Rescue techniques that enable removal of severe intravascular catheter kinking are always worthwhile. We herein demonstrate the novel employment of a GuideLiner support catheter to assist in the removal of a kinked and entrapped guide catheter within the radial artery during coronary intervention. © 2016 Wiley Periodicals, Inc.
To investigate incidence and patient characteristics of transient ST-segment elevation (TSTE) ACS and to compare outcome of early versus late invasive treatment.
Optimal timing of treatment in TSTE–ACS patients is not outlined in current guidelines and no prospective randomized trials have been done so far.
Post hoc subgroup analysis of patients with TSTE randomized in the ELISA 3 trial. This study compared early (<12 h) versus late (>48 h) angiography and revascularization in 542 patients with high-risk NSTE-ACS. Primary endpoint was incidence of death, reinfarction, or recurrent ischemia at 30 days follow-up.
TSTE was present in 129 patients (24.2%) and associated with male gender, smoking and younger age. The primary endpoint occurred in 8.9% of patients with and 13.0% of patients without TSTE (RR = 0.681, P = 0.214). Incidence of death or MI after 2 year follow-up was 5.7 and 14.6% respectively (RR = 0.384, P = 0.008). Within the group of patients with TSTE, incidence of the primary endpoint was 5.8% in the early and 12.7% in the late treatment group (RR = 0.455, P = 0.213), driven by reduction in recurrent ischemia. Enzymatic infarct size, bleeding and incidence of death or recurrent MI at 2 years follow-up was comparable between the treatment groups.
In high-risk patients with NSTE-ACS, TSTE is frequently seen. Similar to findings in patients with high-risk NSTE-ACS, immediate angiography and revascularization in these patients is feasible but not superior to later treatment. Prospective randomized trials are needed to provide more evidence in the optimal timing of treatment in patients with TSTE-ACS. © 2016 Wiley Periodicals, Inc.
We assessed whether post-operative delirium is associated with healthcare utilization and overall survival after trans-catheter aortic valve replacement.
Delirium, a common syndrome among hospitalized older adults, is associated with increased morbidity and mortality.
We reviewed 294 transcatheter aortic valve replacement cases between June 2008 and February 2015 at a tertiary care academic medical center. Post-operative delirium was identified by confusion assessment method screening and clinician diagnosis.
Delirium was identified in 61 patients (21%). Non-femoral access for trans-catheter aortic valve replacement was more common in delirious patients than in non-delirious patients (41% vs. 27%, P = 0.04). Delirious patients had diminished overall survival after trans-catheter aortic valve replacement compared to non-delirious patients (1-year survival 59% vs. 84%, log-rank P = 0.002). After adjusting for age, Society of Thoracic Surgeons predicted 30-day mortality, and access type; delirium remained independently associated with diminished overall survival (hazard ratio 2.01, 95% confidence interval 1.21–3.33, P = 0.007). The delirium group had longer mean hospital stay (13.3 ± 9.5 days vs. 6.7 ± 3.8 days, P < 0.001) and a higher rate of discharge to a rehabilitation facility (61% vs. 27%, P < 0.001), but there was no difference in 30-day hospital re-admission rates or 30-day mortality based on delirium status.
Delirium occurs in one out of five patients after trans-catheter aortic valve replacement and is associated with diminished survival and increased healthcare utilization. Further studies are needed to clarify whether strategies aimed at reducing delirium after trans-catheter aortic valve replacement may improve outcomes in this high-risk subset. © 2016 Wiley Periodicals, Inc.
Prosthesis-patient mismatch (PPM) is defined as a small effective orifice area (EOA) of a normally functioning prosthetic valve in relation to patient body size. Even moderate impediment to forward flow has been associated with an increase in all-cause mortality. We report an unusual cause of PPM where a transcatheter implantation of a large EOA valve in an aortic position results in relative PPM in a patient with morbid obesity. © 2016 Wiley Periodicals, Inc.
To assess the feasibility and safety of the 7 French (Fr) Glidesheath Slender for complex transradial (TR) percutaneous coronary interventions (PCI).
The TR approach is increasingly used worldwide for coronary and peripheral vascular interventions. However, the small size of the radial artery remains an important limitation for the use of large-bore guiding catheters (>6 Fr), restricting thereby the treatment of highly complex lesions through the TR approach. The 7 Fr Glidesheath slender (Terumo, Tokyo, Japan) is a new dedicated radial sheath with a thinner wall and hydrophilic coating. It combines an inner diameter compatible with any 7 Fr guiding catheter and an outer diameter smaller than current 7 Fr sheaths.
Prospective multicenter registry of complex TR PCI cases using the 7 Fr Glidesheath Slender to determine the procedural success, rates of vascular complications, radial spasm, and radial artery occlusion (RAO).
A total of 60 patients were included. Procedural success was 97% with only one access-site crossover. The use of a 7 Fr guiding catheter was indicated for the treatment of highly complex coronary lesions including distal left main (LM) disease (n = 20), complex non-LM bifurcation lesions (n = 16), chronic total occlusion (n = 15), and severely calcified vessels requiring rotational atherectomy (n = 10). There were three vascular access-site complications (4.7%) including two moderate (type II) local hematoma and one uncomplicated guiding catheter-induced brachial artery dissection. None of the patients experienced major bleeding. The occurrence of radial spasm was reported in seven patients (11%). Doppler ultrasound imaging of the radial artery at 1 month was available in 62 of 64 radial access with three cases of RAO (4.8%).
Use of the 7 Fr Glidesheath slender for complex coronary interventions is feasible and associated with a high rate of procedural success and a low rate of vascular complications. These favorable results need be confirmed in larger multicenter studies. © 2016 Wiley Periodicals, Inc.
To compare indications and clinical outcomes of two contemporary left atrial appendage (LAA) percutaneous closure systems in a “real-world” population.
Percutaneous LAA occlusion is an emerging therapeutic option for stroke prevention in atrial fibrillation. Some questions however remain unanswered, such as the applicability of results of randomized trials to current clinical practice. Moreover, currently available devices have never been directly compared.
We retrospectively analyzed consecutive patients who underwent LAA closure at San Raffaele Hospital, Milan, Italy between 2009 and 2015. Clinical indications and device selection were left to operators' decision; routine clinical and transesophageal echocardiography (TEE) follow-up was performed.
One-hundred and sixty-five patients were included in the study, of which 99 were treated with the Amplatzer Cardiac Plug (ACP) and 66 with the Watchman system. During the follow-up period (median 15 months, interquartile range 6–26 months) five patients died. The incidence of ischemic events was low, with one patient suffering a transient ischemic attack and no episodes recorded of definitive strokes. Twenty-six leaks ≥1 mm were detected (23%); leaks were less common with the ACP and with periprocedural three-dimensional TEE evaluation, but were not found to correlate with clinical events. Clinical outcomes were comparable between the two devices.
Our data show excellent safety and efficacy of LAA closure, irrespectively of the device utilized, in a population at high ischemic and hemorrhagic risk. The use of ACP and 3D-TEE minimized the incidence of residual leaks; however, the clinical relevance of small peri-device flow warrants further investigation. © 2016 Wiley Periodicals, Inc.
We sought to establish the typical location of the common femoral artery (CFA) bifurcation, the origin and most inferior reflection of the inferior epigastric artery (IEA) relative to the femoral head (FH) and whether patient demographics predicted anatomical variations.
In the absence of ultrasound guidance or prior imaging, the precise location of the CFA bifurcation and IEA can only be determined following access site angiography. Fluoroscopic landmarks are commonly used to estimate the location of the CFA bifurcation, but the position of the IEA is less well characterized.
Prospectively collected data on 989 patients with femoral angiography in the FAUST trial were analyzed. The level of CFA bifurcation and the origin and most inferior reflection of the IEA were classified by angiography. Logistic regression was used to explore whether baseline demographics were associated with anatomic variations.
The CFA bifurcation occurs below the middle 1/3rd of the femoral head in 95% of patients, and no patient factors are predictive of a high bifurcation. The IEA origin has a more variable anatomically pattern, with high BSA, male gender, and white race associated with a low IEA origin.
Operators should attempt to access the CFA at the level of the middle 1/3rd of the FH to maximize the chance of CFA cannulation. However, this location carries an 11% risk of being at or above the IEA origin. Baseline demographics were of limited utility for predicting anatomic variants of the CFA bifurcation and the course of the IEA. © 2016 Wiley Periodicals, Inc.
Although ischemia-guided revascularization improves clinical outcomes, morphological determinants of clinically relevant myocardial ischemia have not been studied. To identify intravascular ultrasound (IVUS)-derived anatomical parameters for predicting myocardial perfusion defect and its extent.
A total of 103 patients (88 stable and 15 unstable angina) with 153 lesions (angiographic diameter stenosis of 30–80%) underwent stress myocardial perfusion computed tomography (CT) and IVUS pre-procedure. The volume of CT perfusion defect and %CT perfusion defect in the target vessel territories were measured.
The CT perfusion defect was seen in 76 (50%) lesions. The independent determinants for the presence of CT perfusion defect were IVUS-minimal lumen area (MLA) (adjusted OR = 0.56, 95% CI = 0.38–0.82), plaque burden (adjusted OR = 1.07, 95% CI = 1.02–1.11) and involvement of left main or left anterior descending artery (adjusted OR = 4.13, 95% CI = 1.75–9.78, all P < 0.05). The CT perfusion defect was predicted by IVUS-MLA <2.28mm2 (sensitivity 74%, specificity 82%) and plaque burden >77% (sensitivity 79%, specificity 78%) as thresholds. The independent determinants for the volume of CT perfusion defect were the involvement of left main or left anterior descending artery (β = 16.43, standard errors = 4.387, P = 0.020) and a greater plaque burden (β = 0.56, standard errors = 0.163, P = 0.026).
IVUS-derived morphological parameters were useful to predict the presence of CT perfusion defect and the size of myocardial ischemia that were primarily determined by lesion severity and subtended myocardial territory. © 2016 Wiley Periodicals, Inc.
Progeria syndrome is a very rare disease with early demise in the second decade due to cardiovascular disease. Most events are sudden and fatal, leaving no time for medical or interventional therapies; no such interventional therapy has been reported. We present a 13 years old boy who previously had suffered from dissection of both internal carotid arteries; he now presented with exercise-induced angina. Both CT-scan and angiography revealed severe stenotic lesions at the origin of the right coronary artery and left anterior descending artery, typical for dissection. Coronary artery stenting resolved the symptoms. © 2016 Wiley Periodicals, Inc.
Healthcare self-efficacy (HCSE), the perceived confidence to manage one's health care, has been identified as a critical component in the transition process from pediatric to adult-oriented care for childhood cancer survivors (CCSs). HCSE is amenable to intervention and associated with long-term follow-up care among CCSs. However, factors associated with HCSE have not been fully explored among CCSs.
We identified correlates of HCSE among a sample of CCSs (n = 193). Descriptive statistics and linear regression methods were used in this cross-sectional analysis.
In univariate analyses, higher physical and psychosocial quality of life, posttraumatic growth, and religious/spiritual importance were associated with higher HCSE. Attendance at a survivorship clinic, having a regular source of care (both noncancer and oncologist), and any type of health insurance were also associated with HCSE. Hispanic ethnicity was negatively associated with HCSE relative to non-Hispanics. In a multivariable model, psychosocial quality of life, religious/spiritual importance, survivorship clinic attendance, having a regular oncologist, and Hispanic ethnicity remained significantly associated with HCSE.
CCSs who reported greater well-being, who rated religion and spirituality of high importance, and who accessed specialized cancer services expressed greater HCSE. Hispanic CCSs, however, reported less HCSE than non-Hispanics. Interventions that attend to the quality of life and spiritual needs of CCSs have potential to build HCSE to support the healthcare transition process. Because Hispanic CCSs may be at risk of lower perceived confidence to navigate their health care, culturally competent, efficacy-enhancing interventions are needed for this population.
Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent side effect of pediatric cancer treatment. The presentation of CIPN, trajectory and completeness of recovery over the first 6 months postchemotherapy, and the influence of patient and treatment characteristics on recovery are described.
Sixty-seven children and adolescents treated for non-CNS cancers were evaluated for CIPN using the pediatric modified total neuropathy score (ped-mTNS) while on treatment and 3 and 6 months postchemotherapy. Differences between diagnostic groups and treatment type were evaluated as well as change in scores over time. Risk factors for on-treatment and persistent CIPN at 6 months were identified.
Overall, ped-mTNSs were in the abnormal range for 86.5% during treatment and scores decreased over time (initial 9.3 ± 0.6, 6 months 4.3 ± 0.4; F = 38.14, P < 0.001). By 6 months posttreatment, mean scores and percentage of children with abnormal scores were reduced to 2.4 ± 0.3 and 11.5%, respectively, in the ALL group, but remained higher at 5.7 ± 0.7 and 57%, respectively, for lymphoma, and 5.2 ± 1.0 and 60%, respectively, for other solid tumors. At 6 months posttreatment, light touch deficits and foot strength deficits remained in 19.4 and 59.7%, respectively, compared with only 4.9 and 9.8% of the control population. Subjects who were older at exposure, female, or who received etoposide in addition to vincristine were at higher risk for on-treatment CIPN. On-treatment sensory abnormalities were associated with increased risk of persistent CIPN.
While CIPN improves in most pediatric patients, significant numbers, especially those treated for lymphoma or other solid tumors, have remaining neuropathic signs and symptoms 6 months posttreatment.
Prior research has demonstrated the reliability and validity of the Neurological Predictor Scale (NPS) in relation to intelligence and adaptive functioning in survivors of pediatric brain tumors. To extend these findings, this study examined the relationship between the NPS and core neurocognitive skills hypothesized to underlie broad outcome measures of IQ and adaptive functioning.
Sixty-one adulthood survivors of childhood brain cancers (Mage = 24 years, SD = 6) on average 16 years after diagnosis completed neuropsychological assessments examining attention (Wechsler Memory Scale Digit Span Forward), processing speed (Symbol Digit Modalities Test), and working memory (Auditory Consonant Trigrams). The medical information necessary to compute the NPS was extracted from a thorough medical record review.
The NPS score significantly predicted processing speed (R2 = 0.28, P < 0.05) and working memory (R2 = 0.15, P < .05) outcomes over and above each individual risk factor. NPS was significantly associated with attention outcomes after covarying for age (R2 = 0.13, P < 0.05) over and above each risk factor except presence of hormone deficiency, hydrocephalus, and chemotherapy. These three variables were not significantly associated with attention outcomes in this sample.
Our findings suggest that survivors with more treatments and neurological sequelae experience greater deficits in working memory, processing speed, and attention. Further, the NPS affords the ability to predict how cumulative neurological factors impact core cognitive outcomes many years after initial diagnosis.
Survivors of heritable retinoblastoma carry a high risk to develop second cancers. Eye-preserving radiotherapy raises this risk, while the impact of chemotherapy remains less defined.
This population-based study characterizes the impact of all treatment modalities on second cancers incidence and type after retinoblastoma treatment in Germany. Data on second cancer incidence in 648 patients with heritable retinoblastoma treated between 1940 and 2008 at the German national reference center for retinoblastoma were analyzed to identify associations with treatment.
The cumulative incidence ratio (per 1,000 person years) of second cancers was 8.6 (95% confidence interval 7.0–10.4). Second cancer incidence was influenced by type of retinoblastoma treatment but not by the year of diagnosis or by sex. Radiotherapy and systemic chemotherapy increased the incidence of second cancers (by 3.0- and 1.8-fold, respectively). While radiotherapy was specifically associated with second cancers arising within the periorbital region in the previously irradiated field, chemotherapy was the strongest risk factor for second cancers in other localizations. Soft tissue sarcomas and osteosarcomas were the most prevalent second cancers (standardized incidence ratio 179.35 compared to the German population).
Second cancers remain a major concern in heritable retinoblastoma survivors. Consistent with previous reports, radiotherapy increased second cancer incidence and influenced type and localization. However, chemotherapy was the strongest risk factor for second malignancies outside the periorbital region. Our results provide screening priorities during life-long oncological follow-up based on the curative therapy the patient has received and emphasize the need for less-detrimental therapies for children with heritable retinoblastoma.
Patients with Wiskott–Aldrich syndrome (WAS) are predisposed to malignancy and autoimmunity in addition to infections. We report a male child with WAS, who had presented with recurrent pneumonia, eczema, thrombocytopenia, autoimmune hemolytic anemia, and vasculitic skin lesions. Genetic analysis revealed a classical genotype WAS 155C>T; R41X. At 2 years of follow-up, he developed persistent headache and progressive hepatomegaly. Brain imaging showed a mass in the right frontal region, which on histopathology was shown to be high-grade non-Hodgkin lymphoma. Magnetic resonance cholangiopancreatography showed features of sclerosing cholangitis. This report extends the clinical spectrum and highlights unusual manifestations of sclerosing cholangitis and intracranial lymphoma in a patient with WAS.
OBJECTIVE: Breast cancer is one of the most aggressive and pervasive cancers identified in females. Dexmedetomidine (Dex) is an efficient anesthetic used in surgery. Our study aimed to explore the role of Dex in the malignancy of breast cancer cells in vitro and in vivo. Further, we investigate the molecular mechanism involved in the function of Dex on breast cancer cells.
MATERIALS AND METHODS: The methyl thiazolyl tetrazolium (MTT) assay was applied to detect cell proliferation. The migration and invasion capacity of MDA-MB-231 cells was tested by wound healing assay and transwell assay. Western blot analysis was performed to quantify the protein expression levels of α2-adrenoceptor and ERK.
RESULTS: The proliferation, migration and invasion ability of MDA-MB-231 cells was gradually increased after treatment of Dex in a dose-dependent manner in vitro. In addition, Dex could significantly elevate the volume and weight of xenotransplant tumor in vivo. Furthermore, Dex up-regulated the protein level of a2-adrenoceptor and consistently enhanced the phosphorylation of ERK without changing the total level of it. Similarity, over-expression of a2-adrenoceptor via its agonist Clonidine could mimic the function of Dex on breast cancer.
CONCLUSIONS: These data suggest that Dex could promote the proliferation, migration and invasion of breast cancer cells through the activation of α2B-adrenoceptor /ERK signaling.
L'articolo Dexmedetomidine regulate the malignancy of breast cancer cells by activating α2-adrenoceptor/ERK signaling pathway sembra essere il primo su European Review.
OBJECTIVE: Bone marrow mesenchymal stem cells (BMMSCs) have been widely applied in osteonecrosis. However, lack of biomechanical support limited application of BMMSCs. And porous tantalum (PTA) has been identified as a cell-friendly scaffold for bone regeneration. Herein, we aimed to investigate the efficacy of PTA seeded with BMMSCs in the treatment of osteonecrosis.
MATERIALS AND METHODS: After the production of PTA seeded with BMMSCs, MTT and GFP were performed to identify the proliferation and adhesion of BMMSCs respectively, which was further examined by scanning electron microscopy (SEM). And real-time PCR was also used to determine mRNA level of osteogenic markers, including Alp, OCN, OPN, Col I and Runx-2 in BMMSCs. Nineteen adult rabbits were applied for building steroid-associated osteonecrosis (SAON) models. Bone formation rate (BFR) and mineral apposition rate (MAR) were determined. And Goldner Trichrome Staining was used in these SAON models, which further confirmed the efficacy of PTA seeded with BMMSCs in SAON.
RESULTS: PTA seeded with BMMSCs showed excellent biocompatibility. Additionally, SEM assay showed that BMMSCs adhered tightly and spread fully in the pores of PTA. Next, the expression of ALP and OPN mRNA in BMMSCs were significantly (p < 0.05) higher in the PTA-treated group compared to those in the PTA-untreated group. Furthermore, compared to those treated by only PTA, the dynamic bone formation in rabbits treated by PTA seeded with BMMSCs was significantly increased (p < 0.001) at both week 3rd and week 6th.
CONCLUSIONS: The product, PTA seeded with BMMSCs, was successfully produced, and was determined as high efficacy for treatment of steroid-associated osteonecrosis. PTA seeded with BMMSCs may afford a promising option for treating osteonecrosis.
L'articolo Porous tantalum seeded with bone marrow mesenchymal stem cells attenuates steroid-associated osteonecrosis sembra essere il primo su European Review.
OBJECTIVE: Ghrelin had been known to promote gastric motility in human and animals previously. We aim to investigate the role of ghrelin in chemotherapy-induced nausea and vomiting.
MATERIALS AND METHODS: In the present study, we observed the changes in food intake, kaolin consumption, body weight, plasma ghrelin concentration and expression of ghrelin and its receptor GHS-R1a in the stomach and nucleus tractus solitaries (NTS) in cisplatin-treated rats, and the effects of ghrelin microinjected into NTS on the discharge activity of gastric distension (GD) responsive neurons and gastric motility were also observed.
RESULTS: Cisplatin induced the decrease in food intake and the increase in kaolin consumption of rats. In addition, mRNA expression of GHS-R1a in the stomach and NTS increased significantly after cisplatin treatment. The discharge activity of GD excited (GD-E) and GD inhibited (GD-I) neurons in cisplatin-treated rats was weaker than that of saline treatment, while ghrelin administration into NTS excited most of GD-E and GD-I neurons. Cisplatin induced the decrease in gastric contraction while ghrelin administrated into NTS promoted the gastric motility significantly. However, the amplitude and frequency of gastric contraction promoted by ghrelin in NTS of cisplatin-treated rats were lower than that of saline treated rats. The effects of ghrelin could be completely blocked by its receptor antagonist BIM28163.
CONCLUSIONS: These results indicated that ghrelin in the NTS might participate in the regulation of GD-neurons and gastric motility via its receptor in cisplatin-treated rats.
L'articolo Involvement of ghrelin in nucleus tractus solitaries on gastric signal afferent and gastric motility in cisplatin-treated rats sembra essere il primo su European Review.
OBJECTIVE: To investigate the potential preventive effect of resveratrol in rats exposed to acoustic trauma (AT).
MATERIALS AND METHODS: In this experimental study, Wistar albino rats were divided into three groups: Group 1 (Control, n = 6), Group 2 (AT, n = 6), and Group 3 (resveratrol + AT). The rats in Group 2 were exposed to AT. The rats in Group 3 received resveratrol (300 mg/kg/day) via gavage for 7 days. On day 7, the rats were exposed to AT 10 min following resveratrol treatment. Histological sections of the cochleae were examined using light microscopy, transmission (TEM), and scanning electron microscopy (SEM).
RESULTS: The cochlear hair cells, stereocilia, and Deiters’ cells of the control group appeared normal in all microscopic evaluations. In Group 2, light microscopy revealed predominantly inner hair cell loss, although the outer hair cells were affected. TEM and SEM examination showed severe loss of stereocilia and SEM revealed stereocilia arranged in an asymmetric array. The cochlear structure in Group 3 appeared well preserved under the light microscope, and although TEM and SEM revealed stereocilia loss, the hair cells and stereocilia appeared near normal compared with those of Group 2.
CONCLUSIONS: Resveratrol may have a protective effect against AT damage in the cochlea, most likely through its antioxidant activity. Our results may be useful for studies in humans exposed to AT and noise-induced hearing loss related to chronic exposure to occupational noise.
L'articolo Potential protective effect of resveratrol on acoustic trauma: electron microscopy study sembra essere il primo su European Review.
OBJECTIVE: Breast cancer is the most frequently diagnosed cancer among women in over 75% of countries worldwide accounting for one in four of all cancers in women. Highly agglutinative staphylococcin (HAS), a mixture of Staphylococcus aureus culture filtrates, has been used clinically as an immunomodifier in the treatment of a number of tumors for many years. The aim of present study is to evaluate the therapeutic effects and safety of treating advanced breast cancer patients with a combined therapy of HAS and vinorelbine-based chemotherapy compared to patients who receive standard chemotherapy alone.
PATIENTS AND METHODS: A total of 62 patients with advanced breast cancer were divided into 2 study groups. One group received intravenous injections of HAS and vinorelbine-based chemotherapy (n=31) compared to a control group assigned to receive vinorelbine-based standard chemotherapy (n=31).
RESULTS: Patients with advanced breast cancer who received HAS combined therapy showed a significantly higher overall response rate (Complete Response + Partial Response) of 67.7% compared with patients who received systemic chemotherapy alone (51.6%; p < 0.05). Overall, the occurrence of adverse effects was not significantly different between study groups. HAS was able to remedy the immunosuppressing effects of standard chemotherapy in these patients.
CONCLUSIONS: Treatment of advanced breast cancer with of HAS – in combination with vinorelbine-based chemotherapy – was generally more effective and just as safe compared to treatment with vinorelbine-based standard chemotherapy alone.
L'articolo Treatment of advanced breast cancer with a combination of highly agglutinative staphylococcin and vinorelbine-based chemotherapy sembra essere il primo su European Review.
OBJECTIVE: The present planned to elucidate the mechanistic role zinc supplementation in the modulation of p53 post-translational acetylation, the activity of cyclooxygenase-2 (COX-2) along with other biophysical parameters during benzo(a)pyrene (BP) induced lung carcinogenesis in mice.
MATERIALS AND METHODS: The mice were segregated into four groups viz., normal control, BP treated, BP + zinc and zinc alone treated. Lung carcinogenesis was induced by a single intra-peritoneal (IP) injection of BP (100 mg/kg body weight). Zinc was supplemented to mice at dose levels of 227 mg/kg body weight in drinking water. All the treatments were continued for 20 weeks.
RESULTS: The BP caused a significant rise in the expression of p53. On the other hand, protein expressions of acetylated (lys382)-p53 were significantly decreased, following BP treatment. Also, a significant decrease was observed in the enzyme activities of caspase 3 and caspase 9. Moreover, BP treatment brought about a significant increase in the activity of COX-2. Supplementation of zinc to BP treated mice stimulated acetylation of p53 as observed by an increase in the protein expression of acetylated (lys382)-p53. Also, the enzyme activities of caspase 3 and caspase 9 showed a significant elevation upon zinc supplementation. On the other hand, the zinc supplementation brought about moderation in the expression of enzymatic activity of COX-2 which was restored within the normal limits. Further, BP treatment recorded increased 3H-thymidine uptake as well as enhanced 14C-glucose uptake and its turnover which were reduced significantly following simultaneous treatment with zinc.
CONCLUSIONS: The treatment with zinc has the potential to modulate p53 acetylation to stimulate apoptosis against experimentally induced lung carcinogenesis.
L'articolo Study to elucidate molecular mechanism behind zinc chemo-preventive role during lung carcinogenesis sembra essere il primo su European Review.
OBJECTIVE: Despite a growing interest toward the interplay between H. pylori and gastric microbiota, few data are available about this correlation. The aim of this study was to explore the relationship between H. pylori infection and gas production during lactulose breath test.
MATERIALS AND METHODS: Data of patients undergoing both 13C-urea breath test (UBT) and lactulose breath test (LBT) under standard conditions in our GI unit were retrospectively analyzed. GI symptoms, such as dyspepsia, bloating, abdominal pain/discomfort, and epigastric pain on an eleven-point scale were also analyzed and correlate with the results of those tests. H2 and CH4 were calculated using the trapezoidal rule; a considerable CH4 production was defined by AUCCH4 ≥1200 ppm*4h. Statistical analyses were performed with Fisher’s exact test and independent samples Mann-Whitney test.
RESULTS: Data of 136 patients during a period of time of 3 months were analyzed. 36 patients (26.5%) showed a positive UBT. We do not find any difference as regards age, sex, symptom complaints, and small intestinal bacterial overgrowth between HP negative and positive patients. A greater methane production was observed in infected rather than non-infected patients (47.2% vs. 26% respectively, p=0.02). Furthermore, 25% infected and 10% non-infected produced greater amounts of CH4 compared to H2, resulting in a AUCCH4/AUCH2 ratio >1 (p=0.046).
CONCLUSIONS: This study shows for the first time, a significant association between H. pylori infection and methane production, suggesting that H. pylori might influence gut microbiota composition. Further studies are needed to clarify mechanisms underlying this phenomenon.
L'articolo Helicobacter pylori infection is associated with high methane production during lactulose breath test sembra essere il primo su European Review.
Vagally mediated heart rate variability (vmHRV) is a measure of cardiac vagal tone, and is widely viewed as a physiological index of the capacity to regulate emotions. However, studies have not directly tested whether vmHRV is associated with the ability to facially express emotions. In extending prior work, the current report tested links between resting vmHRV and the objectively assessed ability to facially express emotions, hypothesizing that higher vmHRV would predict greater expressive skill. Eighty healthy women completed self-reported measures, before attending a laboratory session in which vmHRV and the ability to express six emotions in the face were assessed. A repeated measures analysis of variance revealed a marginal main effect for vmHRV on skill overall; individuals with higher resting vmHRV were only better able to deliberately facially express anger and interest. Findings suggest that differences in resting vmHRV are associated with the objectively assessed ability to facially express some, but not all, emotions, with potential implications for health and well-being.
Focus is assumed to be able to enhance the salience of a focused constituent and thereby facilitate the interpretation of a pronoun that refers to a focused antecedent relative to an unfocused antecedent. To assess how discourse-based focus structure influences the interpretation of a pronoun and whether this process is modulated by the grammatical role of the antecedent, we conducted an ERP study in which the focus status of a pronoun's potential antecedents was manipulated by means of a wh-question-answer structure. We found that, relative to those in the focused position, pronouns referring to antecedents in the unfocused position evoked enhanced positive responses in both early (180–230 ms) and late time windows (400–800 ms). Moreover, while a larger positivity was evoked by object-referring pronouns compared to subject-referring pronouns in the 400–800 ms time window over the right hemisphere, there was no effect of grammatical role in the 180–230 ms time window. These findings indicate that, while the initial stage of pronoun resolution is modulated by focus information assigned via a wh-question structure, integration of the pronoun and its antecedent into a coherent discourse representation at the later stage could be constrained by various factors, including the focus status and possibly the grammatical role of the antecedent.
Recent behavioral studies indicate that emotion counter-regulation automatically allocates attention to events that are opposite in the valence to the experienced emotional state. The present study explored the effect of emotion counter-regulation on response inhibition by using ERPs in a go/no-go paradigm. We recruited 58 subjects and randomly assigned them to either the angry priming group (watching Nanjing Massacre movie clips) or the neutral priming group (watching “mending a computer” movie clips). The behavioral results revealed that participants in the angry priming group responded significantly more accurately to go happy and no-go angry faces than go angry and no-go happy faces. The analyses of ERPs revealed that the amplitudes of the no-go N2 and no-go P3 were significantly larger for the happy faces than for the angry faces in the angry priming group. However, no such effects were found in the neutral priming group. These results suggest that highly aroused angry emotion could prompt a priority response to happy emotion stimuli and restrict the responses to angry emotion stimuli through emotion counter-regulation.
Learning from feedback is a prerequisite for adapting to the environment. Prediction error signals coded by midbrain dopamine (DA) neurons are projected to the basal ganglia and anterior cingulate cortex (ACC). It has been suggested that neuronal activity shifts away from the DA system when feedback is delayed. The feedback-related negativity (FRN), an ERP that is generated in the ACC and has been shown to be sensitive to feedback valence and prediction error magnitude, was found to be reduced for delayed feedback. It has, however, not yet been investigated if the FRN for delayed feedback reflects a reward prediction error. In this study, effects of feedback delay (1 s vs. 7 s) on the processing of expected and unexpected positive and negative feedback were investigated in a between-subjects design in healthy human participants conducting a probabilistic feedback learning task. FRN and P300 amplitudes were decreased for subjects learning from delayed compared to immediate feedback. Importantly, the FRN, extracted from the negative-positive feedback difference wave, was significantly smaller for expected compared to unexpected feedback for both the immediate and delayed feedback conditions. Expectancy effects for the P300 were also seen, but did not interact with feedback valence. These results demonstrate an influence of feedback expectancy, and thus the prediction error, on early feedback processing even for delayed feedback, suggesting that neuronal structures underlying feedback processing are comparable for immediate and delayed feedback, at least to some extent. Modulations of the P300 by feedback delay may be linked to feedback salience.
We report pharmacokinetics, efficacy, and safety data for a new 150 mg alectinib capsule in ALK+ non-small-cell lung cancer in a multicenter, open-label pharmacologic study (JP28927). Eligible patients (≥20 years, locally advanced/metastatic ALK+ disease, ALK inhibitor-naïve and -pretreated [including crizotinib refractory]) were randomized 1:1 to receive one of two sequences of alectinib 300 mg twice daily (comprising different schedules of 20/40 mg and 150 mg capsules) until investigator-determined lack of clinical benefit. Co-primary endpoints were: bioequivalence of alectinib 20/40 mg versus 150 mg; food effect with 150 mg; and safety. Thirty-five patients were enrolled; median treatment duration was 13.1 months (range 1.1−15.0). Under fasting conditions, exposure of the two formulations was similar; mean AUClast ± standard deviation 3230 ± 914 h•ng/mL versus 3710 ± 1040 h•ng/mL, respectively, for 150 mg versus 20/40 mg capsules. Food effect with 150 mg alectinib was negligible. Treatment-related adverse events in >20% of patients were constipation (31.4%), dysgeusia (25.7%), and decreased white blood cell and neutrophil count (22.9% each). No treatment-related grade 4/5 events occurred. Median time to response was 1.2 months (95% CI 1.1−2.1). For the full analysis set (n = 35) and crizotinib-failure subpopulations (n = 23), overall response rate was 70.0% (95% CI 50.6−85.3) and 65.0% (95% CI 40.8−84.6), and median progression-free survival was 13.9 months (95% CI 11.1−not reached) and 12.9 months (95% CI 3.9−not reached), respectively. The 150 mg capsule had a similar exposure profile to 20/40 mg capsules. Alectinib demonstrated promising efficacy and was well tolerated.
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OBJECTIVE: The progression of cardiovascular disease is blunted by regular exercise training as a common non-pharmacological treatment. Recent findings have confirmed that central aortic pressure is more strongly related to cardiovascular events than brachial blood pressure. The aim of the study was to evaluate the influence of a single bout of significant physical effort on central aortic pressure and pulse wave velocity in young male athletes.
PATIENTS AND METHODS: The study group consisted of 16 healthy male athletes undergoing regular endurance training. The subjects of the study (21.6 ± 2.85 years of age) underwent a submaximal exercise test consisting of cycling for 30 minutes. Aortic pulse wave velocity (PWV) and derivatives (augmentation index set to 75 heart beats, AIx75; pulse pressure amplification, PPA), ejection duration (ED), subendocardial viability ratio (SEVR) and central blood pressure were examined before and after the exercise test Blood pressure and pulse waveform were evaluated in the supine position after a 15-minute rest by means of the oscillometric method the oscillometric method.
RESULTS: Comparing the rest condition to the period immediately following the exercise test, athletes showed lower central than peripheral systolic blood pressure both before (129 ± 11 mmHg and 112 ± 8 mmHg, respectively, p < 0.001) and after (130 ± 10 mmHg to 112 ± 8 mmHg, respectively, p < 0.001) the test. They also showed a decrease of ED from 339.7 ± 44.4 ms to 326.9 ± 41.4 ms (p < 0.02) and an increase of PPA from 136.2 ± 5.4% to 140.3 ± 5.0% (p < 0.02), whereas PWV, AIx75 and SEVR changed insignificantly.
CONCLUSIONS: We confirm that PPA is sensitive to an instant change in aortic elasticity. Furthermore, the hemodynamic response to a single physical effort composed of shorter ejection time and increased relative elasticity of the aorta prevents impairment of oxygen supply to the heart musculature.
L'articolo Influence of physical effort on aortic stiffness in young male athletes sembra essere il primo su European Review.
OBJECTIVE: Coronary angiography has a limitation to determine the severity of intermediate stenosis (30-70%)1,2. Fractional flow reserve (FFR) is a method for the assessment of the intermediate stenosis severity3. The effect of coronary artery disease (CAD) severity on the FFR results is not clear. In this study, we aimed to expose the effect of CAD severity calculated with Syntax and Gensini scores on FFR results.
PATIENTS AND METHODS: We scanned patients data (n=378) who had undergone fractional flow reserve measurements in our center. Patients with acute coronary syndrome in the last month, moderate or severe valvular diseases, acute heart failure, serious bradycardia, atrial fibrillation/flutter, severe left ventricular hypertrophy or patient with deficient data were excluded. 351 patients were included in the study. Syntax and Gensini scores were calculated and compared with FFR results. Hemodynamically significant result for FFR, ratio <0.80 was accepted.
RESULTS: The negative correlation between high Gensini, high Syntax scores and FFR results was statistically significant. Especially patients with Syntax scores >22 had notable more crucial lesions in FFR measurements (p<0.001). Cardiovascular disease risk factors such as age, gender, hypertension, diabetes mellitus and dyslipidemia did not correlate with the FFR results. Patients with intermediate stenosis (30-70%) and high Gensini and high Syntax scores were found to have more hemodynamically significant on FFR measurements (FFR <0.80).
CONCLUSIONS: Intermediate lesions with high Syntax score should be evaluated by hemodynamic procedures and treated more carefully with optimal medical treatment or revascularization. Revascularization method of CAD with high Syntax score should be decided with hemodynamic procedures as FFR measurements.
L'articolo The impact of the extent and severity of coronary artery disease on fractional flow reserve measurements sembra essere il primo su European Review.
