110 results on '"Yeboah F"'
Search Results
2. Expression of RAS and RAB interactor 1 (RIN1) in head and neck tumors at selected hospital in Ghana.
- Author
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Osei Saahene, Roland, Barnes, Precious, Yeboah, F. A., Agbo, Elvis, Asante, Du-Bois, and Arhin, Samuel Kofi
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NECK tumors ,HEAD tumors ,IMMUNOSTAINING ,RAS proteins ,NECK ,SALIVARY glands ,PARANASAL sinuses - Abstract
Background: Head and neck tumors (HNT) are tumors of the paranasal sinuses, the salivary glands and the upper aerodigestive tract. RIN1 is a Ras effector protein regulating epithelial cell properties and has been implicated in a number of cancers. Method: The aim of this study was to investigate the expression of RIN1 in head and neck tumors. RIN1 expression was assessed using quantitative real-time PCR (qRT-PCR) and immunohistochemical staining on archival head and neck tissue samples between 2014 and 2020. Results: RIN1 expression was low in tissue samples as compared with the normal head and neck tissues. High and low RIN1 levels were compared with ages ≤40, >40 in the head and neck tumors of p-value 0.02. There was a significant difference with p-values of 0.001 when poor and well-moderate malignant tumors were compared. Conclusion: Our data suggests that RIN1may play an important role in head and neck tumor progression and that its expression may provide baseline data to facilitate identification of new molecular targeted therapeutics. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Clinicohistologic Characteristics of Breast Cancer in Ghanaian Patients
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Ahenkorah Fondjo L, Kafui Akakpo P, Gustav Imbeah E, Leonard Derkyi-Kwarteng, and Agyemang-Yeboah F
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medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Cancer ,Retrospective cohort study ,Disease ,medicine.disease ,Gastroenterology ,Lesion ,medicine.anatomical_structure ,Breast cancer ,Internal medicine ,medicine ,General Earth and Planetary Sciences ,Stage (cooking) ,medicine.symptom ,business ,Lymph node ,Mastectomy ,General Environmental Science - Abstract
Background Breast cancer is the leading cause of cancer morbidity and mortality worldwide. The management and prognosis of breast cancer depend heavily on the different histologic and molecular biologic features of the tumour. The different histologic types describe the distinct growth patterns and cytological features of the tumour. Methodology This is a retrospective study of archival breast cancer excision and mastectomy specimen at KBTH from 2012-2016. 729 cases were retrieved over the period and examined by two pathologists independently. Demography of the cases, tumour size, grade, histologic type, stage, mitosis, site of lesion etc. were entered into SPSS and analysed with chi-square done with P-value set at P < 0.05. Results and Conclusion The mean age of presentation is 52.45 ± 12.75 years. The commonest histologic type of breast cancer is invasive carcinoma (NOS) forming (87%). Only 1.2% of male presented with breast cancer with the other percentage in females. Most (88%) of the tumours were greater than 5cm at the time of surgery. The tumours are of high grade (II and III) forming 88%. Seventy-eight percent of cases presented with late stage of the disease (≥ stage IIB). There was association between histologic type and vascular invasion (P < 0.000) and lymph node involvement (P = 0.010). Moreover, tumour size showed an association with tumour grade (P < 0.05). This study has shown that breast cancer among Ghanaian patients has a worse histologic type with poor tumour characteristics giving it poor prognosis.
- Published
- 2020
4. Prognostic Worth of Epidermal Growth Factor Receptor (EGFR) in Patients with Head and Neck Tumors
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Barnes, Precious, primary, Yeboah, F. A., additional, Zhu, Jinling, additional, Saahene, Roland Osei, additional, Obirikorang, Christian, additional, Adinortey, Michael Buenor, additional, Amoani, Benjamin, additional, Kyei, Foster, additional, Akakpo, Patrick, additional, and Awuku, Yaw Asante, additional
- Published
- 2020
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5. AFRICA’S EVOLVING EMPLOYMENT STRUCTURE
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Yeboah, F. Kwame and Jayne, T.S.
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Productivity Analysis ,Agricultural and Food Policy ,Africa ,employment ,Labor and Human Capital ,International Development ,Food Security and Poverty - Abstract
Using nationally representative, multi-year survey data for nine African countries, this study documents trends in the sectoral composition of Africa’s work force. The study highlights differences in sectoral employment trends by age category, gender, and rural vs. urban areas. By analyzing sectoral employment shifts over the past decade, we can gain insights about the strength and robustness of economic transformation processes in much of Sub-Saharan Africa. While substantial differences across countries warrant caution against overgeneralization, the last decade has witnessed a sharp increase in the rate at which Africans are exiting farming in favor of off-farm activities. Today, farming accounts for 50 to 70% of the total number of jobs recorded among Africa’s working-age population, down from 70 to 80% just 10 years ago. These employment shifts signify that economic transformation is clearly underway in much of the region. In some countries, however, the labor force is moving out of farming very slowly. Countries experiencing the most rapid labor force exit out of farming over the past decade tend to have achieved relatively strong agricultural productivity growth since 2000.
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- 2016
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6. Comparative analysis of extracted heights from topographic maps and measured reduced levels in Kumasi, Ghana
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Ayer, J, primary, Agyemang, A.B., additional, Yeboah, F, additional, Osei Jnr, E.M., additional, Abebrese, S, additional, and Suleman, I, additional
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- 2016
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7. Die Transplantatüberlebenszeit homologer Rattenhaut nach gleichzeitiger Applikation von ALG und Freundschem Adjuvans
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Seifert, J., Agyare-Yeboah, F., Brendel, W., Linder, F., editor, Röher, H.-D., editor, and Rudolph, H., editor
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- 1973
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8. The myth of Africa's ageing farmers.
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Yeboah, F. Kwame and Jayne, T. S.
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- 2020
9. Economic and environmental impacts of mining activities in Ghana
- Author
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Dehtiarova, Iryna Borysivna and Yeboah, F.
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mining industry ,гірничодобувна промисловість ,горнодобывающая промышленность - Abstract
Mining for many decades served as an important component of countries revenue source especially for developing countries that have been endowed with the mineral wealth. If properly managed, countries can grow their economies with proceeds from mining activities in the form of royalties and foreign exchange earnings for the export of mineral related products. Such benefits from the mining sector have in most cases been used as justification and a social license for exploration and exploitation of minerals in most communities. When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/31067
- Published
- 2013
10. From Theory to Practice: Exploring Sustainable Solutions to Africa's Developmental Challenges.
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Yeboah, F. Kwame and Jayne, T. S.
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- *
SUSTAINABLE development ,ECONOMIC conditions in Africa - Published
- 2018
11. Keynote speech at the 2nd Annual Conference of the Africa Graduate Student Association (AGSA) at Michigan State University, East Lansing, MI.
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Yeboah, F. Kwame and Jayne, T. S.
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- *
ECONOMIC development , *SOCIAL science research - Published
- 2017
12. Volume Constraint Model and Algorithm for the 0-1 Knapsack Problem
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Ofosu, M.A., primary, Amponsah, S.K., additional, and Appau-Yeboah, F., additional
- Published
- 2015
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13. Nm Lipid Analysis of Platelet Membranes of Patients with Coronary Artery Diseases: Case Studies
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A. Yeboah, F., Gibbons, Wa, and Preedy, V.
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Platelets ,Coronary Heart Disease ,Lipids ,Proton Nuclear Magnetic Resonance (Nmr) - Abstract
A high - resolution proton nuclear magnetic resonance (Nmr) was used to investigate platelet membrane lipid composition of subjects who have been definitively diagnosed as having various forms of coronary heart disease (CAD). The one dimensional (1D) proton spectra were recorded at a temperature of 298° K in Fourier transform(FT) mode with 16K data points, using a 45° detection pulse and 2.0 acquisition time with a solvent presaturation during relaxation to remove excess water signal. The major phospholipids and cholesterol present were identified and estimated and compared to those of normal individual’s platelet membrane. Platelet cholesterol content as analysed by the proton Nmr in all the 3 patients investigated were significantly elevated (p
- Published
- 2000
14. Clinical and epidemiological characterisation of Burkitt’s lymphoma: an eight-year case study at Komfo Anokye Teaching Hospital, Ghana
- Author
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Owusu, L., primary, Yeboah, F. A, additional, Osei-Akoto, A., additional, Rettig, T., additional, and Arthur, F. K. N., additional
- Published
- 2010
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15. Energy and economic analysis of closed-loop plasma waste-to-power generation model and in comparison with Incineration and Micro-Turbine Models
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Baidoo, Ransford R., primary, Yeboah, F., additional, and Singh, H., additional
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- 2009
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16. Exergy and energy analysis of plasma waste-to-power generation model
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Baidoo, Ransford R., primary, Ferguson, F., additional, and Yeboah, F., additional
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- 2009
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17. Assessing Depreciation For Valuation Purposes – A Decompositional Approach
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Gyamfi-Yeboah, F, primary and Ayitey, J, additional
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- 2009
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18. The Road to Advanced Glycation End Products: A Mechanistic Perspective
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Cho, S.-J., primary, Roman, G., additional, Yeboah, F., additional, and Konishi, Y., additional
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- 2007
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19. Protecting Buildings Against Bioterrorism--Review of Guidance and Tools.
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Yeboah, F. E., Chowdhury, F., Ilias, S., Singh, H., and Sparks, L.
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BIOTERRORISM , *BIOLOGICAL warfare , *ANTHRAX , *TERRORISM , *NATIONAL security , *INTERNATIONAL crimes , *COMMERCIAL buildings , *SUBVERSIVE activities - Abstract
Ever since the September 11, 2001, terrorist attacks and the subsequent anthrax incidents in the US, attempts have been made to thwart further attacks and other forms of terrorism. Attacks involving chemical and/or biological agents (CBA) are among the most dreaded because of the ease with which they can be produced and disseminated as well as their fatal potency. Protecting buildings and built-in environments against bioterrorism or CBA attacks are key issues in homeland security. Unfortunately, the threat posed by chemical and/or biological agents is so complex that building professionals should be educated about what they are, possible scenarios of their release, how they may be detected, how buildings may be ‘immunized’ against such threats, etc. Terrorists will try to cause as many casualties as possible, with high-occupancy structures such as commercial buildings being at elevated risk in any such CBA release. Building owners and building professionals should, therefore, have some level of understanding and appreciation of the dangers that such an attack poses. This paper reviews some of the necessary guidance and tools that are available for educating building professionals on protecting building occupants against CBA attacks. [ABSTRACT FROM AUTHOR]
- Published
- 2007
20. Analysis of glycated proteins by mass spectrometric techniques: qualitative and quantitative aspects
- Author
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Yeboah, F. K., primary and Yaylayan, V. A., additional
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- 2001
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21. Iron deficiency in rural Ghanaian children
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Agyei-Frempong, M. T., primary, Asare, G., additional, Owiredu, W. K. B. A., additional, and Yeboah, F. O., additional
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- 2001
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22. Electrolyte monitoring in the management of essential hypertension
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Agyei-Frimpong, M.T., primary, Ngala, R. A., additional, Liang, E. F., additional, Owiredu, W.B.K.A., additional, and Yeboah, F. A., additional
- Published
- 2000
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23. Ubiquitin expression in coeliac disease
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Yeboah, F. A., primary and White, D., additional
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- 2000
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24. Composition of Fish Consumed by the James Bay Cree
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Belinsky, D.L., primary, Kuhnlein, H.V., additional, Yeboah, F., additional, Penn, A.F., additional, and Chan, H.M., additional
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- 1996
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25. Proton Nuclear Magnetic Resonance Lipid Profiling of Intact Platelet Membranes
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Yeboah, F A, primary, Adosraku, R K, additional, Nicolaou, A, additional, and Gibbons, W A, additional
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- 1995
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26. Adiposity and hyperleptinemia during the first trimester among pregnant women with preeclampsia
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Yeboah FA, Ngala RA, Bawah AT, Asare-Anane H, Alidu H, Hamid AWM, and Wumbee JDK
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Preeclampsia ,Adiposity ,Hyperleptinemia ,percentage of body fat and pregnancy. ,Gynecology and obstetrics ,RG1-991 - Abstract
Francis Agyemang Yeboah,1 Robert Amadu Ngala,1 Ahmed Tijani Bawah,2 Henry Asare-Anane,3 Huseini Alidu,2 Abdul-Wahab Mawuko Hamid,2 Joshua Dokurugu Kwame Wumbee4 1Department of Molecular Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, 2Department of Medical Laboratory Science, University of Health and Allied Sciences, Ho, 3Department of Chemical Pathology, School of Biomedical and Allied Health Sciences, University of Ghana, Accra, 4Internal Quality Control Unit, Quality Control Directorate, Kumasi Technical University, Kumasi, Ghana Background: Leptin levels start increasing from the early stages of pregnancy, irrespective of the maternal body mass index. Leptin levels are increased in pregnant women with preeclampsia (PE) and may precede the clinical onset of the disease, with peaks occurring around 28 weeks of gestation. This study was aimed at determining whether serum leptin concentration and body fat percentage are significantly altered during the first trimester in pregnancies that subsequently develop PE and whether such changes are useful in predicting the disease.Materials and methods: This was a prospective longitudinal study conducted among pregnant women in Ho municipality. A cohort of 314 pregnant women was monitored from the first antenatal visit to delivery period at the Volta Regional Hospital, Ho, Ghana. Maternal serum leptin and lipid profile were analyzed and body fat percentage determined during first trimester. Body mass index was also calculated.Results: First trimester serum leptin level (P
- Published
- 2017
27. Effect of Limited Solid-State Glycation on the Conformation of Lysozyme by ESI-MSMS Peptide Mapping and Molecular Modeling
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Yeboah, F. K., Alli, I., Yaylayan, V. A., Yasuo, K., Chowdhury, S. F., and Purisima, E. O.
- Abstract
Although protein glycation has been implicated in the alteration of protein functionality, both in vivo (in biological systems) and in vitro (in food systems), the effect of the protein-bound glycan moiety on the structure/conformation of proteins that result in the modification of functionality is not clear. In this article, we report a study of the conformational changes of glycated lysozyme using LC-ESI-MSMS peptide mapping, and molecular modeling. A comparison of the RP-HPLC of the tryptic digests of unglycated and glycated lysozyme showed markedly different chromatographic profiles. Analysis of the peptide composition of the chromatographic fractions of the tryptic digests revealed that glycation of lysozyme resulted in the modification of its conformation. Glycation-induced changes in the conformation of lysozyme resulted in the exposure of its active site region to increased proteolytic activity of trypsin. Molecular simulation of triglycated lysozyme also showed that limited glycation of lysozyme caused reorientation of the active site residues (Arg 45, Arg 68, Asn 44, and Trp 62) and increased solvent accessibility into the active site region of the protein. The results of the modeling experiment corroborated the results of the RP-HPLC and ESI-MSMS peptide mapping.
- Published
- 2004
28. Blood haemoglobin measurement as a predictive indicator for the progression of HIV/AIDS in resource-limited setting
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Yeboah Francis A and Obirikorang Christian
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Medicine - Abstract
Abstract Background Anaemia is a frequent complication of infection with the human immunodeficiency virus (HIV) and may have multiple causes. The objective of this study was to find out if blood haemoglobin measurement could be used as an indicator for the progression of HIV/AIDS in resource-limited setting. Methods Two hundred and twenty-eight (228) consented People Living with HIV/AIDS (PLWHAs) who were placed in three groups according to their CD4 counts were used in the study. The three groups were those with CD4 counts (1) ≥ 500 mm-3; (2) 200-499 mm-3; and (3) <200 mm-3. One hundred (100) sex, age-matched and healthy HIV-seronegative individuals were used as control subjects. Blood haemoglobin, blood haematocrit, Red cell indices which included Mean Cell Volume, Mean Cell Haemoglobin Concentration and Mean Cell Haemoglobin and CD4 count were analysed in all subjects. Results The mean blood haemoglobin concentrations in those with CD4 counts <200 mm-3, 200-499 mm-3 and ≥ 500 mm-3 (8.83 ± 0.22 g/dl, 10.03 ± 0.31 g/dl and 11.3 ± 0.44 g/dl respectively) were significantly lower when compared with the control group (14.29 ± 0.77 g/dl) (p < 0.0001). The mean blood haematocrit levels in those with CD4 counts <200 mm-3, 200-499 mm-3 and ≥ 500 mm-3 (23.53 ± 0.85%, 28.28 ± 0.77% and 33.54 ± 1.35% respectively) were also significantly lower when compared with the control group (41.15 ± 2.15%) (p < 0.0001). The red cell indices were also lower in the subjects when compared with the control group. Using the Pearson's correlation, there was a significant and positive correlation between the blood haemoglobin level and their CD4 counts (r2 = 0.1755; p < 0.0001). Conclusion Anaemia in People Living with HIV/AIDS, if persistent, is associated with substantially decreased survival. From our analysis, there was a decrease in the blood haemoglobin, levels as the HIV infection progressed and our findings are consistent with those of other studies of anaemia as a prognostic factor in HIV infection. Haemoglobin levels could be measured easily where resources for more sophisticated laboratory markers such as viral load or even CD4 lymphocyte count are not available given that measurement of the CD4 lymphocyte count requires flow cytometry, an expensive technique unavailable in many developing countries. Regular measurements could help to determine which patients are at greatest risk of disease progression, allowing these patients to be identified for closer monitoring or therapeutic intervention.
- Published
- 2009
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29. Current Approaches to Design Space Development and Regulatory Applications for Drug Products: Findings from the IQ Utilization of Design Space for Filings Working Group Survey.
- Author
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Miesle JE, Osei-Yeboah F, Pauli-Bruns A, Chen B, Manceva S, Wade JB, Yin S, Desai D, Dirat O, Bhugra C, and Stauffer F
- Subjects
- Surveys and Questionnaires, Humans, Pharmaceutical Preparations chemistry, Drug Design, Quality Control, Drug Industry methods, Drug Development methods, Drug Development legislation & jurisprudence
- Abstract
Purpose: The concept of a Design Space (DSp) was introduced in ICH Q8 as a tool within the quality-by-design (QbD) approach to pharmaceutical development with the intent of being globally applicable. However, there appears to be variance in the regulatory agency expectations in pharmaceutical product filing and implementation of DSp. This paper presents some of the current industry perspective on design space., Methods: The Utilization of Design Space for Filings (UDSpF) Working Group in the Innovation and Quality (IQ) Consortium conducted a survey to establish a baseline for the current understanding of DSp among IQ member companies and assess the similarities and/or differences in strategies when filing a DSp. The survey focused on how IQ member companies approach DSp development, the primary drivers for the DSp, the presentation of the DSp in the filing, DSp verification and the benefits and flexibility anticipated and/or realized., Results: A total of 14 responses were received and analyzed representing a small sample size but a large proportion of the innovator industry/large pharmaceutical companies. The survey results revealed that DSp is not yet a commonplace for small molecule drug products and may not even be utilized as much in large molecule drug products. The benefits of DSp, with respect to enhanced process understanding, are well understood by the sponsors; however, the benefits of filed DSp with respect to manufacturing flexibility are not fully realized in the commercial lifecycle of the product. There are also challenges in gaining consistent buy-in/value proposition for DSp among cross-functional teams within organizations., Conclusions: There are still gaps in design space implementation for its full benefit in the pharmaceutical industry. The WG has presented a unified view from member companies on the approach to DSp considering when/where the DSp experiments are conducted and on the extent of the DSp development proposed in a dossier., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2024
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30. Acute epigastric pain unveiling biventricular myocardial infarction: A case report.
- Author
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Diallo TH, Djafarou Boubacar R, Nana Yeboah F, Ekhya Amoumoune F, Mohamed Aden F, Bendagha N, and Fellat R
- Abstract
Acute coronary syndromes are a clinical entity frequently encountered in practice and are responsible for significant morbidity and mortality, despite therapeutic advances. The initiation of early reperfusion therapy reduces mortality and morbidity and improves patients' prognosis, but this depends on how quickly patients receive their treatment. Although it is often easy to diagnose in the presence of typical symptoms, certain patients, such as diabetics, sometimes have atypical symptoms, resulting in a delay in management. In nearly 50% of cases, inferior wall ischaemia is accompanied by right ventricular myocardial infarction; the clinical outcomes range from no hemodynamic compromise to severe hypotension and cardiogenic shock. In this article, we present the case of a 54-year-old male patient with active smoking and poorly controlled type 2 diabetes as cardiovascular risk factors who initially consulted at the first hour for epigastric pain, for which he received symptomatic treatment. As the symptoms persisted, he was admitted to our department at the eighth hour, where he was diagnosed with a biventricular infarction., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)
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- 2024
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31. Tissue Microarray Immunohistochemical Staining for Androgen Receptor in Breast Cancer in a Ghanaian Cohort.
- Author
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Duduyemi BM, Ayibor WG, and Agyemang-Yeboah F
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- Humans, Female, Ghana epidemiology, Middle Aged, Adult, Receptors, Progesterone metabolism, Breast Neoplasms pathology, Breast Neoplasms metabolism, Receptors, Estrogen metabolism, Aged, Cohort Studies, Receptor, ErbB-2 metabolism, Neoplasm Grading, Receptors, Androgen metabolism, Immunohistochemistry, Triple Negative Breast Neoplasms pathology, Triple Negative Breast Neoplasms metabolism, Tissue Array Analysis, Biomarkers, Tumor metabolism
- Abstract
Background: Despite the advancement in therapy, breast cancer still remains the most common malignancy in women globally due in part to its heterogeneity. Triple-negative breast cancer (TNBC) represents up to 20% of all breast cancer variants, an aggressive disease with poorer outcomes compared to other breast cancer subtypes. No targeted therapies are currently approved for TNBC, and newer treatment approaches are seriously needed. Androgen receptor (AR), another hormonal receptor, is often expressed in breast cancer, and its role depends on the relative levels of circulating estrogens and androgens. This study aimed to assess the expression of AR in breast cancer in a tertiary hospital in Ghana., Methodology: Immunohistochemical staining for AR was performed on tissue microarray (TMA) blocks, of which estrogen receptor, progesterone receptor, and Her-2/neu had already been done. 197 cases were suitable for the study. Results from the immunostaining were analyzed using the SPSS version 23 for descriptive statistics and correlations (χ2 and Pearson tests)., Results: 197 TMA cases were used. TNBCs constitute 61.9% of the cancers. The majority of these tumors were grade III, ductal carcinoma NST. The mean age was 49.86 ± 14.09, and the modal age group was 40-49 years. Our cases showed 23% AR expression in triple-negative cancers. The study also established that AR is more frequently expressed in low-grade tumors compared to high-grade ones., Conclusion: There is an appreciable level of AR expression in our cases; however, most are quadruple negative. However, AR is more frequently expressed in low-grade tumors than high-grade ones., (Copyright © 2024 Copyright: © 2024 Annals of African Medicine.)
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- 2024
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32. Ultra-fast genetically encoded sensor for precise real-time monitoring of physiological and pathophysiological peroxide dynamics.
- Author
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Berndt A, Lee J, Won W, Kimball K, Neiswanger C, Schattauer S, Wang Y, Yeboah F, Ruiz M, Evitts K, Rappleye M, Bremner S, Chun C, Smith N, Mack D, Young J, Lee CJ, and Chavkin C
- Abstract
Hydrogen Peroxide (H
2 O2 ) is a central oxidant in redox biology due to its pleiotropic role in physiology and pathology. However, real-time monitoring of H2 O2 in living cells and tissues remains a challenge. We address this gap with the development of an optogenetic hydRogen perOxide Sensor (oROS), leveraging the bacterial peroxide binding domain OxyR. Previously engineered OxyR-based fluorescent peroxide sensors lack the necessary sensitivity and response speed for effective real-time monitoring. By structurally redesigning the fusion of Escherichia coli (E. coli) ecOxyR with a circularly permutated green fluorescent protein (cpGFP), we created a novel, green-fluorescent peroxide sensor oROS-G. oROS-G exhibits high sensitivity and fast on-and-off kinetics, ideal for monitoring intracellular H2 O2 dynamics. We successfully tracked real-time transient and steady-state H2 O2 levels in diverse biological systems, including human stem cell-derived neurons and cardiomyocytes, primary neurons and astrocytes, and mouse brain ex vivo and in vivo . These applications demonstrate oROS's capabilities to monitor H2 O2 as a secondary response to pharmacologically induced oxidative stress and when adapting to varying metabolic stress. We showcased the increased oxidative stress in astrocytes via Aβ-putriscine-MAOB axis, highlighting the sensor's relevance in validating neurodegenerative disease models. Lastly, we demonstrated acute opioid-induced generation of H2 O2 signal in vivo which highlights redox-based mechanisms of GPCR regulation. oROS is a versatile tool, offering a window into the dynamic landscape of H2 O2 signaling. This advancement paves the way for a deeper understanding of redox physiology, with significant implications for understanding diseases associated with oxidative stress, such as cancer, neurodegenerative, and cardiovascular diseases., Competing Interests: Additional Declarations: There is NO Competing Interest.- Published
- 2024
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33. Severe pulmonary hypertension associated with hypothyroidism and mixed aortic valve disease: A case report.
- Author
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Diallo TH, Nana Yeboah F, Djafarou Boubacar R, Faraj R, Boui-Issoui K, Sidi Mhamed ES, El Ghiati H, Diallo ID, Mouine N, and Benyass A
- Abstract
Pulmonary hypertension is a condition characterised by elevated pulmonary arterial pressures secondary to various aetiologies; the most common ones are left heart diseases. Similarly, an association between thyroid diseases and pulmonary hypertension has been reported in some cases, but the pathophysiological relationship has not been fully elucidated. Etiological investigation is an important step in the management of pulmonary hypertension and determines the appropriate treatment. In this report, we present a case of severe pulmonary hypertension in a 57-year-old woman, in which mixed aortic valve disease and hypothyroidism were involved., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)
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- 2024
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34. Differences in PPD- and mitogen-induced T-cell activation marker expression characterize immunopathology in acute tuberculosis patients.
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Acheampong I, Minadzi D, Laing EF, Frimpong M, Vivekanandan MM, Yeboah A, Adankwah E, Aniagyei W, Arthur JF, Lamptey M, Abass MK, Kumbel F, Osei-Yeboah F, Gawusu A, Debrah LB, Owusu DO, Debrah A, Mayatepek E, Seyfarth J, Phillips RO, and Jacobsen M
- Subjects
- Humans, Mitogens pharmacology, Tuberculin, T-Lymphocytes, Antigens, Bacterial, Tuberculosis, Mycobacterium tuberculosis
- Abstract
Impaired T-cell responses to mitogens and high T-cell activation marker (TAM) expression on Mycobacterium tuberculosis-specific T-cells characterize immunopathology in patients with tuberculosis (TB). In a study of patients with TB (n = 60) and asymptomatic contacts (controls, n = 37), we found that TB patients had higher CD38
+ T-cell proportions specific for M. tuberculosis protein (PPDMtb ), yet total proportions of PPDMtb -specific T-cells were comparable. Notably, both activated (CD38+ ) and total IFN-γ+ T-cells from TB patients had lower mitogen (phytohemagglutinin, PHA)-induced responses. This impaired mitogen response improved the classification efficacy of the TAM-TB assay, especially employing the PPD/PHA-induced T-cell ratio., (© 2024. The Author(s).)- Published
- 2024
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35. Structure-guided engineering of a fast genetically encoded sensor for real-time H 2 O 2 monitoring.
- Author
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Lee JD, Won W, Kimball K, Wang Y, Yeboah F, Evitts KM, Neiswanger C, Schattauer S, Rappleye M, Bremner SB, Chun C, Smith N, Mack DL, Young JE, Lee CJ, Chavkin C, and Berndt A
- Abstract
Hydrogen Peroxide (H
2 O2 ) is a central oxidant in redox biology due to its pleiotropic role in physiology and pathology. However, real-time monitoring of H2 O2 in living cells and tissues remains a challenge. We address this gap with the development of an optogenetic hydRogen perOxide Sensor (oROS), leveraging the bacterial peroxide binding domain OxyR. Previously engineered OxyR-based fluorescent peroxide sensors lack the necessary sensitivity or response speed for effective real-time monitoring. By structurally redesigning the fusion of Escherichia coli (E. coli) ecOxyR with a circularly permutated green fluorescent protein (cpGFP), we created a novel, green-fluorescent peroxide sensor oROS-G. oROS-G exhibits high sensitivity and fast on-and-off kinetics, ideal for monitoring intracellular H2 O2 dynamics. We successfully tracked real-time transient and steady-state H2 O2 levels in diverse biological systems, including human stem cell-derived neurons and cardiomyocytes, primary neurons and astrocytes, and mouse neurons and astrocytes in ex vivo brain slices. These applications demonstrate oROS's capabilities to monitor H2 O2 as a secondary response to pharmacologically induced oxidative stress, G-protein coupled receptor (GPCR)-induced cell signaling, and when adapting to varying metabolic stress. We showcased the increased oxidative stress in astrocytes via Aβ-putriscine-MAOB axis, highlighting the sensor's relevance in validating neurodegenerative disease models. oROS is a versatile tool, offering a window into the dynamic landscape of H2 O2 signaling. This advancement paves the way for a deeper understanding of redox physiology, with significant implications for diseases associated with oxidative stress, such as cancer, neurodegenerative disorders, and cardiovascular diseases.- Published
- 2024
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36. Diminished Interleukin-7 receptor expression on T-cell subsets in tuberculosis patients.
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Acheampong I, Minadzi D, Adankwah E, Aniagyei W, Vivekanandan MM, Yeboah A, Arthur JF, Lamptey M, Abass MK, Kumbel F, Osei-Yeboah F, Gawusu A, Laing EF, Batsa Debrah L, Owusu DO, Debrah A, Mayatepek E, Seyfarth J, Phillips RO, and Jacobsen M
- Subjects
- Humans, CD4-Positive T-Lymphocytes metabolism, CD8-Positive T-Lymphocytes metabolism, Interleukin-7 metabolism, T-Lymphocyte Subsets metabolism, Receptors, Interleukin-7 genetics, Receptors, Interleukin-7 metabolism, Tuberculosis
- Abstract
Immunopathology in human tuberculosis affects T-cell phenotype and functions. Previous studies identified impaired T-cell sensitivity to Interleukin (IL)-7 accompanied by lower IL-7 receptor α-chain (IL-7Rα) expression in patients with acute tuberculosis. In the present study, we characterized affected T-cell subsets and determined the influence of tuberculosis disease severity and treatment response. Tuberculosis patients (n = 89) as well as age- and gender-matched asymptomatic contacts (controls, n = 47) were recruited in Ghana. Mycobacterium (M.) tuberculosis sputum burden was monitored prior to and during treatment. Blood samples from all patients and controls were analyzed for IL-7Rα expression and T-cell markers by multi-colour flow cytometry. CD4
+ and CD8+ T-cells of tuberculosis patients showed generally lower IL-7Rα expression as compared to controls. Concomitantly, tuberculosis patients had higher proportions of naïve and lower proportions of memory CD4+ T-cells. Notably, a subset of CD27 positive central memory T-cells (Tcm ), which lacked IL-7Rα expression was enriched in tuberculosis patients as compared to controls. M. tuberculosis sputum burden was not associated with differences in IL-7Rα expression. Treatment duration and response showed no clear effects although IL-7Rα expression patterns were highly variable. These results suggested generally impaired generation of memory CD4+ T-cells and enrichment of a Tcm subset without IL-7Rα expression in patients with tuberculosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)- Published
- 2023
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37. Effect of drug loading and relative humidity on the mechanical properties and tableting performance of Celecoxib-PVP/VA 64 amorphous solid dispersions.
- Author
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Osei-Yeboah F and Sun CC
- Subjects
- Celecoxib, Humidity, Elastic Modulus, Pyrrolidines
- Abstract
The mechanical properties of polymer-based amorphous solid dispersions (ASDs) are susceptible to changes in relative humidity (RH) conditions. The purpose of this study is to understand the impact of RH on both the mechanical properties and tableting performance of Celecoxib-polyvinyl pyrrolidone vinyl acetate co-polymer (PVP/VA 64) ASDs. The ASDs were prepared by solvent evaporation technique to obtain films for nanoindentation, which were also pulverized to obtain powder for compaction. Our results show that higher RH corresponds to lower Hardness, H, and Elastic Modulus, E. At a given RH, both the E and H increase with drug loading to a maximum and decrease with further drug loading. Using ASD powders with a narrow particle size range (d50 = 9-14 µm), we have demonstrated that increasing RH from 11% to 67% leads to improved tablet tensile strength for pure PVP/VA 64 and the ASDs. However, the extent of the increase in tablet tensile strength depends on their mechanical properties, H and E, and drug loading. At a higher compaction pressure and a higher RH, the effect of ASD mechanical properties on tabletability is less because the particles are nearly fully deformed so that bonding areas are approximately the same. Thus, difference in tablet strength is mainly contributed by the inter-particulate forces of attraction. Understanding the impact of these key processing conditions, i.e., RH and compaction pressure, will guide the design of an ASD tablet formulation with robust manufacturability., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)
- Published
- 2023
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38. Monocyte pathology in human tuberculosis is due to plasma milieu changes and aberrant STAT signalling.
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Ahor HS, Schulte R, Adankwah E, Harelimana JD, Minadzi D, Acheampong I, Vivekanandan MM, Aniagyei W, Yeboah A, Arthur JF, Lamptey M, Abass MK, Kumbel F, Osei-Yeboah F, Gawusu A, Debrah LB, Owusu DO, Debrah A, Mayatepek E, Seyfarth J, Phillips RO, and Jacobsen M
- Subjects
- Humans, Macrophages, CD40 Antigens, Plasma, Monocytes, Tuberculosis
- Abstract
Monocyte-derived macrophages contribute centrally to immune protection in Mycobacterium tuberculosis infection and changes in monocyte phenotype characterize immunopathology in tuberculosis patients. Recent studies highlighted an important role of the plasma milieu in tuberculosis immunopathology. Here, we investigated monocyte pathology in patients with acute tuberculosis and determined tuberculosis plasma milieu effects on phenotype as well as cytokine signalling of reference monocytes. Patients with tuberculosis (n = 37) and asymptomatic contacts (controls n = 35) were recruited as part of a hospital-based study in the Ashanti region of Ghana. Multiplex flow cytometry phenotyping of monocyte immunopathology was performed and effects of individual blood plasma samples on reference monocytes prior to and during treatment were characterized. Concomitantly, cell signalling pathways were analysed to elucidate underlying mechanisms of plasma effects on monocytes. Multiplex flow cytometry visualization characterized changes in monocyte subpopulations and detected higher expression of CD40, CD64 and PD-L1 in monocytes from tuberculosis patients as compared to controls. Aberrant expression normalized during anti-mycobacterial treatment and also CD33 expression decreased markedly. Notably, higher CD33, CD40 and CD64 expression was induced in reference monocytes when cultured in the presence of plasma samples from tuberculosis patients as compared to controls. STAT signalling pathways were affected by the aberrant plasma milieu and higher levels of STAT3 and STAT5 phosphorylation was found in tuberculosis plasma-treated reference monocytes. Importantly, high pSTAT3 levels were associated with high CD33 expression and pSTAT5 correlated with CD40 as well as CD64 expression. These results suggested plasma milieu effects with potential implications on monocyte phenotype and function in acute tuberculosis., (© 2023 The Authors. Immunology published by John Wiley & Sons Ltd.)
- Published
- 2023
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39. Impaired T-cell response to phytohemagglutinin (PHA) in tuberculosis patients is associated with high IL-6 plasma levels and normalizes early during anti-mycobacterial treatment.
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Vivekanandan MM, Adankwah E, Aniagyei W, Acheampong I, Minadzi D, Yeboah A, Arthur JF, Lamptey M, Abass MK, Kumbel F, Osei-Yeboah F, Gawusu A, Debrah LB, Owusu DO, Debrah A, Mayatepek E, Seyfarth J, Phillips RO, and Jacobsen M
- Subjects
- Humans, Cytokines metabolism, Mycobacterium tuberculosis, Phytohemagglutinins pharmacology, Interferon-gamma, Interleukin-22, Interleukin-6 blood, T-Lymphocytes immunology, Tuberculosis drug therapy
- Abstract
Purpose: Human tuberculosis is characterized by immunopathology that affects T-cell phenotype and functions. Previous studies found impaired T-cell response to phytohemagglutinin (PHA) in patients with acute tuberculosis. However, the influence of disease severity, affected T-cell subsets, and underlying mechanisms remain elusive., Methods: Here we investigated PHA-induced and antigen-specific T-cell effector cytokines in tuberculosis patients (n = 55) as well as in healthy asymptomatic contacts (n = 32) from Ghana. Effects of Mycobacterium (M.) tuberculosis sputum burden and treatment response were analyzed and compared during follow-up. Finally, cytokine characteristics of the aberrant plasma milieu in tuberculosis were analyzed as a potential cause for impaired PHA response., Results: PHA-induced IFN-γ expression was significantly lower in sputum-positive tuberculosis patients as compared to both, contacts and paucibacillary cases, and efficiently discriminated the study groups. T-cell responses to PHA increased significantly early during treatment and this was more pronounced in tuberculosis patients with rapid treatment response. Analysis of alternative cytokines revealed distinct patterns and IL-22, as well as IL-10, showed comparable expression to IFN-γ in response to PHA. Finally, we found that high IL-6 plasma levels were strongly associated with impaired IFN-γ and IL-22 response to PHA., Conclusion: We conclude that impaired T-cell response to PHA stimulation in acute tuberculosis patients (i) was potentially caused by the aberrant plasma milieu, (ii) affected differentially polarized T-cell subsets, (iii) normalized early during treatment. This study shed light on the mechanisms of impaired T-cell functions in tuberculosis and yielded promising biomarker candidates for diagnosis and monitoring of treatment response., (© 2023. The Author(s).)
- Published
- 2023
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40. Diversity of cervicovaginal human papillomavirus (HPV) genotypes and naturally occurring E6/E7 DNA polymorphisms of HPV-16 in Ghana.
- Author
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Kaba G, Stevenson A, Sakyi SA, Konney TO, Bhatia R, Titiloye NA, Oppong SA, Agyemang-Yeboah F, Cuschieri K, and Graham SV
- Subjects
- Humans, Female, Human papillomavirus 16 genetics, Ghana epidemiology, Human Papillomavirus Viruses, Papillomavirus E7 Proteins genetics, Repressor Proteins genetics, Papillomaviridae genetics, DNA, Polymorphism, Single Nucleotide genetics, Genotype, Papillomavirus Infections epidemiology, Oncogene Proteins, Viral genetics
- Abstract
Human papillomavirus (HPV) E6 and E7 oncogene expression is essential for cervical carcinogenesis. Evidence exists that E6/E7 variants may have different transforming activities while the risk of HPV-16 variants (A/D) differs by race/ethnicity. We determined the type-specific diversity of HPV infection in women with high grade cervical disease or cervical cancer in Ghana and investigated naturally occurring E6/E7 DNA variants in this population. HPV genotyping was carried out on 207 cervical swab samples collected from women referred to a gynaecology clinic at two teaching hospitals in Ghana. HPV-16, HPV-18 and HPV-45 were detected in 41.9%, 23.3% and 16.3% of cases respectively. HPV-16 E6/E7 DNA sequencing was performed in 36 samples. Thirty samples contained E6/E7 variants of the HPV-16-B/C lineage. 21/36 samples were of the HPV-16C1 sublineage variant and all contained the E7 A647G(N29S) single nucleotide polymorphism (SNP). This study reveals the diversity of E6/E7 DNA and the dominance of HPV16 B/C variants in cervicovaginal HPV infection in Ghana. Type-specific HPV diversity analysis indicates that most Ghanaian cervical disease cases are vaccine preventable. The study provides an important baseline from which for the impact of vaccine and antivirals on clinically relevant HPV infection and associated disease can be measured., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2023
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41. BCG-Vaccinated Children with Contact to Tuberculosis Patients Show Delayed Conversion of Mycobacterium tuberculosis -Specific IFN-γ Release.
- Author
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Owusu DO, Adankwah E, Aniagyei W, Acheampong I, Minadzi D, Yeboah A, Arthur JF, Lamptey M, Vivekanandan MM, Abass MK, Kumbel F, Osei-Yeboah F, Gawusu A, Batsa Debrah L, Debrah A, Mayatepek E, Seyfarth J, Phillips RO, and Jacobsen M
- Abstract
Mycobacterium (M.) bovis BCG vaccination is recommended for healthy babies after birth in several countries with a high prevalence of tuberculosis, including Ghana. Previous studies showed that BCG vaccination prevents individuals from developing severe clinical manifestations of tuberculosis, but BCG vaccination effects on the induction of IFN-γ after M. tuberculosis infection have hardly been investigated. Here, we performed IFN-γ-based T-cell assays (i.e., IFN-γ Release Assay, IGRA; T-cell activation and maturation marker assay, TAM-TB) in children who had contact with index tuberculosis patients (contacts). These contacts were classified as either being BCG vaccinated at birth ( n = 77) or non-BCG-vaccinated ( n = 17) and were followed up at three timepoints for a period of one year to determine immune conversion after M. tuberculosis exposure and potential infection. At baseline and month 3, BCG-vaccinated contacts had significantly lower IFN-γ levels after stimulation with M. tuberculosis -specific proteins as compared to non-BCG-vaccinated contacts. This resulted in decreased proportions of positive IGRA results (BCG-vaccinated: 60% at baseline, 57% at month 3; non-BCG-vaccinated: 77% and 88%, respectively) at month 3. However, until month 12, immune conversion in BCG-vaccinated contacts led to balanced proportions in IGRA responders and IFN-γ expression between the study groups. TAM-TB assay analyses confirmed higher proportions of IFN-γ-positive T-cells in non-BCG-vaccinated contacts. Low proportions of CD38-positive M. tuberculosis -specific T-cells were only detected in non-BCG-vaccinated contacts at baseline. These results suggest that BCG vaccination causes delayed immune conversion as well as differences in the phenotype of M. tuberculosis -specific T-cells in BCG-vaccinated contacts of tuberculosis patients. These differences are immune biomarker candidates for protection against the development of severe clinical tuberculosis manifestations.
- Published
- 2023
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42. Plasma cytokine levels characterize disease pathogenesis and treatment response in tuberculosis patients.
- Author
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Vivekanandan MM, Adankwah E, Aniagyei W, Acheampong I, Yeboah A, Arthur JF, Lamptey MNK, Abass MK, Gawusu A, Kumbel F, Osei-Yeboah F, Debrah LB, Owusu DO, Debrah A, Mayatepek E, Seyfarth J, Phillips RO, and Jacobsen M
- Subjects
- Humans, Cytokines, Interleukin-10, Chemokine CXCL10, Interleukin-6, Tuberculosis drug therapy, Tuberculosis microbiology, Mycobacterium tuberculosis
- Abstract
Background: Mycobacterium (M.) tuberculosis-caused immunopathology is characterized by aberrant expression of plasma cytokines in human tuberculosis. Disease severity and long-term anti-mycobacterial treatment are potentially influenced by immunopathology and normalization of plasma cytokine levels during therapy may indicate treatment efficacy and recovery., Study Design and Methods: In this study, we analyzed the concentrations of selected plasma cytokines (i.e., IL-6, IP-10, IL-10, IL-22, IFNγ, GM-CSF, IL-8) and M. tuberculosis sputum burden in patients with tuberculosis (n = 76). Cytokine levels were compared to healthy contacts (n = 40) and changes under treatment were monitored (i.e., 6 and 16 weeks after treatment start). According to differences in M. tuberculosis sputum burden and conversion, tuberculosis patients were classified as paucibacillary as well as 'rapid' or 'slow' treatment responders. A subgroup of tuberculosis patients had fatal disease courses., Results: Six of seven cytokines were significantly higher in tuberculosis patients as compared to contacts and four of these (i.e., IL-6, IP-10, IL-10, and IL-22) were detectable in the majority of tuberculosis patients. IL-6 showed the strongest discriminating capacity for tuberculosis disease and in combination with IL-10 concentrations efficiently classified paucibacillary tuberculosis cases as well as those with fatal disease outcome. In addition, IL-6 and IP-10 levels decreased significantly after 6 weeks of treatment and analyses of subgroups with differential treatment response showed delayed decline of IL-6 levels in slow treatment responders., Conclusions: Combinations of different plasma cytokine (namely, IL-6, IL-10, and IP-10) efficiently classified tuberculosis patients with differential mycobacterial burden and especially IL-6 qualified as a biomarker candidate for early treatment response., (© 2022. The Author(s).)
- Published
- 2023
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43. Improving the Manufacturability of Cohesive and Poorly Compactable API for Direct Compression of Mini-tablets at High Drug Loading via Particle Engineering.
- Author
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Chen L, Lin Y, Irdam E, Madden N, and Osei-Yeboah F
- Subjects
- Powders, Particle Size, Pressure, Tablets, Drug Compounding
- Abstract
Purpose: To utilize a particle engineering strategy to improve the manufacturability of a cohesive and poorly compactable API at high drug loading for direct compression of mini-tablets., Methods: A high-shear mixer was used for wet milling during the API manufacturing process to obtain target particle size distributions. The targeted particles were characterized and formulated into blends by mixing with excipients. The formulated blends were compressed directly into mini-tablets using a compaction simulator. The tablet hardness, weight variation, and friability of the mini-tablets were characterized and compared with mini-tablets prepared with hammer milled APIs., Results: Compared to the hammer milled APIs, the wet milled APIs, had smoother surface, narrower particle size distributions and demonstrated a better flow properties. Moreover, the mini-tablets produced with the wet milled APIs exhibited better weight uniformity, robust tablet mechanical strength and ultimately better friability. In addition, unlike the hammer milled process, the wet milling process is controllable and easy to scale up., Conclusions: This study successfully implemented API particle engineering through a high shear wet milling process to produce particles suitable for robust drug product manufacturing., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2022
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44. Prevalence and Distribution of Vaccine-Preventable Genital Human Papillomavirus(HPV) Genotypes in Ghanaian Women Presenting for Screening.
- Author
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Donkoh ET, Asmah RH, Agyemang-Yeboah F, Dabo EO, and Wiredu EK
- Subjects
- Cervix Uteri, Cross-Sectional Studies, Early Detection of Cancer, Female, Genotype, Ghana epidemiology, Humans, Papillomaviridae genetics, Prevalence, Alphapapillomavirus, Papillomavirus Infections diagnosis, Papillomavirus Infections epidemiology, Papillomavirus Infections prevention & control, Papillomavirus Vaccines therapeutic use, Uterine Cervical Neoplasms diagnosis, Uterine Cervical Neoplasms epidemiology, Uterine Cervical Neoplasms prevention & control
- Abstract
Background: Cervical cancer is the most common gynaecologic cancer in Ghana where it is also the second most common cause of all female cancers. A number of vaccines are available to provide both individual and population-level protection against persistent infection with high-risk human papillomaviruses (HR-HPV) and reduce the burden of cervical cancer. Data on the epidemiology of vaccine-preventable papillomaviruses in Ghana is scant., Methods: A cross-sectional observational study was implemented from May 2011 to November 2014 to understand the epidemiology of genital human papillomavirus (HPV) genotypes and cervical dysplasia in the Greater Kumasi area of Ghana. A nested multiplex polymerase chain reaction (NMPCR) assay incorporating degenerate E6/E7 consensus primers and type-specific primers was used for the detection and typing of eighteen (18) HPV genotypes among women who had never attended cervical screening prior to this study., Results: The general prevalence of HPV infection in Kumasi was 37.2%. The age-standardized prevalence was 40.9% overall. The frequency of HR-HPV genotypes present in decreasing order were HPV-52, -56, -35, -18, -58, -68, -51, -39, -45, -16, -59, -33 and -31. Low-risk HPVs were also detected in the following order: HPV-42, -43, -66, -6/11 and -44., Conclusions: The study shows that currently available prophylactic vaccines have the potential to be useful in the primary prevention of HPV infections in the country. This study strengthens the belief that prophylactic HPV vaccination could be a long-term strategy to reduce the burden of HPV infections and potentially reduce the burden of HPV-associated cancers and epithelial cell abnormalities among health-seeking women in Kumasi. Efforts to make vaccines available to young girls should be prioritized.
- Published
- 2022
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45. Prevalence of vaccine and non-vaccine human papillomavirus types among women in Accra and Kumasi, Ghana: a cross-sectional study.
- Author
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Debrah O, Agyemang-Yeboah F, Donkoh ET, and Asmah RH
- Subjects
- Adult, Aged, Cross-Sectional Studies, Female, Genotype, Ghana epidemiology, Human papillomavirus 16, Human papillomavirus 18 genetics, Humans, Middle Aged, Papillomaviridae genetics, Prevalence, Young Adult, Papillomavirus Infections epidemiology, Papillomavirus Infections prevention & control, Papillomavirus Vaccines therapeutic use, Uterine Cervical Neoplasms epidemiology, Uterine Cervical Neoplasms prevention & control
- Abstract
Background: Human Papillomavirus (HPV) infection is the main etiological factor for pre-invasive and invasive cervical cancer. HPV type-specific vaccination is being widely recommended to control the burden of disease, but the genotype-specific distribution of HPV may vary in different countries. The aim of the study was to determine the prevalence and distribution of HPV genotypes among women attending reproductive health services in Ghana, their associated risk factors, and to assess the potential coverage of identified HPV genotypes by three licensed vaccines among these women., Method: Women presenting for reproductive health services in two regional hospitals in Accra and Kumasi from October 2014 to March 2015 were conveniently recruited into the study (n = 317). HPV-DNA detection and genotype identification were carried out by a nested multiplex PCR assay that combines degenerate E6/E7 consensus primers and type-specific primers for the detection and typing of eighteen HPV genotypes. Cytology was performed to screen women for cervical cancer lesions. Risk factors for HPV infection were analyzed by logistic regression. Statistical significance was accepted for p < 0.05., Results: The age of study participants ranged from 21 to 76 years. Among women positive for HPV, 35.0% were infected with high-risk HPV, 14.5% with probable high-risk HPV, and 17.0% with low-risk HPV. The prevalence of HPV 16/18 was 8.2%, HPV 6/11/16/18 was 9.1% and HPV 6/11/16/18/31/33/45/52/58 was 28.4%. The most prevalent among HR-HPV were types 52 (18.3%) and 58 (8.8%). HPV positivity may be associated with educational background (p < 0.001), age at first pregnancy (p = 0.028), and age at coitarche (p = 0.016)., Conclusions: Our study revealed a high prevalence of HR-HPV infection among women. The high prevalence of HR HPV indicates that multivalent vaccines will be useful for controlling HPV burden in general population contexts. The distribution of HPVs in this population suggests that of the three currently available vaccines the nonavalent vaccine, which protects against seven HPV types in addition to HPV 16 and 18, has the highest coverage of HPV infections among Ghanaian women. Healthcare officials planning to reduce the transmission of HPV and cervical cancer must consider the coverage of the nonavalent vaccine as an advantage., (© 2021. The Author(s).)
- Published
- 2021
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46. Pericardiectomy for constrictive pericarditis in a resource constraint setting.
- Author
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Okyere I, Okyere P, Ameyaw E, Brenu SG, Tamatey M, and Agyemang Yeboah F
- Abstract
Introduction: Constrictive pericarditis is the endpoint of the natural history of acute pericarditis of different aetiologies where a chronic inflammatory process results in a thickened, fibrotic and inelastic pericardium with consequent impairment of diastolic function and systemic congestion., Aim: To evaluate the clinical features, diagnosis, surgical management and outcome of patients with constrictive pericarditis as managed in a local setting of a tertiary hospital in Ghana., Material and Methods: A retrospective review of the medical records of patients who had undergone pericardiectomy for constrictive pericarditis at a teaching hospital., Results: Ten patients underwent pericardiectomy for the period of study. There were 8 (80%) males and 2 (20%) females. The mean age was 20.4 ±17.2 years. Six of the patients 6 (60%) were in NYHA class III. Preoperative diagnostics included chest X-ray, echocardiography, and computed tomography scan. The surgical approach for the pericardiectomy was median sternotomy. The mean operative time was 159.9 ±43.0 min. The mean postoperative days spent before being discharged was 6.9 ±2.3 days. Nine (90%) of the patients were in NYHA class I after a mean follow-up of 19.3 ±16.7 months. One patient died 6 weeks after surgery with heart failure and one patient was lost to follow-up., Conclusions: Surgical pericardiectomy via median sternotomy is still the standard modality of treatment for constrictive pericarditis with excellent results even in resource constraint settings., Competing Interests: The authors report no conflict of interest., (Copyright: © 2021 Polish Society of Cardiothoracic Surgeons (Polskie Towarzystwo KardioTorakochirurgów) and the editors of the Polish Journal of Cardio-Thoracic Surgery (Kardiochirurgia i Torakochirurgia Polska).)
- Published
- 2021
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47. Knock-Down of HDAC2 in Human Induced Pluripotent Stem Cell Derived Neurons Improves Neuronal Mitochondrial Dynamics, Neuronal Maturation and Reduces Amyloid Beta Peptides.
- Author
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Frankowski H, Yeboah F, Berry BJ, Kinoshita C, Lee M, Evitts K, Davis J, Kinoshita Y, Morrison RS, and Young JE
- Subjects
- Acyltransferases metabolism, Biomarkers metabolism, Brain metabolism, Brain physiology, Cell Differentiation physiology, Cells, Cultured, Humans, Mitochondria physiology, Neurodegenerative Diseases metabolism, Neurodegenerative Diseases pathology, Protein Isoforms metabolism, Amyloid beta-Peptides metabolism, Histone Deacetylase 2 metabolism, Induced Pluripotent Stem Cells metabolism, Mitochondria metabolism, Mitochondrial Dynamics physiology, Neurons metabolism, Neurons physiology
- Abstract
Histone deacetylase 2 (HDAC2) is a major HDAC protein in the adult brain and has been shown to regulate many neuronal genes. The aberrant expression of HDAC2 and subsequent dysregulation of neuronal gene expression is implicated in neurodegeneration and brain aging. Human induced pluripotent stem cell-derived neurons (hiPSC-Ns) are widely used models for studying neurodegenerative disease mechanisms, but the role of HDAC2 in hiPSC-N differentiation and maturation has not been explored. In this study, we show that levels of HDAC2 progressively decrease as hiPSCs are differentiated towards neurons. This suppression of HDAC2 inversely corresponds to an increase in neuron-specific isoforms of Endophilin-B1, a multifunctional protein involved in mitochondrial dynamics. Expression of neuron-specific isoforms of Endophilin-B1 is accompanied by concomitant expression of a neuron-specific alternative splicing factor, SRRM4 . Manipulation of HDAC2 and Endophilin-B1 using lentiviral approaches shows that the knock-down of HDAC2 or the overexpression of a neuron-specific Endophilin-B1 isoform promotes mitochondrial elongation and protects against cytotoxic stress in hiPSC-Ns, while HDAC2 knock-down specifically influences genes regulating mitochondrial dynamics and synaptogenesis. Furthermore, HDAC2 knock-down promotes enhanced mitochondrial respiration and reduces levels of neurotoxic amyloid beta peptides. Collectively, our study demonstrates a role for HDAC2 in hiPSC-neuronal differentiation, highlights neuron-specific isoforms of Endophilin-B1 as a marker of differentiating hiPSC-Ns and demonstrates that HDAC2 regulates key neuronal and mitochondrial pathways in hiPSC-Ns.
- Published
- 2021
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48. Development of a quantitative method to evaluate the printability of filaments for fused deposition modeling 3D printing.
- Author
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Xu P, Li J, Meda A, Osei-Yeboah F, Peterson ML, Repka M, and Zhan X
- Subjects
- Drug Industry, Polymers, Solubility, Excipients, Printing, Three-Dimensional
- Abstract
Lack of a conventional quantitative characterization method for filament printability has been recognized as a critical barrier to fused deposition modeling (FDM) 3D printing application. In this study, a small molecule drug, indomethacin, was utilized as a model compound. Polymers with various solubility were mixed with model drug and extruded into filaments using hot melt extrusion method. Thirty-two filaments with or without indomethacin were evaluated by texture analyzer to study the correlation between mechanical properties and the printability. Three different texture analysis methods were utilized and compared, and a parameter "toughness" calculated by stiffness test was identified to quantitatively describe the printability of filaments in the FDM 3D printer. The toughness threshold value of printable filament was defined as a process window of certain FDM printing. This study provides a quantitative way to evaluate and predict filament printability, and it has great potential to be applied to FDM filament development and quality control in the pharmaceutical industry., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2020
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49. A systematic evaluation of poloxamers as tablet lubricants.
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Dun J, Osei-Yeboah F, Boulas P, Lin Y, and Sun CC
- Subjects
- Administration, Oral, Drug Compounding, Drug Liberation, Kinetics, Ritonavir administration & dosage, Solubility, Stearic Acids chemistry, Tablets, Cellulose chemistry, Excipients chemistry, Lactose chemistry, Lubricants chemistry, Poloxamer chemistry, Ritonavir chemistry
- Abstract
Lubricants are important for both preserving the tooling of high-speed tablet presses and attaining quality tablets. Magnesium stearate (MgSt) is most commonly used due to its superior lubrication efficiency; however, it can lead to negative effects on tabletability and dissolution. In this study, we have systematically evaluated two poloxamers, P188 and P407, for their suitability as alternative tablet lubricants. For two excipients with different mechanical properties, i.e., microcrystalline cellulose and lactose, both poloxamers exhibit acceptable lubrication efficiency without negatively impacting tabletability. Compared to 1% MgSt, the performance of 2% of both poloxamers in an experimental tablet formulation of ritonavir led to better lubrication, higher tabletability, and enhanced in vitro drug release. Thus, the use of P188 and P407 as alternative tablet lubricants deserves further evaluations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2020
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50. Dynamic behaviors of α-synuclein and tau in the cellular context: New mechanistic insights and therapeutic opportunities in neurodegeneration.
- Author
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Yeboah F, Kim TE, Bill A, and Dettmer U
- Subjects
- Animals, Brain metabolism, Humans, Neurodegenerative Diseases therapy, Protein Aggregation, Pathological genetics, Protein Aggregation, Pathological metabolism, Protein Aggregation, Pathological therapy, Protein Folding, Neurodegenerative Diseases genetics, Neurodegenerative Diseases metabolism, alpha-Synuclein genetics, alpha-Synuclein metabolism, tau Proteins genetics, tau Proteins metabolism
- Abstract
α-Synuclein (αS) and tau have a lot in common. Dyshomeostasis and aggregation of both proteins are central in the pathogenesis of neurodegenerative diseases: Parkinson's disease, dementia with Lewy bodies, multi-system atrophy and other 'synucleinopathies' in the case of αS; Alzheimer's disease, frontotemporal dementia, progressive supranuclear palsy and other 'tauopathies' in the case of tau. The aggregated states of αS and tau are found to be (hyper)phosphorylated, but the relevance of the phosphorylation in health or disease is not well understood. Both tau and αS are typically characterized as 'intrinsically disordered' proteins, while both engage in transient interactions with cellular components, thereby undergoing structural changes and context-specific folding. αS transiently binds to (synaptic) vesicles forming a membrane-induced amphipathic helix; tau transiently interacts with microtubules forming an 'extended structure'. The regulation and exact nature of the interactions are not fully understood. Here we review recent and previous insights into the dynamic, transient nature of αS and tau with regard to the mode of interaction with their targets, the dwell-time while bound, and the cis and trans factors underlying the frequent switching between bound and unbound states. These aspects are intimately linked to hypotheses on how subtle changes in the transient behaviors may trigger the earliest steps in the pathogenesis of the respective brain diseases. Based on a deeper understanding of transient αS and tau conformations in the cellular context, new therapeutic strategies may emerge, and it may become clearer why existing approaches have failed or how they could be optimized., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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