Atomic and nanoscale imaging of a cellulose nanofiber and Pd nanoparticles composite using lower-voltage high-resolution TEM.
We have examined the advanced application of transmission electron microscopy (TEM) for the structural characterization of a composite of cellulose nanofiber (CNF) and palladium (Pd) nanoparticles. In the present study, we focused on electron-irradiation damage and optimization of high-resolution TEM imaging of the composite. The investigation indicates that the CNF breaks even under low-electron-dose conditions at an acceleration voltage of 200 kV. We then applied lower-voltage TEM at 60 kV using a spherical aberration corrector and a monochromator, in order to reduce electron-irradiation damage and improve the spatial resolution. The TEM observation achieved high-resolution imaging and revealed the existence of small Pd nanoparticles, around 2 nm in diameter, supported on the CNF. It is considered that the use of a monochromator in combination with spherical aberration correction contributed to the atomic and nanoscale imaging of the composite, owing to the improvement of the information limit under a lower-acceleration voltage.


High prevalence of occult hepatitis C virus infection in patients with chronic hepatitis B virus infection.
Hepatitis C virus (HCV) infection in the absence of detectable antibodies against HCV and of viral RNA in serum is called occult HCV infection. Its prevalence and clinical significance in chronic hepatitis B virus (HBV) infection is unknown. HCV RNA was tested for in the liver samples of 52 patients with chronic HBV infection and 21 (40 %) of them were positive for viral RNA (occult HCV infection). Liver fibrosis was found more frequently and the fibrosis score was significantly higher in patients with occult HCV than in negative ones, suggesting that occult HCV infection may have an impact on the clinical course of HBV infection.


In Vitro Anti-cancer Effect of Crataegus oxyacantha Berry Extract on Hormone Receptor Positive and Triple Negative Breast Cancers via Regulation of Canonical Wnt Signaling Pathway.
Breast cancer treatment strategy depends mainly on the receptor status. Our aim was to identify a herbal preparation, effective against breast cancer, irrespective of hormone sensitivity, and to understand its molecular mechanism. The rich antioxidant composition of hawthorn (Crataegus oxyacantha) makes it a promising anti-cancer drug candidate. Polyphenol-rich methanolic extract of C. oxyacantha berry (M.Co) was found to be cytotoxic on hormone receptor positive (MCF-7) and triple negative (MDA-MB-231) breast cancer cell lines, at a dose (75 μg/ml) safe on normal cells. It could effectively inhibit tumor cell proliferation and arrest cell cycle at G1/S transition in both cell lines. Molecular targets were selected from different levels of canonical Wnt signaling pathway (such as autocrine and antagonistic ligands, receptor, effector, cytoplasmic components, downstream targets, and pathway antagonist), since they are frequently found dysregulated in all breast cancers and their aberrant activation is associated with cancer stem cell expansion. M.Co could significantly downregulate the expression of Wnt pathway agonists and upregulate that of Wnt antagonists at transcriptional and translational levels, in both cell lines. To conclude, C. oxyacantha berry extract is effective against breast cancer irrespective of its hormone dependency, and cancer growth inhibition at stem cell level can be expected.


Expression of p21WAF1 is dependent on the activation of ERK during vitamin E-succinate-induced monocytic differentiation.
Vitamin E-succinate (VES) induced monocvtic differentiation of HL-60 human leukemia cells. Treatment with VES increased the nitroblue tetrazolium reduction activity, and the expression of monocyte specific cell surface antigen, CD14 and c-fms. During the monocytic differentiation of HL-60 cells that were induced by VES, the phosphorylation of extracellular signal-regulated protein kinase (ERK) was increased by 12 h and then gradually decreased to a level that was similar to that of the control. However, the phosphorylation levels of p38 and JNK, as well as the expression levels of ERK, p38, and JNK, were unchanged by the VES treatment. Treatment with VES also induced hypophosphorylation of the retinoblastoma protein and an increase of the p21WAF1 protein level. VES-induced ERK phosphorylation was abolished by the ERK inhibitor, PD98059, which resulted in a remarkable prevention of VES-induced monocytic differentiation. Inhibition of the ERK activity by PD98059 also diminished the VES-induced p21WAF1 protein expression, but did not change the phosphorylation state of the retinoblastoma protein. Collectively, these data suggest that the ERK signaling pathway mediates the up-regulation of the p21xWAF1 expression that is induced by VES, which is required for monocytic differentiation of HL 60 cells.


Prevention of liver steatosis through fish oil supplementation: correlation of oxidative stress with insulin resistance and liver fatty acid content.
Non-alcoholic fatty liver disease (NAFLD) is triggered by a nutritional-metabolic alteration characterized by triacylglicerides acumulation, insulin resistance (IR), oxidative stress and depletion of polyunsaturated fatty acid (PUFA). The n-3 PUFA, such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, would be hepatoprotective against the development of NAFLD by stimulating lipolysis and inhibit lipogenesis. So, fish oil supplementation (EPA + DHA) prevents HFD-induced NAFLD. In this context, the aim of this study is to evaluate the correlation between liver oxidative stress with IR and levels of PUFA in supplemented mice. Male mice C57BL/6J (n = 9) were fed for 12th week: a) control diet (20% protein, 70% carbohydrate, 10% lipids), b) control diet and fish oil supplementation (200 mg EPA+DHA/kg/day), c) high fat diet (20% protein, 20% carbohydrate, 60% lipids), and d) high fat diet and fish oil supplementation. Liver steatosis (histology), insulin resistance (HOMA), liver oxidative stress (GSH/GSSG, carbonyl protein and 8-isoprostanes) and liver fatty acid content were evaluated. The significant decrease in liver oxidative stress parameters (p < 0.05, ANOVA followed by Newman Keuls test) were correlated (Pearson test) with HOMA and levels of PUFA, along with the hepatoprotection observed. It concludes that prevention of NAFLD by supplementation with fish oil (EPA+DHA) is dependent of the prevention of liver oxidative stress, IR and PUFA depletion.


Professional patient-centred care is what counts.
I'm a nursing auxiliary, soon to be degree student, and I have a different hair colour pretty much every week. Like Mary Walls Penney, the nursing home nurse who was confronted about her appearance (Nursing Standard online), I also have tattoos on show. However, I work in a day surgery unit and have never received negative comments about my appearance. Actually, patients often comment on my hair or tattoos; it's usually a nice ice breaker. What matters is being professional and caring.


Coronary artery bypass grafting for Kawasaki disease.
Kawasaki disease (KD) is the leading cause of pediatric ischemic heart disease. The incidence of serious coronary sequelae is low and about 2% - 3% of patients with KD, but once myocardial infarction occurs in children, the mortality is quite high and 22% at the first infarction.This study aimed to evaluate the efficacy of coronary artery bypass grafting (CABG) in patients with KD. Eight patients with a history of KD underwent CABG between October 1997 and July 2005. The number of bypass grafts placed was 2 to 4 per patient (mean 2.5 +/- 0.8). Various bypass grafts were used in patients, i.e. the left internal mammary artery (LIMA) in 3 patients, bilateral internal mammary artery (IMA) in 2 patients, LIMA plus gastroepiploic artery (GEA) in 1 patient and total saphenous vein grafts (SVGs) in 2 patients. The combined procedures included ventricular aneurysmectomy in 1 patient, mitral valve plasty in 1 and right coronary aneurysmectomy in 1. One patient was not able to wean from cardiopulmonary bypass (CPB), after being supported with intra-aortic balloon pump (IABP), the patient was weaned from CPB successfully. One patient died of low cardiac output syndrome and acute renal failure 19 days after operation. Other patients recovered and were discharged uneventfully. During the follow-up that ranged from 3 to 57 months (mean 27 months), clincal angina disappeared or improved. Cardiac function was in Class I - II (NYHA). CABG is a safe and effective procedure for Kawasaki coronary artery disease. However long-term results need to be followed up.


Adherence to the Grampian joint drug formulary in general practice.
A joint drug formulary covering both hospital and general practice prescribing has been in existence in Grampian since 1990. The aims of this study were to measure adherence to this formulary in general practice and to identify who had initiated non-formulary drugs. The drug therapy of elderly patients on presentation to hospital was compared to the formulary. Of the 449 drugs prescribed 377 (84%) were recommended in the formulary. The main areas of non-formulary prescribing were antidepressants, hypnotics, nitrates and diuretics, with some non-formulary drugs being initiated by hospital prescribers. The method described was found to be extremely simple and had the advantage that it reflected actual prescribing at the time of the study.


The senescent microenvironment promotes the emergence of heterogeneous cancer stem-like cells.
There is a well-established association between aging and the onset of metastasis. Although the mechanisms through which age impinges upon the malignant phenotype remain uncharacterized, the role of a senescent microenvironment has been emphasized. We reported previously that human epithelial cells that undergo telomere-driven chromosome instability (T-CIN) display global microRNA (miR) deregulation and develop migration and invasion capacities. Here, we show that post-crisis cells are not able to form tumors unless a senescent microenvironment is provided. The characterization of cell lines established from such tumors revealed that these cells have acquired cell autonomous tumorigenicity, giving rise to heterogeneous tumors. Further experiments demonstrate that explanted cells, while displaying differences in cell differentiation markers, are all endowed of enhanced stem cell properties including self-renewal and multilineage differentiation capacity. Treatments of T-CIN+ cells with senescence-conditioned media induce sphere formation exclusively in cells with senescence-associated tumorigenicity, a capacity that depends on miR-145 repression. These results indicate that the senescent microenvironment, while promoting further transdifferentiations in cells with genome instability, is able to propel the progression of premalignant cells towards a malignant, cell stem-like state.


Aberrant DNA methylation profile of hepatocellular carcinoma and surgically resected margin.
Field cancerization currently described the theory of tumorigenesis and, until now, has been described in almost all organ systems except in liver. For this reason, we explore the presence of field cancerization in liver and its underlying clinical implication in hepatocellular carcinoma (HCC). In our study, methylation profile of HCC and surgically resected margin (SRM) were established by methylation-specific PCR. Liver cirrhosis (LC), chronic hepatitis and normal liver were treated in the same way as the background control. The correlation analysis among the methylation profile of HCC, SRM and clinicopathological data of HCC patients was made respectively. Our results showed that methylation abnormities related to HCC, but not background disease existed in histologically negative SRM. Monoclonal and polyclonal models may coexist in field cancerization in liver. Patients with RIZ1 methylation in SRM had a shorter disease free survival. The local recurrence trend of early and later recurrence in HCC is potentially related to a second field tumor. From these results, we can suggest that field cancerization exists in liver. The study of field cancerization in liver plays an important role in hepatocarcinogenesis. Second field tumor derived form field cancerization may have important implications in HCC prognosis assessment that is worthy of further study.


Cardiac arrest during laparotomy with argon beam coagulation of metastatic ovarian cancer.
The argon beam coagulation (ABC) is a safe and effective tool for surgical cytoreduction of metastatic ovarian carcinomas. A 66-year-old woman with newly diagnosed advanced stage epithelial ovarian cancer underwent primary cytoreductive surgery involving ABC of tumor implants. Intraoperatively, she experienced cardiac arrest during use of the ABC. She was successfully resuscitated. The etiology of the arrest was thought to be secondary to a venous gas embolism. The risk associated with venous gas embolism in a laparotomy case is exceedingly low. This is the first case report of venous gas embolism during ABC in a surgical procedure for gynecologic malignancy. Proper monitoring and support services should always be immediately available when using ABC.


Alcoholism and prescription drug abuse in the elderly: St. Louis University grand rounds.
This Grand Rounds will review the problem of alcoholism and prescription drug abuse in the elderly. Several case vignettes will be presented. The pharmacology of alcohol and potentially addictive prescription medications will be reviewed. The clinical presentation of and psychiatric symptoms associated with these disorders will be discussed. The process of addiction and issues regarding the clinical evaluation of the elderly addict will be discussed. The medical complications of these disorders will be reviewed, followed by a discussion of guidelines for the appropriate use of these drugs in the elderly. The grand rounds will conclude with a discussion of the treatment of patients with these disorders.


Detection of virulence genes in resistant enterococci isolated from pediatric patients at high risk for nosocomial infections.
The study of virulence genes carried by enterococci has become of greater relevance as nosocomial enterococcal infections have become more prevalent and possibly more severe. Surveillance swabs were performed on children less than 18 months of age in an intensive care unit in Iran in 2012-2013. Multiplex PCR and sequencing methods were used to detect gelE, esp and asa1 genes in enterococci with intermediate or full resistance to vancomycin. The rate of carriage of the genes was gelE (91%), esp (79%) and asa1 (87%). The majority of enterococcal strains with resistance to vancomycin carry genes for all three potential virulence factors that were analyzed in this study. This might explain why enterococcal infections appear to be more virulent than in the past.


Investigation of transport properties of coronene·TCNQ cocrystal microrods with coronene microrods and TCNQ microsheets.
Coronene·TCNQ cocrystal microrods, coronene microrods, and TCNQ microsheets were constructed by a drop-casting method. Prototype devices were fabricated and their field-effect-transistor (FET) performances were investigated. It is found that coronene·TCNQ microrods had exhibited an n-type characteristic and showed better FET performances than TCNQ microsheets.


Dual-task performance in early stage dementia: differential effects for automatized and effortful processing.
Attentional functions of individuals with early stage Alzheimer's disease (AD) and normal older adults (NC) were studied using a concurrent-task paradigm. Fourteen patients (5 men, 9 women) and 14 age- and sex-matched normal adults engaged in speeded unimanual tapping and speaking tasks during single- and dual-task trials. Speaking tasks were either relatively automatized (Speech Repetition) or relatively effortful (Speech Fluency). As single-task tapping rates were slower for the AD participants than for the NC participants, a proportional decrement score was used as an index of interference in the dual-task conditions. Interference during concurrent-task performance was greater when the cognitive task was effortful for both the NC and the AD groups. Although AD patients suffered higher levels of interference than NC participants while performing the effortful speech task, the two groups showed equivalent small changes in tapping speed while combining the automatized speaking and tapping tasks. Results suggest that a general-purpose attentional processing resource declines in the early stages of AD but dual-task performance is well-maintained when the component tasks are relatively automatized.


SCAR-based real time PCR to identify a biocontrol strain (T1) of Trichoderma atroviride and study its population dynamics in soils.
Strains of Trichoderma spp. are known for their antagonistic properties against plant pathogens, some are already on the market, others are under development. In order to launch a strain on the market its perfect identification at the species and strain levels is needed. The aim of this study is to (i) design a SCAR marker for specific identification of strain T1 of Trichoderma atroviride and (ii) monitor population dynamics of this strain in soil by real time PCR. A primer pair targeting a 141-bp fragment enabled specific detection of this strain without cross detection of autochthonous populations of Trichoderma in several field soils. In two soils, population dynamics assessed by real time PCR and the soil plate technique gave similar results. The molecular tools developed in this study satisfy the requirement for specific identification of the biocontrol strain and for detection and quantification of T. atroviride T1 population in complex environments.


Live attenuated pseudorabies virus developed using the CRISPR/Cas9 system.
Currently, pseudorabies virus (PRV) variant strains are outbreaking in China; these variants belong to genotype II PRV. The traditional Bartha-K61 vaccine has failed to provide complete protection against the emergent variant strains. Therefore, rapid attenuation of current epidemic strains is needed for effective PRV control. In this study, we report a rapid method for editing the PRV genome using the CRISPR-Cas9 system. We developed a triple gE/gI/TK gene-inactivated HeN1 PRV strain, because mice were more susceptible to PRV infection, we then evaluated the attenuation of PRV in the mice and demonstrated that modified PRV was fully attenuated. Furthermore, the attenuated strain also induced immune protection in response to a parental PRV challenge. Overall, we showed that PRVs can be rapidly attenuated using CRISPR-Cas9 technology, which will be critical for PRV control, especially when new variant PRV strains emerge.


Erythrocyte Lewis antigen phenotypes of dyspeptic patients in Taiwan--correlattion of host factor with Helicobacter pylori infection.
Because of the molecular mimicry between Helicobacter pylori lipopolysaccharide and host Lewis blood-group antigens, Lewis antigen may mediate specific H. pylori binding to surface epithelial cells in gastric mucosa. We, therefore, tested whether different Lewis antigen phenotypes have different prevalence rates of H. pylori infection, and determined the specific H. pylori-related disease entities or histologic features. A total of 342 dyspeptic patients without previous anti-H. pylori therapy were enrolled after endoscopy. The Lewis phenotypes, defined as Le(a-b-), Le(a-b+), Le(a+b-), and Le(a+b+) subtypes, were determined from the expression or absence of Lewis antigens (Le(a) and Le(b)) on erythrocytes in each patient using monoclonal antibodies. The H. pylori-specific gastric histology was evaluated using the updated Sydney's system. Of 342 patients, 233 (68.1%) had H. pylori infection. The H. pylori infection rates were significantly higher in patients with Lewis phenotypes Le(a+b-) and Le(a+b+) (p < 0.05). Patients expressing the Le(a) antigen had a higher H. pylori infection rate than those without the Le(a) antigen (80.8 vs 64%, p < 0.005). In H. pylori-infected patients, patients expressing Le(b) antigen had a lower rate of gastroduodenal ulcers than those without Le(b) antigen (46.9 vs 61.4%, p < 0.05). H. pylori-positive patients who expressed the Le(b) antigen had higher bacterial density and inflammation severity in the gastric cardia than those who did not. Patients who expressed the Le(a) antigen had lower bacterial density, less chronic inflammation severity, and lower frequency of lymphoid follicles in the gastric cardia than those who did not (p < 0.05). The erythrocyte Lewis phenotype can be a significant host factor related to susceptibility, different histologic patterns, and clinical outcomes of H. pylori infection in Taiwan.


Long-term changes in blood-brain barrier permeability and white matter following prolonged systemic inflammation in early development in the rat.
Epidemiological evidence in human fetuses links inflammation during development with white matter damage. Breakdown of the blood-brain barrier has been proposed as a possible mechanism. This was investigated in the present study by inducing a prolonged inflammatory response in newborn rats, with intraperitoneal injections of lipopolysaccharide (LPS; 0.2 mg/kg) given at postnatal (P) day 0, P2, P4, P6 and P8. An acute phase response was present over the whole period of injections. Changes in blood-brain barrier permeability were determined for small (sucrose and inulin) and large (protein) molecules. During and immediately after the inflammatory response, plasma proteins were detected in the brain only within white matter tracts, indicating an increased permeability of the blood-brain barrier to protein during this period. The alteration in permeability to protein was transient. In contrast, the permeability of the blood-brain barrier to 14C-sucrose and 14C-inulin was significantly higher in adult animals that had received serial LPS injections during development. Adult animals receiving a single 1 mg/kg LPS injection at P0 showed no alteration in blood-brain barrier permeability to either small or larger molecules. A significant decrease in the volume of CNPase immunoreactive presumptive white matter tracts occurred in the external capsule and corpus callosum at P9. These results demonstrate that a prolonged systemic inflammatory response in the early postnatal period in rats causes size selective increases in blood-brain barrier permeability at different stages of brain development and results in changes in white matter volume.


Mastectomy Incision Design to Optimize Aesthetic Outcomes in Breast Reconstruction.
Choosing the optimal mastectomy incision must account for oncologic, reconstructive, and aesthetic considerations, including nipple preservation, mastectomy skin margins and potential for skin involvement, mastectomy skin perfusion and viability, mastectomy skin excess, previous breast scars, the reconstructive plan, and inconspicuous new scar placement. In the present study, we aimed to assess breast reconstruction aesthetics, as they are influenced by mastectomy incision design. Nine commonly utilized mastectomy incision patterns were grouped into 3 categories: hidden scar, vertical scar, and transverse scar. Twenty plastic surgeons were asked to blindly grade before and after photographs of reconstructed breasts with regard to scar visibility and position and according to their influence on breast aesthetics. Statistically significant differences were observed between the study groups. Mastectomies and reconstructions performed through hidden incisions yield the most aesthetic results. Vertical scars are favorable to transverse scars. In the case of bilateral reconstructions, symmetric scar placement is paramount to optimizing aesthetic outcomes. The mastectomy incision pattern significantly affects the aesthetic outcomes in breast reconstruction. Patterns borrowed from cosmetic breast surgery consistently yield highly aesthetic outcomes. Surgeons must consider oncologic factors and patient characteristics in choosing an ideal incision for each patient.


Cardiac dysfunction in Multisystem Inflammatory Syndrome in Children: An Italian single-center study.
Multisystem inflammatory syndrome in children (MIS-C) is a novel condition temporally associated with SARS-CoV2 infection. Cardiovascular involvement is mainly evident as acute myocardial dysfunction in MIS-C. The aim of this study was to describe the cardiac dysfunction in patients with MIS-C, defining the role of severity in the clinical presentations and outcomes in a single cohort of pediatric patients. A single-center retrospective study on patients diagnosed with MIS-C, according to the Center for Disease Control and Prevention (CDC) definition, and referred to Vittore Buzzi Children's Hospital in Milan from November 2020 to February 2021. Patients were managed according to a local approved protocol. According to the admission cardiac left ventricular ejection fraction (LVEF), the patients were divided into group A (LVEF < 45%) and group B (LVEF ≥45%). Pre-existing, clinical, and laboratory factors were assessed for evaluating outcomes at discharge. Thirty-two patients were considered. Cardiac manifestations of MIS-C were reported in 26 patients (81%). Group A included 10 patients (9 M/1F, aged 13 years [IQR 5-15]), and group B included 22 patients (15 M/7 M, aged 9 years [IQR 7-13]). Significant differences were noted among clinical presentations (shock, diarrhea, intensive care unit admission), laboratory markers (leucocytes, neutrophils, and protein C-reactive), and cardiac markers (troponin T and N-terminal pro B-type Natriuretic Peptide) between the groups, with higher compromission in Group A. We found electrocardiogram anomalies in 14 patients (44%) and rhythm alterations in 3 patients (9%), without differences between groups. Mitral regurgitation and coronary involvement were more prevalent in group A. Total length of hospital stay and cardiac recovery time were not statistically different between groups. A recovery of cardiac functioning was reached in all patients. Despite significant differences in clinical presentations and need for intensive care, all of the MIS-C patients with significant cardiac involvement in this study completely recovered. This suggests that the heart is an involved organ and did not influence prognosis if properly treated and supported in the acute phase.


Metastatic colonic and gastric polyps from breast cancer resembling hyperplastic polyps.
Breast cancer metastasis to the gastrointestinal tract is relatively rare and is generally found when patients complain of symptoms such as gastrointestinal obstruction. Herein, we report a case with metastatic colonic and gastric lesions from breast cancer, with the formation of mucosal polyps which resembled typical hyperplastic polyps.A 47-year-old woman underwent curable surgery for breast cancer and received standard systemic treatments. Her primary tumor was composed of a mix of invasive lobular and ductal carcinomas. During adjuvant endocrine therapy, she developed multiple colonic metastases, identified by colonoscopy performed as part of a general health check-up. She had no symptoms. Small elevated sessile polyps in the transverse colon and rectum showed histological features of signet-ring cell type adenocarcinoma, similar to the invasive lobular component of the primary breast cancer. During treatments for recurrent disease, she also developed multiple gastric metastases, with the same endoscopic and pathological features as the colonic lesions. Her treatment regimen was switched to oral chemotherapy, and she has since maintained stable disease for nearly 3 years. Multiple bone metastases eventually developed, and she was again switched to another systemic treatment but, to date, has remained free of symptoms.We emphasize that the endoscopic findings of the metastatic lesions in the colon and stomach in this case highly resembled hyperplastic polyps. Since biopsy is not always performed for hyperplastic polyps in the gastrointestinal tract, we believe that this case report may encourage endoscopists to offer biopsies to the patient who has a history of breast cancer.


[Computers and angiology. Doppler test of the supra-aortic trunk].
Computing is the hegemonic technique of tomorrow. It is perfectly applicable in angeiology, not so much for the indexing of varices which has proved its worth on card ever since Professor Tournay's schematic organization and teaching, but for the running of the surgery (not really specific), arterial disorders, phlebites, dealing with signals, mail, statistics. This "evolutive" work uses Gosling's index for the comparative study of the supra-aortic trunks.


Scarcity of HIV/AIDS risk-reduction materials targeting the needs of older adults among state departments of public health.
This study investigated the availability of printed human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) education/prevention materials from state departments of public health within the United States, which specifically targeted the older adult population. Information on HIV/AIDS from public health departments in each of the 50 states was solicited, obtained, and analyzed for applicability to an older adult population. Although all 50 states responded to our request for publications, only 15 states (30%) provided publications that were specifically intended for an older adult audience. The title, date of publication, and publisher of publications that were considered "specific to older adults" are provided. These findings suggest that there is a general lack of HIV/AIDS prevention literature specifically tailored for older adults available through state departments of public health.


Adult student satisfaction in an accelerated RN-to-BSN program: a follow-up study.
This mixed-method study revealed accelerated RN-to-BSN (bachelor of science in nursing) students' levels of satisfaction with a wide range of college services in a small university. Building on seminal research on the topic [Boylston, M. T., Peters, M. A., & Lacey, M. (2004). Adult student satisfaction in traditional and accelerated RN-to-BSN programs. Journal of Professional Nursing, 20, 23-32.], the Noel-Levitz Adult Student Priorities Survey (ASPS) and qualitative interview data revealed primary factors involved in nontraditional (adult) accelerated RN-to-BSN student satisfaction. The ASPS assesses both satisfaction with and importance of the following factors: academic advising effectiveness, academic services, admissions and financial aid effectiveness, campus climate, instructional effectiveness, registration effectiveness, safety and security, and service excellence. Of these factors, participants considered instructional effectiveness and academic advising effectiveness as most important and concomitantly gave high satisfaction ratings to each. In contrast, convenience of the bookstore, counseling services, vending machines, and computer laboratories were given low importance ratings. The participants cited convenience as a strong marketing factor. Loss of financial aid or family crisis was given as a reason for withdrawal and, for most students, would be the only reason for not completing the BSN program. Outcomes of this investigation may guide faculty, staff, and administrators in proactively creating an educational environment in which a nontraditional student can succeed.


Parafoveal word perception: a further case against semantic preprocessing.
Three experiments were performed to explore the processing of parafoveal information. A foveal and a parafoveal word pair were presented within the time frame of a single fixation, but short enough to prevent successful refixation of the parafoveal word. Subjects reporting partial parafoveal word information were not able to use this information to bias their choice in a forced-choice task requiring some semantic information from the parafoveal word for correct performance. This result was observed even though correct parafoveal word identification was facilitated if the foveal stimulus was related to the parafoveal word. Further, the data strongly suggest that information is obtained initially from the fixated words, regardless of whether foveal word presentation precedes or follows the parafoveal stimulus.


A conservative approach to testicular rupture in adolescent boys.
Management for blunt trauma with breach of the renal capsule or bladder (extraperitoneal) has largely become nonsurgical since a conservative approach proved to be effective and safe. Currently the recommendation for managing testicular rupture is surgical exploration and débridement or orchiectomy. We report outcomes in boys diagnosed with testicular rupture and treated without surgical intervention. In the last year we conservatively treated 7 consecutive boys with delayed presentation of testicular rupture after blunt scrotal trauma. Patients were treated with scrotal support, antibiotics to prevent abscess, rest, analgesics and serial ultrasound. We report clinical information and outcomes. The 7 boys were 11 to 14 years old and presented 1 to 5 days after injury. Trauma was to the left testis in 3 cases and to the right testis in 4. Patients presented with mild to moderate pain and similar scrotal swelling. Ultrasound findings consistently revealed hematocele and increased echogenicity. Blood flow was present in the injured portion of the testes in 3 cases and to the remainder of the affected testicle in 6 of the 7 boys. In the remaining boy an adequate waveform was not seen in either testicle, which the radiologist thought was secondary to prepubertal status. Other findings included scrotal edema, irregular contour and seminiferous tubule extrusion. Followup was greater than 6 months in all cases. Five boys were seen at the office and the 2 remaining had telephone followup. In all cases hematocele resolved, testicular size stabilized without atrophy and echogenicity normalized in the 5 patients with followup ultrasound. One patient required surgical repair of hydrocele 4 months after trauma but no other patient needed surgical exploration. No abscess or infection developed. A conservative approach in a select group of adolescent boys with testicular rupture can result in resolution of the fracture and maintenance of testicular architectural integrity.


Endotoxin-induced hypoxic-ischemic tolerance is mediated by up-regulation of corticosterone in neonatal rat.
Previous studies suggest that the endotoxin lipopolysaccharide (LPS) may have dual effects on brain damage induced by hypoxia-ischemia (HI) in 7-d-old rats, depending on the exposure paradigm. Although a 4-h interval between LPS administration and HI results in sensitization to HI brain injury, tolerance is observed when LPS is administered 24 h before HI. Our hypothesis is that endogenous corticosteroids are important in acquiring tolerance to HI. Neonatal rats received a single injection of LPS (1.0 mg/kg) either 4 h or 24 h before HI, or two LPS injections (4 h and 24 h) before HI. Increased brain injury was seen in animals subjected to a single LPS injection made 4 h before HI. In contrast, both the single 24-h exposure and the double injections of LPS resulted in tolerance to HI brain damage. To study the effects of corticosteroids on HI tolerance, RU486, a glucocorticoid receptor blocker, was subcutaneously injected at the same time as LPS (1.0 mg/kg), 24 h before HI stress. RU486-LPS treatment counteracted the LPS-induced tolerance effect, and aggravated the HI-induced brain injury compared with the vehicle-LPS-treated group. RU486 did not aggravate the HI-induced brain injury produced 24 h later in saline-injected animals. LPS (1.0 mg/kg) injected into 6-d-old rats transiently up-regulated serum corticosterone levels (119.6, 57.9, 56.8, and 28.3 ng/mL at 6, 12, 24, and 48 h after the LPS injection, respectively). We conclude that endotoxin-induced up-regulation of endogenous corticosterone appears to be critical for acquiring endotoxin-induced HI tolerance.


Substance P in Solution: Trans-to-Cis Configurational Changes of Penultimate Prolines Initiate Non-enzymatic Peptide Bond Cleavages.
We report ion mobility spectrometry and mass spectrometry studies of the non-enzymatic step-by-step degradation of substance P (subP), an 11-residue neuropeptide, with the sequence Arg1-Pro2-Lys3-Pro4-Gln5-Gln6-Phe7-Phe8-Gly9-Leu10-Met11-NH2, in ethanol. At elevated solution temperatures (55 to 75 °C), several reactions are observed, including a protonation event, i.e., [subP+2H]2+ + H+ → [subP+3H]3+, that appears to be regulated by a configurational change and two sequential bond cleavages (the Pro2-Lys3 peptide bond is cleaved to form the smaller nonapeptide Lys3-Met11-NH2 [subP(3-11)], and subsequently, subP(3-11) is cleaved at the Pro4-Gln5 peptide bond to yield the heptapeptide Gln5-Met11-NH2 [subP(5-11)]). Each of the product peptides [subP(3-11) and subP(5-11)] is accompanied by a complementary diketopiperazine (DKP): cyclo-Arg1-Pro2 (cRP) for the first cleavage, and cyclo-Lys3-Pro4 (cKP) for the second. Insight about the mechanism of degradation is obtained by comparing kinetics calculations of trial model mechanisms with experimental data. The best model of our experimental data indicates that the initial cleavage of subP is regulated by a conformational change, likely a trans→cis isomerization of the Arg1-Pro2 peptide bond. The subP(3-11) product has a long lifetime (t1/2 ~ 30 h at 55 °C) and appears to transition through several structural intermediates prior to dissociation, suggesting that subP(3-11) is initially formed with a Lys3-trans-Pro4 peptide bond configuration and that slow trans→cis isomerization regulates the second bond cleavage event as well. From these data and our model mechanisms, we obtain transition state thermochemistry ranging from ΔH‡ = 41 to 85 kJ mol-1 and ΔS‡ = - 43 to - 157 J mol-1 K-1 for each step in the reaction. Graphical Abstract.


Quantifying Genuine Multipartite Correlations and their Pattern Complexity.
We propose an information-theoretic framework to quantify multipartite correlations in classical and quantum systems, answering questions such as what is the amount of seven-partite correlations in a given state of ten particles? We identify measures of genuine multipartite correlations, i.e., statistical dependencies that cannot be ascribed to bipartite correlations, satisfying a set of desirable properties. Inspired by ideas developed in complexity science, we then introduce the concept of weaving to classify states that display different correlation patterns, but cannot be distinguished by correlation measures. The weaving of a state is defined as the weighted sum of correlations of every order. Weaving measures are good descriptors of the complexity of correlation structures in multipartite systems.


Implications of potential cure in acute myelogenous leukemia: development of subsequent cancer and return to work.
Chemotherapy produces extended remissions, and potential cures, in a small minority of patients with acute myeloid leukemia (AML). We explored whether potentially cured patients were at increased risk of subsequent invasive cancer and were able to return to work. Potentially cured patients were defined as those in first or second complete remission (CR) for at least 3 years based on hazard rates for recurrence or death in CR, which declined sharply after this time. Patients who received allogeneic marrow transplant were excluded. We used questionnaires, phone contact, and chart review to obtain information about subsequent cancer and work status. The number of patients who developed invasive cancer was compared with the number expected based on age, gender, and years of follow-up using the Connecticut Tumor Registry. A total of 215 patients met our criteria for potential cure: 203 in first CR and 12 in second CR (of 1,663 treated between 1965 and December, 1992). At a median of 9.2 years from first or second CR, 163 (76%) remain alive in CR. Fifteen patients developed 18 invasive cancers (expected number of patients, 8.8; observed/expected, 1.70; 95% CI, 0.96 to 2.84; P = . 06). Patients initially treated between 1973 to 1979, patients above the potentially cured cohort's median age of 40 years, and those who presented with abnormalities of chromosomes 5 and/or 7 were more likely to develop subsequent cancer, whereas the observed/expected ratio for younger patients was 1.05 (95% CI, 0.13 to 3.80; P = .56). Seventy-four percent of the patients who were working full-time and who were under age 50 at time of treatment for AML have been working full-time in the last 6 months. Only 17 of 56 patients who are currently not working cited physical limitation as the reason. Patients with potentially cured AML are likely to be able to return to work, and at least if younger do not, on average, have an increased risk of invasive cancer.


[Portable gas chromatography for determining airborne acrylonitrile in workplaces].
To establish a method for rapid determination of airborne acrylonitrile using a portable gas chromatograph. A single standard sample of acrylonitrile was prepared in a laboratory and sampled by the built-in constant flow pump of the portable gas chromatograph. The sample was then preconcentrated by the preconcentrator, thermally desorbed, separated by capillary columns, and detected by a micro argon ionization detector to determine the retention time. Retention time was then used to perform qualitative analysis. Under the set condition of gas chromatography, the external standard method was used to create a standard curve for quantitative analysis of acrylonitrile. The linear range of acrylonitrile on the portable gas chromatograph was 0.25 to 3.00 mg/m(3). The regression equation was y = 10(-5) x-0.0275, r = 0.9977. The limit of detection was 0.005 mg/m(3), and the lower limit of quantification was 0.25 mg/m(3). The relative standard deviation was lower than 7.09%, and the degree of accuracy was 91.09-105.54%. Portable gas chromatography is a simple, repeatable, and accurate method for rapid determination of airborne acrylonitrile.


Further assessment of an in vitro screen that may help identify organophosphorus pesticides that are more acutely toxic to the young.
Some, but not all, organophosphorus pesticides are more acutely toxic to the young as compared to adults. We have developed an in vitro assay that measures the detoxification potential (via carboxylesterase and A-esterases) of tissues. Previous results using this in vitro screen correlated with the marked in vivo sensitivity of the young to chlorpyrifos and also correlated with the equal sensitivity of the young and adult to methamidophos (Padilla et al., 2000). We have now extended these observations to two other pesticides that have already been shown in the literature to be more toxic to the young: parathion (paraoxon) and malathion (malaoxon). In our in vitro assay, liver or plasma from 7-d-old rats were much less efficacious than adult tissues at detoxification of the active metabolites of these two pesticides. Using our in vitro assay we also tested the active metabolite of diazinon, diazoxon, and again found that young liver or plasma possessed much less detoxification capability than adult tissues. From these results, we predicted that young animals would be more sensitive to diazinon, which, in fact, was the case: When postnatal day (PND) 17 or adult rats were given a dosage of 75 mg/kg diazinon, adult brain cholinesterase (ChE) was only inhibited 38%, while the brain ChE in the PND 17 animals showed much more inhibition (75%). We conclude that our in vitro screen may prove to be a useful, quick, convenient test for identifying which organophosphorus pesticides may be more acutely toxic to the young as compared to adults.


Cardiomyopathy: molecular and immunological aspects (review).
Idiopathic cardiomyopathy is reviewed from molecular standpoint. About a half of all patients with hypertrophic cardiomyopathy show intra-familial occurrence. In familial hypertrophic cardiomyopathy, nine gene abnormalities have been discovered in the sarcomere, i.e. the genes of beta cardiac myosin heavy chain, cardiac troponin T, alpha-tropomyosin, cardiac myosin binding protein-C, essential or regulatory myosin light chain, cardac troponin I, alpha-cardiac actin, and titin. Sudden death can occur in patients with familial-type hypertrophic cardiomyopathy with abnormalities of the cardiac troponin T or troponin I gene, even if hypertrophy is not marked. Some cases of familial dilated cardiomyopathy show gene abnormalities for cytoskeletal components such as desmin and laminin A/C. Mutations of the delta-sarcoglycan gene have also been discovered in familial or sporadic dilated cardiomyopathy. Mutations in mitochondrial genes have been observed in both hypertrophic and dilated cardiomyopathy. It is postulated that chronic viral myocarditis may sometimes lead to dilated cardiomyopathy, and hepatitis C virus is also thought to be an etiological factor. Immunological abnormalities have also been reported, such as autoantibodies against myosin, beta-receptors, ADP/ATP carrier proteins.


Logical schema acquisition from text-based sources for structured and non-structured biomedical sources integration.
In this paper we present a novel approach to integrate non-structured and structured sources of biomedical information. We part from previous research on database integration conducted in the context of the EC funded INFOGENMED project. In this project we developed the ONTOFUSION system, which provides a robust framework to integrate large sets of structured biomedical sources. Methods and tools provided by ONTOFUSION cannot be used to integrate non-structured sources, since the latter usually lack a logical schema. In this article we introduce a novel method to extract logical schemas from text-based collections of biomedical information. Non-structured sources equipped with a logical schema can be regarded as regular structured sources, and thus can be bridged together using the methods and tools provided by ONTOFUSION. To test the validity of this approach, we carried out an experiment with a set of five cancer databases.


Insertion of Exogenous Genes within the ORF1a Coding Region of Porcine Astrovirus.
A tagged or reporter astrovirus can be a valuable tool for the analysis of various aspects of the virus life cycle, and to aid in the development of genetically engineered astroviruses as vectors. Here, transposon-mediated insertion mutagenesis was used to insert a 15-nucleotide (nt) sequence into random sites of open reading frame 1a (ORF1a) based on an infectious full-length cDNA clone of porcine astrovirus (PAstV). Five sites in the predicted coiled-coil structures (CC), genome-linked protein (VPg), and hypervariable region (HVR) in ORF1a of the PAstV genome were identified that could tolerate random 15 nt insertions. Incorporation of the commonly used epitope tags, His, Flag, and HA, into four of the five insertion sites permitted the production of infectious viruses and allowed recognition by specifically tagged monoclonal antibodies. The results of immuno-fluorescent assays showed that Flag-tagged ORF1a protein overlapped partially with capsid and ORF2b proteins in the cytoplasm. Improved light-oxygen-voltage (iLOV) gene was also introduced at the insertion sites of CC, VPg, and HVR. Only one viable recombinant reporter PAstV expressing iLOV inserted in HVR was recovered. Biological analysis of the reporter virus showed that it displayed similar growth characteristics, and yet produced less infectious virus particles, when compared with the parental virus. The recombinant virus carrying the iLOV fused with the HVR of ORF1a protein maintained its stability and showed green fluorescence after 15 passages in cell cultures. The resultant fluorescently tagged virus could provide a promising tool for the rapid screening of antiviral drugs as well as allowing the visualization of PAstV infection and replication in living cells.


PCR inhibition by reverse transcriptase leads to an overestimation of amplification efficiency.
This study addresses the problem of PCR inhibition by reverse transcriptase. It has been shown that the inhibition occurs mostly when a small amount of RNA is taken for RT reaction, and it is more visible for rarely expressed transcripts. We show here that the inhibition takes place regardless of what amount of template is utilized for RT. The inhibition possesses a global nature, i.e. the amplification of any given transcript may be compromised with different levels of inhibition. The process of inhibition also explains wrongfully derived PCR amplification efficiencies, sometimes more than 100%, when the sequential dilutions of unpurified RT sample are utilized to build the calibration curve. The RT influences PCR not only by inhibiting it. When microgram(s) of RNA are taken for RT reaction, reverse transcriptase may cause overamplification of some transcripts under certain PCR conditions. The possible mechanism of RT influence on PCR is presented, and a purification method is implemented to remove the effects of RT on PCR.


Roles of the Cannabinoid System in the Basal Ganglia in Parkinson's Disease.
Parkinson's disease (PD) is a neurodegenerative disease usually caused by neuroinflammation, oxidative stress and other etiologies. Recent studies have found that the cannabinoid system present in the basal ganglia has a strong influence on the progression of PD. Altering the cannabinoid receptor activation status by modulating endogenous cannabinoid (eCB) levels can exert an anti-movement disorder effect. Therefore, the development of drugs that modulate the endocannabinoid system may be a novel strategy for the treatment of PD. However, eCB regulation is complex, with diverse cannabinoid receptor functions and the presence of dopaminergic, glutamatergic, and γ-aminobutyric signals interacting with cannabinoid signaling in the basal ganglia region. Therefore, the study of eCB is challenging. Here, we have described the function of the cannabinoid system in the basal ganglia and its association with PD in three parts (eCBs, cannabinoid receptors, and factors regulating the cannabinoid metabolism) and summarized the mechanisms of action related to the cannabinoid analogs currently aimed at treating PD. The shortcomings identified from previous studies and the directions that should be explored in the future will provide insights into new approaches and ideas for the future development of cannabinoid-based drugs and the treatment of PD.


Graphene-Based Materials as Solid Phase Extraction Sorbent for Trace Metal Ions, Organic Compounds, and Biological Sample Preparation.
Graphene is a new carbon-based material that is of interest in separation science. Graphene has extraordinary properties including nano size, high surface area, thermal and chemical stability, and excellent adsorption affinity to pollutants. Its adsorption mechanisms are through non-covalent interactions (π-π stacking, electrostatic interactions, and H-bonding) for organic compounds and covalent interactions for metal ions. These properties have led to graphene-based material becoming a desirable adsorbent in a popular sample preparation technique known as solid phase extraction (SPE). Numerous studies have been published on graphene applications in recent years, but few review papers have focused on its applications in analytical chemistry. This article focuses on recent preconcentration of trace elements, organic compounds, and biological species using SPE-based graphene, graphene oxide, and their modified forms. Solid phase microextraction and micro SPE (µSPE) methods based on graphene are discussed.


[Effect of antisense oligonucleotides on myo-intimal hyperplasia in a model of abdominal aortic injury in the rat].
Restenosis at a rate > 30% at 6 months is the major complication of both coronary and peripheral arterial angioplasty. Restenosis is mainly due to proliferation of smooth muscle cells, extracellular matrix and collagen which form a neointima. The proto-oncogene c-myb is a gene with an immediate response which has been implicated in the proliferation and alteration of the phenotype of smooth muscle cells. The antisenses are molecules of single-helix DNA the sequence of which is inverse to that of messenger RNA of the target proto-oncogene. They therefore have the possibility of forming a double helix with the messenger RNA and of preventing its translation. The antisenses of c-myb have already been successfully tested in in vitro and in vivo models of neointimal proliferation. The aim of this study was to demonstrate the efficacy of c-myb antisenses on the proliferation of smooth muscle cells in a model of abdominal aortic injury in the rat. Thirty-five male Wistar rats with an average weight of 350 grams were operated. Smooth muscle cell proliferation was obtained by desendothelialisation of the abdominal aorta from the level of the left renal vein to the aortic bifurcation. Using a randomised, double-blind protocol, 17 rats were given 500 microliters of pluronic gel (control group), 9 a sense oligonucleotide of c-myb in 500 microliters of pluronic gel (sense group) and 9 a c-myb antisense oligonucleide in 500 microliters of pluronic gel (antisense group). Two rats were given fluorescinlabelled antisenses; one was sacrificed 4 hours and the other 24 hours later.(ABSTRACT TRUNCATED AT 250 WORDS)


Three-color cytofluorometric analysis of CD8 cell subsets in HIV-1 infection.
Previous studies have shown that CD8 cell subsets, some expressing activation markers, are elevated in human immunodeficiency virus (HIV) infection. To assess the overlap of these subsets, we used three-color flow cytometry to phenotype CD8 cells in cryopreserved mononuclear cells from uninfected controls and from people infected with HIV, in CDC classes II, III, and IV (n = 12 per group). There were several CD8 subset changes observed in association with HIV infection. A shift from a naive (CD45RA+CD45RO-) to a memory (CD45RA-CD45RO+) phenotype occurred in the CD8 subset, but the intermediate phenotype (CD45RA+CD45RO+) was unchanged. Increases in DR+CD8 and CD38+CD8 cells were noted in both naive and memory CD8 subsets, defined by CD45RA or CD45RO expression. Both the CD57+ and CD57- subsets of DR+CD8 cells were increased, whereas only the CD57+ subset of CD38+CD8 cells was elevated. The increase in CD57+CD8 cells reflected a selective rise in CD57+CD8 cells coexpressing CD38, DR, and CD45RO. The CD38+ DR+ CD8 subset was markedly increased and was apparently derived from both the CD38-DR-CD8 and CD38+DR-CD8 subsets. Compared with classes II and III, the CDC class IV group showed an increased proportion of CD8 cells expressing CD38; higher percentages of CD38+DR+CD8, CD38+CD45RA-CD8, and DR+CD45RO+CD8 subsets; and decreased percentages of CD38-CD45RA+CD8 and CD38-CD57-CD8 cells.(ABSTRACT TRUNCATED AT 250 WORDS)


A case of propofol-induced oropharyngeal angioedema and bronchospasm.
Propofol (2,6-diisopropylphenol) is an ultrashort-acting sedative agent with sedative and amnestic effects that is used not only for anesthesia but also for sedation during minor outpatient procedures and endoscopic examinations. Rare cases of anaphylaxis following propofol administration have been reported in the medical literature. Documentation of anaphylaxis is often lacking because the cause and effect relationship is often hard to prove. Only a minority of patients get referred for allergy testing to confirm the offending drug. Here we report a 74-year-old woman who had an anaphylactic reaction with severe oropharyngeal edema and bronchospasm for a few minutes after receiving propofol during endoscopic examination. An allergy skin test was positive for both propofol and soybean. Soybean in the intralipid is one component of propofol, and we concluded that this anaphylaxis was caused by soybean.


Integrated N- and O-Glycomics of Acute Myeloid Leukemia (AML) Cell Lines.
Acute myeloid leukemia (AML) is characterized by a dysregulated expansion of poorly differentiated myeloid cells. Although patients are usually treated effectively by chemotherapy, a high rate of relapsed or refractory disease poses a major hurdle in its treatment. Recently, several studies have proposed implications of protein glycosylation in the pathobiology of AML including chemoresistance. Accordingly, associations have been found between specific glycan epitopes and the outcome of the disease. To advance this poorly studied field, we performed an exploratory glycomics study characterizing 21 widely used AML cell lines. Exploiting the benefits of porous graphitized carbon chromatography coupled to tandem mass spectrometry (PGC nano-LC-MS2), we qualitatively and quantitatively profiled N- and O-linked glycans. AML cell lines exhibited distinct glycan fingerprints differing in relevant glycan traits correlating with their cellular phenotype as classified by the FAB system. By implementing transcriptomics data, specific glycosyltransferases and hematopoietic transcription factors were identified, which are candidate drivers of the glycan phenotype of these cells. In conclusion, we report the varying expression of glycan structures across a high number of AML cell lines, including those associated with poor prognosis, identified underlying glycosyltransferases and transcription factors, and provide insights into the regulation of the AML glycan repertoire.


Modified Tumor Classification With Inclusion of Tumor Characteristics Improves Discrimination and Prediction Accuracy in Oral and Hypopharyngeal Cancer Patients Who Underwent Surgery.
Several histopathological characteristics have a significant prognostic impact on recurrence and survival rates in head and neck squamous cell carcinoma (HNSCC). We conducted a retrospective study on patients with HNSCC to compare traditional pathological T (pT) classification to a new T classification system that incorporates these histopathological characteristics.Newly diagnosed patients with HNSCC (n = 349) post major surgery were identified from the cancer registry database between 2004 and 2013. The pT and new T classification systems were compared with respect to recurrence-free survival (RFS), disease-specific survival (DSS), and survival rates using the Cox proportional hazards model with adjustments. The discriminatory ability of these 2 classification systems was evaluated using the adjusted hazard ratio (HR) and Akaike information criterion (AIC) in a multivariate regression model. The prediction accuracy was assessed using Harrell's C-statistic.The new T classification, which incorporated tumor size, extent, and location with histopathological features had better discriminatory ability and monotonicity of gradients than did pT classification. The new T4 classification yielded a higher adjusted HR in RFS (HR, 4.11; 95% confidence interval [CI], 7.75-9.65) and in DSS (HR, 4.39; 95% CI, 1.6-12.03), and a lower AIC in recurrence (927 vs 969) and survival rates (791 vs 833).The new T classification system had better discriminatory ability in RFS and DSS compared with the routinely used American Joint Committee on Cancer (AJCC) pT classification system. Therefore, this new T classification system, which includes tumor size, location, extent, and histopathological features, could be used as an alternative to AJCC pT classification for patients with HNSCC.


A novel model of human implantation: 3D endometrium-like culture system to study attachment of human trophoblast (Jar) cell spheroids.
There is an urgent need to develop optimized experimental models to examine human implantation. These studies aimed to (i) establish a human endometrium-like three-dimensional (3D) culture system, and (ii) examine the attachment of trophoblast-like Jar spheroids to the culture. In the present work, 3D endometrial cultures were constructed with fibrin-agarose as matrix scaffold, and using epithelial and stromal cells from both human primary cultures and established cell lines. An attachment assay between trophoblast cells and the 3D culture was developed. Epithelial cells (cytokeratin(+)) concentrated on top of the matrix forming a monolayer, and stromal cells (vimentin(+)) resided within the matrix, resembling the normal endometrial structure. The capability of primary epithelial cells to form glands spontaneously was observed. Human trophoblast cells (Jar cells) were hCG(+) by immunostaining, allowed to form spheroids, and confirmed to secrete hCG into the medium. Time-dependent experiments demonstrated a high rate of attachment of Jar spheroids to the epithelium, and adhesion was strongly related to the various cell types present in the 3D culture. An architecturally and functionally competent 3D endometrial culture system was established, that coupled with Jar spheroids mimicking trophoblast cells, provides a unique in vitro model for the study of certain aspects of human implantation.


Organic Base Enabled Nickel-Catalyzed Mono-α-Arylation of Feedstock Solvents.
We report on our successful development of the first metal-catalyzed mono-α-arylation of carbonyl compounds employing a soluble organic base. The scope of these Ni/DalPhos-catalyzed transformations encompasses a range of (hetero)aryl halides (Cl, Br, I) and phenol-derived electrophiles (sulfonates, carbonates, carbamates, sulfamates), including active pharmaceutical ingredients (chloroquine, clozapine), in combination with the typically problematic feedstock small molecule substrates acetone, dimethylacetamide, and for the first time with any metal catalyst/base, ethyl acetate.


Arterial blood pressure estimation using ultrasound: Clinical results on healthy volunteers and a medicated hypertensive volunteer.
This study presents a non-occlusive and non-invasive ultrasound-based technique to measure blood pressure. Most popular clinically-used arterial blood pressure measurement techniques suffer from important weaknesses including being inaccurate, invasive, or occlusive. In the proposed technique, an ultrasound probe is placed on the patient's carotid artery and the contact force between the probe and the tissue is slowly increased while ultrasound images and contact force data are recorded. From this data, the artery is segmented and the segmentation data is sent into an optimization procedure; after post-processing, blood pressure is displayed to the user. This technique was applied to 24 healthy single-visit volunteers, one multi-visit healthy volunteer, and one multi-visit medicated hypertensive volunteer. Compared to the oscillometric cuff, the accuracy and precision of the algorithm-reported systolic pressure is -2.4 ± 10.2 mmHg, and for diastolic pressure is -0.3 ± 8.2 mmHg. This method has the potential to occupy a clinical middle-ground between the arterial catheter and the oscillometric cuff.


Recurrent infusion phlebitis induced by cyclosporine.
To report a case of recurrent infusion phlebitis during cyclosporine treatment, which, as of October 14, 2004, is a previously unreported adverse effect of this drug. A 28-year-old man previously diagnosed with ulcerative colitis was admitted to the internal medicine department due to exacerbation of the condition and treated with intravenous hydrocortisone, followed by treatment with intravenous cyclosporine. During this treatment, the patient experienced quick, recurrent, and significant infusion phlebitis. The intravenous catheter and its site needed to be replaced repeatedly during the continuum of treatment, eventually leading to complete remission of the ulcerative colitis. After 8 months, the patient was still in remission, with no permanent signs of damage to the involved phlebitic veins. Infusion phlebitis induced by drugs is a common phenomenon that causes pain and difficulty in a patient's treatment. Many drugs, mainly antibiotics and cytotoxic drugs, have previously been reported to induce infusion phlebitis. We describe the first report of a patient with cyclosporine-induced recurrent infusion phlebitis. According to the Naranjo probability scale, the relationship of the encountered phlebitis to cyclosporine therapy is probable. Recurrent infusion phlebitis is a previously unreported adverse effect encountered during treatment with cyclosporine. This important adverse effect must be considered when treating patients with this unique drug.


Denture base adaptation, retention, and mechanical properties of BioHPP versus nano-alumina-modified polyamide resins.
Background. Continuous development of denture base materials has led to the introduction of innovative alternatives to polymethyl methacrylate. The present study aimed to evaluate the mechanical properties, adaptation, and retention of alumina nanoparticles (Al2O3 NPs) modified polyamide resin versus BioHPP (high-performance polymer) denture base materials. Methods. Four groups of specimens, one control (group I) (unmodified polyamide) and two groups (groups II and III) (2.5 and 5 wt% Al2O3 NP-modified polyamide, respectively) versus BioHPP specimen group (group IV), were tested for surface microhardness and flexural strength. Complete dentures fabricated from 5 wt% Al2O3 NP-modified polyamide resin and BioHPP were used to evaluate denture base adaptation and retention. Results. The higher concentration in the alumina NP-modified polyamide group (5 wt%) demonstrated significantly higher flexural strength values and insignificantly higher hardness values than the lower concentration (2.5 wt%). There was a significant increase in the BioHPP group in both flexural strength and surface hardness compared to all polyamide groups. A statistically insignificant difference was observed between the two denture base materials regarding mean misfit values of the calculated total tissue surface area and four of the total seven evaluated areas. Satisfactory and comparable retention values were observed for both denture base materials. Conclusion. BioHPP and Al2O3 NP-modified polyamide resin could be used as a promising alternative denture base material with good adaptation, retention, and mechanical properties.


A Bayesian spatiotemporal model for very large data sets.
Functional MRI provides a unique perspective of neuronal organization; however, these data include many complex sources of spatiotemporal variability, which require spatial preprocessing and statistical analysis. For the latter, Bayesian models provide a promising alternative to classical inference, which uses results from Gaussian random field theory to assess the significance of spatially correlated statistic images. A Bayesian approach generalizes the application of these ideas in that (1) random fields are used to model all spatial parameters, not solely observation error, (2) their smoothness is optimized, and (3) a broader class of models can be compared. The main problem, however, is computational, due to the large number of voxels in a brain volume. Sampling methods are time-consuming; however, approximate inference using variational Bayes (VB) offers a principled and transparent way to specify assumptions necessary for computational tractability. Penny et al. (2005b) described such a scheme using a joint spatial prior and approximated the joint posterior density with one that factorized over voxels. However, a further computational bottleneck is encountered when evaluating the log model evidence used to compare models. This has lead to dividing a brain volume into slices and treating each independently. This amounts to approximating the spatial prior over a full volume with stacked 2D priors. That is, smoothness along the z-axis is not included in the model. Here we describe a VB scheme that approximates the zero mean joint spatial prior with a non-zero mean empirical prior that factors over voxels, thereby overcoming this problem. We do this by modifying the original VB algorithm of Penny et al. using the conditional form of a so-called conditional autoregressive (CAR) prior to update a marginal prior over voxels. We refer to this as a spatially-informed voxel-wise prior (SVP) and use them to spatially regularise general linear model (GLM) and autoregressive (AR) coefficients (over time to model serial correlations). This algorithm scales more favourably with the number of voxels providing a truly 3D spatiotemporal model over volumes containing tens of thousands of voxels. We compare the scaling of compute times with the number of voxels and performance with a joint prior applied to synthetic and single-subject data.


Selenium compounds inhibit I kappa B kinase (IKK) and nuclear factor-kappa B (NF-kappa B) in prostate cancer cells.
Selenium compounds are potential chemopreventive agents for prostate cancer. There are several proposed mechanisms for their anticancer effect, including enhanced apoptosis of transformed cells. Because the transcription factor nuclear factor-kappa B (NF-kappa B) is often constitutively activated in tumors and is a key antiapoptotic factor in mammalian cells, we tested whether selenium inhibited NF-kappa B activity in prostate cancer cells. In our work, we used sodium selenite and a novel synthetic compound, methylseleninic acid (MSeA), that served as a precursor of the putative active monomethyl metabolite methylselenol. We found that both selenium forms inhibited cell growth and induced apoptosis in DU145 and JCA1 prostate carcinoma cells. Sodium selenite and MeSeA, at the concentrations that induced apoptosis, inhibited NF-kappa B DNA binding induced by tumor necrosis factor-alpha and lipopolysaccharide in DU145 and JCA1 prostate cells. Both compounds also inhibited kappa B. Luciferase reporter activity in prostate cells. A key to NF-kappa B regulation is the inhibitory kappa B (I kappa B) proteins that in response to diverse stimuli are rapidly phosphorylated by I kappa B kinase complex, ubiquitinated, and undergo degradation, releasing NF-kappa B factor. We showed that sodium selenite and MSeA inhibited I kappa B kinase activation and I kappa B-alpha phosphorylation and degradation induced by TNF-alpha and lipopolysaccharide in prostate cells. NF-kappa B blockage by I kappa B-alpha d.n. mutant resulted in the sensitization of prostate carcinoma cells to apoptosis induced by selenium compounds. These results suggest that selenium may target the NF-kappa B activation pathway to exert, at least in part, its cancer chemopreventive effect in prostate.


iQuant™ Analyser: A rapid quantitative immunoassay reader.
Lateral flow immunoassays (LFIA) used in rapid quantitative point of care testing require an accurate, reliable and easy to operate instrument to read the LFIA kit and calculate the quantitative result value. We present iQuant® Analyser, an immunoassay reader designed for reading the Quanti® range of LFIA test kits for key markers such as HbA1C, Vitamin D, TSH etc. The instrument utilizes a laser based confocal optics system to capture the test and control lines from the LFIA kit, digitizes the fluorescent signal with high spatiotemporal resolution, computes necessary peak area ratios, applies calibration curves and declares the final result in an automated manner with minimal operator input. The instrument uses kit specific calibration information embedded on each LFIA test kit, to compute the final clinical parameter without using any external calibration chip. An intuitive icon based interface enables easy operation with minimal key presses, suited for point of care applications. The technology is designed in a modular manner to enable the instrument to perform tests on various parameters such as HbA1C, TSH, and Vitamin D etc without any hardware changes, using test-specific LFIA kits. The functional performance of the iQuant Analyser was verified over the range of expected area ratio values with standard reference cartridges that provided stable fluorescent lines. Repeatability of the instrument was found to be excellent with coefficient of variation (CoV) of area ratios found to be less than 1%. The inter-instrument reproducibility was also found to be good with CoV less than 4 %. Tests using blood samples with Quanti LFIA kits verified the accuracy of HbA1C results to be acceptable as per international standards with errors <; 4 %. The iQuant Analyser is a portable, easy to use rapid quantitative immunoassay reader best suited for point of care applications.


Optimization of betacyanins from agricultural by-products using pressurized hot water extraction for antioxidant and in vitro oleic acid-induced steatohepatitis inhibitory activity.
Pressurized hot water extraction (PHWE) is proposed to recover betacyanins from agricultural by-products (pitaya fruits peels (PFP), red beet stalks (RBS), and cactus pear peels (CPP)). The extraction yield of betacyanins was optimized by response surface methodology. The optimal PHWE conditions were attained and the actual yields of betacyanins under optimal conditions were well matched with the predicted yields. In addition, betacyanin pigment compositions as well as superoxide anion scavenging activity of individual betacyanins extract (BE) produced in optimal PHWE conditions were characterized by HPLC-ESI/MSn and cyclic voltammetry. Furthermore, the inhibitory activity of three BEs on oleic acid-induced steatohepatitis in cellular model was comparatively investigated. The results showed that unlike PFP, RBS, and CPP presented excellent efficacy in decreasing intracellular triglyceride and reactive oxygen species, inhibiting the release of alanine aminotransferase and aspartate aminotransferase as well as regulating fatty acid synthase and carnitine palmitoyltransferase 1 mRNAs expression. Practical applications In this study, PHWE, is firstly proposed for the enhancement of the extraction of betacyanins from three agricultural by-products. Betacyanin-rich extracts by PHWE method exhibit excellent activities in inhibition of ROS and regulation of lipid metabolism in hepatic cells. It suggests that PHWE has a strong potentiality in keeping bioactivity of BEs, which is significant for the production of betacyanins functional foods.


Anti-N-methyl-D-aspartate receptor encephalitis: a patient with refractory illness after 25 months of intensive immunotherapy.
N-methyl-D-aspartate receptor (NMDAR) antibody encephalitis is an autoimmune encephalitis that can be paraneoplastic and usually responds to treatment. It is quickly becoming the most common paraneoplastic encephalitis. We present a case of a woman in her late 30s who developed psychiatric symptoms that progressed to encephalopathy, seizures, autonomic instability, and hyperkinetic movements. The patient was found to have an ovarian teratoma and serum and cerebrospinal fluid NMDAR antibodies. Despite resection of the teratoma and treatment with immunosuppressive therapy, the patient progressed to a minimally conscious state. She was supported medically in our institution for 25 months. During her hospitalization, she was treated with multiple immunosuppressive agents. With each treatment, we analyzed the serum and cerebrospinal fluid for NMDAR antibodies. While there was some initial reduction in the serum antibodies, the spinal fluid antibodies remained persistently elevated. The patient did not have any clinical improvement and eventually died after the family decided to withdraw care. As far as we know, this case represents the longest active treatment without improvement of a patient with anti-NMDAR encephalitis. The patient had persistently high cerebrospinal fluid and serum antibody titers, which may be of prognostic significance.


Teratogenicity of all-trans retinoic acid during early embryonic development in the cynomolgus monkey (Macaca fascicularis).
The embryotoxic and teratogenic potential of all-trans retinoic acid was assessed following exposure prior to and during early organogenesis in the cynomolgus monkey (Macaca fascicularis). Sixteen pregnant females were orally administered all-trans retinoic acid (Tretinoin, Hoffmann-La Roche) once daily from GD 10-20 and twice daily from GD 21-24 at three different dosages, 5 (n = 9), 10 (n = 6) and 20 mg/kg (n = 1). Adverse clinical signs resembling hypervitaminosis A were observed in one animal at 5 mg/kg, in three animals at 10 mg/kg, and in the animal treated with 20 mg/kg all-trans retinoic acid. Maternal weight loss was observed in the 10- and 20-mg/kg groups. A dose-dependent increase in embryolethality was observed, with 22% (2/9), 50% (3/6), and 100% (1/1) occurring at 5, 10, and 20 mg/kg, respectively. The majority of embryonic deaths occurred between GD 16 and 20; the incidence of these early losses was higher than in historical and concurrent controls. No malformations, but a single growth-retarded fetus, was observed in the 5-mg/kg group. Craniofacial malformations, consisting of external ear defects, mandibular hypoplasia, cleft palate, and temporal bone abnormalities, were seen in three viable fetuses in the 10-mg/kg group. Skeletal variations were common to the majority (70%, 7/10) of viable fetuses in both dose groups and were increased relative to historical controls (32%, 25/77). Unlike previous studies with 13-cis-retinoic acid during the pre- and early organogenic stages of development (Hummler et al., Teratology 42:263-272, 1990), no thymic hypo- or aplasia or heart anomalies were observed, which may be attributable to the slightly longer 13-cis retinoic acid treatment period, i.e., GD 10-27. However, external ear and temporal bone defects were common to both all-trans and 13-cis retinoic acid. The similarity observed in the malformation syndrome induced by both all-trans and 13-cis retinoic acid in the cynomolgus monkey and 13-cis retinoic acid embryopathy in humans supports this macaque species as a model for further developmental toxicity studies of vitamin A-related compounds.


Method for computing the optimal signal distribution and channel capacity.
An iterative method for computing the channel capacity of both discrete and continuous input, continuous output channels is proposed. The efficiency of new method is demonstrated in comparison with the classical Blahut - Arimoto algorithm for several known channels. Moreover, we also present a hybrid method combining advantages of both the Blahut - Arimoto algorithm and our iterative approach. The new method is especially efficient for the channels with a priory unknown discrete input alphabet.


Dynamic light-scattering and preliminary crystallographic studies of the sensor domain of the haem-based oxygen sensor FixL from Rhizobium meliloti.
FixL is a transmitter protein in a two-component system which acts as an oxygen sensor when the symbiotic Rhizobia resides in root nodules of host plants. The oxygen-sensor domain of Rhizobium meliloti FixL (RmFixLH) was purified by His-tag affinity and isoelectronic focusing chromatographies, without the use of gel-filtration chromatography. Dynamic light-scattering measurements of RmFixLH thus obtained revealed it to be monodispersive and present as a homodimer in solution. A single crystal of RmFixLH in the met (Fe3+) form was grown in 100 mM acetic acid/NaOH buffer at pH 4.6 in the presence of 200 mM ammonium acetate, using 40%(w/v) PEG 4000 as a precipitant. A crystal of the ferrous CO form of RmFixLH was also prepared by reduction of the met crystal with Na2S2O4 in an atmosphere of CO. The crystals (0.2 x 0.05 x 0.01 mm) belong to the monoclinic system (C2) with unit-cell parameters a = 60.94, b = 37.44, c = 54.14 A, beta = 115.29 degrees and diffract X-rays to 1.7 A resolution at station BL44B2 of SPring-8, Japan. Bijvoet difference Patterson maps show a clear peak corresponding to the haem iron in RmFixLH.


Emotional intelligence and perceived stress.
Many studies have reported that high levels of stress and psychological morbidity occur in students in the health care profession. Stress has been defined as the strain that accompanies a demand perceived to be either challenging (positive) or threatening (negative) and, depending on the appraisal, may be either adaptive or debilitating. The aim of the present survey was to gain some understanding of the explanatory factors for stress and an evaluation of the role that emotional intelligence (EI) plays in the experience of perceived stress (PS). It also aimed to compare EI and PS and explore the association between academic background, satisfaction with career choice and EI, and PS in first year dental students. A cross-sectional survey was conducted at the Faculty of Dentistry, University of the Western Cape. First year dental undergraduates who had completed at least six months of their dental degree course during 2005/06 were invited to complete a set of questionnaires on emotional intelligence and perceived stress. Demographic questions included gender and age. Students were also asked if they had a previous qualification from a higher education institution and if they were satisfied with their decision to study dentistry. Ninety eight completed the questionnaires representing a response rate of 96%. 43 were male (44%) and 55 female (56%), Results of t-tests indicated that low scorers on the EI scale were more likely to be (i) younger compared to older students (p<0.001), (ii) those without compared to those with a previous higher education qualification (p<0.001), and (iii) those who were not satisfied compared to those who were satisfied with their decision to study dentistry (p<0.001). Statistically significant differences were noted in mean PS scores between (i) male and female students (p<0.05), (ii) younger compared to older students (p<0.001), (iii) those without compared to those with previous higher education qualification (p<0.001), and (iv) those who were not satisfied compared to those who were satisfied with their decisions to study dentistry (p<0.001). Correlation analysis between EI and PS indicated a statistically significant inverse relationship between EI and PS (coefficient =-0.50, p=0.001). Stepwise regression analysis identified significant predictors of PS as gender, previous higher education qualification, satisfaction with decision to study dentistry and EI. The t statistic indicates that EI is relatively the most important predictor of PS. The finding that low EI is associated the stress suggests two possible strategies: firstly, selection of prospective students could be based on EI, and there should be interventions to enhance students' emotional intelligence.


Acute normovolaemic haemodilution--2 case studies.
Acute normovolaemic haemodilution (ANH) is a technique used to preserve a patient's owns red blood cells and reduce the incidence of heterogeneous blood transfusion. This paper describes the use of the technique in a dog and a kitten. A significant benefit of ANH can be shown in the canine case presented. The dog lost 1800 ml of blood during surgery but the haematocrit was only reduced to 33% 6 hours after the end of surgery. The kitten, however, did not benefit from ANH. It lost a small volume of blood during surgery and developed complications. This paper also describes some of the potential complications that may occur. To the best of my knowledge, this is the 1st clinical description of ANH in a dog and a cat.


High prevalence of complement component C6 deficiency among African-Americans in the south-eastern USA.
Complement component C6 is a part of the membrane attack complex that forms a pore-like structure in cell membranes following complement activation. Deficiency of terminal complement components including C6 predisposes individuals to infection with Neisseriae. Using polymerase chain reaction/single-strand conformation polymorphism analysis followed by DNA sequencing, we screened genomic DNA from 200 randomly chosen blacks and an equal number from whites for three loss-of-function C6 mutations. Ten blacks and two whites were found to be heterozygous for one of the mutations. Two of the mutations, 1195delC and 1936delG, were found exclusively in black individuals. A third previously undescribed mutation, 878delA, was found at equal frequency among the two groups. The difference between the two groups was significant (P = 0.027), indicating that C6 deficiency due to these three mutations is more common among blacks than whites in the local area, principally Jefferson County, Alabama. In addition, three previously undescribed point mutations, two of which result in amino acid substitutions, were identified within exon 6. A review of the county health department records over the past 6 years revealed a higher incidence of meningococcal meningitis in blacks due to serogroups Y and W-135 which paralleled the difference in the estimated prevalence of C6 deficiency. Among black residents of the county (n = 235 598) there were 15 cases of meningitis due to these two serogroups, compared with two cases in the white population (n = 422 604) (P = 0.002). We conclude that C6 deficiency is more common among blacks than whites in the south-eastern United States, with a frequency approaching 1 in 1600 black individuals.


Effects of biopolymer encapsulation on trans fatty acid digestibility in an in vitro human digestion system.
The purpose of this study was to examine the effects of biopolymer encapsulation on the digestion of trans fatty acids by using an in vitro human digestion model. We simulated the main components of the human digestive system using a dialysis tubing system that contained synthetic saliva, gastric juice, and digestive enzymes of the small intestine. Trans fatty acid-enriched fat was encapsulated with 1% chitosan, pectin, cellulose, and β-glucan, and passed through the model system. Samples of trans fatty acid-enriched fat that were unencapsulated were more digestible than those that were encapsulated in biopolymers. Moreover, the levels of trans octadecenoic acids (18 : 1t) formed during the digestion of trans fatty acid-enriched fat were decreased upon biopolymer encapsulation. Fat samples enriched with trans fatty acids that were encapsulated with pectin or chitosan had lower free fatty acid contents and lipid oxidation values than unencapsulated control samples. These findings improve our understanding of the effects of biopolymer encapsulation on the digestion of total lipids and trans fatty acids within the gastrointestinal tract.


Engineering bone tissue substitutes from human induced pluripotent stem cells.
Congenital defects, trauma, and disease can compromise the integrity and functionality of the skeletal system to the extent requiring implantation of bone grafts. Engineering of viable bone substitutes that can be personalized to meet specific clinical needs represents a promising therapeutic alternative. The aim of our study was to evaluate the utility of human-induced pluripotent stem cells (hiPSCs) for bone tissue engineering. We first induced three hiPSC lines with different tissue and reprogramming backgrounds into the mesenchymal lineages and used a combination of differentiation assays, surface antigen profiling, and global gene expression analysis to identify the lines exhibiting strong osteogenic differentiation potential. We then engineered functional bone substitutes by culturing hiPSC-derived mesenchymal progenitors on osteoconductive scaffolds in perfusion bioreactors and confirmed their phenotype stability in a subcutaneous implantation model for 12 wk. Molecular analysis confirmed that the maturation of bone substitutes in perfusion bioreactors results in global repression of cell proliferation and an increased expression of lineage-specific genes. These results pave the way for growing patient-specific bone substitutes for reconstructive treatments of the skeletal system and for constructing qualified experimental models of development and disease.


Recombinant human erythropoietin in the treatment of head and neck tumour anaemia.
At the time of first diagnosis, patients with squamous cell carcinoma in the head and neck are often in the advanced stage of their disease, therefore surgery is not a viable option for treatment. These patients also present frequently a high grade of anaemia as a result of either the malignant process itself or of the following therapy. The incidence of anaemia and the need for transfusion depends on several factors, such as the type and intensity of radiotherapy and radiochemotherapy. Multimode therapeutic concepts such as radio-chemotherapy are being applied with increasing frequency, resulting in an ever increasing need for transfusion with great effects on the patient's quality of life. Even more important to tumour patients is the role of the haemaglobin (Hb) value as a prognostic factor for survival and/or local tumour control. A large number of studies show that recombinant human erythropoietin (r-HuEPO) is effective in the treatment of tumour-induced anaemia and prevention and correction of chemotherapy and radiotherapy-induced anaemia. The simultaneous application of r-HuEPO with chemotherapy can prevent patients with head and neck tumours from developing anaemia or can reduce the extent of the anaemia and the need for transfusion. Comparable effects were observed both in patients undergoing platinum-based and non-platinum-based chemotherapy. The direct correlation between anaemia, tumour hypoxia and poor response to radio and/or chemotherapy has been clinically proven. Recombinant human erythropoietin administration improves the therapeutic outcome and the patients' prognosis.


Activation of NF-kappaB in airway epithelial cells is dependent on CFTR trafficking and Cl- channel function.
Polymorphonuclear leukocyte-dominated airway inflammation is a major component of cystic fibrosis (CF) lung disease and may be associated with CF transmembrane conductance regulator (CFTR) dysfunction as well as infection. Mutant DeltaF508 CFTR is mistrafficked, accumulates in the endoplasmic reticulum (ER), and may cause "cell stress" and activation of nuclear factor (NF)-kappaB. G551D mutants also lack Cl- channel function, but CFTR is trafficked normally. We compared the effects of CFTR mutations on the endogenous activation of an NF-kappaB reporter construct. In transfected Chinese hamster ovary cells, the mistrafficked DeltaF508 allele caused a sevenfold activation of NF-kappaB compared with wild-type CFTR or the G551D mutant (P < 0.001). NF-kappaB was also activated in 9/HTEo-/pCep-R cells and in 16HBE/pcftr antisense cell lines, which lack CFTR Cl- channel function but do not accumulate mutant protein in the ER. This endogenous activation of NF-kappaB was associated with elevated interleukin-8 expression. Impaired CFTR Cl- channel activity as well as cell stress due to accumulation of mistrafficked CFTR in the ER contributes to the endogenous activation of NF-kappaB in cells with the CFTR mutation.


Association between restless legs syndrome and hypertension: a preliminary population-based study in South Tyrol, Italy.
Restless legs syndrome (RLS) is a sleep-related movement disorder characterized by an irresistible urge to move the legs accompanied by paresthesia and/or dysesthesia that begins or worsens in the evening and night and that is partially or totally relieved by movement. Many studies have investigated the association between RLS and cardiovascular risk factors, particularly hypertension, leading to conflicting results. The aim of this study was to assess the association between RLS and hypertension considering also other cardiovascular risk factors that could act as confounders. In all, 1709 participants of an on-going adult population-based study performed in South Tyrol, northern Italy, were enrolled. RLS was assessed through face-to-face interviews according to current International Restless Legs Syndrome Study Group diagnostic criteria. The presence of hypertension was self-reported and determined by questionnaires administered by trained study nurses. The association between RLS and hypertension was not significant after adjustment for age, sex, diabetes mellitus, history of myocardial infarction, raised blood lipids and body mass index (odds ratio 1.24, 95% CI 0.85-1.80, P = 0.271). Despite the small sample size of this study, RLS and hypertension were not associated in our adult population after adjustment for possible confounding factors. The presence of other cardiovascular risk factors could play a role as a confounder of this association.


Intersections of endocrine pathways and the epithelial mesenchymal transition in endometrial cancer.
The epithelial mesenchymal transition (EMT) is the process by which cancer cells of epithelial origin, including endometrial cancer, acquire a mesenchymal phenotype with enhanced migratory and invasive capacity, to facilitate metastasis. The regulation of EMT is tissue-specific, and in endometrial cancer, endocrine signaling pathways serve as critical regulators of EMT. The intersections of endocrine signaling and EMT highlight potential avenues for therapeutic intervention to target cancer metastasis with the aim of reduced mortality.


LncRNAs LY86-AS1 and VIM-AS1 Distinguish Plasma Cell Leukemia Patients from Multiple Myeloma Patients.
Long non-coding RNAs (lncRNAs) are functional RNAs longer than 200 nucleotides. Due to modern genomic techniques, the involvement of lncRNAs in tumorigenesis has been revealed; however, information concerning lncRNA interplay in multiple myeloma (MM) and plasma cell leukemia (PCL) is virtually absent. Herein, we aimed to identify the lncRNAs involved in MM to PCL progression. We investigated representative datasets of MM and PCL patients using next-generation sequencing. In total, 13 deregulated lncRNAs (p < 0.00025) were identified; four of them were chosen for further validation in an independent set of MM and PCL patients by RT-qPCR. The obtained results proved the significant downregulation of lymphocyte antigen antisense RNA 1 (LY86-AS1) and VIM antisense RNA 1 (VIM-AS1) in PCL compared to MM. Importantly, these two lncRNAs could be involved in the progression of MM into PCL; thus, they could serve as promising novel biomarkers of MM progression.


Neural basis of confabulation.
We present a case of acute alcohol-induced Korsakoff amnesia. A severe amnestic-confabulatory syndrome characterized the early clinical status. The initial neuropsychological tests demonstrated severe learning deficits plus impaired performance on many, but not all, tests of frontal lobe function. Single-photon emission CT (SPECT) at this stage showed hypoperfusion in the orbital and medical frontal regions and the medial diencephalic area. Four months later, the patient's amnesia remained but there was no confabulation. Repeat neuropsychological tests confirmed an ongoing severe amnesia, but performance on the frontal lobe tests now was normal. Repeat SPECT showed a return to normal perfusion in the frontal brain areas but little improvement in the medial diencephalic region. These findings along with data from the clinical literature suggest that confabulation results from dysfunction of orbital and a medial frontal cortex.


Identification of Expression Profiles Defining Distinct Prognostic Subsets of Radioactive-Iodine Refractory Differentiated Thyroid Cancer from the DECISION Trial.
Several biomarkers have been suggested to have prognostic value in differentiated thyroid carcinomas (DTC) with no validation in the refractory setting, including all tumor subtypes. We aim to correlate RNA expression profiles with survival based on patients included in the DECISION trial. We obtained 247 samples from the 417 patients included in the DECISION study and performed RNAseq analysis (77 million paired-end reads for each sample on HiSeq2000). After quality control, 125 samples were included in the secondary analysis and mapped against the human reference genome (GRCh38) with STAR (v2.5.1b) using ENCODE parameter. Survival analysis was calculated using the Kaplan-Meier method and log-rank test was used for statistical comparison. In this post hoc analysis, we identified three groups of tumors based on their gene expression profile: BRAF-like, RAS-like, and non-BRAF-non-RAS-like (NoBRaL). No significant correlation with sorafenib responders was observed. However, we identified a statistically significant correlation between the RNA-expression profiles and progression-free survival. The BRAF-like profile had a significantly better outcome compared with RAS-like and NoBRaL (11.8, 6.2, and 5.5 months, respectively) [HR: 0.31, 95% confidence interval (CI), 0.17-0.60; P < 0.001 and HR: 0.36 (95% CI, 0.21-0.63); P < 0.001] and HR: 0.36 (95% CI, 0.21-0.63; P < 0.001) and maintained significance as an independent prognostic factor for overall survival in the multivariate analysis for papillary thyroid cancers. To our knowledge, this is the first comprehensive RNA-seq analysis of all histologic subtypes of DTC. The RNA expression profiles identified may suggest a new prognostic parameter to be considered before recommendation of systemic therapies or the design of stratification factors for future clinical trials.


Effect of a CVIS instructional program regarding therapeutic communication on student learning and anxiety.
This quasi-experimental, pretest-posttest design study explored the effect of a computer video-interactive system (CVIS) instructional program regarding therapeutic communication on senior baccalaureate nursing students' learning and anxiety as they anticipated interaction with patients in psychiatric settings. The 75 subjects were randomly divided into two groups. Group I received a basic lecture and a supplementary CVIS instructional program on therapeutic communication, while Group II received the same lecture discussion on therapeutic communication and a videotape. Two hypotheses were tested, using analyses of covariance. Hypothesis I, that Group I would score significantly higher on a therapeutic communication posttest than would Group II, was supported (P less than .001). This finding validates previous observations that computer-video interaction programs do enhance learners' application of knowledge. Hypothesis II, that Group I would evidence significantly less state anxiety at posttest than would Group II, was not supported. Although there were no significant differences for state anxiety scores between the groups at either pretest or posttest, these scores remained higher than reported normative state anxiety scores. This finding suggests that anticipated interaction with psychiatric patients is an anxiety-inducing situation for nursing students.