Regulation of the let-7a-3 Promoter by NF-κB

Changes in microRNA expression have been linked to a wide array of pathological states. However, little is known about the regulation of microRNA expression. The let-7 microRNA is a tumor suppressor that inhibits cellular proliferation and promotes differentiation, and is frequently lost in tumors. We investigated the transcriptional regulation of two let-7 family members, let-7a-3 and let-7b, which form a microRNA cluster and are located 864 bp apart on chromosome 22q13.31. Previous reports present conflicting data on the role of the NF-κB transcription factor in regulating let-7. We cloned three fragments upstream of the let-7a-3/let-7b miRNA genomic region into a plasmid containing a luciferase reporter gene. Ectopic expression of subunits of NF-κB (p50 or p65/RelA) significantly increased luciferase activity in HeLa, 293, 293T and 3T3 cells, indicating that the let-7a-3/let-7b promoter is highly responsive to NF-κB. Mutation of a putative NF-κB binding site at bp −833 reduced basal promoter activity and decreased promoter activity in the presence of p50 or p65 overexpression. Mutation of a second putative binding site, at bp −947 also decreased promoter activity basally and in response to p65 induction, indicating that both sites contribute to NF-κB responsiveness. While the levels of the endogenous primary let-7a and let-7b transcript were induced in response to NF-κB overexpression in 293T cells, the levels of fully processed, mature let-7a and let-7b miRNAs did not increase. Instead, levels of Lin-28B, a protein that blocks let-7 maturation, were induced by NF-κB. Increased Lin-28B levels could contribute to the lack of an increase in mature let-7a and let-7b. Our results suggest that the final biological outcome of NF-κB activation on let-7 expression may vary depending upon the cellular context. We discuss our results in the context of NF-κB activity in repressing self-renewal and promoting differentiation

Knowledge of cervical tuberculosis lymphadenitis and its treatment in pastoral communities of the Afar region, Ethiopia

<p>Abstract</p> <p>Background</p> <p>Infection with <it>Mycobacterium bovis </it>(Mb) predominantly causes cervical TB lymphadenitis (TBL). Raw milk is considered the main source of Mb infection and raw milk is a major food source for Afar pastoralists. The aim of this study was to assess Afar pastoralists' knowledge concerning cervical TBL and its treatment.</p> <p>Methods</p> <p>A community-based cross-sectional survey involving 818 interviewees was conducted in two districts of the Afar Region, Ethiopia. In addition, two focus group discussions (FGDs) were conducted in each of the study areas, one with men and the other with women.</p> <p>Results</p> <p>Of the 818 interviewees [357 (43.6%) females and 461 (56.4%) males], 742 (90.7%) reported that they had knowledge of cervical TBL, mentioning that swelling(s) on the neck resulting in a lesion and scar are common symptoms. However, only 11 (1.5%) individuals mentioned that bacteria or germs are the causative agents of TBL. Three interviewees and a male discussant mentioned drinking raw milk as the cause of TBL. A considerable proportion (34.2%) of the interviewees and almost all the discussants suggested herbal medicine as an effective treatment. Male study participants were 1.82 times more likely to have overall knowledge of TBL than female study participants (adjusted OR, 1.82; 95% CI, 1.32 to 2.51, p < 0.001).</p> <p>Conclusion</p> <p>The pastoral community members in the study areas had little biomedical knowledge of the cause, the source of infection and the transmission route of cervical TBL. Furthermore, most community members believed that herbal medicines are the most effective treatment for TBL. Therefore, TB control programs in the Afar Region require the incorporation of public health education introducing current biomedical knowledge of the disease. In addition, further studies are important to elucidate which medicinal plants are used by Afar pastoralists to treat TBL.</p

Malaria and helminth co-infections in outpatients of Alaba Kulito Health Center, southern Ethiopia: a cross sectional study

<p>Abstract</p> <p>Background</p> <p>Distribution of malaria and intestinal helminths is known to overlap in developing tropical countries of the world. Co-infections with helminth and malaria parasites cause a significant and additive problem against the host. The aim of this study was to asses the prevalence of malaria/helminth co-infection and the associated problems among febrile outpatients that attended Alaba Kulito Health Center, southern Ethiopia November and December 2007. A total of 1802 acute febrile patients were diagnosed for malaria. 458 Giemsa-stained thick and thin blood films were used for identification of <it>Plasmodium </it>species and Stool samples prepared using Kato-Katz technique were used to examine for intestinal helminths. Haemoglobin concentration was measured using a portable spectrophotometer (Hemocue HB 201). Anthropometry-based nutritional assessment of the study participants was done by measuring body weight to the nearest 0.1 kg and height to the nearest 0.1 cm.</p> <p>Findings</p> <p>458 of the total febrile patients were positive for malaria. Co infection with <it>Plasmodium </it>and helminth parasites is associated with significantly (p < 0.001) higher anaemia prevalence than single infection with <it>Plasmodium </it>parasites. And this difference was also significant for haemoglobin concentration (F = 10.18, p = 0.002), in which patients co infected with <it>Plasmodium </it>and helminth parasites showed lower mean haemoglobin concentration. More than one-third of the infected cases in both malaria infections and malaria/helminth co infections are undernourished. However the statistics for the difference is not significant.</p> <p>Conclusion</p> <p>Malaria and soil-transmitted helminthiasis obviously contribute to anaemia and low weight status and these conditions are more pronounced in individuals concurrently infected with malaria and soil-transmitted helminths. Hence, simultaneous combat against the two parasitic infections is very crucial to improve health of the affected communities.</p

Prevalence of soil transmitted nematodes on Nukufetau, a remote Pacific island in Tuvalu

BACKGROUND: The population of Nukufetau, a remote coral atoll island in Tuvalu in the Western Pacific, received annual mass drug administration (MDA) of diethylcarbamazine and albendazole under the Pacific Elimination of Lymphatic Filariasis program in 2001, 2002 and 2003, with the last MDA occurring six months before a cross-sectional survey of the whole population for soil transmitted helminths (STH). METHODS: A cross-sectional survey in May 2004 recruited 206 residents (35.2% of the population) who provided a single faecal sample that was preserved, concentrated and examined microscopically. RESULTS: Overall prevalence of STH was 69.9%; only hookworm and Trichuris trichiura were diagnosed. Trichuris was present in 68.4% with intensity of infection being light in 56.3%, medium in 11.7% and heavy in 0.5%. Hookworm occurred in 11.7% with intensity of infection 11.2% being light and medium in 0.5%. Twenty individuals (9.7%) had dual infections. The prevalence of Trichuris was constant across all ages while the prevalence of hookworm was significantly lower in residents below 30 years of age. In the age group 5–12 years comparison of results with a 2001 survey [1] suggested that the prevalence of STH has declined minimally, due to sustained high prevalence of Trichuris, while hookworm has declined dramatically from 34.4% to 1.6%. CONCLUSION: The results of this survey suggest that although the MDA appears to have reduced hookworm prevalence in residents below 30 years of age, there has been minimal effect on Trichuris prevalence. An integrated program to control STH is required

Accuracy of Urine Circulating Cathodic Antigen (CCA) Test for Schistosoma mansoni Diagnosis in Different Settings of Côte d'Ivoire

We aimed to assess the accuracy of a commercially available rapid diagnostic test for the detection of an infection with the blood fluke Schistosoma mansoni in urine. In total, 446 school children from three different settings of south Côte d'Ivoire provided three stool and three urine samples. Stool samples were examined with the widely used Kato-Katz technique and analyzed with a microscope for S. mansoni eggs. Urine samples were examined with a filtration method for S. haematobium eggs and with a rapid diagnostic test for S. mansoni that is based on detecting circulating cathodic antigens (CCA). We used a commercially available test (designated CCA-A) and an experimental formulation (CCA-B). Examination of nine Kato-Katz thick smears per child revealed a prevalence of S. mansoni in the three settings of 32.9%, 53.1%, and 91.8%. The sensitivity of triplicate Kato-Katz from the first stool sample was comparable to a single CCA-A (47.9–94.2% vs. 56.3–89.6%), and significantly higher than the sensitivity of a single CCA-B test (10.4–75.0%). CCA-A showed a considerably lower specificity than CCA-B (76.9–84.2% vs. 96.7–100%). In the settings studied in south Côte d'Ivoire, the CCA-A test holds promise for the diagnosis of S. mansoni, whereas results with CCA-B were suboptimal

Factors Associated with High Prevalence of Intestinal Protozoan Infections among Patients in Sana'a City, Yemen

Intestinal protozoan diseases in Yemen are a significant health problem with prevalence ranging from 18% to 27%. The present study is a cross-sectional study aimed at determining the factors associated with the high prevalence of intestinal protozoan infections among patients seeking health care in Sana'a City, the capital of Yemen. (0.4%). Multivariate analysis using forward stepwise logistic regression based on intestinal protozoan infections showed that contact with animals (OR = 1.748, 95% CI = 1.168–2.617) and taking bath less than twice a week (OR = 1.820, 95% CI = 1.192–2.779) were significant risk factors of protozoan infections. infections being most common. Statistical analysis indicated that low personal hygiene and contact with animals were important predictors for intestinal protozoan infections. As highlighted in this study, in order to effectively reduce these infections, a multi-sectoral effort is needed. Preventive measures should include good hygienic practices, good animal husbandry practices, heightened provision of educational health programs, health services in all governorates including rural areas. Furthermore, it is also essential to find radical solutions to the recent water crises in Yemen

Rapid ethical assessment on informed consent content and procedure in Hintalo-Wajirat, Northern Ethiopia: a qualitative study

Background Informed consent is a key component of bio-medical research involving human participants. However, obtaining informed consent is challenging in low literacy and resource limited settings. Rapid Ethical Assessment (REA) can be used to contextualize and simplify consent information within a given study community. The current study aimed to explore the effects of social, cultural, and religious factors during informed consent process on a proposed HPV-serotype prevalence study. Methodology A qualitative community-based REA was conducted in Adigudom and Mynebri Kebeles, Northern Ethiopia, from July to August 2013. Data were collected by a multi-disciplinary team using open ended questions concerning informed consent components in relation to the parent study. The team conducted one-to-one In-Depth Interviews (IDI) and Focus Group Discussions (FGDs) with key informants and community members to collect data based on the themes of the study. Tape recorded data were transcribed in Tigrigna and then translated into English. Data were categorized and thematically analyzed using open coding and content analysis based on pre-defined themes. Results The REA study revealed a number of socio-cultural issues relevant to the proposed study. Low community awareness about health research, participant rights and cervical cancer were documented. Giving a vaginal sample for testing was considered to be highly embarrassing, whereas giving a blood sample made participants worry that they might be given a result without the possibility of treatment. Verbal consent was preferred to written consent for the proposed study. Conclusion This rapid ethical assessment disclosed important socio-cultural issues which might act as barriers to informed decision making. The findings were important for contextual modification of the Information Sheet, and to guide the best consent process for the proposed study. Both are likely to have enabled participants to understand the informed consent better and consequently to comply with the study

Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2016: A Systematic Analysis for the Global Burden of Disease Study

Importance: The increasing burden due to cancer and other noncommunicable diseases poses a threat to human development, which has resulted in global political commitments reflected in the Sustainable Development Goals as well as the World Health Organization (WHO) Global Action Plan on Non-Communicable Diseases. To determine if these commitments have resulted in improved cancer control, quantitative assessments of the cancer burden are required. Objective: To assess the burden for 29 cancer groups over time to provide a framework for policy discussion, resource allocation, and research focus. Evidence Review: Cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs) were evaluated for 195 countries and territories by age and sex using the Global Burden of Disease study estimation methods. Levels and trends were analyzed over time, as well as by the Sociodemographic Index (SDI). Changes in incident cases were categorized by changes due to epidemiological vs demographic transition. Findings: In 2016, there were 17.2 million cancer cases worldwide and 8.9 million deaths. Cancer cases increased by 28% between 2006 and 2016. The smallest increase was seen in high SDI countries. Globally, population aging contributed 17%; population growth, 12%; and changes in age-specific rates, -1% to this change. The most common incident cancer globally for men was prostate cancer (1.4 million cases). The leading cause of cancer deaths and DALYs was tracheal, bronchus, and lung cancer (1.2 million deaths and 25.4 million DALYs). For women, the most common incident cancer and the leading cause of cancer deaths and DALYs was breast cancer (1.7 million incident cases, 535¿000 deaths, and 14.9 million DALYs). In 2016, cancer caused 213.2 million DALYs globally for both sexes combined. Between 2006 and 2016, the average annual age-standardized incidence rates for all cancers combined increased in 130 of 195 countries or territor. CONCLUSIONS AND RELEVANCE Large disparities exist between countries in cancer incidence,deaths, and associated disability. Scaling up cancer prevention and ensuring universal access to cancer care are required for health equity and to fulfill the global commitments fornoncommunicable disease and cancer control.The Institute for Health Metricsand Evaluation received funding from the Bill &Melinda Gates Foundation