Influence of water hardness on zinc toxicity in Daphnia magna.

Zinc is an essential trace metal required for the maintenance of multiple physiological functions. Due to this, organisms can experience both zinc deficiency and toxicity. Hardness is recognized as one of the main modifying physiochemical factors regulating zinc bioavailability. Therefore, the present study analyzed the effect of hardness on zinc toxicity using Daphnia magna. Endpoint parameters were acute-toxicity, development, reproduction, and expression data for genes involved in metal regulation and oxidative stress. In addition, the temporal expression profiles of genes during the initiation of reproduction and molting were investigated. Water hardness influenced the survival in response to exposures to zinc. A zinc concentration of 50 µg/l in soft water (50 mg CaCO3 /L) caused 73% mortality after 96 h exposure, whereas the same zinc concentration in the hardest water did not cause any significant mortality. Moreover, increasing water hardness from 100 to 200 mg CaCO3 /L resulted in a reduced number of offspring. Fecundity was higher at first brood for groups exposed to higher Zn concentrations. The survival data were used to assess the precision of the bioavailability models (Bio-met) and the geochemical model (Visual MINTEQ). As the Bio-met risk predictions overestimated the Zn toxicity, a competition-based model to describe the effects of hardness on zinc toxicity is proposed. This approach can be used to minimize differences in setting environmental quality standards. Moreover, gene expression data showed that using the toxicogenomic approach was more sensitive than the physiological endpoints. Therefore, data presented in the study can be used to improve risk assessment for zinc toxicity.

Phenotypic Detection of Carbapenem-Resistant Gram-Negative Bacilli from a Clinical Specimen in Sidama, Ethiopia: A Cross-Sectional Study.

BACKGROUND: Carbapenem-resistant gram-negative bacteria are an emergent source of both community-acquired and healthcare-associated infection that poses a substantial hazard to public health. This study aimed to conclude the magnitude of carbapenem resistance gram-negative bacteria from a clinical specimen at Hawassa University Comprehensive Specialized Hospital. METHODS: A hospital-based cross-sectional study was accompanied from February 13 to June 7, 2020, in which consecutive patients with 103 gram-negative bacteria were encompassed. The isolates included were 54 urine, 17 blood, 17 pusses, 4 cerebrospinal fluid (CSF), 3 aspirates, 3 effusions, 2 stools, 2 ear discharges, and 1 nasal swab. A semi-structured questionnaire was used to gather socio-demographic data from the attendant and clinical data from the patient's chart. Patients admitted in any wards and visited outpatients department were included for the study if gram-negative bacteria was identified for those who accepted the consent. A routine manual culture, Gram's staining and biochemical tests used to identify the bacteria. Antibiotic susceptibility was determined for twelve antibiotics including cotrimoxazole, ceftazidime, meropenem, gentamycin, chloramphenicol, ampicillin, ciprofloxacin, cefotaxime, cefuroxime, nitrofurantoin, piperacillin-tazobactam, and amikacin using the Kirby-Bauer disc diffusion method. Modified carbapenem inactivation (mCIM) method was used to determine carbapenem resistance using meropenem disk as per the recommendation of Clinical and Laboratory Standards Institute guideline. Statistical package for social science software version 21 was used for data entry and analysis. The odds ratio at 95% confidence interval (CI) and p-value <0.05 were taken as a statistically significant association. RESULTS: Generally, 111 gram-negative bacteria were identified from 103 patients. Of 111 isolates, thirteen isolates (nine resistance and four intermediates) were identified in disk diffusion testing for meropenem. Of this, 10 isolates were carbapenemases producer with the overall rates of 9% in the Modified carbapenem inactivation method (mCIM). Pseudomonas spp. 3 (30.0%), E. coli, K. pneumonia, Acinetobacter spp. each two (20.0%), and K. oxytoca 1 (10.0%) were identified as carbapenemases positive. The rates of the multidrug, extensive, pan drug were 86.5, 43.3, and 1.8, respectively. Ampicillin 94 (97.9%), followed by cefuroxime 52 (91.2%), cefotaxime 94 (88.7%), cotrimoxazole 58 (88.1%), ceftazidime 40 (83.3%), ciprofloxacin 47 (77.1%), nitrofurantoin 35 (70.0%), gentamycin 71 (65.7%), with high level of resistance. However, piperacillin-tazobactam 41 (48.8%), chloramphenicol 25 (47.2%), meropenem 13 (11.7%), and amikacin 9 (8.5%) were with low rates of resistance. In this study, there were no variables statically associated with carbapenem resistance that is p > 0.05. CONCLUSION: Our study showed that carbapenem-resistant gram-negative bacilli are 9% in the study area. Our finding signposts that ampicillin, cefuroxime, cefotaxime, cotrimoxazole, ceftazidime, ciprofloxacin, nitrofurantoin, and gentamycin with a high rate of resistance >50%. However, piperacillin-tazobactam, chloramphenicol, meropenem, and amikacin were at low rates of resistance. Therefore, a measure should be taken to contain carbapenem resistance gram-negative bacteria in the study area. Further, study with better method needs to be conducted to conclude the real scenario of carbapenem resistance.

Sero-prevalence of rubella among pregnant women in Sub-Saharan Africa: a meta-analysis.

Background: Rubella continues to be a leading cause of vaccine-preventable congenital birth defects and permanent organ damage, especially in developing countries. For women who are infected with the rubella virus (RV) before conception or during the first trimester of pregnancy, the unborn child has up to a 90% probability of developing congenital rubella syndrome. There are limited data on the seroprevalence of the rubella virus among pregnant women in Sub-Saharan Africa. Therefore, the aim of this study was done to determine the pooled seroprevalence of rubella among pregnant women in Sub-Saharan Africa. Methods: The PRISMA guidelines protocol was followed to write the systematic review and meta-analysis. Published studies were searched in Medline, PubMed, Google scholar, advance google and Cochrane Library. The search terms on the databases are: "rubella"OR "rubeo*", "rubella"AND"seroepidemiology", "seroprevalen *" OR "prevalen*", "seroprevalen *" OR "seroimmun*", "rubella antibod*"AND "pregnan*", "seroprevalen *" AND "sub-Saharan Africa".The heterogeneity of studies was weighed using Cochran's Q test and I2 test statistics. Publication bias was assessed by using Egger's and Begg's test. Results: Twenty-eight studies were included in this meta-analysis. The pooled seroprevalence of anti-RV IgG among pregnant women in Sub-Saharan African was 89.0% (95%CI: 84.6-92.3), and the pooled prevalence of anti-RV IgM among pregnant women in Sub-Saharan Africa was 5.1% (95%CI: 2.6-9.9). Conclusion: This meta-analysis showed that seronegativity and acute infection with RV among pregnant women in sub-Saharan Africa is high compared to other studies and the WHO threshold among women of child-bearing age. This finding calls for primary health care providers to make the community aware of this rubella-susceptible group and its healthcare burden, with the desired outcome that sub-Saharan Africa countries would introduce an implementation strategy for rubella vaccination of pregnant women and women of child-bearing age.

Pneumococcal nasopharyngeal carriage and antimicrobial susceptibility profile in children under five in southern Ethiopia.

Background: Streptococcus pneumonia causes high morbidity and mortality, particularly in children under five. Nasopharyngeal (NP) carriage predisposes individuals to pneumococcal infection and horizontal spread within the community. Overuse of antibiotics has been linked to increased risk of antimicrobial resistance to S. pneumonia. We investigated NP carriage rate and resistance to commonly prescribed antibiotics in under-five children visiting a public referral center in southern Ethiopia. Methods: In total, 413 under 5 children who visited the outpatient department for a health check-up, immunization or acute mild illnesses underwent NP sampling. Parent/caregiver surveys were administered at the clinic. Sterile plastic applicator rayon tipped swabs were used for NP sampling. Antimicrobial susceptibility testing was performed using modified the disk diffusion method. Results: S. pneumonia NP carriage was observed in 39% [95% confidence interval (CI): 34.4-43.8]. Living with one or more sibling (AOR (adjusted odds ratio) 1.95: 95% CI: 1.01, 3.76), age group of 3-23 months (AOR 2.31: 95% CI: 1.07, 4.98), co-sleeping with family (AOR 2.09, 95% CI: 1.16, 3.79), attendance at kindergarten/day-care (AOR 1.84: 95% CI: 1.09, 3.11) and malnutrition independently increased S. pneumonia carriage at the individual level. S. pneumonia was highly resistant to Oxacillin (38.5%), Tetracycline (37.3%), and Trimethoprim-sulfamethoxazole (34.2%). Multi-drug resistance was observed in 42.2% of isolates. Conclusions: A high streptococcal NP carriage rate was observed in under-five children. The high level of resistance to commonly used antibiotics calls for enhancing national surveillance of resistance patterns and enforce antibiotic stewardship efforts.

Prevalence of intestinal parasitic infections in Hawassa University students' clinic, Southern Ethiopia: a 10-year retrospective study.

OBJECTIVE: The purpose of this study was to determine the prevalence of intestinal parasitic infections among patients who had attended Hawassa University students' clinic, Southern Ethiopia. RESULT: Over the 10 years period, a total of 13,679 patients visiting Hawassa University students' clinic were included in the study. A total of 6553 (47.9%) patients were positive for at least one intestinal parasite. The overall prevalence of intestinal helminth and protozoan infections was 20.3% and 27.6% respectively. There were four dual infections and one triple infection. E. histolytica/E. dispar trophozoite was the most common identified parasite, which was seen in 18% of the patients while Enterobius vermicularis (0.1%) was the least reported parasite. Other parasites identified were Ascaris lumbricoides (15.0%), Hookworm species (2.0%), Taenia species (1.8%), Hymenolepis nana (0.7%), Strongyloides stercoralis (0.3%), Trichuris trichuria (0.2%), and Shistosoma mansoni (0.2%). The prevalence of helminthes was higher in females (23.3%) than in males (19.5%) (P < 0.00001) while that of protozoan infections was 28.5% in males than females (23.8%) (574/2414) (P < 0.00001).

Species differences in ligand interaction and activation of estrogen receptors in fish and human.

Estrogen receptor (ER) sequences vary between species and this suggests that there are differences in the ligand-specificity, leading to species-specific effects. This would indicate that it is not possible to generalize effects across species. In this study, we investigated the differences in activation potencies and binding affinities of ER´s alpha (α) and beta (ß) in human, zebrafish and sea bream to elucidate species differences in response to estradiol, estrone, estriol and methyltestosterone. In vitro analysis showed that estradiol had the highest activity for all the ER´s except for human ERß and seabream ERß2. Alignment of the ligand binding domain and ligand binding pocket (LBP) residues of the three species showed that different residues were involved in the LBPs which led to differences in pocket volume, affected binding affinity and orientation of the ligands. By combining in silico and in vitro results, it was possible to identify the ligand specificities of ER´s. The results demonstrated that the human ER´s show lower resolution in ligand-dependent activation, suggesting higher promiscuity, than the zebrafish and seabream ER´s. These results show species-specificity of ER´s and suggest that species-specific differences must be taken into consideration when studying different exposure scenarios.

Depression, Anxiety and Their Correlates Among Patients With HIV in South Ethiopia: An Institution-Based Cross-Sectional Study.

Background: Depressive and anxious symptoms are more regularly seen in HIV-infected people than in the general population. This investigation planned to evaluate the magnitude and factors related to depressive and anxiety symptoms among HIV patients in South Ethiopia, 2018. Methods: This was an institution-based cross-sectional study directed among 363 HIV-infected individuals who had a customary visit at Hawassa University Comprehensive Specialized Hospital and Yirgalem Hospital, Ethiopia, who were incorporated into the study through systematic sampling techniques. The hospital anxiety and depression scale (HADS) was utilized to take a look at anxious and depressive symptoms. Results: The mean age of the respondents was 37.66 years (SD ±10.03). The prevalence of depression and anxiety were 32.0% and 34.4%, respectively. Patients who were living alone [AOR = 1.94, (95% CI: 1.06, 3.56)], had poor social support [AOR = 5.57, (95% CI: 1.20, 10.84)] or had HIV-related perceived stigma [AOR = 2.35, (95% CI: 1.44, 3.84)] were more likely to have depression as compared to their counterparts. Those with a previous history of mental illness [AOR = 3.36, (95% CI: 1.31, 8.61)] and poor social support [AOR = 6.67, (95% CI: 1.47, 10.33)] were more likely to have anxiety symptoms. Conclusion: The prevalence of anxiety and depression in the current study was high. Concerned health departments of the country should create guidelines to screen and treat depression and anxiety among HIV patients. Further research on hazard factors of depression and anxiety ought to be examined to strengthen and expand these findings.

Scabies outbreak investigation and risk factors in Kechabira district, Southern Ethiopia: unmatched case control study.

OBJECTIVE: Scabies is an infection of the skin, which caused by human itch mite Sarcoptes scabiei. It is a common health problem in Ethiopia, especially during disasters, poor sanitation and overcrowded living condition. However, investigation on scabies outbreak and associated factors was absent or scarce in the country in general and in the study area in particular. Hence, this study was intended to investigate scabies outbreak, identify risk factors, and recommend preventive measures in Kechabira district, Kembata Tembaro zone, Southern Ethiopia. RESULT: We identified a total of 243 scabies cases line listed with overall prevalence of 2.5% and attack rate of (AR) 20.5 per 1000 populations and no death was reported. Of the suspected cases 126 (51.9%) were males and 117 (48.1%) were females. The median age was 24 years with inter-quartile range (IQR) of 22 years. The highest cases were seen in children aged 5-14 (50.6%) years. The cases were seen in three villages and the highest incidence was in Burchana, 23.9 per 1000 population. Identified determinant factors for scabies outbreak were sharing clothes with scabies patients (AOR = 6.08, 95% CI [1.54-23.92], and households having greater than six family members AOR = 38.755, 95% CI [8.084-185.787].

Prevalence and risk factors of tungiasis among children of Wensho district, southern Ethiopia.

BACKGROUND: Tungiasis is an ectoparasitic infestation, which still has public health importance in deprived populations of developing countries. Data on the prevalence and risk factors of tungiasis is rare in Ethiopia. Hence, this study was designed to determine the prevalence and risk factors of tungiasis among children in Wensho district, southern Ethiopia. METHODS: From February to May 2016, we conducted a community-based cross-sectional study on 366 children 5-14 years old. Data about the presence and severity of tungiasis were obtained through inspection and data on risk factors were collected through interviews of parents/guardians of the children using structured questionnaire and through observation of the housing environment using structured checklist. RESULTS: Two hundred fifteen (58.7%, 95% confidence interval [CI]: 53.7%, 63.8%) of the 366 children were infested with Tunga penetrans. Most lesions were localized in the feet and the distribution of the disease by sex was similar (57.4% among males and 60.3% among females). Children of illiterate mothers (adjusted odds ratio [AOR]: 3.62, 95% CI: 1.35, 9.73) and children whose mothers have attended only primary education (AOR: 2.72, 95% CI: 1.06, 6.97), children from cat owning households (AOR: 4.95, 95% CI: 1.19, 20.60) and children who occasionally use footwear (AOR: 7.42, 95% CI: 4.29, 12.83) and those who never use footwear (AOR: 12.55, 95% CI: 3.38, 46.58) had a significantly higher odds of tungiasis infestation. CONCLUSION: Tungiasis is an important public health problem with considerable morbidity among children in Wensho. Hence, implementation of tungiasis prevention strategies such as promoting shoes wearing, provision of health education, fumigating the residential houses and applying insecticides on pets are recommended.

Trend of Malaria Cases in Hana and Keyafer Health Centers, South Omo Zone, Southern Ethiopia.

BACKGROUND: Data registered in health facilities about malaria are vital source of information regarding the trend and pattern of the disease. Moreover the data also used to evaluate the impact of the intervention methods and to plan malaria control accordingly. The aim of this study was to assess the number of malaria cases in the service providing health institutions of South Omo Zone, SNNPR, over a period of seven years, 2008-2014. METHODS: A retrospective review of routinely collected and recorded data on malaria was conducted at Hana and Keyafer health centers located in South OmoZone, during December-March/2014. RESULT: This retrospective study examined records of 54,160 presumptive and confirmed malaria cases registered over seven years (January 2008-December 2014). Among the registered, a total of 22,494 laboratory confirmed malaria cases were reported. The mean annual prevalence of malaria was 3213, with total slide positivity rate (SPR) of 41.53%. The seven years' overall trend of malaria occurrence in the study sites showed a fluctuating trend from 2008 to 20114. P. falciparum was the predominant species with no trend shift in seven years period. Plasmodium falciparum accounted for 61.03% and Plasmodium vivax for 32.44%. Most of the confirmed cases were males (63.26%) and most were above 15 years old (70.7%). Rainfall at lag of one month was significantly predicting number of cases at Hana Health center (P< 0.001), though it was found to be not significant in case of Keyafer Health Center. CONCLUSION: The finding of the retrospective study revealed that malaria still remains as a public health problem in the study areas. The deadly species P. falciparium was most predominant, and the age group above 15 was more infected. Hence, malaria intervention methods should be scaled up in the study sites.

Discovery of novel 5-methyl-1H-pyrazole derivatives as potential antiprostate cancer agents: Design, synthesis, molecular modeling, and biological evaluation.

Androgen receptor (AR) signaling functions as a core driving force for the progression of prostate cancer (PCa), and AR has been proved to be an effective therapeutic target even for castration-resistant prostate cancer (CRPC). Herein, structural modification via a fragments splicing strategy was performed based on two lead compounds T3 and 10e, leading to the discovery of a series of 5-methyl-1H-pyrazole derivatives. AR reporter gene assay revealed compounds A13 and A14 as potent AR antagonists. Some of the compounds in this series inhibited growth of PCa LNCaP cells more efficiently than enzalutamide. A13 and A14 also showed improved metabolic stability compared with 10e in human liver microsomes.

TBECH, 1,2-dibromo-4-(1,2 dibromoethyl) cyclohexane, alters androgen receptor regulation in response to mutations associated with prostate cancer.

Point mutations in the AR ligand-binding domain (LBD) can result in altered AR structures leading to changes of ligand specificity and functions. AR mutations associated to prostate cancer (PCa) have been shown to result in receptor activation by non-androgenic substances and anti-androgenic drugs. Two AR mutations known to alter the function of anti-androgens are the ART877A mutation, which is frequently detected mutation in PCa tumors and the ARW741C that is rare and has been derived in vitro following exposure of cells to the anti-androgen bicalutamide. AR activation by non-androgenic environmental substances has been suggested to affect PCa progression. In the present study we investigated the effect of AR mutations (ARW741C and ART877A) on the transcriptional activation following exposure of cells to an androgenic brominated flame retardant, 1,2-dibromo-4-(1,2 dibromoethyl) cyclohexane (TBECH, also named DBE-DBCH). The AR mutations resulted in higher interaction energies and increased transcriptional activation in response to TBECH diastereomer exposures. The ART877A mutation rendered AR highly responsive to low levels of DHT and TBECH and led to increased AR nuclear translocation. Gene expression analysis showed a stronger induction of AR target genes in LNCaP cells (ART877A) compared to T-47D cells (ARWT) following TBECH exposure. Furthermore, AR knockdown experiments confirmed the AR dependency of these responses. The higher sensitivity of ART877A and ARW741C to low levels of TBECH suggests that cells with these AR mutations are more susceptible to androgenic endocrine disrupters.

Survey of Medicinal Plants Used to Treat Malaria by Sidama People of Boricha District, Sidama Zone, South Region of Ethiopia.

In Ethiopia, malaria control has been complicated due to resistance of the parasite to the current drugs. Thus, new drugs are required against drug-resistant Plasmodium strains. Historically, many of the present antimalarial drugs were discovered from plants. This study was, therefore, conducted to document antimalarial plants utilized by Sidama people of Boricha District, Sidama Zone, South Region of Ethiopia. An ethnobotanical survey was carried out from September 2011 to February 2012. Data were collected through semistructured interview and field and market observations. Relative frequency of citation (RFC) was calculated and preference ranking exercises were conducted to estimate the importance of the reported medicinal plants in Boricha District. A total of 42 antimalarial plants belonging to 27 families were recorded in the study area. Leaf was the dominant plant part (59.0%) used in the preparation of remedies and oral (97.4%) was the major route of administration. Ajuga integrifolia scored the highest RFC value (0.80). The results of this study revealed the existence of rich knowledge on the use of medicinal plants in the study area to treat malaria. Thus, an attempt should be made to conserve and evaluate the claimed antimalarial medicinal plants with priority given to those that scored the highest RFC values.

Evaluation of the antiplasmodial properties of selected plants in southern Ethiopia.

BACKGROUND: The majority of the Ethiopian population is at risk of malaria largely caused by Plasmodium falciparum. The resistance of the parasite to existing drugs is the main challenge in the control of the disease and thus new therapeutic drugs are required. In Ethiopia, people use different plant species to treat malaria. However, very few of them have so far been evaluated for their safety level and antimalarial activity. Thus, the aim of this study was to evaluate the safety and antimalarial activity of extracts of Ajuga integrifolia, Clerodendrum myricoides, Melia azedarach, Peponium vogelii and Premna schimperi, locally used by the Sidama people of Ethiopia to treat malaria. METHODS: The safety level of 80 % methanol extracts of the plants were evaluated using standard acute toxicity test procedure. The antiplasmodial activity of 80 % methanol extracts of the plants were assessed in vivo using Swiss albino mice against chloroquine sensitive rodent malaria parasite, Plasmodium berghei, using the standard 4-day suppressive test procedure at doses of 200,400 and 800 mg/kg/day. The 80 % methanol extract of Ajuga integrifolia that exhibited better antimalarial activity was fractionated using different solvents and screened for its phytochemical constituents and evaluated in vivo for its antimalarial activity at doses of 100, 200 and 400 mg/kg/day. RESULTS: All extracts given at the three different doses caused no lethal effect on mice in 24 h and within 10 days of observation. All extracts and fractions exhibited antimalarial activity in a dose dependant manner. The highest inhibition was exhibited by the crude extracts of A. integrifolia (35.17 %) at 800 mg/kg/day (P < 0.05). Among fractions of A. integrifolia, n-butanol fraction demonstrated the highest inhibition (29.80 %) at 400 mg/kg/day (P < 0.05). The extracts and fractions prolonged the survival time and prevented weight loss of the mice, but did not prevent PCV reduction. Phytochemical test on Ajuga integrifolia indicated the presence of alkaloids, flavonoids, saponins, terpenoids, anthraquinone, steroids, tannins, phenols and fatty acids. CONCLUSIONS: Findings show that the plants are non-toxic and demonstrate antimalarial activity in a dose dependant manner suporting claims of their traditional therapeutic value for malaria treatment. However, further in-depth investigation is required to assess the potential of the plants towards the development of new antimalarial agent.

The brominated flame retardants TBP-AE and TBP-DBPE antagonize the chicken androgen receptor and act as potential endocrine disrupters in chicken LMH cells.

Increased exposure of birds to endocrine disrupting compounds has resulted in developmental and reproductive dysfunctions. We have recently identified the flame retardants, allyl-2,4,6-tribromophenyl ether (TBP-AE), 2-3-dibromopropyl-2,4,6-tribromophenyl ether (TBP-DBPE) and the TBP-DBPE metabolite 2-bromoallyl-2,4,6-tribromophenyl ether (TBP-BAE) as antagonists to both the human androgen receptor (AR) and the zebrafish AR. In the present study, we aimed at determining whether these compounds also interact with the chicken AR. In silico modeling studies showed that TBP-AE, TBP-BAE and TBP-DBPE were able to dock into to the chicken AR ligand-binding pocket. In vitro transfection assays revealed that all three brominated compounds acted as chicken AR antagonists, inhibiting testosterone induced AR activation. In addition, qRT-PCR studies confirmed that they act as AR antagonists and demonstrated that they also alter gene expression patterns of apoptotic, anti-apoptotic, drug metabolizing and amino acid transporter genes. These studies, using chicken LMH cells, suggest that TBP-AE, TBP-BAE and TBP-DBPE are potential endocrine disrupters in chicken.

In silico and biological analysis of anti-androgen activity of the brominated flame retardants ATE, BATE and DPTE in zebrafish.

The brominated flame retardants (BFRs) 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (TBECH or DBE-DCBH) and allyl 2,4,6-tribromophenyl ether (ATE or TBP-AE) are alternative BFRs that have been introduced to replace banned BFRs. TBECH is a potential endocrine disrupter in human, chicken and zebrafish and in a recent study we showed that ATE, along with the structurally similar BFR 2,3-dibromopropyl 2,4,6-tribromophenyl ether (DPTE or TBP-DBPE) and its metabolite 2-bromoallyl 2,4,6-tribromophenyl ether (BATE or TBP-BAE) are potential endocrine and neuronal disrupters in human. In this study we analyzed ATE, BATE and DPTE for zebrafish androgen receptor (zAR) modulating properties. In silico analysis with two softwares, Molecular Operating Environment (MOE) and Internal Coordinate Mechanics (ICM), showed that ATE, BATE and DPTE bind to zAR. In vitro AR activation assay revealed that these three BFRs down-regulate 11-ketotestosterone (KT) mediated zAR activation. Exposure to 10 µM DPTE resulted in reduced hatching success and like TBECH, BATE and DPTE at 10 µM also had teratogenic properties with 20% and 50% back-bone curvature respectively. Gene transcription analysis in zebrafish embryos as well as in juveniles showed down-regulation of the androgen receptor and androgen response genes, which further support that these BFRs are androgen antagonists and potential endocrine disrupting compounds. Genes involved in steroidogenesis were also down-regulated by these BFRs. In view of this, the impact of these BFRs on humans and wildlife needs further analysis.

Identification of a group of brominated flame retardants as novel androgen receptor antagonists and potential neuronal and endocrine disrupters.

Brominated flame-retardants (BFRs) are used in industrial products to reduce the risk of fire. However, their continuous release into the environment is a concern as they are often persistent, bioaccumulating and toxic. Information on the impact these compounds have on human health and wildlife is limited and only a few of them have been identified to disrupt hormone receptor functions. In the present study we used in silico modeling to determine the interactions of selected BFRs with the human androgen receptor (AR). Three compounds were found to dock into the ligand-binding domain of the human AR and these were further tested using in vitro analysis. Allyl 2,4,6-tribromophenyl ether (ATE), 2-bromoallyl 2,4,6-tribromophenyl ether (BATE) and 2,3-dibromopropyl-2,4,6-tribromophenyl ether (DPTE) were observed to act as AR antagonists. These BFRs have recently been detected in the environment, in house dust and in aquatic animals. The compounds have been detected at high concentrations in both blubber and brain of seals and we therefore also assessed their impact on the expression of L-type amino acid transporter system (LAT) genes, that are needed for amino acid uptake across the blood-brain barrier, as disruption of LAT gene function has been implicated in several brain disorders. The three BFRs down-regulated the expression of AR target genes that encode for prostate specific antigen (PSA), 5α-reductases and ß-microseminoprotein. The potency of PSA inhibition was of the same magnitude as the common prostate cancer drugs, demonstrating that these compounds are strong AR antagonists. Western blot analysis of AR protein showed that ATE, BATE and DPTE decreased the 5α-dihydrotestosterone-induced AR protein levels, further confirming that these BFRs act as AR antagonists. The transcription of the LAT genes was altered by the three BFRs, indicating an effect on amino-acid uptake across cellular membranes and blood-brain barrier. This study demonstrated that ATE, BATE and DPTE are potent AR antagonists and the alterations in LAT gene transcription suggest that these compounds can affect neuronal functions and should be considered as potential neurotoxic and endocrine disrupting compounds.

1,2-Dibromo-4-(1,2 dibromoethyl) cyclohexane (TBECH)-mediated steroid hormone receptor activation and gene regulation in chicken LMH cells.

The incorporation of brominated flame retardants into industrial and household appliances has increased their occurrence in the environment, resulting in deleterious effects on wildlife. With the increasing restraints on available compounds, there has been a shift to using brominated flame retardants that has seen the production of alternative brominated flame retardants such as 1,2-dibromo-4-(1,2 dibromoethyl) cyclohexane (TBECH), which has been detected in the environment. In previous in silico and in vitro studies the authors have shown that TBECH can activate both the human androgen receptor (hAR) and the zebrafish AR (zAR) suggesting that it is a potential endocrine disruptor. The present study was aimed at determining the interaction of TBECH with the chicken AR (cAR). In the present study, TBECH bound to cAR, but in vitro activation assay studies using the chicken LMH cell line showed it had a potency of only 15% compared with testosterone. Sequence difference between ARs from different species may contribute to the different responses to TBECH. Further quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) analysis showed that TBECH interacted with and altered the expression of both thyroid receptors and estrogen receptors. In addition, the qRT-PCR analysis showed that TBECH altered the transcription pattern of genes involved in inflammatory, apoptotic, proliferative, DNA methylation, and drug-metabolizing pathways. This demonstrates that TBECH, apart from activating cAR, can also influence multiple biological pathways in the chicken.

Prevalence of parasitic infections in HIV-positive patients in southern Ethiopia: a cross-sectional study.

INTRODUCTION: Intestinal parasitic infections are a major public health burden in tropical countries. Although all HIV/AIDS patients are susceptible to parasitic infections, those having lower immune status are at greater risk. The aim of this study was to determine the prevalence of intestinal parasitic infections in patients living with HIV/AIDS. METHODOLOGY: This was a facility-based cross-sectional study. A total of 343 consecutively sampled HIV/AIDS patients from the HIV care clinic of Hawassa University Referral Hospital were included. Subjects were interviewed for demographic variables and diarrheal symptoms using structured questionnaires. Stool examinations and CD4 cells counts were also performed. RESULTS: The prevalence of intestinal parasitic infection was 47.8% among HIV/AIDS patients; single helminthic infection prevalence (22.7%) was higher than that the prevalence of protozoal infections (14.6%). About 54% of study participants had chronic diarrhea while 3.4% had acute diarrhea. The prevalence of intestinal parasites in patients with chronic diarrhea was significantly higher than in acute diarrhea (p <0.05). Non-opportunistic intestinal parasite infections such as Ascaris lumbricoides, Taenia spp., and hookworm were commonly found, regardless of immune status or diarrheal symptoms. Opportunistic and non-opportunistic intestinal parasitic infection were more frequent in patients with a CD4 count of <200/mm(3) (OR=9.5; 95% CI: 4.64-19.47) when compared with patients with CD4 counts of ≥500 cells/mm(3). CONCLUSIONS: Intestinal parasitic infections should be suspected in HIV/AIDS-infected patients with advanced disease presenting with chronic diarrhea. Patients with low CD4 counts should be examined critically for intestinal parasites, regardless of diarrheal status.