Transcriptional and Clonal Characterization of Cytotoxic T Cells in Crescentic Glomerulonephritis.

SIGNIFICANCE STATEMENT: T-cell infiltration is a hallmark of crescentic GN (cGN), often caused by ANCA-associated vasculitis. Pathogenic T-cell subsets, their clonality, and downstream effector mechanisms leading to kidney injury remain to be fully elucidated. Single-cell RNA sequencing and T-cell receptor sequencing revealed activated, clonally expanded cytotoxic CD4 + and CD8 + T cells in kidneys from patients with ANCA-associated cGN. In experimental cGN, kidney-infiltrating CD8 + T cells expressed the cytotoxic molecule, granzyme B (GzmB), which induced apoptosis in renal tissue cells by activation of procaspase-3, and aggravated disease pathology. These findings describe a pathogenic function of (clonally expanded) cytotoxic T cells in cGN and identify GzmB as a mediator and potential therapeutic target in immune-mediated kidney disease. BACKGROUND: Crescentic GN (cGN) is an aggressive form of immune-mediated kidney disease that is an important cause of end stage renal failure. Antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis is a common cause. T cells infiltrate the kidney in cGN, but their precise role in autoimmunity is not known. METHODS: Combined single-cell RNA sequencing and single-cell T-cell receptor sequencing were conducted on CD3 + T cells isolated from renal biopsies and blood of patients with ANCA-associated cGN and from kidneys of mice with experimental cGN. Functional and histopathological analyses were performed with Cd8a-/- and GzmB-/- mice. RESULTS: Single-cell analyses identified activated, clonally expanded CD8 + and CD4 + T cells with a cytotoxic gene expression profile in the kidneys of patients with ANCA-associated cGN. Clonally expanded CD8 + T cells expressed the cytotoxic molecule, granzyme B (GzmB), in the mouse model of cGN. Deficiency of CD8 + T cells or GzmB ameliorated the course of cGN. CD8 + T cells promoted macrophage infiltration and GzmB activated procaspase-3 in renal tissue cells, thereby increasing kidney injury. CONCLUSIONS: Clonally expanded cytotoxic T cells have a pathogenic function in immune-mediated kidney disease.

Relationship between health care interactions and care partner burden.

INTRODUCTION: Older adults often rely on care partners, such as family and friends, to assist with their health-related needs associated with aging. Care partner burden is associated with higher rehospitalization rates and poorer health outcomes for older adults. This study examines the relationship between 3 types of health care interactions and care partner burden. METHOD: Secondary data analyses using cross-sectional data from the 2017 National Study of Caregiving were conducted. A total of 2,313 care partners (representing approximately 21.2 million) of living Medicare beneficiaries age 65 and older were included in the analyses. Multivariable logistic regression analyses were used to determine the relationship between health care interactions and care partner burden. RESULTS: Care partners with burden were significantly more likely to be female (p = .049); white (p = .011); and a spouse, adult child, or grandchild of the older adult (p < .001). Logistic regression analyses showed that making medical appointments (Adjusted Odds Ratio [AOR] = 1.53, 95% CI: 1.13-2.07) and coordinating care between providers (AOR = 1.72, 95% CI: 1.27-2.32) were significantly associated with care partner burden. DISCUSSION: Care partners of older adults who helped make medical appointments or coordinated care between providers were significantly more likely to report burden compared to those who did not assist with these health care interactions. It is essential that health care systems and providers determine ways to make health care interactions less burdensome for care partners. Care delivery approaches that align with family systems thinking may help reduce care partner burden by strengthening health care interactions. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Identification of serological markers for pre- and postoperative fasting periods.

BACKGROUND & AIMS: Prolonged preoperative fasting periods lead to catabolic states and decelerate recovery after surgery. Valid plasma markers reflecting the patients' metabolic state may improve tailored nutrition support before surgery. Within this study, we sought to advance the knowledge on fasting time-sensitive plasma markers that allow the metabolic characterisation of surgical patients for an optimised preoperative metabolic preparation. METHODS: Patients scheduled for elective surgery of the upper (n = 23) or lower (n = 27) gastrointestinal tract participated in a prospective observational study. Patients' charateristics and nutritional status were recorded and blood samples were drawn on the day of admission. Further blood samples were collected before skin incision of the surgical procedure, on postoperative day 3 and on the day of discharge. Values of clinical chemistry, electrolytes, hemograms and plasma amino acids were determined and correlated with fasting times. RESULTS: Preoperative fasting times were positively correlated with plasma levels of valine, leucine, serine, α-amino butyric acid, free fatty acids, 3-hydroxy butyric acid and significantly negative correlated with chloride and glutamic acid. Postoperative fasting times were correlated with erythrocytes, leukocytes and plasma levels of albumin, CRP, HDL, asparagine and 3-methylhistidine. The multivariate regression analysis revealed glutamic acid and valine as significant independent predictors of preoperative fasting periods. The regression model showed best performance (sensitivity of 90.91% and specificity of 92.31%) to detect patients fasted for ≥20 h. CONCLUSION: Valine and glutamic acid appear as independent metabolic markers for accurate prediction of prolonged fasting periods, independent of the overall nutritional status, age or BMI of patients.

Feasibility and utility of a cognitive screening for risk stratification in hospitalized older patients.

OBJECTIVES: To determine whether the Mini-Cog can be applied by nursing staff to hospitalized elderly patients for cognitive impairment associated risk stratification. METHODS: This explorative prospective multicenter cohort study was carried out among 2522 patients aged 70 and older, hospitalized due to physical illness in eight hospitals in Rhineland-Palatinate, Germany. All patients were asked to conduct the Mini-Cog at the day of admission and were clustered into low-performance, intermediate-performance, and good-performance categories by trained nursing staff and two experienced geronto-psychiatrists as gold standard. Complications in the course of the treatment were monitored. RESULTS: The Mini-Cog was conducted in 1398 (54%) out of 2522 eligible patients. Mini-Cog scores assessed by nursing staff differed from the gold standard in 327 cases (23.9%). According to the area under the curve (AUC), nursing staff identified cognitively low-performing patients almost as well as the geronto-psychiatrists (AUC = 0.862; 95% CI, 0.83-0.89; P < 0.001, accuracy 89.6%). Overall, 241 (17.6%) patients were classified as low performing. These patients had a significantly higher probability of suffering from at least one complication (odds ratio [OR] = 3.13; 95% CI, 2.09-4.70; calculated by a logistic regression model, adjusted for age), and they had a higher probability to show behavioral symptoms. CONCLUSION: Even under naturalistic conditions, nursing staff detected cognitively low-performing inpatients with the Mini-Cog. Using this short screening instrument should enable to predict complications of hospitalized older patients associated with cognitive impairment, a precondition to implement targeted care for this vulnerable patient group.

Incubation of Immune Cell Grafts With MAX.16H5 IgG1 Anti-Human CD4 Antibody Prolonged Survival After Hematopoietic Stem Cell Transplantation in a Mouse Model for Fms Like Tyrosine Kinase 3 Positive Acute Myeloid Leukemia.

Despite the constant development of innovative therapeutic options for hematological malignancies, the gold-standard therapy regimen for curative treatment often includes allogeneic hematopoietic stem cell transplantation (HSCT). The graft-vs.-leukemia effect (GVL) is one of the main therapeutic goals that arises from HSCT. On the other hand, graft-vs.-host disease (GVHD) is still one of the main and most serious complications following allogeneic HSCT. In acute myeloid leukemia (AML), HSCT together with high-dose chemotherapy is used as a treatment option. An aggressive progression of the disease, a decreased response to treatment, and a poor prognosis are connected to internal tandem duplication (ITD) mutations in the Fms like tyrosine kinase 3 (FLT3) gene, which affects around 30% of AML patients. In this study, C3H/HeN mice received an allogeneic graft together with 32D-FLT3ITD AML cells to induce acute GVHD and GVL. It was examined if pre-incubation of the graft with the anti-human cluster of differentiation (CD) 4 antibody MAX.16H5 IgG1 prevented the development of GVHD and whether the graft function was impaired. Animals receiving grafts pre-incubated with the antibody together with FLT3ITD AML cells survived significantly longer than mice receiving untreated grafts. The observed prolonged survival due to MAX.16H5 incubation of immune cell grafts prior to transplantation may allow an extended application of additional targeted strategies in the treatment of AML.

Consideration and checkboxes: incorporating ethics and science into the 3Rs.

Members of the research community aim to both produce high-quality research and ensure that harm is minimized in animals. The primary means of ensuring these goals are both met is the 3Rs framework of replacement, reduction, and refinement. However, some approaches to the 3Rs may result in a 'check box mentality' in which IACUC members, researchers, administrators, and caretakers check off a list of tasks to evaluate a protocol. We provide reasons for thinking that the 3Rs approach could be enhanced with more explicit discussion of the ethical assumptions used to arrive at an approved research protocol during IACUC review. Here we suggest that the notion of moral considerability, and all of the related issues it gives rise to, should be incorporated into IACUC discussions of 3Rs deliberations during protocol review to ensure that animal wellbeing is enhanced within the constraints of scientific investigation.

Geriatric Anxiety Scale: item response theory analysis, differential item functioning, and creation of a ten-item short form (GAS-10).

BACKGROUND: The Geriatric Anxiety Scale (GAS; Segal et al. (Segal, D. L., June, A., Payne, M., Coolidge, F. L. and Yochim, B. (2010). Journal of Anxiety Disorders, 24, 709-714. doi:10.1016/j.janxdis.2010.05.002) is a self-report measure of anxiety that was designed to address unique issues associated with anxiety assessment in older adults. This study is the first to use item response theory (IRT) to examine the psychometric properties of a measure of anxiety in older adults. METHOD: A large sample of older adults (n = 581; mean age = 72.32 years, SD = 7.64 years, range = 60 to 96 years; 64% women; 88% European American) completed the GAS. IRT properties were examined. The presence of differential item functioning (DIF) or measurement bias by age and sex was assessed, and a ten-item short form of the GAS (called the GAS-10) was created. RESULTS: All GAS items had discrimination parameters of 1.07 or greater. Items from the somatic subscale tended to have lower discrimination parameters than items on the cognitive or affective subscales. Two items were flagged for DIF, but the impact of the DIF was negligible. Women scored significantly higher than men on the GAS and its subscales. Participants in the young-old group (60 to 79 years old) scored significantly higher on the cognitive subscale than participants in the old-old group (80 years old and older). CONCLUSIONS: Results from the IRT analyses indicated that the GAS and GAS-10 have strong psychometric properties among older adults. We conclude by discussing implications and future research directions.

Medical provider attitudes about behavioral health consultants in integrated primary care: a preliminary study.

Integrated behavioral health increases service utilization and treatment success, particularly with high-risk populations. This study assessed medical personnel's attitudes and perceptions of behavioral health clinicians (BHCs) in primary care using a brief self-report measure. A 6-item survey was given to medical providers (n = 45) from a health care system that includes integrated behavioral health services. Survey items assessed providers' attitudes and perceptions about BHCs. Attitudes about behavioral health were largely favorable. For all items, 73.3% to 100% of participants endorsed strongly agree or agree. Chi-square analyses revealed that those who interacted more frequently with BHCs were more comfortable discussing behavioral health issues with their patients, χ²(6, n = 45) = 13.43, p < .05, and that physicians believe that BHCs help patients effectively address their behavioral health problems, χ²(2, n = 45) = 6.36, p < .05. Age, gender, and health center in which the providers worked were not significantly related to any survey items. Medical providers surveyed believe that BHCs are valuable members of integrated health care, improving their abilities to provide care and to address their patients' physical and behavioral health problems. Although these preliminary results are promising, the setting surveyed has well-integrated behavioral health care services and thus might not be representative of other settings without such integration. Future studies should address medical providers' opinions of BHCs in a variety of settings with larger samples.

Late life anxiety is associated with decreased memory and executive functioning in community dwelling older adults.

This study assessed the degree to which anxiety and depression symptoms are associated with memory and executive functioning among community-dwelling older adults (N=120; M age=74.9 years, SD=7.2 years; 62% women). Participants completed the Geriatric Anxiety Scale, Geriatric Depression Scale, Comorbidity Index, California Verbal Learning Test, Second Edition (CVLT-II), and the Trail Making, Verbal Fluency, and 20 Questions subtests of the Delis-Kaplan Executive Function System (D-KEFS). Multiple regression analyses indicated that anxiety and depression predicted poorer ability to learn new information (CVLT-II, Trials 1-5). Both anxiety and depression predicted performance on the D-KEFS Trail Making test, Number-Letter Switching condition. Anxiety, but not depression, predicted decreased categorization as measured by the D-KEFS 20 Questions, Initial Abstraction Score. Depression but not anxiety, predicted performance on D-KEFS Letter Fluency and Category Fluency. Findings suggest that anxiety and depression have unique relationships with cognitive functioning in community-dwelling older adults.

Impact of polyelectrolytes and their corresponding multilayers to human primary endothelial cells.

The layer-by-layer technique, which allows simple preparation of polyelectrolyte multilayers, came into the focus of research for development of functionalized medical devices. Numerous literature exist that concentrate on the film build-up and the behaviour of cells on polyelectrolyte multilayers. However, in case of very soft polyelectrolyte multilayers, studies of the cell behaviour on these films are sometimes misleading with regard to clinical applications because cells do not die due to cytotoxicity but due to apoptosis by missing cell adhesion. It turns out that the adhesion in vitro, and thus, the viability of cells on polyelectrolyte multilayers is mostly influenced by their mechanical properties. In order to decide, which polyelectrolyte multilayers are suitable for implants, we take this problem into account by putting the substrates with soft films on top of pre-cultured human primary endothelial cells ('reverse assay'). Hence, the present work aims giving a more complete and reliable study of typical polyelectrolyte multilayers with regard to clinical applications. In particular, coatings consisting of hyaluronic acid and chitosan as natural polymers and sulfonated polystyrene and polyallylamine hydrochlorite as synthetic polymers were studied. The adsorption of polyelectrolytes was characterized by physico-chemical methods which show regular buildup. Biological examination of the native or modified polyelectrolyte multilayers was based on their effect to cell adhesion and morphology of endothelial cells by viability assays, immunostaining and scanning electron microscopy. Using the standard method, which is typically applied in literature--seeding cells on top of films--shows that the best adhesion and thus, viability can be achieved using sulfonated polystyrene/polyallylamine hydrochlorite. However, putting the films on top of endothelial cells reveals that hyaluronic acid/chitosan may also be suitable for clinical applications: This result is especially remarkable, since hyaluronic acid and chitosan mediate per se no cytotoxic effects, whereas the individual polyelectrolytes, sulfonated polystyrene and polyallylamine hydrochlorite, and their complexes show slight cytotoxicity.

Prevalence of cognitive impairment, depression, and anxiety symptoms among older adults with glaucoma.

PURPOSE: Two factors which may disrupt the ability to adhere to the treatment for glaucoma are cognitive impairment and mental health complications. Poor adherence to treatment may lead to preventable vision loss. Past research in this area has been limited by little focus on older patients with glaucoma, and the use of brief measures of cognition that may not detect subtle deficits related to Alzheimer disease. PATIENTS AND METHODS: This study examined the prevalence of cognitive impairment, depression, and anxiety in a sample of 41 glaucoma patients at a tertiary care glaucoma clinic. They had a mean age of 70.0 years (SD=9.2 y; range: 51 to 86 y) and 70% (n=30) were female. Two cognitive measures commonly used in detecting dementia were used to measure cognitive functioning. RESULTS: Controlling for age, memory impairment was found in approximately 20% of the sample, and impaired executive functioning was found in approximately 22% of the sample. Forty-four percent of the sample scored in the impaired range on one or more measures. Mild-to-moderate depressive symptoms were found in 12.2% of participants, and 1 person reported clinically significant anxiety. CONCLUSIONS: The results from this study indicate that cognitive impairment may be common in older patients with glaucoma. This has implications for treatment adherence, as difficulties in remembering information may significantly impede the ability to follow instructions from a physician. It is imperative that physicians and caregivers are aware of the prevalence of such conditions, as they are among the first to interact with such individuals. Given the high prevalence of cognitive impairment and depressive symptoms, future research should examine the impact of such factors on glaucoma treatment adherence.

A prospective study on endoscopic ultrasonography criteria to guide management in upper GI submucosal tumors.

UNLABELLED: Endoscopic ultrasonography (EUS) can differentiate between impression and submucosal tumor (SMT) but it is not known whether EUS criteria can reliably guide management. The aim of this prospective study was to assess an approach to recommend removal versus follow-up investigation based on clinical and EUS criteria, with respect to the predictive values to recognize malignancy versus benign lesions. MATERIAL AND METHODS: Over a 7-years time period, all patients referred for the EUS assessment of submucosal upper GI lesions were prospectively enrolled. Extraluminal impressions diagnosed with EUS were not further considered. If submucosal tumors seen with EUS were clearly symptomatic or one of several parameters (tumor size >3 cm, irregular margins, inhomogeneous echotexture and/or enlarged lymph nodes) were found, resection was recommended. The remaining cases were subjected to EUS follow-up. RESULTS: Of cases with 241 submucosal lesions, 65 had impressions and 176 had true submucosal lesions. Of the latter, 29 cases had non-neoplastic lesions (cysts, varices). In 59 cases, removal was deemed necessary due to clinical symptoms and suspicious findings in conventional endoscopy. These subjects underwent either surgical (originating layer, muscularis propria) or endoscopic resection (submucosal origin): 35.6% were malignant, more frequently in the surgical group (41.6% vs 20%). However, in 52.5% (n=31) of the 59 cases with no severe symptoms and true SMT, EUS suggested removal because of their additional criteria. Eighteen patients (12.2%) refused SMT removal and even regular EUS-based follow-up investigation. Clinical follow-up investigation by the family practitioner did not show frank malignancy in these cases (retransferal not registered). Follow-up investigation with EUS was recommended in 70 cases (mean follow-up period, 5 years; range, 1-7 years). The pattern remained unchanged in 67/70, and 2 of the 3 cases with changes underwent surgery for benign leiomyoma (patient refusal, n=1 with no change in the one-year follow-up MRI). CONCLUSIONS: An EUS strategy based on defined characteristics to remove SMT with no severe symptoms and suspicious finding in the conventional endoscopy shows a good adherence to the recommended approach and has a reasonable positive predictive value for malignancy (88%). Clinical symptoms alone or with endoscopic finding are frequently too vague to decide for a reasonable SMT resection. The chosen EUS criteria are valuable to: 1) achieve the primary resection of all potentially malignant SMT and 2) avoid to overlook them as shown by the results of the follow-up investigations with no detected malignant lesion.

Successful transgastric pancreaticography and endoscopic ultrasound-guided drainage of a disconnected pancreatic tail syndrome.

OBJECTIVES: We aim to demonstrate that endoscopic ultrasound (EUS)-guided transgastric pancreaticography/drainage of the pancreatic duct is feasible and successful in healing a persisting pancreaticocutaneous fistula. METHODS: By means of a case report, we describe the following alternative therapeutic procedure. A 76-year-old male had: (1) 10 surgical interventions because of necrotizing acute pancreatitis with a persisting pancreaticocutaneous fistula (volume 200-300 ml/day); (2) an unsuccessful attempt of transpapillary drainage (disrupted duct after necrosectomy). He then underwent a EUS-guided transluminal pancreaticography/drainage of the pancreatic duct. A transgastric puncture was performed followed by, insertion of a guide wire into the dilated tail segment, and expansion of the gastropancreaticostomy using a 10-Fr retriever. A 10-Fr Amsterdam prosthesis was then placed through the guide wire. RESULTS: The procedure was both a technical and clinical success as indicated by fistula occlusion and sufficient internal drainage of the pancreatic juice via the gastropancreaticostomy. No severe complications such as bleeding, perforation stent occlusion or migration were observed during the 15-month follow-up. CONCLUSIONS: Transgastric pancreaticography and EUS-guided drainage of the enlarged pancreatic duct are elegant and feasible alternative options for the treatment of specific pancreatic lesions such as persisting pancreaticocutaneous fistula (complication after necrotizing pancreatitis), after pancreatic resective surgery, chronic pancreatitis and anomaly of the congenital pancreatic or postoperative gastrointestinal anatomy. Moreover, the procedure may represent a valid tool to avoid surgery and more invasive interventions.

Gene biomarkers in diatom Thalassiosira pseudonana exposed to polycyclic aromatic hydrocarbons from contaminated marine surface sediments.

Marine diatoms have a key role in the global carbon fixation and therefore in the ecosystem. We used Thalassiosira pseudonana as a model organism to assess the effects of exposure to environmental pollutants at the gene expression level. Diatoms were exposed to polycyclic aromatic hydrocarbons mixture (PAH) from surface sediments collected at a highly PAH contaminated area of the Mediterranean Sea (Genoa, Italy), due to intense industrial and harbor activities. The gene expression data for exposure to the sediment-derived PAH mixture was compared with gene expression data for in vitro exposure to specific polycyclic aromatic hydrocarbons. The data shows that genes involved in stress response, silica uptake, and metabolism were regulated both upon exposure to the sediment-derived PAH mixture and to the single component. Complementary monitoring of silica in the diatom cultures provide further evidence of a reduced cellular uptake of silica as an end-point for benzo[a]pyrene exposure that could be linked with the reduced gene and protein expression of the silicon transporter protein. However some genes showed differences in regulation indicating that mixtures of structurally related chemical compounds can elicit a slightly different gene expression response compared to that of a single component. The paper provides indications on the specific pathways affected by PAH exposure and shows that selected genes (silicon transporter, and silaffin 3) involved in silica uptake and metabolism could be suitable molecular biomarkers of exposure to PAHs.

Prostaglandin E2 prevents Helicobacter-induced gastric preneoplasia and facilitates persistent infection in a mouse model.

BACKGROUND & AIMS: Persistent infection with the human pathogen Helicobacter pylori increases the risk of gastric cancer. In this study, we investigated the role of cyclooxygenase-2 (COX-2) and its main product, prostaglandin E(2) (PGE(2)), in the development of Helicobacter-induced gastritis and gastric cancer precursor lesions. METHODS: We utilized mouse models of Helicobacter-induced gastric preneoplasia and vaccine-induced protection to study the effects of COX-2 inhibition and PGE(2) treatment on the induction of Helicobacter-specific immune responses and gastric premalignant immunopathology. RESULTS: COX-2 and PGE(2) are up-regulated upon Helicobacter infection in cultured epithelial cells and in the gastric mucosa of infected mice. Inhibition of COX-2 activity with celecoxib significantly accelerated early preneoplasia; conversely, systemic administration of synthetic PGE(2) prevented development of premalignant pathology and completely reversed preexisting lesions by suppressing interferon-gamma production in the infected stomachs. The protective effect of PGE(2) was accompanied by increased Helicobacter colonization in all models. All in vivo effects were attributed to immunosuppressive effects of PGE(2) on CD4(+) T-helper 1 cells, which fail to migrate, proliferate, and secrete cytokines when exposed to PGE(2) in vitro and in vivo. T-cell inhibition was found to be due to silencing of interleukin-2 gene transcription, and could be overcome by supplementation with recombinant interleukin-2 in vitro and in vivo. CONCLUSIONS: COX-2-dependent production of PGE(2) has an important immunomodulatory role during Helicobacter infection, preventing excessive local immune responses and the associated immunopathology by inhibiting the effector functions of pathogenic T-helper 1 cells.

Protective and pathogenic functions of T-cells are inseparable during the Helicobacter-host interaction.

Chronic infection with the bacterial pathogen Helicobacter pylori is closely linked to the development of gastric cancer. Experimental infection of the laboratory mouse strain C57Bl6 mimics the initiation and progression of the disease in humans. Using this model, we have identified a dual role for CD4+ IFN-gamma-secreting T-cells in the control of Helicobacter infection as well as in the induction of preneoplastic gastric pathology. High gastric expression of IFN-gamma was positively correlated with a low Helicobacter burden, and was essential for vaccine-induced protection; on the other hand, elevated levels of the cytokine also, either directly or indirectly, triggered the transformation of the normal gastric mucosa to atrophic, hyperplastic and metaplastic lesions. Based on similar patterns of gene expression changes induced by IFN-gamma in vivo and in cultured gastric epithelial cells, we hypothesize that IFN-gamma may act directly on epithelial cells to stimulate their hyperproliferation, and thus to predispose them to elevated mutation rates and an increased risk of malignant transformation.

Naming test of the Neuropsychological Assessment Battery: convergent and discriminant validity.

This study investigated the convergent and discriminant validity of the naming subtest of the Neuropsychological Assessment Battery (NAB), a measure of word-finding. Seventy community-dwelling adults age 60 and above completed the NAB naming test (Forms 1 and 2), the Boston Naming Test (BNT), and other measures of verbal and visual memory, visuoperceptual skills, processing speed, and abstraction. The NAB naming test correlated highly with the BNT and with established measures of memory. The BNT correlated more strongly with education and with sex. The BNT correlated more strongly with a measure of visuoperceptual skills than the NAB naming test did, suggesting that visuoperception is more involved in the BNT. Divergent validity of the NAB naming was demonstrated by a lack of correlations with less-related measures. Findings suggest that the NAB naming test possesses convergent and divergent validity as a measure of word-finding.

Occurrence of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in Lake Maggiore (Italy and Switzerland).

Samples of air (gas and particulate phases), bulk deposition, aquatic settling material and sediments were collected in Lake Maggiore (LM) in order to determine their content of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs). Air (gas and particulate phases) concentrations were 0.5 pg m(-3), 80 pg m(-3), 13 pg m(-3) and 106 pg m(-3) for SigmaPCDD/Fs, SigmaPCBs, Sigma dioxin-like PCBs (DL-PCBs) and SigmaPBDEs, respectively. Deposition fluxes ranged from 0.7 ng m(-2) d(-1) for SigmaPCDD/Fs to 32 ng m(-2) d(-1) for SigmaPCBs. Aquatic settling material presented concentrations of 0.4 ng g(-1) dry weight (dw) for SigmaPCDD/Fs, 13 ng g(-1) dw for SigmaPCB, 3.4 ng g(-1) dw for SigmaDL-PCBs and 5.7 ng g(-1) dw for SigmaPBDEs. Mean sediment concentrations were 0.4 ng g(-1) dw for SigmaPCDD/Fs, 11 ng g(-1) dw for SigmaPCB, 3 ng g(-1) dw for SigmaDL-PCBs and 5.1 ng g(-1) dw for SigmaPBDEs. Similar PCDD/F and DL-PCB congener patterns in all the environmental compartments of LM point to an important, if not dominant, contribution of atmospheric deposition as source of these pollutants into LM. In contrast, PBDE congener distribution was not similar in the different environmental compartments. BDE 47 dominated air and settling material, while BDE 209 was the predominant congener in the bulk atmospheric deposition. Moreover, sediments showed two distinct PBDE congener profiles. Lower PBDE concentrated sediments were dominated by congeners 47 and 99, while BDE 209 dominated in higher PBDE concentrated samples. This suggests the influence of local sources as well as atmospheric input of PBDEs into LM.

Effect of water/fuel emulsions and a cerium-based combustion improver additive on HD and LD diesel exhaust emissions.

One of the major technological challenges for the transport sector is to cut emissions of particulate matter (PM) and nitrogen oxides (NOx) simultaneously from diesel vehicles to meet future emission standards and to reduce their contribution to the pollution of ambient air. Installation of particle filters in all existing diesel vehicles (for new vehicles, the feasibility is proven) is an efficient but expensive and complicated solution; thus other short-term alternatives have been proposed. It is well known that water/diesel (W/ D) emulsions with up to 20% water can reduce PM and NOx emissions in heavy-duty (HD) engines. The amount of water that can be used in emulsions for the technically more susceptible light-duty (LD) vehicles is much lower, due to risks of impairing engine performance and durability. The present study investigates the potential emission reductions of an experimental 6% W/D emulsion with EURO-3 LD diesel vehicles in comparison to a commercial 12% W/D emulsion with a EURO-3 HD engine and to a Cerium-based combustion improver additive. For PM, the emulsions reduced the emissions with -32% for LD vehicles (mass/km) and -59% for the HD engine (mass/ kWh). However, NOx emissions remained unchanged, and emissions of other pollutants were actually increased forthe LD vehicles with +26% for hydrocarbons (HC), +18% for CO, and +25% for PM-associated benzo[a]pyrene toxicity equivalents (TEQ). In contrast, CO (-32%), TEQ (-14%), and NOx (-6%) were reduced by the emulsion for the HD engine, and only hydrocarbons were slightly increased (+16%). Whereas the Cerium-based additive was inefficient in the HD engine for all emissions except for TEQ (-39%), it markedly reduced all emissions for the LD vehicles (PM -13%, CO -18%, HC -26%, TEQ -25%) except for NOx, which remained unchanged. The presented data indicate a strong potential for reductions in PM emissions from current diesel engines by optimizing the fuel composition.

Helicobacter pylori and gastric cancer: what can be learned by studying the response of gastric epithelial cells to the infection?

The development of gastric adenocarcinoma is closely linked to chronic infection with the bacterial pathogen Helicobacter pylori. One Helicobacter-specific virulence factor in particular, the CagA protein, has emerged as a main effector molecule in the interaction of H. pylori with gastric epithelial cells and has been implicated in gastric carcinogenesis. This review highlights the latest insights that have been gained into the pathogenesis of the disease by transcriptional profiling approaches studying gene expression in normal gastric tissue and gastric cancer tissue from human biopsy material as well as animal models of Helicobacter infection. The potential role of CagA as a bacterial oncoprotein is also discussed.