Epidemiology of schistosomiasis mansoni in three endemic communities in north-east Ethiopia: baseline characteristics before endod based intervention

As part of a pre-intervention baseline data collection the epidemiological characteristics of schistosomiasis mansoni were studied in 3 endemic communities (Kemise, Harbu and Bati towns) in northeast Ethiopia in April and May 1994. The objective was to generate data based on which post-intervention differences (in changes), if any, in transmission level could partly be explained for the 3 towns. After calculating the sample size required for each town 132, 75, 158 households were selected by systematic random sampling from Kemise, Harbu and Bati, respectively and all members of the selected households stool was examined by the Kato's thick smear method. Eighty eight and 85% of the houses harboured one or more cases of Schistosoma mansoni in Kemise and in Bati, respectively, all members of the households being positive in 27% in Kemise and in 28% in Bati. The overall prevalences were 59%, 33% and 51% in Kemise, Harbu and Bati, respectively, with the corresponding geometric mean egg counts (epg) of 240, 123 and 195 for positives and 26.5 and 15 for the whole populations. All ages combined, there were no significant differences due to sex both in prevalence and intensity of infection. By age, children in the 10-14 years age group were most affected (p = 0.007), their prevalences reaching 86%, 52% and 66% in Kemise, Harbu and Bati, respectively and their corresponding geometric mean epg being 377, 157 and 401, respectively. Heavy infection (> 100 epg) reached 42%, 32% and 16% in Kemise, Bati and Harbu, respectively, reaching an average of 55% among the 10-14 years of age. The implications of the epidemiological findings and the possible use of the household approach for rapid assessment of schistosomiasis magnitude in an area are discussed.     

Neocortical neuron number in humans: Effect of sex and age

Modern stereological methods provide precise and reliable estimates of the number of neurons in specific regions of the brain. We decided to estimate the total number of neocortical neurons in the normal human brain and to analyze it with respect to the major macro- and microscopical structural components, to study the internal relationships of these components, and to quantitate the influence of important physiological variables on brain structure. The 94 brains reported represent a consecutive collection of brains from the general Danish population. The average numbers of neocortical neurons were 19 billion in female brains and 23 billion in male brains, a 16% difference. In our study, which covered the age range from 20 years to 90 years, approximately 10% of all neocortical neurons are lost over the life span in both sexes. Sex and age were the main determinants of the total number of neurons in the human neocortex, whereas body size, per se, had no influence on neuron number. Some of the data presented have been analyzed by using new mathematical designs. An equation predicting the total neocortical neuron number in any individual in which sex and age are known is provided. J. Comp. Neurol. 384:312-320, 1997. © 1997 Wiley-Liss, Inc.     

Short-term exposure of Chinook salmon (Oncoryhnchus tshawytscha) to o,p-DDE or DMSO during early life-history stages causes long-term humoral immunosuppression

We evaluated the effect of short-term exposures to a xenobiotic chemical during early life-history stages on the long-term immune competence of chinook salmon (Oncoryhnchus tshawytscha). Immersion of chinook salmon eggs in a nominal concentration of o,p-dichlorodiphenyldichloroethylene (o,p-DDE; 10 ppm) for 1 hr at fertilization followed by immersion in the same dose for 2 hr at hatch resulted in a significant reduction in the ability of splenic leukocytes from fish 1 year after treatment to undergo blastogenesis upon in vitro stimulation with lipopolysaccharide. We also observed that the vehicle, dimethyl sulfoxide (DMSO), caused a significant reduction in the ability of the splenic leukocytes to express surface immunoglobin M (SIgM) at this time. The concentration of o,p-DDE in a pooled sample of whole fry from this treatment was 0.53 microg/g lipid 1 month after first feeding but was undetectable in all other treatments. Mortality rate, time to hatch, fish length, and weight were unaffected by treatment with o,p-DDE. Similarly, sex ratios, gonadal development, and concentrations of plasma estradiol and 11-ketotestosterone were not affected by the treatment. In addition, we found no evidence that plasma lysozyme concentrations or the mitogenic responses of splenic leukocytes to concanavalin A or polyinosinic-polycytidylic acid were influenced by the treatment. In this experiment, a brief period of exposure to o,p-DDE or DMSO during early development was able to induce long-term effects on humoral immune competence of chinook salmon. Such immunosuppression may increase susceptibility to disease, which may in turn be critical to regulating the population.     

Quantitative axial profiles of retinoic acid in the embryonic mouse spinal cord: 9-cis retinoic acid only detected after all-trans-retinoic acid levels are super-elevated experimentally.

Studies using bioassays in normal mice and gene activation in transgenic reporter mice have demonstrated peaks of retinoic acid receptor (RAR) signaling in the brachial and lumbar regions of the spinal cord. Recently, Solomin et al. (Solomin et al. [1998] Nature 395:398-402) detected a retinoid X receptor (RXR) signal in the same region of the developing spinal cord at a slightly later stage than the RAR signal. This finding raises the question of which retinoid ligands underlie RAR and RXR signaling in this part of the embryo. Quantitative measurements of regional differences in retinoid profiles have not been reported previously due to limitation in the sensitivity and specificity of available retinoid detection methods. Here, by using a recently developed ultrasensitive HPLC technique (Sakhi et al. [1998] J. Chromatogr. A 828:451-460), we address this question in an attempt to identify definitively the endogenous retinoids present in different regions of the spinal cord at the stages when regional differences in RAR and RXR signaling have been reported. We find a bimodal distribution of all-trans retinoic acid (at-RA), the ligand for RARs, and relate this to the expression of several retinoid-synthesizing enzymes. However, we do not detect 9-cis-retinoic acid (9-cis-RA), the putative RXR ligand, in any region of the spinal cord unless retinoid levels are massively increased experimentally by gavage feeding pregnant mice with teratogenic doses of at-RA. This study provides for the first time quantitative profiles of endogenous retinoids along the axis of the developing spinal cord, thereby establishing a foundation for more definitive studies of retinoid function in the future. It sets definite limits on how much 9-cis-RA potentially is present and demonstrates that at-RA predominates over 9-cis-RA by at least 30- to 180-fold in different spinal cord regions.     

Multiple symptoms in patients with chronic obstructive pulmonary disease in Norway

This paper examines the prevalence of multiple symptoms and the relationships between future expectations and multiple symptoms in a cross‐sectional study of 100 patients with chronic obstructive pulmonary disease. A questionnaire was used to examine the patients’ symptoms of breathlessness, anxiety, depression, sleeplessness, fatigue, and pain, and their outlook for the future. All patients reported breathlessness, 64% anxiety, 69% depression, 28% sleeplessness, 72% fatigue, and 45% pain. Those with anxiety reported significant depression (P < 0.001), and those with fatigue reported significant depression (P = 0.004). Patients who reported pain also reported significant sleeplessness (P = 0.022). A negative outlook for the future was reported by 42% of patients who also reported significantly more anxiety, depression, sleeplessness, fatigue, and pain (P ≤ 0.049). Multiple symptoms are common in chronic obstructive pulmonary disease, and patients with a pessimistic view of the future reported more symptoms. Those with multiple symptoms and a negative outlook toward the future may benefit from interventions to help them achieve a more positive outlook for the future, which may relieve symptom burden.     

Chlamydia pneumoniae DNA in peripheral blood mononuclear cells in dialysis patients,renal transplant recipients and healthy controls

While nitric oxide (NO) is implicated as an important mediator of hypotension in sepsis and endotoxemia, its role as a mediator of tissue injury in shock is controversial. During porcine endotoxemia (lipopolysaccharide (LPS) 1.7 &#119 g·kg -1 ·h -1 i.v. for 6 h), we compared circulatory and morphological changes in the liver induced by two different NO synthase inhibitors (N G -nitro-L-arginine methyl ester, L-NAME, 25 mg·kg- 1 i.v., and aminoethyl-isothiourea, AE-ITU, 10 mg·kg- 1 i.v.), both given after 3 h. LPS induced time-dependent tissue reactions with edema, sinusoidal dilation, packing of red cells and leukocyte infiltration, progressing to endothelial cell and hepatocyte damage, formation of thrombi, and at 6 h widespread necrosis. These changes were similar in all pigs receiving LPS, regardless of treatment with NOS inhibitors. LPS caused significant increases in aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alpha glutathione S-transferase ( &#102 -GST). L-NAME caused further increases in AST, ALP and &#102 -GST, while AE-ITU prevented the late increase in ALP and &#102 -GST observed in the other LPS groups. LPS reduced liver blood flow by ~ 40%. L-NAME further reduced flow by ~ 50%, while AE-ITU restored liver blood flow to baseline values. Conclusion: L-NAME in endotoxemia had detrimental effects on liver circulation, while AE-ITU improved liver blood flow and attenuated the late increase in liver enzymes. Liver morphology was unaffected within the 3-h observation time after NOS inhibition.     

Proliferation, migration and invasion of human glioma cells exposed to paclitaxel (Taxol) in vitro.

Paclitaxel (Taxol), an anti-cancer drug derived from Taxus species, was tested for its anti-migrational, anti-invasive and anti-proliferative effect on two human glioma cell lines (GaMg and D-54Mg) grown as multicellular tumour spheroids. In addition, the direct effect of paclitaxel on glioma cells was studied using flow cytometry and scanning confocal microscopy. Both cell lines showed a dose-dependent growth and migratory response to paclitaxel. The GaMg cells were found to be 5-10 times more sensitive to paclitaxel than D-54Mg cells. Paclitaxel also proved to be remarkably effective in preventing invasion in a co-culture system in which tumour spheroids were confronted with fetal rat brain cell aggregates. Control experiments with Cremophor EL (the solvent of paclitaxel for clinical use) in this study showed no effect on tumour cell migration, cell proliferation or cell invasion. Scanning confocal microscopy of both cell lines showed an extensive random organization of the microtubules in the cytoplasm. After paclitaxel exposure, the GaMg and the D-54Mg cells exhibited a fragmentation of the nuclear material, indicating a possible induction of apoptosis. In line with this, flow cytometric DNA histograms showed an accumulation of cells in the G2/M phase of the cell cycle after 24 h of paclitaxel exposure. After 48 h, a deterioration of the DNA histograms was observed indicating nuclear fragmentation.     

Declining estimated prevalence of alcohol drinking and smoking among young adults nationally: artifacts of sample undercoverage?

A growing concern in public health surveillance surveys that rely on random digit dialing for sampling is the exclusion of adults in cell-phone-only households. The purpose of this study was to examine whether recent increases in wireless substitution have affected estimates of tobacco and alcohol use in the Behavioral Risk Factor Surveillance System (BRFSS) in a subpopulation with notable cell-phone usage (i.e., young adults). BRFSS data from 2001-2005 were examined. Analyses were limited to participants aged 18-24 years, and the sample contained approximately 18,500 persons in each year. Prevalence estimates were generated with SUDAAN software for three health behaviors: cigarette smoking, binge drinking, and heavy alcohol consumption. In addition, the authors examined sample completeness for young adults relative to US Census estimates. Overall, prevalences of all three health behaviors among young adults were fairly stable between 2001 and 2003 but significantly decreased between 2003 and 2005. These trends are not replicated in national surveys that use area probability samples. The authors found a declining trend in the sample completeness ratio for young adults; it declined from 0.32 in 2001 to 0.15 in 2005. Given the high prevalence of wireless substitution among young adults and the declining sample completeness ratio, the authors suspect that the observed decreases in prevalence are artifacts of undercoverage.     

Comprehensive interrogation of gene lists from genome-scale cancer screens with oncoEnrichR

Genome-scale screening experiments in cancer produce long lists of candidate genes that require extensive interpretation for biological insight and prioritization for follow-up studies. Interrogation of gene lists frequently represents a significant and time-consuming undertaking, in which experimental biologists typically combine results from a variety of bioinformatics resources in an attempt to portray and understand cancer relevance. As a means to simplify and strengthen the support for this endeavor, we have developed oncoEnrichR, a flexible bioinformatics tool that allows cancer researchers to comprehensively interrogate a given gene list along multiple facets of cancer relevance. oncoEnrichR differs from general gene set analysis frameworks through the integration of an extensive set of prior knowledge specifically relevant for cancer, including ranked gene-tumor type associations, literature-supported proto-oncogene and tumor suppressor gene annotations, target druggability data, regulatory interactions, synthetic lethality predictions, as well as prognostic associations, gene aberrations and co-expression patterns across tumor types. The software produces a structured and user-friendly analysis report as its main output, where versions of all underlying data resources are explicitly logged, the latter being a critical component for reproducible science. We demonstrate the usefulness of oncoEnrichR through interrogation of two candidate lists from proteomic and CRISPR screens. oncoEnrichR is freely available as a web-based service hosted by the Galaxy platform ( https://oncotools.elixir.no ), and can also be accessed as a stand-alone R package ( https://github.com/sigven/oncoEnrichR ).