Visual Hallucinations in Eye Disease and Lewy Body Disease

Objective: Visual hallucinations (VH) most commonly occur in eye disease (ED), Parkinson’s disease (PD), and Lewy body dementia (LBD). The phenomenology of VH is likely to carry important information about the brain areas within the visual system generating them. Methods: Data from five controlled cross-sectional VH studies (164 controls, 135 ED, 156 PD, 79 (PDD 48 + DLB 31) LBD) were combined and analysed. The prevalence, phenomenology, frequency, duration, and contents of VH were compared across diseases and gender. Results: Simple VH were most common in ED patients (ED 65% vs. LBD 22% vs. PD 9%, Chi-square [χ2] test: χ2=31.43, df=2, p<0.001), whilst complex VH were more common in LBD (LBD 76% vs. ED 38%, vs PD 28%, Chi-square test: χ2=96.80, df=2, p<0.001). The phenomenology of complex VH was different across diseases and gender. ED patients reported more “flowers” (ED 21% vs. LBD 6% vs. PD 0%, Chi-square test: χ2=10.04, df=2, p=0.005) and “body parts” (ED 40% vs. LBD 17% vs. PD 13%, Chi-square test: χ2=11.14, df=2, p=0.004); in contrast LBD patients reported “people” (LBD 85% vs. ED 67% vs. PD 63%, Chi-square test: χ2=6.20, df=2, p=0.045) and “animals/insects” (LBD 50% vs. PD 42% vs. ED 21%, Chi-square test: χ2=9.76, df=2, p=0.008). Males reported more “machines” (13 % vs. 2%, Chi-square test: χ2=6.94, df=1, p=0.008), whilst females reported more “family members/children” (48% vs. 29%, Chi-square test: χ2=5.10, df=1, p=0.024). Conclusions: The phenomenology of VH is likely related to disease specific dysfunctions within the visual system and to past, personal experiences.

Subunit composition of VRAC channels determines substrate specificity and cellular resistance to Pt-based anti-cancer drugs

Although platinum-based drugs are widely used chemotherapeutics for cancer treatment, the determinants of tumor cell responsiveness remain poorly understood. We show that the loss of subunits LRRC8A and LRRC8D of the heteromeric LRRC8 volume-regulated anion channels (VRACs) increased resistance to clinically relevant cisplatin/carboplatin concentrations. Under isotonic conditions, about 50% of cisplatin uptake depended on LRRC8A and LRRC8D, but neither on LRRC8C nor on LRRC8E. Cell swelling strongly enhanced LRRC8-dependent cisplatin uptake, bolstering the notion that cisplatin enters cells through VRAC. LRRC8A disruption also suppressed drug-induced apoptosis independently from drug uptake, possibly by impairing VRAC-dependent apoptotic cell volume decrease. Hence, by mediating cisplatin uptake and facilitating apoptosis, VRAC plays a dual role in the cellular drug response. Incorporation of the LRRC8D subunit into VRAC substantially increased its permeability for cisplatin and the cellular osmolyte taurine, indicating that LRRC8 proteins form the channel pore. Our work suggests that LRRC8D-containing VRACs are crucial for cell volume regulation by an important organic osmolyte and may influence cisplatin/carboplatin responsiveness of tumors.

[Smoking and digestive tract: a complex relationship. Part 1: Inflammatory bowel disease and cigarette smoking]

Little is known about the effects of smoking on inflammatory bowel diseases (IBD). However the co-occurrence of smoking and IBD often happens in ambulatory care. Smokers have a doubled risk of developing a Crohn's disease with a more active disease course. After quitting, a decrease in risk can be observed after only one year. An inverse relationship is found between smoking and ulcerative colitis. Smoking seems protective for the development of the disease and its course is less active among smokers. Smoking cessation transitorily increases the risk of developing ulcerative colitis. Nevertheless, continuing smoking cannot be justified among those patients given the risks of long-term extra-digestive effects. It is thus important to counsel all smokers with an IBD to quit smoking.

Decreased phosphatidylcholine plasmalogens - A putative novel lipid signature in patients with stable coronary artery disease and acute myocardial infarction.

OBJECTIVE Glycerophospholipids and sphingolipids are structurally heterogeneous due to differences in the O- and N-linked fatty acids and head groups. Sphingolipids also show a heterogeneity in their sphingoid base composition which up to now has been little appreciated. The aim of this study was to investigate the association of certain glycerophospholipid and sphingolipid species with stable coronary artery disease (CAD) and acute myocardial infarction (AMI). METHODS The lipid profile in plasma from patients with stable CAD (n = 18) or AMI (n = 17) was compared to healthy subjects (n = 14). Sixty five glycerophospholipid and sphingolipid species were quantified by LC-MS. The relative distribution of these lipids into lipoprotein fractions was analyzed. RESULTS In the CAD cohort, 45 glycerophospholipid and sphingolipid species were significantly lower compared to healthy controls. In the AMI group, 42 glycerophospholipid and sphingolipid species were reduced. Four PC plasmalogens (PC33:1, PC33:2, PC33:3 and PC35:3) showed the most significant difference. Out of eleven analyzed sphingoid bases, four were lower in the CAD and six in the AMI group. Sphingosine-1-phosphate (S1P) levels were reduced in the AMI group whereas an atypical C16:1 S1P was lower in both groups. Phosphatidylcholine and sphingomyelin species were exclusively present in lipoprotein particles, whereas lysophosphatidylcholines were mainly found in the lipoprotein-free fraction. The observed differences were not explained by the use of statins as confirmed in a second, independent cohort. CONCLUSIONS Reduced levels of four PC plasmalogens (PC33:1, PC33:2, PC33:3 and PC35:3) were identified as a putatively novel lipid signature for CAD and AMI.

Tracking eolian dust with helium and thorium: Impacts of grain size and provenance

Reconstructions of the deposition rate of windblown mineral dust in ocean sediments offer an important means of tracking past climate changes and of assessing the radiative and biogeochemical impacts of dust in past climates. Dust flux estimates in ocean sediments have commonly been based on the operationally defined lithogenic fraction of sediment samples. More recently, dust fluxes have been estimated from measurements of helium and thorium, as rare isotopes of these elements (He-3 and Th-230) allow estimates of sediment flux, and the dominant isotopes (He-4 and Th-232) are uniquely associated with the lithogenic fraction of marine sediments. In order to improve the fidelity of dust flux reconstructions based on He and Th, we present a survey of He and Th concentrations in sediments from dust source areas in East Asia, Australia and South America. Our data show systematic relationships between He and Th concentrations and grain size, with He concentrations decreasing and Th concentrations increasing with decreasing grain size. We find consistent He and Th concentrations in the fine fraction (<5 μm) of samples from East Asia, Australia and Central South America (Puna-Central West Argentina), with Th concentrations averaging 14 μg/g and He concentrations averaging 2 μcc STP/g. We recommend use of these values for estimating dust fluxes in sediments where dust is dominantly fine-grained, and suggest that previous studies may have systematically overestimated Th-based dust fluxes by 30%. Source areas in Patagonia appear to have lower He and Th contents than other regions, as fine fraction concentrations average 0.8 μcc STP/g and 9 μg/g for 4He and 232Th, respectively. The impact of grain size on lithogenic He and Th concentrations should be taken into account in sediments proximal to dust sources where dust grain size may vary considerably. Our data also have important implications for the hosts of He in long-traveled dust and for the 3He/4He ratio used for terrigenous He in studies of extraterrestrial He in sediments and ice. We also investigate the use of He/Th ratios as a provenance tracer. Our results suggest differences in fine fraction He/Th ratios between East Asia, Australia, central South America and Patagonia, with ratios showing a positive relationship with the geological age of source rocks. He/Th ratios may thus provide useful provenance information, for example allowing separation of Patagonian sources from Puna-Central West Argentina or Australian dust sources. He/Th ratios in open-ocean marine sediments are similar to ratios in the fine fraction of upwind dust source areas. He/Th ratios in mid-latitude South Atlantic sediments suggest that dust in this region primarily derives from the Puna-Central West Argentina region (23–32°S) rather than Patagonia (>38°S). In the equatorial Pacific, He/Th ratios are much lower than in extratropical Pacific sediments or potential source areas measured as a part of this study (East Asia, South America, Australia) for reasons that are at present unclear, complicating their use as provenance tracers in this region.

Network Analysis Reveals Sex- and Antibiotic Resistance-Associated Antivirulence Targets in Clinical Uropathogens.

Increasing antibiotic resistance among uropathogenic Escherichia coli (UPEC) is driving interest in therapeutic targeting of nonconserved virulence factor (VF) genes. The ability to formulate efficacious combinations of antivirulence agents requires an improved understanding of how UPEC deploy these genes. To identify clinically relevant VF combinations, we applied contemporary network analysis and biclustering algorithms to VF profiles from a large, previously characterized inpatient clinical cohort. These mathematical approaches identified four stereotypical VF combinations with distinctive relationships to antibiotic resistance and patient sex that are independent of traditional phylogenetic grouping. Targeting resistance- or sex-associated VFs based upon these contemporary mathematical approaches may facilitate individualized anti-infective therapies and identify synergistic VF combinations in bacterial pathogens.

Molecular alterations in nucleotide excision repair genes in malignant glioma and their relevance to malignant progression and drug resistance

Recently, it has become apparent that DNA repair mechanisms are involved in the malignant progression and resistance to therapy of gliomas. Many investigators have shown that increased levels of O6-methyl guanine DNA alkyltransferase, a DNA monoalkyl adduct repair enzyme, are correlated with resistance of malignant glioma cell lines to nitrosourea-based chemotherapy. Three important DNA excision repair genes ERCC1 (excision repair cross complementation group 1), ERCC2 (excision repair cross complementation group 2), and ERCC6 (excision repair cross complementation group 6) have been studied in human tumors. Gene copy number variation of ERCC1 and ERCC2 has been observed in primary glioma tissues. A number of reports describing a relationship between ERCC1 gene alterations and resistance to anti-cancer drugs have been also described. The levels of ERCC1 gene expression, however, have not been correlated with drug resistance in gliomas. The expression of ERCC6 gene transcribes has been shown to vary with tissue types and to be highest in the brain. There have been no comprehensive studies so far, however, of ERCC6 gene expression and molecular alterations in malignant glioma. This project examined the ERCC1 expression levels and correlated them with cisplatin resistance in malignant glioma cell lines. We also examined the molecular alterations of ERCC6 gene in primary glioma tissues and cells and analyzed whether these alterations are related to tumor progression and chemotherapy resistance. Our results indicate the presence of mutations and/or deletions in exons II and V of the ERCC6 gene, and these alterations are more frequent in exon II. Furthermore, the mutations and/or deletions in exon II were shown to be associated with increased malignant grade of gliomas. The results on the Levels of ERCC1 gene transcripts showed that expression levels correlate with cisplatin resistance. The increase in ERCC1 mRNA induced by cisplatin could be down-regulated by cyclosporin A and herbimycin A. The results of this study are likely to provide useful information for clinical treatment of human gliomas. ^

Chronic volatile substance abuse among the adult Kickapoo traditional tribe of Texas: Disease and disability profiles, neuropsychosocial consequences, and social implications for treatment

The purpose of this study, based on secondary data from attendees at a substance abuse clinic for the Kickapoo Healing Grounds in Eagle Pass, Texas, is two fold: (1) to elucidate neuro-behavioral performance of volatile substance abusers in the Kickapoo tribe and (2) to determine factors associated with their treatment completion and rehabilitation as measured by their employment at follow-up. Volatile substance abuse (VSA) is associated with a host of neurological manifestations, and secondary prevention or clinical treatment and rehabilitation remains the mainstay of control efforts. Very little is known about VSA in general, and especially among Native American populations. It is anticipated that the results will help determine and assist other tribes and non-tribal substance abuse centers with treatment planning for volatile substance abusers among Native American populations. ^

Association between severity of Clostridium difficile disease and different types of toxins---A systematic review

Clostridium difficile is the most important and common cause of hospital-acquired diarrhea. Toxin A and B are two important protein toxins responsible for C. difficile disease. This systematic review was undertaken to summarize the association between severity of C. difficile disease and different types of toxins. Only 5 studies were found that met the inclusion criteria. Only two studies reported results that were statistically significant and that the C. difficile disease was more severe in patient with binary toxin genes. Other three studies did not report significant findings but the authors stated that these studies were too small to detect true association. The main difference between the studies which detect association and those which did not detect association was the sample size. Well-designed and large scale studies are needed to strengthen the relationship between severe disease and toxin types. ^

Systematic review of genetic risk score in coronary heart disease and other diseases

In order to better take advantage of the abundant results from large-scale genomic association studies, investigators are turning to a genetic risk score (GRS) method in order to combine the information from common modest-effect risk alleles into an efficient risk assessment statistic. The statistical properties of these GRSs are poorly understood. As a first step toward a better understanding of GRSs, a systematic analysis of recent investigations using a GRS was undertaken. GRS studies were searched in the areas of coronary heart disease (CHD), cancer, and other common diseases using bibliographic databases and by hand-searching reference lists and journals. Twenty-one independent case-control studies, cohort studies, and simulation studies (12 in CHD, 9 in other diseases) were identified. The underlying statistical assumptions of the GRS using the experience of the Framingham risk score were investigated. Improvements in the construction of a GRS guided by the concept of composite indicators are discussed. The GRS will be a promising risk assessment tool to improve prediction and diagnosis of common diseases.^

Cross-culture perspectives on fear of HIV disease and AIDS in health care workers

Health care workers have been known to carry into the workplace a variety of judgmental and negative attitudes towards their patients. In no other area of patient care has this issue been more pronounced as in the management of patients with AIDS. Health care workers have refused to treat or manage patients with AIDS and have often treated them more harshly than identically described leukemia patients. Some health care institutions have simply refused to admit patients with AIDS and even recent applicants to medical colleges and schools of nursing have indicated a preference for schools in areas with low prevalence of HIV disease. Since the attitudes of health care workers do have significant consequences on patient management, this study was carried out to determine the differences in clinical practice in Nigeria and the United States of America as it relates to knowledge of a patient's HIV status, determine HIV prevalence and culture in each of the study sites and how they impact on infection control practices, determine the relationship between infection control practices and fear of AIDS, and also determine the predictors of safe infection control practices in each of the study sites.^ The study utilized the 38-item fear of AIDS scale and the measure of infection control questionnaire for its data. Questionnaires were administered to health care workers at the university teaching hospital sites of Houston, Texas and Calabar in Nigeria. Data was analyzed using a chi-square test, and where appropriate, a student t-tests to establish the demographic variables for each country. Factor analysis was done using principal components analysis followed by varimax rotation to simple structure. The subscale scores for each study site were compared using t-tests (separate variance estimates) and utilizing Bonferroni adjustments for number of tests. Finally, correlations were carried out between infection control procedures and fear of AIDS in each study site using Pearson-product moment correlation coefficients.^ The study revealed that there were five dimensions of the fear of AIDS in health care workers, namely fear of loss of control, fear of sex, fear of HIV infection through blood and illness, fear of death and medical interventions and fear of contact with out-groups. Fear of loss of control was the primary area of concern in the Nigerian health care workers whereas fear of HIV infection through blood and illness was the most important area of AIDS related feats in United States health care workers. The study also revealed that infection control precautions and practices in Nigeria were based more on normative and social pressures whereas it was based on knowledge of disease transmission, supervision and employee discipline in the United States, and thus stresses the need for focused educational programs in health care settings that emphasize universal precautions at all times and that are sensitive to the cultural nuances of that particular environment. ^