Development of Inducible Constructs and Stable Cell Lines for Cbl Expression

The E3 ubiquitin ligase Cbl plays a vital role in the trafficking of ligand-bound EGF-R through the endocytic pathway to its subsequent degradation. The RING finger tail region of the Cbl protein is thought to be critical to this process. Previous studies demonstrated that amino acid substitutions at position 431 or 434 of Cbl can disrupt the normal trafficking of EGF-R. Despite these previous findings regarding trafficking, the role of these mutations on EGF-R signaling has yet to be examined. In this study, we aim to begin to test the effects on signaling of the V431A and F434A mutations in a cellular context by developing pertinent plasmid constructs and generating stable, inducible cell lines for the signaling studies.No embarg

Using SHG Directionality to Characterize Collagen Alteration in Breast Cancer Tumor Microenvironment and Its Prognostic Applications

Although breast cancer is a growing health concern worldwide, the challenge to minimize mortality rate partly comes from the heterogeneity in its pathological characteristics. The tumor microenvironment is a complex hub of signaling cascades that plays a key role for the progression of cancer to develop to metastatic stage. The extracellular matrix (ECM), as a major component of the tumor microenvironment, contains signatures that have cues to understand tumor progression. Here, the unique microstructural collagen alterations specific to reactive stromal/tumor cell interactions and interactions of reactive stromal fibroblasts with different tumor cell types MCF7A and MDA-MB-231 were investigated. Early alterations of collagen were characterized using the label free, collagen specific, multiphoton laser scanning imaging modality known as Second Harmonic Generation microscopy (SHG). The directionality effect of SHG, calculated as the ratio between the forward and backward SHG (FSHG/BSHG), is used to characterize the different collagen signatures locally at 10-pixel (3.52μm) dilation from the cell boundaries. Activated fibroblasts remodel collagen differently resulting significantly higher FSHG/BSHG than deactivated fibroblasts and Wilcoxon rank-sum test gives p0.05) in their FSHG/BSHG ratio

Histopathological Changes of Placenta Associated with Maternal Anaemia in Northeast Ethiopia: A Comparative Study

BACKGROUND: Anaemia during pregnancy affects about half of all pregnant mothers in developing countries; it is the major causes of indirect maternal mortality. Anaemia can directly cause poor growth of fetus in utero due to inadequate oxygen flow to the placental tissue or it is indirect indicator of maternal nutritional deficiency. Mal-development of placenta is the leading cause of maternal and perinatal mortality and an important factor of fetal growth retardation. The aim of this study was to compare histopathological changes of placenta associated with maternal anaemia.METHODS: A comparative cross-sectional study was conducted from May-June, 2018 in Dessie Referral Hospital. A total of 66 placentas (33 anaemic and 33 non-anaemic) were collected after delivery. EPI data version 4.2.0 was used to enter the data while the data were analyzed by using SPSS version 22. Chi-square and oneway ANOVA were used to analyze the data.RESULTS; In pregnancies with maternal anaemia, 75.7% of anaemic placentas terminal villi vessels were increased in number, compared to 15.1% in non-anaemic (p=0.001). Placental calcification was 72.7% in anaemic groups compared to 54% in non-anaemic groups. However, it was insignificant (p=0.12). Intervillous space was wider in anaemic compared to non-anaemic groups (p<0.001).CONCLUSIONS; Chorionic villi capillaries were increased in number, and it was dilated in anaemic placenta, compared to non-anaemic. Intervillous space was significantly wider in anaemic placenta.&nbsp

Investigating Potential Modes of Actions of Mimusops kummel Fruit Extract and Solvent Fractions for Their Antidiarrheal Activities in Mice

Background. Fruits of Mimusops kummel A. DC. (Sapotaceae) are traditionally used for the treatment of diarrhea. The present study aimed at investigating modes of actions of this fruits for antidiarrheal action to guide future drug development process. Methods. Fractions of chloroform, n-butanol, and water were obtained from 80% methanol extract, which was prepared by maceration. Antidiarrheal activities and the modes of actions were investigated in mice. Results. In castor oil induced diarrheal model, the extract delayed onset of diarrhea and reduced number and weight of feces at all tested doses significantly. In this model all fractions significantly delayed onset of diarrhea at all tested doses. Charcoal meal test showed that the extract and all the fractions produced a significant antimotility effect at all tested doses. Enteropooling test showed that the extract as well as n-butanol and aqueous fractions at all tested doses produced a significant decline in volume and weight of intestinal contents, whereas chloroform fraction had substantial effect only at high dose. Conclusion. This study demonstrated that the extract and solvent fractions produced antidiarrheal activities due to dual inhibitory effect, intestinal motility, and fluid secretion, with the aqueous fraction being the most active among fractions in three models

ANTI-TUBERCULOSIS DRUG RESISTANCE IN ETHIOPIA: A MATA- ANALYSIS

Tuberculosis is one of the most dangers of health in the world. Ethiopia ranked seventh from the 22 high burden counties in the world. The main problem is development of resistance to the major anti-tuberculosis drugs actually increasing in Ethiopia. The aim was to review studies done on anti-tuberculosis drug resistance in Ethiopia. Literatures were searched for published articles on anti-tuberculosis drug resistance using the combination of terms; resistance, anti-tuberculosis and Ethiopia. Fifteen studies done in different parts of Ethiopia from 1978-2005 G.C were retrieved without restriction of place & design of study. The primary resistance of the fifteen studies done in various parts of Ethiopia (Addis Ababa, Harar, Bahir Dar, Sidamo, Arsi, and Hosanna) from1978-2005 G.C showed: Isoniazid (H) 1.9%-21.4%, Streptomycin (S) 1.9%-26%, Rifampicin (R) 0%-1.9%, Ethambutol (E) 0%-6.3%, Thiacetazone (T) 2.2%-6.3%, H+S 1.9%-26%, H+T 0%-4.4%, S+T 0%-1.8%, H+R 0%-1.1%, S+R 0%-0.7%, R+T 0%-0.4%, H+E 0%-0.9%, S+E 0%-0.6% ,H+S+T 0%-2.4%, H+S+R 0%-1.1%, H+T+R 0%-0.4%, H+S+E 0%-1.7%, R+H+T+S 0%-0.6% and Multi Drug Resistance 0%-1.3%.Acquired drug resistance: H 5.3%-66.7%, S 1.2%-46%, R 0%-12%, E 0%-5.6%, T0%-29%, H+T 0%-20%, H+S 4.8%- 28%, R+H 0%-8%, R+S 0%-3.5%, S+T 0%-2.3%, H+E 0%-3.6%, R+E 0%-5.6%, S+E 0%- 11.2%, H+S+T 0%-16%, R+S+T 0%-2.3% , R+S+H 0%-4%, H+S+E 0%-3.6%, H+R+E 0%- 3.6%, H+R+S+E 0%-14.3% and Multi Drug Resistance 0%-26.3%. It can be concluded that resistance to the anti-tuberculosis drugs is increasing. National level drug resistance survey is recommended to design policies and strategies to prevent increase of drug resistance. Key words: Resistance, tuberculosis, anti-tuberculosis drugs and Ethiopia

Impact of repeated NeemAzal®-treated blood meals on the fitness of Anopheles stephensi mosquitoes

Background: Herbal remedies are widely used in many malaria endemic countries to treat patients, in particular in the absence of anti-malarial drugs and in some settings to prevent the disease. Herbal medicines may be specifically designed for prophylaxis and/or for blocking malaria transmission to benefit both, the individual consumer and the community at large. Neem represents a good candidate for this purpose due to its inhibitory effects on the parasite stages that cause the clinical manifestations of malaria and on those responsible for infection in the vector. Furthermore, neem secondary metabolites have been shown to interfere with various physiological processes in insect vectors. This study was undertaken to assess the impact of the standardised neem extract NeemAzal® on the fitness of the malaria vector Anopheles stephensi following repeated exposure to the product through consecutive blood meals on treated mice. Methods: Batches of An. stephensi mosquitoes were offered 5 consecutive blood meals on female BALB/c mice treated with NeemAzal® at an azadirachtin A concentration of 60, 105 or 150 mg/kg. The blood feeding capacity was estimated by measuring the haematin content of the rectal fluid excreted by the mosquitoes during feeding. The number of eggs laid was estimated by image analysis and their hatchability assessed by direct observations. Results: A dose and frequency dependent impact of NeemAzal® treatment on the mosquito feeding capacity, oviposition and egg hatchability was demonstrated. In the 150 mg/kg treatment group, the mosquito feeding capacity was reduced by 50% already at the second blood meal and by 50 to 80% in all treatment groups at the fifth blood meal. Consequently, a 50 – 65% reduction in the number of eggs laid per female mosquito was observed after the fifth blood meal in all treatment groups. Similarly, after the fifth treated blood meal exposure, hatchability was found to be reduced by 62% and 70% in the 105 and 150 mg/kg group respectively. Conclusions: The findings of this study, taken together with the accumulated knowledge on neem open the challenging prospects of designing neem-based formulations as multi-target phytomedicines exhibiting preventive, parasite transmission-blocking as well as anti-vectorial properties. Keywords: Malaria, Vectors, Neem, Azadirachtin, Transmission-blocking, Anti-vectoria

Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: a systematic analysis from the Global Burden of Disease Study 2016

Background: A key component of achieving universal health coverage is ensuring that all populations have access to quality health care. Examining where gains have occurred or progress has faltered across and within countries is crucial to guiding decisions and strategies for future improvement. We used the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) to assess personal health-care access and quality with the Healthcare Access and Quality (HAQ) Index for 195 countries and territories, as well as subnational locations in seven countries, from 1990 to 2016. Methods: Drawing from established methods and updated estimates from GBD 2016, we used 32 causes from which death should not occur in the presence of effective care to approximate personal health-care access and quality by location and over time. To better isolate potential effects of personal health-care access and quality from underlying risk factor patterns, we risk-standardised cause-specific deaths due to non-cancers by location-year, replacing the local joint exposure of environmental and behavioural risks with the global level of exposure. Supported by the expansion of cancer registry data in GBD 2016, we used mortality-to-incidence ratios for cancers instead of risk-standardised death rates to provide a stronger signal of the effects of personal health care and access on cancer survival. We transformed each cause to a scale of 0–100, with 0 as the first percentile (worst) observed between 1990 and 2016, and 100 as the 99th percentile (best); we set these thresholds at the country level, and then applied them to subnational locations. We applied a principal components analysis to construct the HAQ Index using all scaled cause values, providing an overall score of 0–100 of personal health-care access and quality by location over time. We then compared HAQ Index levels and trends by quintiles on the Socio-demographic Index (SDI), a summary measure of overall development. As derived from the broader GBD study and other data sources, we examined relationships between national HAQ Index scores and potential correlates of performance, such as total health spending per capita. Findings: In 2016, HAQ Index performance spanned from a high of 97·1 (95% UI 95·8–98·1) in Iceland, followed by 96·6 (94·9–97·9) in Norway and 96·1 (94·5–97·3) in the Netherlands, to values as low as 18·6 (13·1–24·4) in the Central African Republic, 19·0 (14·3–23·7) in Somalia, and 23·4 (20·2–26·8) in Guinea-Bissau. The pace of progress achieved between 1990 and 2016 varied, with markedly faster improvements occurring between 2000 and 2016 for many countries in sub-Saharan Africa and southeast Asia, whereas several countries in Latin America and elsewhere saw progress stagnate after experiencing considerable advances in the HAQ Index between 1990 and 2000. Striking subnational disparities emerged in personal health-care access and quality, with China and India having particularly large gaps between locations with the highest and lowest scores in 2016. In China, performance ranged from 91·5 (89·1–93·6) in Beijing to 48·0 (43·4–53·2) in Tibet (a 43·5-point difference), while India saw a 30·8-point disparity, from 64·8 (59·6–68·8) in Goa to 34·0 (30·3–38·1) in Assam. Japan recorded the smallest range in subnational HAQ performance in 2016 (a 4·8-point difference), whereas differences between subnational locations with the highest and lowest HAQ Index values were more than two times as high for the USA and three times as high for England. State-level gaps in the HAQ Index in Mexico somewhat narrowed from 1990 to 2016 (from a 20·9-point to 17·0-point difference), whereas in Brazil, disparities slightly increased across states during this time (a 17·2-point to 20·4-point difference). Performance on the HAQ Index showed strong linkages to overall development, with high and high-middle SDI countries generally having higher scores and faster gains for non-communicable diseases. Nonetheless, countries across the development spectrum saw substantial gains in some key health service areas from 2000 to 2016, most notably vaccine-preventable diseases. Overall, national performance on the HAQ Index was positively associated with higher levels of total health spending per capita, as well as health systems inputs, but these relationships were quite heterogeneous, particularly among low-to-middle SDI countries. Interpretation: GBD 2016 provides a more detailed understanding of past success and current challenges in improving personal health-care access and quality worldwide. Despite substantial gains since 2000, many low-SDI and middle-SDI countries face considerable challenges unless heightened policy action and investments focus on advancing access to and quality of health care across key health services, especially non-communicable diseases. Stagnating or minimal improvements experienced by several low-middle to high-middle SDI countries could reflect the complexities of re-orienting both primary and secondary health-care services beyond the more limited foci of the Millennium Development Goals. Alongside initiatives to strengthen public health programmes, the pursuit of universal health coverage hinges upon improving both access and quality worldwide, and thus requires adopting a more comprehensive view—and subsequent provision—of quality health care for all populations

Assessment of barriers to the implementation of community-based data verification and immunization data discrepancies between health facilities and the community in Tach Gayint district, Northwest Ethiopia.

AbstractIntroduction: While community-based data verification (CBDV) is critical for effective implementation of immunization programs, limited evidence exists detailing its implementation at the local levels thereby threatening data quality which is used to guide decision making.Aim: To explore the barriers to proper implementation of CBDV and determine the level of immunization data discrepancy between the health facilities and community levels in Tach Gayint district of Northwest Ethiopia.Methods: A Mixed methods approach was used. Interviews with twenty-six key informants’ (health experts) in immunization data, and an additional a sample of 324 infants were recruited. All health centers in the district (6) and 2 health posts from each health center (12 in total) were selected using Simple Random Sampling. Key informant interviewees were purposely included from all health facilities. For quantitative data, samples of infants were proportionally allocated for each health facility as per their DPT/Pentavalent-1 vaccine report. Thematic analysis of the qualitative data and descriptive quantitative analysis were performed using statistical software open-code v-4.02 and STATA v14.1 respectively.Results: Only few health facilities implemented CBDV and consider it to be their routine task. Also, barriers to effective implementation of CBDV such as lack of prioritization, poor capacity among health staff, and conflicting job roles were identified. The highest immunization data discrepancy among community and health facilities was observed for the measles-one vaccine (35.4%), and the minimum was for DPT/Pentavalent-1 (25.6%).Conclusion: This study revealed a poor level of CBDV implementation and barriers to its effective implementation which include lack of prioritizing CBDV, limited capacity among health staff in performing CBDV, and conflicting job roles among health staff. There was a high level of immunization data discrepancy for measles-1 and DTP/Pentalent-3 vaccines. Based on our finding, we make the following recommendations: building skills among health workers to perform CBDV, enhancing availability and use of standard CBDV tools, ensuring monitoring, and control mechanism, and setting clear definition of roles regarding CBDV, as well as closing the gap in level of immunization data discrepancy could help foster effective implementation of CBDV. [Ethiop. J. Health Dev. 2021; 35(SI-3):09-15]Key words: Immunization, CBDV, Data discrepancy, Data qualit

Assessment of immunization data management practices, facilitators, and barriers to immunization data quality in the health facilities of Tach Gayint district, Northwest Ethiopia

AbstractIntroduction: Although data quality mainly depends upon the proper management of its primary sources, limited studies examined immunization data management practice in Ethiopia.Aim: To explore data management practices, facilitators, and barriers to immunization data quality among front-line immunization experts in the Tach Gayint district of Northwest Ethiopia.Methods: A mixed method study design was applied using document review and key-informant interviews. Quantitative data was collected through document review from 18 health facilities and 26 key-informant interviews, were conducted on experts of immunization for qualitative data. A STATA version 14.1 was used for quantitative data analysis. Qualitative data was transcribed verbatim and translated back into English. Data was coded, reduced, and searched for salient patterns. Thematic analysis was done using open-code version 4.02.Results: The Health Management Information System data recording tools were often lacking. The significant number (83.3%) of health facilities practiced immunization information display, while dissemination at the local level was low. The key informants mentioned that they were responsible for conducting regular Performance Monitoring Team (PMT) and Lots Quality Assurance Sampling (LQAS) as facilitators. Furthermore, a shortage of recording tools, limited supportive supervision, vertical reporting, impracticality of Lots of Quality Assurance Sampling (LQAS) at the health posts, poor implementation of Community Health Information System (CHIS), and mass vaccination were barriers identified to immunization data quality.Conclusion: We found that majority of health workers use locally developed tools instead of using the standard data recording and reporting tools. Regular Performance Monitoring Team meetings and Lots Quality Assurance Sampling assessment were found to be facilitators. Furthermore, limited supportive supervision, vertical reporting and poor implementation of Community Health Information System were barriers. Therefore, strengthening the use of standard recording and reporting tools, conducting regular supportive supervision, and implementing routine vaccination services are recommended to improve the data management practice. [Ethiop. J. Health Dev. 2021; 35(SI-3):28-38]Key words: Immunization, Data management practice, Data quality, Information us

Incidence of persistent metopic suture and extra sacral foramina in Ethiopian population

Lack of knowledge of variations in human morphology and their magnitude compared to normal anatomy may have significant clinical consequences. Accurate knowledge of anatomical variations provides important information in medico-legal issues, forensic interpretation, diagnostics, imaging and patient management including surgical procedures. Although underreported, it is believed that a significant proportion of clinical malpractice is due to suboptimal knowledge of anatomical variations. The present study aims to assess the anatomical variations of locomotor system structures in twenty-four formalin fixed cadavers used for dissection as part of Gross Anatomy course for medical students. The study was conducted in six medical schools in Ethiopia in the academic year 2015/2016. Following critical observation and careful dissection, photographs were taken accordingly. Our findings show a complete persistence of metopic suture in 4.2 % of frontal bone, incedence of five anterior and five posterior sacral foramina in 4.2 % of sacral bones and biceps brachii muscle with three heads of origin in 2.1 % of brachia. Altogether, the findings show the incidence of anatomical variants of clinical importance that need consideration during surgical procedures, diagnosis - especially in distinguishing fracture of bones - and patient management in Ethiopian population with diverse socio-economic background and geographical origin