surgery of Trauma Multi-Institutional Trials Committee prospective, cohort trial was conducted at four Level I Trauma Centers. Major trauma patients were screened for an IVCD of 12 mm or less or IVCCI of 50% or less on initial focused assessment sonographic evaluations for trauma. A second IVCD was obtained 40 minutes to 60 minutes later, after standard-of-care fluid resuscitation. Patients whose second measured IVCD was less than 10 mm were deemed nonrepleted (NONREPLETED), those 10 mm or greater were repleted (REPLETED). Prehospital and initial resuscitation fluids and 24FR were recorded. Demographics, Injury Severity Score, arterial blood gasses, length of stay, interventions, and complications were recorded. Means were compared by ANOVA and categorical variables were compared via χ. Receiver operating characteristic curves analysis was used to compare the measures as 24FR predictors. RESULTS: There were 4,798 patients screened, 196 were identified with admission IVCD of 12 mm or IVCCI of 50% or less, 144 were enrolled. There were 86 REPLETED and 58 NONREPLETED. Demographics, initial hemodynamics, or laboratory measures were not significantly different. NONREPLETED had smaller IVCD (6.0 ± 3.7 mm vs. 14.2 ± 4.3 mm, p < 0.001) and higher IVCCI (41.7% ± 30.0% vs. 13.2% ± 12.7%, p < 0.001) but no significant difference in IJVD or IJVCCI. REPLETED had greater 24FR than NONREPLETED (2503 ± 1751 mL vs. 1,243 ± 1,130 mL, p = 0.003). Receiver operating characteristic analysis indicates IVCDMIN predicted 24FR (area under the curve [AUC], 0.74; 95% confidence interval [CI], 0.64-0.84; p < 0.001) as did IVCCI (AUC, 0.75; 95% CI, 0.65-0.85; p < 0.001) but not IJVDMIN (AUC, 0.48; 95% CI, 0.24-0.60; p = 0.747) or IJVCI (AUC, 0.54; 95% CI, 0.42-0.67; p = 0.591). CONCLUSION: Ultrasound assessed IVCDMIN and IVCCI response initial resuscitation predicts 24-hour fluid resuscitation requirements. LEVEL OF EVIDENCE: Diagnostic tests or criteria, level II.

Detecting direct oral anticoagulants in trauma patients using liquid chromatography-mass spectrometry: A novel approach to medication reconciliation.

BACKGROUND: Accurate medication reconciliation in trauma patients is essential but difficult. Currently, there is no established clinical method of detecting direct oral anticoagulants (DOACs) in trauma patients. We hypothesized that a liquid chromatography-mass spectrometry (LCMS)-based assay can be used to accurately detect DOACs in trauma patients upon hospital arrival. METHODS: Plasma samples were collected from 356 patients who provided informed consent including 10 healthy controls, 19 known positive or negative controls, and 327 trauma patients older than 65 years who were evaluated at our large, urban level 1 trauma center. The assay methodology was developed in healthy and known controls to detect apixaban, rivaroxaban, and dabigatran using LCMS and then applied to 327 samples from trauma patients. Standard medication reconciliation processes in the electronic medical record documenting DOAC usage were compared with LCMS results to determine overall accuracy, sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of the assay. RESULTS: Of 356 patients, 39 (10.96%) were on DOACs: 21 were on apixaban, 14 on rivaroxaban, and 4 on dabigatran. The overall accuracy of the assay for detecting any DOAC was 98.60%, with a sensitivity of 94.87% and specificity of 99.05% (PPV, 92.50%; NPV, 99.37%). The assay detected apixaban with a sensitivity of 90.48% and specificity of 99.10% (PPV, 86.36%; NPV 99.40%). There were three false-positive results and two false-negative LCMS results for apixaban. Dabigatran and rivaroxaban were detected with 100% sensitivity and specificity. CONCLUSION: This LCMS-based assay was highly accurate in detecting DOACs in trauma patients. Further studies need to confirm the clinical efficacy of this LCMS assay and its value for medication reconciliation in trauma patients. LEVEL OF EVIDENCE: Diagnostic Test, level III.

Tailor-Made Semiconducting Polymers for Second Near-Infrared Photothermal Therapy of Orthotopic Liver Cancer.

Liver tumor is one of the most lethal cancers due to its low ratio of surgical resection, high recurrence rate, and invasiveness. Photothermal therapy (PTT) possesses many advantages for cancer therapy because of its noninvasive nature. However, most PTT is conducted in the first near-infrared (NIR-I) window, so second near-infrared (NIR-II) photosensitizers with higher penetrating ability and clinical prospects are seriously desirable. Herein, a semiconducting polymer with optimized absorption in NIR-I and NIR-II regions is obtained by ternary copolymerization methodology. The prepared nanoparticle (NP) from the semiconducting polymer is used for treatment of orthotopic liver cancer upon laser irradiation. Compared with an 808 nm laser, a 1064 nm laser leads to more effective inhibition toward orthotopic liver cancer in the same conditions. These results thus demonstrate that the NIR-II polymeric NPs may inspire another aspect for highly efficient therapy of various orthotopic cancers.

Screening for Harassment, Abuse, and Discrimination among Surgery Residents: An EAST Multicenter Trial.

Estimating the prevalence of harassment, verbal abuse, and discrimination among residents is difficult as events are often under-reported. The purpose of this study was to determine the prevalence of discrimination and abuse among surgical residents using the HITS (Hurt, Insulted, Threatened with harm or Screamed at) screening tool. A multicenter, cross-sectional, survey-based study was conducted at five academic teaching hospitals. Of 310 residents, 76 (24.5%) completed the survey. The HITS screening tool was positive in 3.9 per cent. The most common forms of abuse included sexual harassment (28.9%), discrimination based on gender (15.7%), and discrimination based on ethnicity (7.9%). There was a positive correlation between individuals who reported gender discrimination and racial discrimination (r = 0.778, n = 13, P = 0.002). Individuals who experienced insults were more likely to experience physical threats (r = 0.437, n = 79, P < 0.001) or verbal abuse (r = 0.690, n = 79, P < 0.001). Discrimination and harassment among surgical residents in academic teaching hospitals across the United States is not uncommon. Further research is needed to determine the impact of these findings on resident attrition.

Betulin inhibits lipopolysaccharide/D-galactosamine-induced acute liver injury in mice through activating PPAR-γ.

Betulin is a phenolic flavonoid which has been reported to possess a mass of pharmacological properties, especially anti-inflammatory activity. The purpose of this study was to explore the protective effects and possible mechanism of betulin against lipopolysaccharide/D-galactosamine (LPS/D-Gal)-induced acute liver injury. D-Gal and LPS were intraperitoneally injected to develop acute liver injury animal model. Betulin (2, 4 or 8 mg/kg) were given 1 h before LPS/D-Gal instillation. Liver tissues and plasma samples were collected 9 h after LPS/D-Gal were given. The results indicated that betulin dramatically decreased liver pathologic changes, myeloperoxidase (MPO) activity, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Simultaneously, the levels of interleukin (IL-1ß) and tumor necrosis factor (TNF-α) in serum and liver tissues were both attenuated by betulin. Besides, betulin suppressed NF-κB pathway activation in a dose-dependently manner. Betulin increased the expression of PPAR-γ in a dose-dependent manner. In conclusion, all these results revealed that betulin could possess potential therapeutic effect for LPS/D-Gal-induced acute liver injury.

MicroRNA-152 Suppresses Human Osteosarcoma Cell Proliferation and Invasion by Targeting E2F Transcription Factor 3.

MicroRNA-152 (miR-152) expression has been reported to be downregulated in osteosarcoma (OS). However, the role of miR-152 in OS is not well documented. In the present study, we aimed to explore the function and underlying mechanism of miR-152 in OS. We found that miR-152 was underexpressed in OS tissues and cell lines. Decreased miR-152 was inversely correlated with lymph node metastasis and advanced clinical stage. Overexpression of miR-152 significantly inhibited cell proliferation, colony formation, migration, and invasion of OS cells. Bioinformatics analyses showed that miR-152 directly targeted E2F transcription factor 3 (E2F3), as further confirmed by a dual-luciferase reporter assay. E2F3 expression was upregulated and inversely correlated with miR-152 expression level in human OS tissues. Moreover, the inhibitory effects of miR-152 on OS growth and invasion were attenuated by E2F3 overexpression. Taken together, our findings indicated that miR-152 reduced OS growth and invasion by targeting E2F3 and provided new evidence of miR-152 as a potential therapeutic target for OS.

Pneumatosis Intestinalis Predictive Evaluation Study: A multicenter epidemiologic study of the American Association for the Surgery of Trauma.

BACKGROUND: Our group has previously published a retrospective review defining variables predictive of transmural bowel ischemia in the setting of pneumatosis intestinalis (PI). We hypothesize this prospective study will confirm the findings of the retrospective review, enhancing legitimacy to the predictive factors for pathologic PI previously highlighted. METHODS: Data were collected using the Research Electronic Data Capture. Forward logistic regression was utilized to identify independent predictors for pathologic PI. Statistical significance was defined as p ≤ 0.05. RESULTS: During the 3-year study period, 127 patients with PI were identified. Of these, 79 had benign disease, and 49 pathologic PI defined by the presence of transmural ischemia during surgical exploration or autopsy. Laboratory values such as elevated international normalized ratio (INR), decreased hemoglobin, and a lactate value of greater than 2.0 mmol/L were predictive of pathologic PI, as well as clinical factors including adynamic ileus, peritoneal signs on physical examination, sepsis, and hypotension. The location was also a significant factor, as patients with small bowel PI had a higher incidence of transmural ischemia than colonic PI. On multiple logistic regression, lactate value of greater than 2.0 mmol/L (odds ratio, 5.1, 1.3-19.5; p = 0.018), elevated INR (odds ratio, 3.2, 1.1-9.6; p = 0.031), peritonitis (15.0, 2.9-78; p = 0.001), and decreased hemoglobin (0.70, 0.50-0.97, 0.031) remained significant predictors of transmural ischemia (area under the curve, 0.90; 0.83-0.97). A lactate value of 2.0 mmol/L or greater and peritonitis are common factors between the retrospective review and this prospective study. CONCLUSIONS: We recommend surgical exploration to be strongly considered for those PI patients presenting also with a lactate greater than 2 mmol/L and/or peritonitis. We suggest strong suspicion for necrosis in those patient with PI and small bowel involvement, ascites on computed tomography scan, adynamic ileus, anemia, and a high INR. LEVEL OF EVIDENCE: Prognostic study, level II; therapeutic study, level II.

Acute single dose of ketamine relieves mechanical allodynia and consequent depression-like behaviors in a rat model.

Both chronic pain and depression are debilitating diseases, which often coexist in clinic. However, current analgesics and antidepressants exhibit limited efficacy for this comorbidity. The present study aimed to investigate the effect of ketamine on the comorbidity of inflammatory pain and consequent depression-like behaviors in a rat model established by intraplantar administration of complete Freunds adjuvant (CFA). The mechanical withdrawal threshold, thermal withdrawal latency, open field test, forced swimming test, and sucrose preference test were evaluated after the CFA injection and ketamine treatment. The hippocampus was harvested to determine the levels of interleukin (IL)-6, IL-1ß, indoleamine 2,3-dioxygenase (IDO), kynurenine (KYN), 5-hydroxytryptamine (5-HT), and tryptophan (TRP). The inflammatory pain-induced depression-like behaviors presented on 7days and lasted to at least 14days after the CFA injection. Single dose of ketamine at 20mg/kg relieved both the mechanical allodynia and the associated depression-like behaviors as demonstrated by the attenuated mechanical withdrawal threshold, reduced immobility time in the forced swim test, and increased sucrose preference after ketamine treatment. The total distance had no significant change after the CFA injection or ketamine treatment in the open field test. Simultaneously, ketamine reduced the levels of IL-6, IL-1ß, IDO, and KYN/TRP ratio and increased the 5-HT/TRP ratio in the hippocampus. In conclusion, acute single dose of ketamine can rapidly attenuate mechanical allodynia and consequent depression-like behaviors and down-regulate hippocampal proinflammatory responses and IDO/KYN signal pathway in rats.

Defining the cervical spine clearance algorithm: A single-institution prospective study of more than 9,000 patients.

BACKGROUND: Variability exists in the approach to cervical spine (c-spine) clearance after significant trauma. Using concurrently gathered data on more than 9,000 such patients, the current study develops an evidence-based and readily adoptable algorithm for c-spine clearance aimed at timely removal of collar, optimal use of imaging, and appropriate spine consultations. METHODS: Prospective study of adult blunt trauma team alert (TTA) patients presenting at a Level I trauma center who underwent screening computed tomography (CT) to diagnose/rule out c-spine injury (January 2008 to May 2014). Regression analysis comparing patients with and without c-spine injury-fracture and/or ligament-was used to identify significant predictors of injury. The predictors with the highest odds ratio were used to develop the algorithm. RESULTS: Among 9,227 patients meeting inclusion criteria, c-spine injury was identified in 553 patients (5.99%). All 553 patients had a c-spine fracture, and of these, 57 patients (0.6% of entire population and 10.31% of patients with injury) also had a ligamentous injury. No patient with a normal CT result was found to have an injury. The five greatest predictors of ligament injury that follow were used to develop the algorithm: (1) CT evidence of ligament injury; (2) fracture pattern "not" isolated transverse/spinous process; (3) neurologic symptoms; (4) midline tenderness; and (5) Glasgow Coma Scale score <15. CONCLUSION: TTA patients should undergo screening c-spine CT to rule out injury. Most patients will have a negative CT and can have their collars removed. A select group of patients will require collars and spine consultation and a smaller subset of magnetic resonance imaging to rule out ligament injury. LEVEL OF EVEDINCE: Therapeutic study, level III.

MicroRNA-874 inhibits growth, induces apoptosis and reverses chemoresistance in colorectal cancer by targeting X-linked inhibitor of apoptosis protein.

MicroRNA-874 (miR-874) is downregulated and acts as a tumor suppressor in several types of cancers, whereas the biological function of miR-874 in colorectal cancer (CRC) remains unclear. The aims of the present study were to investigate the clinical significance, biological effects, and the underlying mechanisms of miR-874 in CRC. Reverse transcription-quantitative PCR (RT-qPCR) was used to detect miR-874 expression in CRC cell lines and tissue samples. MTT and colony formation assays and flow cytometry were performed to analyze the effects of miR-874 expression on growth, apoptosis and the chemoresistance of CRC cells. Regulation of putative miR-874 targets was determined by dual-luciferase reporter assays. RT-qPCR and western blot assays were performed to detected the levels of X-linked inhibitor of apoptosis protein (XIAP) mRNA and protein expression. It was found that expression of miR-874 was downregulated in CRC tissues and cell lines, and its expression was significantly negatively correlated with TNM stage and lymph node metastasis of the CRC patients. Functional assays revealed that restoration of miR-874 inhibited proliferation, reduced colony formation, enhanced apoptosis, as well as decreased the 5-fluorouracil (5-FU) resistance of the CRC cells. Through luciferase activity assay, RT-qPCR and western blot analysis, XIAP was shown to be a direct target of miR-874. In addition, XIAP expression was significantly increased in the CRC tissues and cell lines, and was inversely correlated with miR-874 expression. Importantly, downregulation of XIAP in CRC cells had an effect similar to that of miR-874 overexpression. Taken together, these data showed that miR-874 inhibits growth, increases apoptosis and enhances chemosensitivity in CRC cells by targeting XIAP, suggesting that miR-874 may be a potential molecular target for the treatment of human CRC.

A multi-institutional analysis of prehospital tourniquet use.

BACKGROUND: Recent military studies demonstrated an association between prehospital tourniquet use and increased survival. The benefits of this prehospital intervention in a civilian population remain unclear. The aims of our study were to evaluate tourniquet use in the civilian population and to compare outcomes to previously published military experience. We hypothesized that incorporation of tourniquet use in the civilian population will result in an overall improvement in mortality. METHODS: This is a preliminary multi-institutional retrospective analysis of prehospital tourniquet (MIA-T) use of patients admitted to nine urban Level 1 trauma centers from January 2010 to December 2013. Patient demographics and mortality from a previous military experience by Kragh et al. (Ann Surg. 2009;249:1-7) were used for comparison. Patients younger than 18 years or with nontraumatic bleeding requiring tourniquet application were excluded. Data were analyzed using a two-tailed unpaired Student's t test with p < 0.05 as significant. RESULTS: A total of 197 patients were included. Tourniquets were applied effectively in 175 (88.8%) of 197 patients. The average Injury Severity Score (ISS) for MIA-T versus military was 11 ± 12.5 versus 14 ± 10.5, respectively (p = 0.02). The overall mortality and limb amputation rates for the MIA-T group were significantly lower than previously seen in the military population at 6 (3.0%) of 197 versus 22 (11.3%) of 194 (p = 0.002) and 37 (18.8%) of 197 versus 97 (41.8%) of 232 (p = 0.0001), respectively. CONCLUSION: Our study is the largest evaluation of prehospital tourniquet use in a civilian population to date. We found that tourniquets were applied safely and effectively in the civilian population. Adaptation of this prehospital intervention may convey a survival benefit in the civilian population. LEVEL OF EVIDENCE: Epidemiologic study, level V.

Computed tomographic scan: it's not just about the fracture.

BACKGROUND: Computed tomography (CT) scan is the criterion standard to rule out cervical spine (c-spine) injury after blunt trauma. Many algorithms still include other tools to exclude ligamentous injuries that often lead to unnecessary prolonged collar use. The purpose of this study was to determine the accuracy of CT to rule out any clinically significant c-spine injury that would require intervention. METHODS: We performed a retrospective review of a prospective study of blunt trauma patients between January 2008 and December 2012 at a Level 1 trauma center. For those patients identified with ligamentous injury, further chart review was performed to determine how it was diagnosed and treated. RESULTS: A total of 5,676 patients were identified. The median age was 39.0 years (18-103 years), median Glasgow Coma Scale (GCS) score was 15 (3-15), median Injury Severity Score (ISS) was 5 (1-75), median length of stay was 2 days (1-175 days), and mortality was 2.6%. The incidence of any injury to the c-spine was 7.4% (420 of 5,676). The incidence of fracture was 7.2% (409 of 5,676), while that of ligamentous injury was 0.92% (52 of 5,676). Of the 52 patients with ligamentous injury, 20 (38.4%) were suspected by CT. However, for those that were not suspected, all had associated fractures identified by CT, requiring further interventions. Hence, CT had a 100% sensitivity and specificity in ruling out c-spine injuries. CONCLUSION: CT scan of the c-spine is an excellent tool to rule out c-spine injury. For patients with a normal CT finding of the c-spine, no further imaging is necessary, and collars should be cleared as soon as possible. LEVEL OF EVIDENCE: Prognostic study, level II; diagnostic study, level II.

Protective effect of stellate ganglion block on delayed cerebral vasospasm in an experimental rat model of subarachnoid hemorrhage.

Stellate ganglion block (SGB) is a blockade of sympathetic ganglia innervating the head and neck, and is known to function through vasodilation of the target region. However, the effectiveness of SGB in relieving cerebral vasospasm (CVS) through dilation of intracerebral vessels has not been evaluated. The aim of the present study is to investigate the therapeutic effects of SGB in a rat model of subarachnoid hemorrhage (SAH) complicated by delayed CVS, and explore the underlying mechanisms. The SAH model was established by double injection of autologous arterial blood into the cisterna magna. We simulated SGB by transection of the cervical sympathetic trunk (TCST), and measured changes in the diameter, perimeter and cross-sectional area of the basilar artery (BA) and middle cerebral artery (MCA) to evaluate its vasodilatory effect. To investigate the underlying mechanisms, we determined the expression level of vasoactive molecules endothelin-1 (ET-1) and calcitonin gene-related peptide (CGRP) in the plasma, and apoptotic modulators Bcl-2 and Bax in the hippocampus. We found a significant increase in the diameter, perimeter and cross-sectional area of the BA and right MCA in SAH rats subjected to TCST. Application of SGB significantly reduced the expression of ET-1 while increasing that of CGRP in SAH rats. We also found a significant increase in the expression of Bcl-2 and decrease in the expression of Bax in the hippocampus of SAH rats subjected to TCST, when compared to untreated SAH rats. The mechanism of action of SGB is likely mediated through alterations in the ratio of ET-1 and CGRP, and Bax and Bcl-2. These results suggest that SGB can alleviate the severity of delayed CVS by inducing dilation of intracerebral blood vessels, and promoting anti-apoptotic signaling. Our findings provide evidence supporting the use of SGB as an effective and well-tolerated approach to the treatment of CVS in various clinical settings.