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Objective/background: The GeneXpert MTB/RIF assay (Xpert) was endorsed as the initial diagnostic tool in people suspected of human immunodeficiency virus-associated or drug-resistant tuberculosis (TB). However, information regarding the performance of Xpert for diagnosing smear-negative TB in high burden settings remains limited. We evaluated the diagnostic accuracy of Xpert and the impact of bleach concentration on the performance of Xpert using smear-negative sputum samples from human immunodeficiency virus-negative patients., Methods: One spot and one morning smear-negative sputum samples per patient were examined using Xpert and culture at the Mycobacteriology Research Center of Jimma University, Ethiopia. The sputum culture on both Löwenstein-Jensen and/or Mycobacteria Growth Indicator Tube was the gold-standard., Results: Of 185 smear-negative presumptive pulmonary TB cases, 19 (10.3%) had culture-proven TB. The sensitivity of Xpert on spot and morning sputum was similar (63.2%). Testing two specimens per patient insignificantly increased the sensitivity of Xpert. Bleach concentration and pelleting improved the sensitivity of Xpert over unprocessed sputum in paired samples (73.8% vs. 63.2%) without affecting the specificity (95%). Bleach concentration and pelleting allowed an additional seven cases of TB (missed on the first and second direct Xperts) to be detected, five of which were from culture-negative cases., Conclusion: Testing of a single sputum sample by Xpert can reach reasonable sensitivity and results would be available on the same day, avoiding loss of patients and treatment delay. The sensitivity of Xpert was improved after bleach concentration and pelleting, although its added value needs further study on a larger scale., (Copyright © 2016 Asian-African Society for Mycobacteriology. Published by Elsevier Ltd. All rights reserved.)

Objective: To determine whether community-based prenatal and intrapartum care in Ethiopia results in a lower stillbirth rate., Methods: Between May and December 2014, a randomly selected sample of women in northern and eastern Ethiopia who had delivered a neonate in the preceding 12months completed a face-to-face survey about their experiences of maternal services and the fetal outcome for each delivery. The stillbirth rates among women delivering at home and at health facilities were compared., Results: Overall, 4442 women completed surveys. Stillbirth was reported by 42 (1.7%) of the 2437 women who had received prenatal care and 53 (2.8%) of the 1921 women who did not receive prenatal care (P=0.01). The stillbirth rate was similar among women who delivered in a health center (27/1417 [1.9%]), in a hospital (6/126 [4.8%]), and at home (62/2725 [2.3%]; P=0.13). However, women experiencing an intrapartum emergency were twice as likely to deliver in a health facility (odds ratio 2.6, 95% confidence interval 2.2-3.0). Satisfaction with health-center care was moderately good (median score 77.5/100)., Conclusion: The stillbirth rate was reduced among women receiving prenatal care, although delivering in a health facility did not reduce the risk of stillbirth. Improving the quality of health-center care could lead to their planned use for childbirth, which might reduce stillbirth rates., (Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Heitziquinone (7), a new benzophenanthridine alkaloid, together with five known compounds; isoarnottianamide (5), rhoifoline B (6), isobauerenol (8), 6-hydroxypellitorine (9) and sylvamide (10), were isolated as minor compounds from the hexane extract of stem bark from Zanthoxylum heitzii. Four previously reported compounds (1-4) were found, as well. Compounds 5 and 7 were both found to exist as 4:1 mixtures of two atropisomers. The structures were elucidated by 1D and 2D NMR spectroscopy and by mass spectrometry. Compounds 5-10 were identified for the first time in this species, and they are all rare natural compounds. Pellitorine (4), one of the main compounds from the hexane bark extract, was found to be responsible for the brine shrimp larvae toxicity (LC50 37 μM, 8 μg/ml) of the crude extract (LC50 24 μg/ml). Low cytotoxicity against a macrophage cell line was observed., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: In Africa, fewer than half of patients receiving therapy for multidrug-resistant TB (MDR TB) are successfully treated, with poor outcomes reported for HIV-coinfected patients., Methods: A standardised second-line drug (SLD) regimen was used in a non-governmental organisation-Ministry of Health (NGO-MOH) collaborative community and hospital-based programme in Ethiopia that included intensive side effect monitoring, adherence strategies and nutritional supplementation. Clinical outcomes for patients with at least 24 months of follow-up were reviewed and predictors of treatment failure or death were evaluated by Cox proportional hazards models., Results: From February 2009 to December 2014, 1044 patients were initiated on SLD. 612 patients with confirmed or presumed MDR TB had ≥ 24 months of follow-up, 551 (90.0%) were confirmed and 61 (10.0%) were suspected MDR TB cases. 603 (98.5%) had prior TB treatment, 133 (21.7%) were HIV coinfected and median body mass index (BMI) was 16.6. Composite treatment success was 78.6% with 396 (64.7%) cured, 85 (13.9%) who completed treatment, 10 (1.6%) who failed, 85 (13.9%) who died and 36 (5.9%) who were lost to follow-up. HIV coinfection (adjusted HR (AHR): 2.60, p<0.001), BMI (AHR 0.88/kg/m(2), p=0.006) and cor pulmonale (AHR 3.61, p=0.003) and confirmed MDR TB (AHR 0.50, p=0.026) were predictive of treatment failure or death., Conclusions: We report from Ethiopia the highest MDR TB treatment success outcomes so far achieved in Africa, in a setting with severe resource constraints and patients with advanced disease. Intensive treatment of adverse effects, nutritional supplementation, adherence interventions and NGO-MOH collaboration were key strategies contributing to success. We argue these approaches should be routinely incorporated into programmes., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: Diagnosis of tuberculous lymphadenitis using fine-needle aspiration cytology is a simple and safe but low-specificity method, whereas conventional smear microscopy has variable sensitivity due to low bacterial load. We evaluated the diagnostic performance of fluorescent light-emitting diode (LED) microscopy on routinely collected fine-needle aspirates from tuberculous lymphadenitis presumptive cases., Methods: Fine-needle aspirates were collected from patients clinically suspected of having tuberculous lymphadenitis as part of routine diagnosis. Smear preparation was performed from the aspirate and processed for cytology, conventional Ziehl-Neelsen and LED microscopy. The remaining aspirate was processed for culture on Lowenstein-Jensen media. Capilia TB-Neo test was used to differentiate M. tuberculosis complex from non-tuberculous mycobacteria., Result: A total of 144 tuberculous lymphadenitis presumptive cases were included. 66.7% (96/144) were positive for M. tuberculosis complex on culture. Only one isolate was identified as non-tuberculous mycobacteria. The detection rates of Ziehl-Neelsen and LED microscopy were 18.8% (27/144) and 34% (49/144), respectively. As compared to culture, sensitivity was 25.0% [95% CI: 16.3-33.7] for Ziehl-Neelsen microscopy and 45.8% [95% CI: 35.9-55.8] for LED microscopy. The specificity was 93.8% [95% CI: 86.9-100] for Ziehl-Neelsen microscopy and 89.6% [95% CI: 80.9-98.2] for LED microscopy. LED microscopy showed a statistically significant increase in sensitivity and similar specificity compared to Ziehl-Neelsen microscopy. Mean reading time of positive slides was 2.62 min/slide for Ziehl-Neelsen and 1.60 min/slide for LED microscopy. Cytology showed sensitivity of 82.3% and specificity of 54.2%. LED microscopy detected TB bacilli in 33.3% of cases cytologically classified as suppurative abscess., Conclusion: The LED microscopy for tuberculous lymphadenitis had significantly higher sensitivity and shorter screening time than Ziehl-Neelsen microscopy. Use of LED microscopy among cases classified as suppurative abscess on fine-needle aspirate cytology improves evidence-based diagnosis of presumptive tuberculous lymphadenitis cases. Moreover, LED microscopy could be considered as an alternative approach in settings where fine-needle aspirate cytology is impractical., (© 2015 John Wiley & Sons Ltd.)

Introduction: The diagnosis of tuberculous lymphadenitis (TBL) remains challenging. The routinely used methods (cytology and smear microscopy) have sub-optimal sensitivity. Recently, WHO recommends GeneXpert to be used as the initial diagnostic test in patients suspected of having extra-pulmonary tuberculosis (EPTB). However, this was a conditional recommendation due to very low-quality evidence available and more studies are needed. In this study we evaluated the performance of Xpert for the diagnosis of TBL on concentrated fine needle aspirates (FNA) in Southwest Ethiopia., Methods: FNA was collected from presumptive TBL cases. Two smears were prepared from each aspirate and processed for cytology and conventional microscopy. The remaining aspirate was treated with N-acetyl-L-cysteine-NaOH and centrifuged for 15minutes at 3000g. The concentrated sediment was used for culture and Xpert test. Capilia TB-Neo test was used to differentiate M. tuberculosis complex (MTBC) from non-tuberculous mycobacteria (NTM). Composite bacteriological methods (culture and/or smear microscopy) were considered as a reference standard., Result: Out of 143 enrolled suspects, 64.3% (92/143) were confirmed TBL cases by the composite reference standard (CRS). Xpert detected M. tuberculosis complex (MTBC) in 60.1% (86/143) of the presumptive TBL cases. The sensitivity of Xpert compared to CRS was 87.8% [95% CI: 81.0-94.5] and specificity 91.1% [95% CI: 82.8-99.4]. The sensitivity was 27.8% for smear microscopy and 80% for cytology compared to CRS. Cytology showed the lowest specificity (57.8%). Xpert was positive in 4 out of 45 culture- and smear-negative cases. Among 47 cytomorphologically non-TBL cases, 15 were positive on Xpert. More than half of Xpert-positive cases were in the range of very low cut-off threshold values (28

Background: The genetic diversity of Plasmodium falciparum has been extensively studied in various countries. However, limited data are available from Ethiopia. This study was conducted to evaluate the extent of genetic diversity of P. falciparum in Kolla-Shele, in the southwest of Ethiopia., Methods: A total of 88 isolates from patients with uncomplicated P. falciparum attending Kolla-Shele Health Centre was collected from September to December, 2008. After extraction of DNA by Chelex method, the samples were genotyped by using nested-PCR of msp1 (block 2) and msp2 (block 3) including their allelic families: K1, MAD20, RO33 and FC27, 3D7/IC1, respectively., Results: Allelic variation in both msp1 and msp2 were identified in the 88 blood samples. For msp1 67% (59/88) and msp2 44% (39/88) were observed. K1 was the predominant msp1 allelic family observed in 33.9% (20/59) of the samples followed by RO33 and MAD20. Of the msp2 allelic family 3D7/IC1 showed higher frequency (21.5%) compared to FC27 (10.3%). A total of twenty-three alleles were detected; of which, eleven were from msp2 and twelve from msp2 genes. Fifty-nine percent of isolates had multiple genotypes and the overall mean multiplicity of infection was 1.8 (95% CI: 1.48-2.04). The heterozygosity index was 0.79 and 0.54for msp1 and msp2, respectively. There was no statically significant difference in the multiplicity of infection by either age or parasite density (P > 0.05)., Conclusion: This genetic diversity study showed the presence of five allelic types in the study area, with dominance K1 in the msp1 family and 3D7/IC1 in the msp2 family. Multiple infections were observed in nearly 60% of the samples.

Background: The diagnostic accuracy of fine-needle aspiration (FNA) cytology for the diagnosis of tuberculous lymphadenitis (TBLN) is confounded by mimicking cytomorphologic disorders. The objective of this study was to determine whether supplementing FNA cytology with bacteriological methods improves the overall accuracy of TBLN diagnosis., Methods: Two hundred presumptive TBLN cases were included in the study. FNA specimens were collected and examined for cytomorphologic changes, for acid-fast bacilli (AFB) by microscopy and for mycobacterial growth on culture. Culture was done using Lowenstein-Jensen (LJ) medium and mycobacteria growth indicator tube (BACTEC MGIT 960 TB detection system). Differentiation between M. tuberculosis complex (MTBc) and non-tuberculous mycobacteria (NTM) was done by using 500 μg/ml para-nitrobenzoic acid (PNB) susceptibility testing., Results: Cytomorphology detected TBLN among 80% (160/200) of the presumptive cases. Culture results were available for 188 cases. Twelve samples were excluded due to contamination on both culture methods. Culture confirmed cases accounted for 78% (147/188) of which MTBc constituted 97.3% (143/147). Among presumptive cases, classified by FNA cytology as 'abscess', 11 were culture positive. Microscopy detected 31.3% (46/147) of culture confirmed mycobacterial lymphadenitis of which 11% (4/37) were diagnosed non-suggestive for tuberculosis (TB) by FNA cytology. Compared to culture (LJ & BACTEC MGIT 960) and AFB microscopy as composite gold standard, FNA cytology had a sensitivity of 88.4% and a specificity of 48.8%. The positive predictive value was 86.1% while the negative predictive value was 54.1%. The confirming power and the ROC curve area was 1.73 and 0.69, respectively., Conclusion: FNA cytology showed a relatively high sensitivity but a low specificity. Combining bacteriological methods with FNA cytology in an endemic region like Ethiopia improves the overall accuracy of the diagnosis of mycobacterial lymphadenitis, which in turn may lead to better patient management.

Background: About 60% of new HIV infections occur in HIV sero-discordant couples as 30% of married HIV positives have negative spouse. Although HIV-discordant couples are at 10% annual risk of acquiring HIV infection and large number of new HIV infections occur in stable partnerships, most HIV prevention programs focus on reducing casual sexual partners, condom use, and increasing fidelity among married partners. The purpose is assessment of sero-discordance among couples and associated factors., Methods: The study was facility based cross sectional survey of couples who tested for HIV in 2011 and lived together at least 1 year period. The sample size was 154 couples (308 individuals) and necessary ethical issues were considered., Results: Among 152 couples (304 individuals) who received VCT, HIV sero-prevalence in this study was found to be 11(3.6%). The prevalence in females 8(5.3%) was higher than that in males 3(2.0%). Of all participants, 9(3.0%) were found to be sero-discordant, 2(0.7%) concordant positive and 293(96.4%) concordant negative. Of all couples 9(5.9%) were found to be sero-discordant, 2(1.3%) concordant positive and 141(92.8%) concordant negative. Of the 9 sero-discordant couples, the 7(4.6%) prevalence in females was higher than 2(1.3%) in males. And, among 9 discordant couples, 5 of them were premarital sex partner and the rest 4 were married couples. Premarital couples were significantly discordant than married couples, AOR=1.68; 95%CI (1.36- 5.40). HIV discordance was also significantly associated with having number of two or more sexual partners than one sexual partner AOR=4.06; 95%CI (2.41-10.13)., Conclusion: The study indicated high prevalence of HIV discordance and increased risk of vulnerability. Therefore, couples should be aware of their own and their partners' sero-status before and after engagement. Again, the following risk reduction methods were recommended: education of discordant couples on 100% correct condom use, and if condom breaks, or if they forget to use, Post-Exposure Prophylaxis must be established; for those who are not volunteer to use condom and/or have a child, early initiation of ART to positive partner.

Background: Tuberculous lymphadenitis (TBLN) is the most common form of extrapulmonary tuberculosis. The cytomorphological features of lymph node smears have reduced specificity for the diagnosis of tuberculosis. The diagnosis of TBLN with direct smear microscopy lacks sensitivity due to the limited number of bacilli in lymph node aspirate. Therefore, we aimed to assess whether the concentration of lymph node aspirate improves the sensitivity of acid fast smear microscopy for the diagnosis of tuberculous lymphadenitis., Methods: A cross-sectional comparative study was conducted on 200 patients clinically suspected for tuberculous lymphadenitis in Jimma, Ethiopia. Lymph node aspirate was collected. The first two drops were used for cytomorphological study and direct acid fast staining. The remaining aspirate was treated with N-acetyl-L-cysteine (NALC) and concentrated by centrifugation at 3000 g for 15 minutes. The sediment was used for acid fast staining and culture. Differentiation of M. tuberculosis complex (MTBC) from non-tuberculous mycobacteria (NTM) was done by para-nitrobenzoic acid susceptibility test., Result: Complete data were available for 187 study subjects. 68% (127/187) were positive for M. tuberculosis on culture. Four isolates, 2.1% (4/187), were identified as NTM. The detection rate of direct smear microscopy was 25.1% and that of the concentration method 49.7%. Cytomorphologically, 79.7% of cases were classified as TBLN. The sensitivity of direct smear microscopy was 34.6%, for concentrated smear microscopy 66.1%, and for cytomorphology 89.8%. Two AFB positive cases on concentration method were non-tuberculosis mycobacteria (NTM). The concentration method yielded a positive result from seven cases diagnosed as suppurative abscess by cytology. Both for the direct and concentration methods the highest rate of AFB positivity was observed in smears showing caseous necrosis alone. Smear positivity rate decreased with the appearance of epithelioid cell aggregates., Conclusion: The concentration of lymph node aspirates for acid fast smear microscopy had significantly higher sensitivity than direct microscopy.

Background: Accurate early diagnosis and prompt treatment is one of the key strategies to control and prevent malaria in Ethiopia where both Plasmodium falciparum and Plasmodium vivax are sympatric and require different treatment regimens. Microscopy is the standard for malaria diagnosis at the health centres and hospitals whereas rapid diagnostic tests are used at community-level health posts. The current study was designed to assess malaria microscopy capacity of health facilities in Oromia Regional State and Dire Dawa Administrative City, Ethiopia., Methods: A descriptive cross-sectional study was conducted from February to April 2011 in 122 health facilities, where health professionals were interviewed using a pre-tested, standardized assessment tool and facilities' laboratory practices were assessed by direct observation., Results: Of the 122 assessed facilities, 104 (85%) were health centres and 18 (15%) were hospitals. Out of 94 health facilities reportedly performing blood films, only 34 (36%) used both thin and thick smears for malaria diagnosis. The quality of stained slides was graded in 66 health facilities as excellent, good and poor quality in 11(17%), 31 (47%) and 24 (36%) respectively. Quality assurance guidelines and malaria microscopy standard operating procedures were found in only 13 (11%) facilities and 12 (10%) had involved in external quality assessment activities, and 32 (26%) had supportive supervision within six months of the survey. Only seven (6%) facilities reported at least one staff's participation in malaria microscopy refresher training during the previous 12 months. Although most facilities, 96 (79%), had binocular microscopes, only eight (7%) had the necessary reagents and supplies to perform malaria microscopy. Treatment guidelines for malaria were available in only 38 (31%) of the surveyed facilities. Febrile patients with negative malaria laboratory test results were managed with artemether-lumefantrine or chloroquine in 51% (53/104) of assessed health facilities., Conclusions: The current study indicated that most of the health facilities had basic infrastructure and equipment to perform malaria laboratory diagnosis but with significant gaps in continuous laboratory supplies and reagents, and lack of training and supportive supervision. Overcoming these gaps will be critical to ensure that malaria laboratory diagnosis is of high-quality for better patient management.

Pulmonarins A and B are two new dibrominated marine acetylcholinesterase inhibitors that were isolated and characterized from the sub-Arctic ascidian Synoicum pulmonaria collected off the Norwegian coast. The structures of natural pulmonarins A and B were tentatively elucidated by spectroscopic methods and later verified by comparison with synthetically prepared material. Both pulmonarins A and B displayed reversible, noncompetitive acetylcholinesterase inhibition comparable to several known natural acetylcholinesterase inhibitiors. Pulmonarin B was the strongest inhibitor, with an inhibition constant (Ki) of 20 μM. In addition to reversible, noncompetitive acetylcholinesterase inhibition, the compounds displayed weak antibacterial activity but no cytotoxicity or other investigated bioactivities.

Background: Whereas street vended foods are readily available sources of meals for many people across the world, the microbial safety of such food is always uncertain. In developing countries the major sources of food-borne illnesses are street vended foods. The aim of this study was thus to assess the prevalence and antibiogram of bacteria from white lupin in Bahir Dar Town., Methods: A total of 40 samples were processed for detection of indicator bacteria and pathogens from December, 2011 to February, 2012 using standard bacteriological techniques. Antimicrobial susceptibility test was performed using the Kirby-Bauer disk diffusion method., Results: The total coliform counts were 954.2±385 and 756.2±447.3 at the surface and the core of white lupin, respectively. On the other hand, the fecal coliform counts were 880.9±396.6 and 662.1±461.9 at surface and the core, respectively. There was a statistically significant difference in total colifoms and fecal coliform counts between the surface and core of white lupin (p <0.05). Escherichia coli 29 (72.5%), Salmonella spp. 23 (57.5%) and Shigella spp. 8 (20%) were the pathogens isolated. Most bacterial isolates were resistant to tetracycline, cotriamoxazole and erythromycin whereas many of them were sensitive to chloramphenicol, nalidixic acid, gentamicin and ciprofloxacin. The overall multiple antimicrobial resistances rate was 75%., Conclusion: This study revealed contamination of white lupin and a potential health to consumers, and the bacteria isolated showed high rates of multiple drug resistance. Surveillance of antimicrobial resistance should be done on food borne pathogens. In addition, further studies should be conducted on the bacteriological quality of waters used for soaking white lupin.

The brominated tryptophan-derived ent-eusynstyelamide B (1) and three new derivatives, eusynstyelamides D, E, and F (2-4), were isolated from the Arctic bryozoan Tegella cf. spitzbergensis. The structures were elucidated by spectroscopic methods including 1D and 2D NMR and analysis of mass spectrometric data. The enantiomer of 1, eusynstyelamide B, has previously been isolated from the Australian ascidian Eusynstyela latericius. Antimicrobial activities are here reported for 1-4, with minimum inhibitory concentrations (MIC) as low as 6.25 μg/mL for 1 and 4 against Staphylococcus aureus. Eusynstyelamides 2 and 3 showed weak cytotoxic activity against the human melanoma A 2058 cell line.

Bioassay-guided fractionation of the sub-Arctic ascidian Synoicum pulmonaria collected off the Norwegian coast led to the isolation of a novel family of brominated guanidinium oxazolidinones named synoxazolidinones A and B (1 and 2). The backbone of the compounds contains a 4-oxazolidinone ring rarely seen in natural products. The structure of the compounds was determined by spectroscopic methods. The synoxazolidinones exhibited antibacterial and antifungal activities.

Accidental needlestick injuries sustained by health-care workers are a common occupational hazard and a public health issue in health-care settings. An analytical cross-sectional study was conducted and 30.9% of health-care workers had experienced at least one needlestick injury in the previous year.

Objective: Resistin causes insulin resistance and diabetes in mice whereas in humans it is linked to inflammation and atherosclerosis. Few human genetic studies of resistin in inflammation and atherosclerosis have been performed. We hypothesized that the -420C>G putative gain-of-function resistin variant would be associated with inflammatory markers and atherosclerosis but not with metabolic syndrome or adipokines in humans., Design and Methods: We examined the association of three resistin polymorphisms, -852A>G, -420C>G and +157C>T, and related haplotypes with plasma resistin, cytokines, C-reactive protein (CRP), adipokines, plasma lipoproteins, metabolic syndrome and coronary artery calcification (CAC) in nondiabetic Caucasians (n = 851)., Results: Resistin levels were higher, dose-dependently, with the -420G allele (CC 5.9 +/- 2.7 ng/ml, GC 6.5 +/- 4.0 ng/ml and GG 7.2 +/- 4.8 ng/ml, trend P = 0.04) after age and gender adjustment [fold higher for GC + GG vs. CC; 1.07 (1.00-1.15), P < 0.05)]. The -852A>G single nucleotide polymorphism (SNP) was associated with higher soluble tumour necrosis factor-receptor 2 (sol-TNFR2) levels in fully adjusted models [1.06 (95% CI 1.01-1.11), P = 0.01)]. The estimated resistin haplotype (GGT) was associated with sol-TNFR2 (P = 0.04) and the AGT haplotype was related to CRP (P = 0.04) in the fully adjusted models. Resistin SNPs and haplotypes were not associated with body mass index (BMI), fasting glucose, insulin resistance, metabolic syndrome, adipokines or CAC scores., Conclusions: Despite modest associations with plasma resistin and inflammatory biomarkers, resistin 5' variants were not associated with metabolic parameters or coronary calcification. This suggests that resistin is an inflammatory cytokine in humans but has little influence on adiposity, metabolic syndrome or atherosclerosis.

Background: Niacin has multiple lipoprotein effects that may provide cardiovascular benefit when added to statin monotherapy., Methods: In this randomized, placebo-controlled trial (n = 75) of magnetic resonance imaging of carotid atherosclerosis, we performed a secondary comparison of combination niacin-statin (simvastatin 20 mg/Niacin-ER 2G [S20/N]) to monotherapy with moderate (20 mg [S20]) and high-dose (80 mg [S80]) simvastatin on lipids, apolipoproteins (apo), low density lipoprotein (LDL) and high density lipoprotein (HDL) particle subclasses, and inflammatory markers., Results: At baseline, average age was 71, 72% were male, 62.5% used statins, and average LDL-cholesterol was 111 mg/dL. At 12 months, S20/N, compared to S80, significantly reduced apoB (-36.6% vs -11.9%; P = .05) and lipoprotein(a) (-18% vs +3.5%; P = .001) and had at least an equivalent effect on LDL-cholesterol (-39.3% vs -24.3%; P = .24). The combination reduced the proportion of subjects with atherogenic LDL pattern-B (50% to 11.5%) compared to S80 (56% to 56%) (P = .01). Despite increases in plasma free fatty acids (+62.4%; F = 5.65, P = .005 vs S20 and S80), plasma triglycerides (-29.4%; F = 6.88, P = .002 vs S20 and S80), and very-low-density lipoprotein (-44.2%; F = 7.94, P < .001 vs S20 and S80), levels were reduced by S20/N. S20/N increased HDL-cholesterol levels (+18.1%) as compared to S20 (0%) and S80 (+5.9%) (P < .001 vs both statin arms), largely due to an increase in HDL particle size (+4.6%; P = .01 vs both statin arms)., Conclusions: We demonstrate that full-dose niacin/moderate-dose simvastatin combination has sustained benefits on atherogenic apoB lipoproteins, at least comparable to high-dose simvastatin, while also raising HDL-cholesterol. Results of large clinical trials will inform whether niacin-statin combinations reduce cardiovascular disease events.

We examined the changes in forest status and people's livelihoods through building future scenarios for Chilimo Forest in Central Ethiopia where participatory forest management (PFM) is being implemented. Participatory methods were employed to collect data, and a dynamic modeling technique was applied to explore trends over time. By integrating the more quantitative model outputs with qualitative insights, information on forests and livelihoods was summarized and returned to users, both to inform them and get feedback. A scenario of open access without PFM provides higher income benefits in the short term but not over the longer term, as compared to a scenario with PFM. Follow up meetings were organized with national decision makers to explore the possibility of new provisions in the national forest proclamation related to joint community-state ownership of forests. Project implementers must constantly work towards improving short term incentives from PFM, as these may be insufficient to garner support for PFM. Other necessary elements for PFM to succeed include: ensuring active participation of the communities in the process; and, clarifying and harmonizing the rules and regulations at different levels.

Benthic marine invertebrates collected from sub-Arctic regions of northern Norway, were found to be a promising source of novel bioactive compounds against human and fish pathogenic bacteria and fungi. Lyophilized material from seven species of ascidians, six sponges and one soft alcyonid coral were extracted with 60% acidified acetonitrile (ACN). After separation into an ACN-rich phase (ACN-extract) and an aqueous phase, and subsequent solid-phase extraction of the aqueous phase, fractions differing in polarity were obtained and screened for antibacterial and antifungal activities, along with the more lipophilic ACN-extracts. Antimicrobial activity was determined against two gram-negative, two gram-positive bacteria, and two strains of fungi. Notably, all the invertebrate species in the study showed activity against all four strains of bacteria and the two strains of fungi. In general, the aqueous fractions displayed highest antimicrobial activity, and the most potent extracts were obtained from the colonial ascidian Synoicum pulmonaria which displayed activity against bacteria and fungi at a concentration of 0.02 mg/ml; the lowest concentration tested.

The objective of this observational cohort study at Georgetown University Hospital from January 1, 1994 through December 31, 1997 was to investigate race, Candida sepsis, and duration of oxygen exposure in infants with retinopathy of prematurity (ROP) with birth weight < or = 1,000 g. The incidence of ROP was 70.8% (114/161). The incidence of stage III or greater ROP in the Caucasian infants was significantly higher at 46.7% (14/30) than in the African-American infants at 23.8% (20/84) with p < 0.02. In addition, the incidence of threshold disease was higher in Caucasian infants 33.3% (10/30) when compared to African-American infants 9.5% (8/84) with p < 0.002. Using multiple logistic regression, African-American race was found to be an independent protective factor against developing severe ROP [adjusted odds ratio 0.39; 95% confidence interval (UCI) 0.16-0.97]. Extremely-low-birth-weight African-American infants with comparable severity of illness (including birth weight, gestational age, duration of supplemental oxygen exposure, and Candida sepsis) are less likely to develop severe ROP than Caucasian infants., (Copyright 2002 S. Karger AG, Basel)

Background: The reported effect of gender on retinopathy of prematurity has been controversial. The goal of this study was to determine the effect of gender on oxygen-induced retinopathy in a mouse model., Methods: Oxygen-induced retinopathy was produced in C57BL6 mice by exposure to 75% oxygen from postnatal day (P) 7 for 5 days. Animals were returned to room air on P12 and killed on P17-21. Gender was determined by inspection. Retinopathy was evaluated by a retinopathy scoring system and by quantifcation of extraretinal neovascular nuclei on retinal sections., Results: Both males and females developed similar degrees of retinopathy. Males had a median total retinopathy score of 9 (25th, 75th quartile: 8, 11) and females had score of 9 (25th, 75th quartile: 7, 10). Retinal subscores of blood vessel growth, blood vessel tufts, extraretinal neovascularzation, haemorrhage and blood vessel tortuosity were similar in both groups. Males and females had a similar number of neovascular nuclei on retinal sections., Conclusions: Gender does not alter the development of oxygen-induced retinopathy in the C57BL6 mouse.

Purpose: The purpose of this study was to determine the effect of an angiotensin converting enzyme inhibitor, captopril, on oxygen-induced retinopathy (OIR) in the mouse. Endothelin-1 (ET-1) expression is assessed in a mouse model of OIR., Methods: OIR was produced in C57BL6 mice. Captopril (0.5mg/kg/d SC) was given from P7 (post natal day 7) for 5 days. Retinopathy was assessed by a retinal scoring system and by quantification of extra retinal neovascular nuclei on retinal sections at P17 to P20. The expression of ET-1 was determined using a reverse transcriptase polymerase chain reaction., Results: Pups treated with captopril during hyperoxia had a lower median retinopathy score of 4.5 (25th, 75th quartile: 3, 6.4) compared with animals exposed to hyperoxia alone with median score 9.5 (25th, 75th quartile: 7.1, 10.4; P < 0.001). The pups treated with captopril during hyperoxia had significant reduction in number of nuclei extending beyond the inner limiting membrane (15.8 +/- 16.7, mean +/- SD) when compared with the animals exposed to hyperoxia only (50.4 +/- 28.0; P < 0.01). ET-1 expression in the retina increased 4.1-fold from P7 to P12 and a 1.9-fold increase from P12 to P17. Overall, there was an 8-fold increase in ET-1 expression from P7 to P17. Hyperoxia increased ET-1 expression by 2.1-fold at P12 over room air-reared animals. At P17, there was a 2.9-fold increase in retinal ET-1 expression when compared with room air. At P17, there was a 6.2-fold suppression in ET-1 expression in captopril-treated animals when compared with the oxygen only-treated animals., Conclusions: Captopril reduces retinal neovascularization in a mouse model of oxygen-induced retinopathy. ET-1 expression is increased from P7 to P17, altered by hyperoxic exposure and relative hypoxic recovery and modulated by captopril in a mouse model of OIR.

TNF-alpha has been found in the retina. Hyperoxia and hypoxia regulate TNF-alpha expression. TNF-alpha is an important factor in inflammation and angiogenesis. Dexamethasone inhibits TNF-alpha production. Changes in TNF-alpha expression in the retina may play an important role in the development of oxygen-induced retinopathy. Oxygen-induced retinopathy was produced in C57BL6 mice by exposure to 75% oxygen at Postnatal Day 7 (P7) for 5 days and the mice recovered in room air until Day 17 (P17). Dexamethasone was administered at 0.5 mg/kg/day once daily subcutaneously during the 5 days of oxygen exposure. TNF-alpha expression was evaluated at Day 7 prior to oxygen exposure, at Day 12 (P12) immediately upon removal from oxygen, and at Day 17, the time of maximal vasoproliferation by RT-PCR. TNF-alpha is developmentally regulated in the retinae of C57BL6 mice. From P7 to P12, there is a 3-fold increase in TNF-alpha expression and from P7 to P17 there is a 2.7-fold increase. There was 2.7-fold suppression in expression immediately following oxygen exposure at P12. The expression was dramatically increased at P17, the time of maximal vasoproliferation. Dexamethasone inhibited the expression of TNF-alpha at P17 by 6.4-fold. At this dose, it also suppressed the baseline TNF-alpha expression in the mouse model. In summary, TNF-alpha is altered in the development of oxygen-induced retinopathy in the mouse. It increased markedly during the vasoproliferative phase and was suppressed by dexamethasone. Modulation of TNF-alpha expression may provide a potential site of action for future therapeutic targets., (Copyright 2001 Academic Press.)

Purpose: Administration of corticosteroids soon after birth has been reported to have deleterious, protective, and no effect on retinopathy of prematurity. Conflicting results may be due to timing of corticosteroid administration. The goal of this study was to determine effects of pretreatment and late dexamethasone on retinopathy in a mouse model., Methods: The C57BL6 mouse model of oxygen-induced retinopathy (by placing animals in 75% oxygen from postnatal days 7 through 12) was used to create retinal neovascularization. Dexamethasone at 0.5 mg/kg per day was administered from day 1 through day 5 in the pretreatment group. The late-treatment group received 5 days of dexamethasone at the same dose beginning on day 12. Mice were killed at days 17 through 20, and retinal vasculature was assessed by a retinal scoring system of wholemount preparation after high-molecular-weight fluorescein-labeled dextran perfusion. In addition, retinal neovascularization was assessed by quantification of extraretinal neovascular nuclei in retinal sections. Statistical significance was defined as P: < 0.05 and was determined by the Kruskal-Wallis test, Mann-Whitney test, and Student's t-test., Results: Oxygen-exposed animals that received treatment with dexamethasone before oxygen exposure had an improvement in retinopathy, with a median score of 6 (5,7; 25th,75th quartiles) compared with 10 (8,11) in the untreated oxygen-exposed (P: < 0.05). The group treated late (after oxygen exposure) with dexamethasone had a median score of 10 (9,11). Pretreatment reduced extraretinal vascularization, when assessed by quantification of neovascular nuclei, to a mean +/- SEM of 19 +/- 9, significantly less than in the untreated oxygen-exposed group (55 +/- 12; P: < 0.05). No difference was observed in the late-treatment group when compared with the untreated oxygen-exposed group. Significant growth retardation, indicated by body weight, was observed in the pretreatment (P: < 0.01) and late-treatment (P: < 0. 05) groups when compared with the control group., Conclusions: Timing of dexamethasone administration was critical to the inhibition of development of retinopathy in the mouse model. Degree of growth retardation, measured by body weight, also appeared to be time dependent. These data may explain the different results of clinical observations with respect to corticosteroid treatment, timing, and development of retinopathy.