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1. Outcome of Diabetic Keto Acidosis Treatment and Associated Factors Among Adult Patients Admitted to Emergency and Medical Wards at St. Paul’s Hospital, Addis Ababa Ethiopia, 2023: A Cross-Sectional Study

Author: Derse TK, Haile MT, and Chamiso TM
Subjects: morbidity, die, replacement, improvement and mortality, Specialties of internal medicine, RC581-951
Abstract: Tsegamlak Kuemlachew Derse,1 Michael Tamene Haile,2 Tekalign Markos Chamiso3 1Department of Critical and Emergency Nursing, St. Paul’s Millennium Medical College, Addis Ababa, Ethiopia; 2Department of Pediatrics and Child Health Nursing, St. Paul’s Millennium Medical College, Addis Ababa, Ethiopia; 3Department of Cardiovascular Nursing, St. Paul’s Millennium Medical College, Addis Ababa, EthiopiaCorrespondence: Tsegamlak Kuemlachew Derse; Tekalign Markos Chamiso, St.Paul’s Hospital MMC, Addis Ababa, Ethiopia, Email tsega441@gmail.com; tekalign.markos@sphmmc.edu.etBackground: Diabetic ketoacidosis is a potentially fatal disease that affects adults. Therefore, rapid detection and treatment are required to decrease mortality rates. Most of the earlier research on diabetic ketoacidosis in Ethiopia concentrated on its prevalence and associated factors. This study aimed to assess the treatment outcomes of diabetic ketoacidosis and its associated factors in adult patients admitted to St. Paul’s Hospital Millennium Medical College, Addis Ababa, Ethiopia, in 2023.Methods: This institution-based retrospective cross-sectional study was conducted with a sample size of 357. The data were entered in Epidata version 4.6 and exported to the Statistical Package for the Social Sciences (SPSS) version 25 for analysis. Adjusted Odds Ratio (AOR) with a 95% confidence interval was estimated to determine its association with outcome of treatment.Results: Three hundred fifty-seven diabetic ketoacidosis patients’ charts were reviewed. Fourteen (3.9%) diabetic ketoacidosis (DKA) patients had died. Those Patients with diabetic ketoacidosis who had acute comorbidity (presence of sepsis) (AOR = 3.24, 95% CI: 1.20– 10.2), international unit (IU) insulin administration in the 1st 24 hours (AOR = 8.046, 95% CI: 3.881– 25.32), fluid replacement in the 1st 24 hours (AOR = 5.84, 95% CI: 1.53– 10.07), and potassium replacement (AOR = 3.08, 95% CI: 1.835– 5.817) were independently associated with treatment outcome of diabetic ketoacidosis. Insulin administration for the first 24 hours more than > 60 IU insulin showed improvement in treatment outcome by 8.04 times more likely than less < 60 IU insulin administration for the first 24 hours. More > 6 liters fluid replacement in the first 24 hours had improvement in treatment outcome by 5.84 times more likely than < 6 liters fluid replacement.Conclusion: A considerable proportion of the patients with diabetic ketoacidosis died at St. Paul’s hospital millennium medical college. Stakeholders must emphasize the treatment of patients with diabetes (diabetic ketoacidosis), according to the recommendations of local and international guidelines.Keywords: morbidity, die, replacement, improvement and mortality
Published: 2023

2. The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

Author: Sepanlou, S, Safiri, S, Bisignano, C, Ikuta, K, Merat, S, Saberifiroozi, M, Poustchi, H, Tsoi, D, Colombara, D, Abdoli, A, Adedoyin, R, Afarideh, M, Agrawal, S, Ahmad, S, Ahmadian, E, Ahmadpour, E, Akinyemiju, T, Akunna, C, Alipour, V, Almasi-Hashiani, A, Almulhim, A, Al-Raddadi, R, Alvis-Guzman, N, Anber, N, Angus, C, Anoushiravani, A, Arabloo, J, Araya, E, Asmelash, D, Ataeinia, B, Ataro, Z, Atout, M, Ausloos, F, Awasthi, A, Badawi, A, Banach, M, Bejarano Ramirez, D, Bhagavathula, A, Bhala, N, Bhattacharyya, K, Biondi, A, Bolla, S, Boloor, A, Borzì, A, Butt, Z, Cámera, L, Campos-Nonato, I, Carvalho, F, Chu, D, Chung, S, Cortesi, P, Costa, V, Cowie, B, Daryani, A, de Courten, B, Demoz, G, Desai, R, Dharmaratne, S, Djalalinia, S, Do, H, Dorostkar, F, Drake, T, Dubey, M, Duncan, B, Effiong, A, Eftekhari, A, Elsharkawy, A, Etemadi, A, Farahmand, M, Farzadfar, F, Fernandes, E, Filip, I, Fischer, F, Gebremedhin, K, Geta, B, Gilani, S, Gill, P, Gutirrez, R, Haile, M, Haj-Mirzaian, A, Hamid, S, Hasankhani, M, Hasanzadeh, A, Hashemian, M, Hassen, H, Hay, S, Hayat, K, Heidari, B, Henok, A, Hoang, C, Hostiuc, M, Hostiuc, S, Hsieh, V, Igumbor, E, Ilesanmi, O, Irvani, S, Jafari Balalami, N, James, S, Jeemon, P, Jha, R, Jonas, J, Jozwiak, J, Kabir, A, Kasaeian, A, Kassaye, H, Kefale, A, Khalilov, R, Khan, M, Khan, E, Khater, A, Kim, Y, Koyanagi, A, La Vecchia, C, Lim, L, Lopez, A, Lorkowski, S, Lotufo, P, Lozano, R, Magdy Abd El Razek, M, Mai, H, Manafi, N, Manafi, A, Mansournia, M, Mantovani, L, Mazzaglia, G, Mehta, D, Mendoza, W, Menezes, R, Mengesha, M, Meretoja, T, Mestrovic, T, Miazgowski, B, Miller, T, Mirrakhimov, E, Mithra, P, Moazen, B, Moghadaszadeh, M, Mohammadian-Hafshejani, A, Mohammed, S, Mokdad, A, Montero-Zamora, P, Moradi, G, Naimzada, M, Nayak, V, Negoi, I, Nguyen, T, Ofori-Asenso, R, Oh, I, Olagunju, T, Padubidri, J, Pakshir, K, Pana, A, Pathak, M, Pourshams, A, Rabiee, N, Radfar, A, Rafiei, A, Ramezanzadeh, K, Rana, S, Rawaf, S, Rawaf, D, Reiner RC, J, Roever, L, Room, R, Roshandel, G, Safari, S, Samy, A, Sanabria, J, Sartorius, B, Schmidt, M, Senthilkumaran, S, Shaikh, M, Sharif, M, Sharifi, A, Shigematsu, M, Singh, J, Soheili, A, Suleria, H, Teklehaimanot, B, Tesfay, B, Vacante, M, Vahedian-Azimi, A, Valdez, P, Vasankari, T, Vu, G, Waheed, Y, Weldegwergs, K, Werdecker, A, Westerman, R, Wondafrash, D, Wondmieneh, A, Yeshitila, Y, Yonemoto, N, Yu, C, Zaidi, Z, Zarghi, A, Zelber-Sagi, S, Zewdie, K, Zhang, Z, Zhao, X, Naghavi, M, Malekzadeh, R, Sepanlou SG, Safiri S, Bisignano C, Ikuta KS, Merat S, Saberifiroozi M, Poustchi H, Tsoi D, Colombara DV, Abdoli A, Adedoyin RA, Afarideh M, Agrawal S, Ahmad S, Ahmadian E, Ahmadpour E, Akinyemiju T, Akunna CJ, Alipour V, Almasi-Hashiani A, Almulhim AM, Al-Raddadi RM, Alvis-Guzman N, Anber NH, Angus C, Anoushiravani A, Arabloo J, Araya EM, Asmelash D, Ataeinia B, Ataro Z, Atout MMW, Ausloos F, Awasthi A, Badawi A, Banach M, Bejarano Ramirez DF, Bhagavathula AS, Bhala N, Bhattacharyya K, Biondi A, Bolla SR, Boloor A, Borzì AM, Butt ZA, Cámera LA, Campos-Nonato IR, Carvalho F, Chu DT, Chung SC, Cortesi PA, Costa VM, Cowie BC, Daryani A, de Courten B, Demoz GT, Desai R, Dharmaratne SD, Djalalinia S, Do HT, Dorostkar F, Drake TM, Dubey M, Duncan BB, Effiong A, Eftekhari A, Elsharkawy A, Etemadi A, Farahmand M, Farzadfar F, Fernandes E, Filip I, Fischer F, Gebremedhin KBB, Geta B, Gilani SA, Gill PS, Gutirrez RA, Haile MT, Haj-Mirzaian A, Hamid SS, Hasankhani M, Hasanzadeh A, Hashemian M, Hassen HY, Hay SI, Hayat K, Heidari B, Henok A, Hoang CL, Hostiuc M, Hostiuc S, Hsieh VC, Igumbor EU, Ilesanmi OS, Irvani SSN, Jafari Balalami N, James SL, Jeemon P, Jha RP, Jonas JB, Jozwiak JJ, Kabir A, Kasaeian A, Kassaye HG, Kefale AT, Khalilov R, Khan MA, Khan EA, Khater A, Kim YJ, Koyanagi A, La Vecchia C, Lim LL, Lopez AD, Lorkowski S, Lotufo PA, Lozano R, Magdy Abd El Razek M, Mai HT, Manafi N, Manafi A, Mansournia MA, Mantovani LG, Mazzaglia G, Mehta D, Mendoza W, Menezes RG, Mengesha MM, Meretoja TJ, Mestrovic T, Miazgowski B, Miller TR, Mirrakhimov EM, Mithra P, Moazen B, Moghadaszadeh M, Mohammadian-Hafshejani A, Mohammed S, Mokdad AH, Montero-Zamora PA, Moradi G, Naimzada MD, Nayak V, Negoi I, Nguyen TH, Ofori-Asenso R, Oh IH, Olagunju TO, Padubidri JR, Pakshir K, Pana A, Pathak M, Pourshams A, Rabiee N, Radfar A, Rafiei A, Ramezanzadeh K, Rana SMM, Rawaf S, Rawaf DL, Reiner RC Jr, Roever L, Room R, Roshandel G, Safari S, Samy AM, Sanabria J, Sartorius B, Schmidt MI, Senthilkumaran S, Shaikh MA, Sharif M, Sharifi A, Shigematsu M, Singh JA, Soheili A, Suleria HAR, Teklehaimanot BF, Tesfay BE, Vacante M, Vahedian-Azimi A, Valdez PR, Vasankari TJ, Vu GT, Waheed Y, Weldegwergs KG, Werdecker A, Westerman R, Wondafrash DZ, Wondmieneh AB, Yeshitila YG, Yonemoto N, Yu C, Zaidi Z, Zarghi A, Zelber-Sagi S, Zewdie KA, Zhang ZJ, Zhao XJ, Naghavi M, Malekzadeh R., Sepanlou, S, Safiri, S, Bisignano, C, Ikuta, K, Merat, S, Saberifiroozi, M, Poustchi, H, Tsoi, D, Colombara, D, Abdoli, A, Adedoyin, R, Afarideh, M, Agrawal, S, Ahmad, S, Ahmadian, E, Ahmadpour, E, Akinyemiju, T, Akunna, C, Alipour, V, Almasi-Hashiani, A, Almulhim, A, Al-Raddadi, R, Alvis-Guzman, N, Anber, N, Angus, C, Anoushiravani, A, Arabloo, J, Araya, E, Asmelash, D, Ataeinia, B, Ataro, Z, Atout, M, Ausloos, F, Awasthi, A, Badawi, A, Banach, M, Bejarano Ramirez, D, Bhagavathula, A, Bhala, N, Bhattacharyya, K, Biondi, A, Bolla, S, Boloor, A, Borzì, A, Butt, Z, Cámera, L, Campos-Nonato, I, Carvalho, F, Chu, D, Chung, S, Cortesi, P, Costa, V, Cowie, B, Daryani, A, de Courten, B, Demoz, G, Desai, R, Dharmaratne, S, Djalalinia, S, Do, H, Dorostkar, F, Drake, T, Dubey, M, Duncan, B, Effiong, A, Eftekhari, A, Elsharkawy, A, Etemadi, A, Farahmand, M, Farzadfar, F, Fernandes, E, Filip, I, Fischer, F, Gebremedhin, K, Geta, B, Gilani, S, Gill, P, Gutirrez, R, Haile, M, Haj-Mirzaian, A, Hamid, S, Hasankhani, M, Hasanzadeh, A, Hashemian, M, Hassen, H, Hay, S, Hayat, K, Heidari, B, Henok, A, Hoang, C, Hostiuc, M, Hostiuc, S, Hsieh, V, Igumbor, E, Ilesanmi, O, Irvani, S, Jafari Balalami, N, James, S, Jeemon, P, Jha, R, Jonas, J, Jozwiak, J, Kabir, A, Kasaeian, A, Kassaye, H, Kefale, A, Khalilov, R, Khan, M, Khan, E, Khater, A, Kim, Y, Koyanagi, A, La Vecchia, C, Lim, L, Lopez, A, Lorkowski, S, Lotufo, P, Lozano, R, Magdy Abd El Razek, M, Mai, H, Manafi, N, Manafi, A, Mansournia, M, Mantovani, L, Mazzaglia, G, Mehta, D, Mendoza, W, Menezes, R, Mengesha, M, Meretoja, T, Mestrovic, T, Miazgowski, B, Miller, T, Mirrakhimov, E, Mithra, P, Moazen, B, Moghadaszadeh, M, Mohammadian-Hafshejani, A, Mohammed, S, Mokdad, A, Montero-Zamora, P, Moradi, G, Naimzada, M, Nayak, V, Negoi, I, Nguyen, T, Ofori-Asenso, R, Oh, I, Olagunju, T, Padubidri, J, Pakshir, K, Pana, A, Pathak, M, Pourshams, A, Rabiee, N, Radfar, A, Rafiei, A, Ramezanzadeh, K, Rana, S, Rawaf, S, Rawaf, D, Reiner RC, J, Roever, L, Room, R, Roshandel, G, Safari, S, Samy, A, Sanabria, J, Sartorius, B, Schmidt, M, Senthilkumaran, S, Shaikh, M, Sharif, M, Sharifi, A, Shigematsu, M, Singh, J, Soheili, A, Suleria, H, Teklehaimanot, B, Tesfay, B, Vacante, M, Vahedian-Azimi, A, Valdez, P, Vasankari, T, Vu, G, Waheed, Y, Weldegwergs, K, Werdecker, A, Westerman, R, Wondafrash, D, Wondmieneh, A, Yeshitila, Y, Yonemoto, N, Yu, C, Zaidi, Z, Zarghi, A, Zelber-Sagi, S, Zewdie, K, Zhang, Z, Zhao, X, Naghavi, M, Malekzadeh, R, Sepanlou SG, Safiri S, Bisignano C, Ikuta KS, Merat S, Saberifiroozi M, Poustchi H, Tsoi D, Colombara DV, Abdoli A, Adedoyin RA, Afarideh M, Agrawal S, Ahmad S, Ahmadian E, Ahmadpour E, Akinyemiju T, Akunna CJ, Alipour V, Almasi-Hashiani A, Almulhim AM, Al-Raddadi RM, Alvis-Guzman N, Anber NH, Angus C, Anoushiravani A, Arabloo J, Araya EM, Asmelash D, Ataeinia B, Ataro Z, Atout MMW, Ausloos F, Awasthi A, Badawi A, Banach M, Bejarano Ramirez DF, Bhagavathula AS, Bhala N, Bhattacharyya K, Biondi A, Bolla SR, Boloor A, Borzì AM, Butt ZA, Cámera LA, Campos-Nonato IR, Carvalho F, Chu DT, Chung SC, Cortesi PA, Costa VM, Cowie BC, Daryani A, de Courten B, Demoz GT, Desai R, Dharmaratne SD, Djalalinia S, Do HT, Dorostkar F, Drake TM, Dubey M, Duncan BB, Effiong A, Eftekhari A, Elsharkawy A, Etemadi A, Farahmand M, Farzadfar F, Fernandes E, Filip I, Fischer F, Gebremedhin KBB, Geta B, Gilani SA, Gill PS, Gutirrez RA, Haile MT, Haj-Mirzaian A, Hamid SS, Hasankhani M, Hasanzadeh A, Hashemian M, Hassen HY, Hay SI, Hayat K, Heidari B, Henok A, Hoang CL, Hostiuc M, Hostiuc S, Hsieh VC, Igumbor EU, Ilesanmi OS, Irvani SSN, Jafari Balalami N, James SL, Jeemon P, Jha RP, Jonas JB, Jozwiak JJ, Kabir A, Kasaeian A, Kassaye HG, Kefale AT, Khalilov R, Khan MA, Khan EA, Khater A, Kim YJ, Koyanagi A, La Vecchia C, Lim LL, Lopez AD, Lorkowski S, Lotufo PA, Lozano R, Magdy Abd El Razek M, Mai HT, Manafi N, Manafi A, Mansournia MA, Mantovani LG, Mazzaglia G, Mehta D, Mendoza W, Menezes RG, Mengesha MM, Meretoja TJ, Mestrovic T, Miazgowski B, Miller TR, Mirrakhimov EM, Mithra P, Moazen B, Moghadaszadeh M, Mohammadian-Hafshejani A, Mohammed S, Mokdad AH, Montero-Zamora PA, Moradi G, Naimzada MD, Nayak V, Negoi I, Nguyen TH, Ofori-Asenso R, Oh IH, Olagunju TO, Padubidri JR, Pakshir K, Pana A, Pathak M, Pourshams A, Rabiee N, Radfar A, Rafiei A, Ramezanzadeh K, Rana SMM, Rawaf S, Rawaf DL, Reiner RC Jr, Roever L, Room R, Roshandel G, Safari S, Samy AM, Sanabria J, Sartorius B, Schmidt MI, Senthilkumaran S, Shaikh MA, Sharif M, Sharifi A, Shigematsu M, Singh JA, Soheili A, Suleria HAR, Teklehaimanot BF, Tesfay BE, Vacante M, Vahedian-Azimi A, Valdez PR, Vasankari TJ, Vu GT, Waheed Y, Weldegwergs KG, Werdecker A, Westerman R, Wondafrash DZ, Wondmieneh AB, Yeshitila YG, Yonemoto N, Yu C, Zaidi Z, Zarghi A, Zelber-Sagi S, Zewdie KA, Zhang ZJ, Zhao XJ, Naghavi M, and Malekzadeh R.
Abstract: Background: Cirrhosis and other chronic liver diseases (collectively referred to as cirrhosis in this paper) are a major cause of morbidity and mortality globally, although the burden and underlying causes differ across locations and demographic groups. We report on results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 on the burden of cirrhosis and its trends since 1990, by cause, sex, and age, for 195 countries and territories. Methods: We used data from vital registrations, vital registration samples, and verbal autopsies to estimate mortality. We modelled prevalence of total, compensated, and decompensated cirrhosis on the basis of hospital and claims data. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost due to premature death and years lived with disability. Estimates are presented as numbers and age-standardised or age-specific rates per 100 000 population, with 95% uncertainty intervals (UIs). All estimates are presented for five causes of cirrhosis: hepatitis B, hepatitis C, alcohol-related liver disease, non-alcoholic steatohepatitis (NASH), and other causes. We compared mortality, prevalence, and DALY estimates with those expected according to the Socio-demographic Index (SDI) as a proxy for the development status of regions and countries. Findings: In 2017, cirrhosis caused more than 1·32 million (95% UI 1·27–1·45) deaths (440 000 [416 000–518 000; 33·3%] in females and 883 000 [838 000–967 000; 66·7%] in males) globally, compared with less than 899 000 (829 000–948 000) deaths in 1990. Deaths due to cirrhosis constituted 2·4% (2·3–2·6) of total deaths globally in 2017 compared with 1·9% (1·8–2·0) in 1990. Despite an increase in the number of deaths, the age-standardised death rate decreased from 21·0 (19·2–22·3) per 100 000 population in 1990 to 16·5 (15·8–18·1) per 100 000 population in 2017. Sub-Saharan Africa had the highest age-standardised death rate among GBD super-regions fo
Published: 2020

3. The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017

Author: Sepanlou, SG, Safiri, S, Bisignano, C, Ikuta, KS, Merat, S, Saberifiroozi, M, Poustchi, H, Tsoi, D, Colombara, DV, Abdoli, A, Adedoyin, RA, Afarideh, M, Agrawal, S, Ahmad, S, Ahmadian, E, Ahmadpour, E, Akinyemiju, T, Akunna, CJ, Alipour, V, Almasi-Hashiani, A, Almulhim, AM, Al-Raddadi, RM, Alvis-Guzman, N, Anber, NH, Angus, C, Anoushiravani, A, Arabloo, J, Araya, EM, Asmelash, D, Ataeinia, B, Ataro, Z, Atout, MMW, Ausloos, F, Awasthi, A, Badawi, A, Banach, M, Bejarano Ramirez, DF, Bhagavathula, AS, Bhala, N, Bhattacharyya, K, Biondi, A, Bolla, SR, Boloor, A, Borzi, AM, Butt, ZA, Alberto Camera, LLA, Campos-Nonato, IR, Carvalho, F, Dinh-Toi, C, Chung, S-C, Cortesi, PA, Costa, VM, Cowie, BC, Daryani, A, de Courten, B, Demoz, GT, Desai, R, Dharmaratne, SD, Djalalinia, S, Hoa, TD, Dorostkar, F, Drake, TM, Dubey, M, Duncan, BB, Effiong, A, Eftekhari, A, Elsharkawy, A, Etemadi, A, Farahmand, M, Farzadfar, F, Fernandes, E, Filip, I, Fischer, F, Gebremedhin, KBB, Geta, B, Gilani, SA, Gill, PS, Alma Gutierrez, R, Haile, MT, Haj-Mirzaian, A, Hamid, SS, Hasankhani, M, Hasanzadeh, A, Hashemian, M, Hassen, HY, Hay, SI, Hayat, K, Heidari, B, Henok, A, Chi, LH, Hostiuc, M, Hostiuc, S, Hsieh, VC-R, Igumbor, EU, Ilesanmi, OS, Irvani, SSN, Balalami, NJ, James, SL, Jeemon, P, Jha, RP, Jonas, JB, Jozwiak, JJ, Kabir, A, Kasaeian, A, Kassaye, HG, Kefale, AT, Khan, RKMA, Khan, EA, Khater, A, Kim, YJ, Koyanagi, A, La Vecchia, C, Lim, L-L, Lopez, AD, Lorkowski, S, Lotufo, PA, Lozano, R, Abd El Razek, MM, Hue, TM, Manafi, N, Manafi, A, Mansournia, MA, Mantovani, LG, Mazzaglia, G, Mehta, D, Mendoza, W, Menezes, RG, Mengesha, MM, Meretoja, TJ, Mestrovic, T, Miazgowski, B, Miller, TR, Mirrakhimov, EM, Mithra, P, Moazen, B, Moghadaszadeh, M, Mohammadian-Hafshejani, A, Mohammed, S, Mokdad, AH, Montero-Zamora, PA, Moradi, G, Naimzada, MD, Nayak, V, Negoi, I, Trang, HN, Ofori-Asenso, R, Oh, I-H, Olagunju, TO, Padubidri, JR, Pakshir, K, Pana, A, Pathak, M, Pourshams, A, Rabiee, N, Radfar, A, Rafiei, A, Ramezanzadeh, K, Rana, SMM, Rawaf, S, Rawaf, DL, Reiner, RC, Roever, L, Room, R, Roshandel, G, Safari, S, Samy, AM, Sanabria, J, Sartorius, B, Schmidt, MI, Senthilkumaran, S, Shaikh, MA, Sharif, M, Sharifi, A, Shigematsu, M, Singh, JA, Soheili, A, Suleria, HAR, Teklehaimanot, BF, Tesfay, BE, Vacante, M, Vahedian-Azimi, A, Valdez, PR, Vasankari, TJ, Giang, TV, Waheed, Y, Weldegwergs, KG, Werdecker, A, Westerman, R, Wondafrash, DZ, Wondmieneh, AB, Yeshitila, YG, Yonemoto, N, Yu, C, Zaidi, Z, Zarghi, A, Zelber-Sagi, S, Zewdie, KA, Zhang, Z-J, Zhao, X-J, Naghavi, M, Malekzadeh, R, Sepanlou, SG, Safiri, S, Bisignano, C, Ikuta, KS, Merat, S, Saberifiroozi, M, Poustchi, H, Tsoi, D, Colombara, DV, Abdoli, A, Adedoyin, RA, Afarideh, M, Agrawal, S, Ahmad, S, Ahmadian, E, Ahmadpour, E, Akinyemiju, T, Akunna, CJ, Alipour, V, Almasi-Hashiani, A, Almulhim, AM, Al-Raddadi, RM, Alvis-Guzman, N, Anber, NH, Angus, C, Anoushiravani, A, Arabloo, J, Araya, EM, Asmelash, D, Ataeinia, B, Ataro, Z, Atout, MMW, Ausloos, F, Awasthi, A, Badawi, A, Banach, M, Bejarano Ramirez, DF, Bhagavathula, AS, Bhala, N, Bhattacharyya, K, Biondi, A, Bolla, SR, Boloor, A, Borzi, AM, Butt, ZA, Alberto Camera, LLA, Campos-Nonato, IR, Carvalho, F, Dinh-Toi, C, Chung, S-C, Cortesi, PA, Costa, VM, Cowie, BC, Daryani, A, de Courten, B, Demoz, GT, Desai, R, Dharmaratne, SD, Djalalinia, S, Hoa, TD, Dorostkar, F, Drake, TM, Dubey, M, Duncan, BB, Effiong, A, Eftekhari, A, Elsharkawy, A, Etemadi, A, Farahmand, M, Farzadfar, F, Fernandes, E, Filip, I, Fischer, F, Gebremedhin, KBB, Geta, B, Gilani, SA, Gill, PS, Alma Gutierrez, R, Haile, MT, Haj-Mirzaian, A, Hamid, SS, Hasankhani, M, Hasanzadeh, A, Hashemian, M, Hassen, HY, Hay, SI, Hayat, K, Heidari, B, Henok, A, Chi, LH, Hostiuc, M, Hostiuc, S, Hsieh, VC-R, Igumbor, EU, Ilesanmi, OS, Irvani, SSN, Balalami, NJ, James, SL, Jeemon, P, Jha, RP, Jonas, JB, Jozwiak, JJ, Kabir, A, Kasaeian, A, Kassaye, HG, Kefale, AT, Khan, RKMA, Khan, EA, Khater, A, Kim, YJ, 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Werdecker, A, Westerman, R, Wondafrash, DZ, Wondmieneh, AB, Yeshitila, YG, Yonemoto, N, Yu, C, Zaidi, Z, Zarghi, A, Zelber-Sagi, S, Zewdie, KA, Zhang, Z-J, Zhao, X-J, Naghavi, M, and Malekzadeh, R
Abstract: BACKGROUND: Cirrhosis and other chronic liver diseases (collectively referred to as cirrhosis in this paper) are a major cause of morbidity and mortality globally, although the burden and underlying causes differ across locations and demographic groups. We report on results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 on the burden of cirrhosis and its trends since 1990, by cause, sex, and age, for 195 countries and territories. METHODS: We used data from vital registrations, vital registration samples, and verbal autopsies to estimate mortality. We modelled prevalence of total, compensated, and decompensated cirrhosis on the basis of hospital and claims data. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost due to premature death and years lived with disability. Estimates are presented as numbers and age-standardised or age-specific rates per 100 000 population, with 95% uncertainty intervals (UIs). All estimates are presented for five causes of cirrhosis: hepatitis B, hepatitis C, alcohol-related liver disease, non-alcoholic steatohepatitis (NASH), and other causes. We compared mortality, prevalence, and DALY estimates with those expected according to the Socio-demographic Index (SDI) as a proxy for the development status of regions and countries. FINDINGS: In 2017, cirrhosis caused more than 1·32 million (95% UI 1·27-1·45) deaths (440 000 [416 000-518 000; 33·3%] in females and 883 000 [838 000-967 000; 66·7%] in males) globally, compared with less than 899 000 (829 000-948 000) deaths in 1990. Deaths due to cirrhosis constituted 2·4% (2·3-2·6) of total deaths globally in 2017 compared with 1·9% (1·8-2·0) in 1990. Despite an increase in the number of deaths, the age-standardised death rate decreased from 21·0 (19·2-22·3) per 100 000 population in 1990 to 16·5 (15·8-18·1) per 100 000 population in 2017. Sub-Saharan Africa had the highest age-standardised death rate among GBD super-regions fo
Published: 2020

4. Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017

Author: Lozano, Rafael, Fullman, Nancy, Abate, Degu, Abay, Solomon M, Abbafati, Cristiana, Abbasi, Nooshin, Abbastabar, Hedayat, Abd-Allah, Foad, Abdela, Jemal, Abdelalim, Ahmed, Abdel-Rahman, Omar, Abdi, Alireza, Abdollahpour, Ibrahim, Abdulkader, Rizwan Suliankatchi, Abebe, Nebiyu Dereje, Abebe, Zegeye, Abejie, Ayenew Negesse, Abera, Semaw F, Abil, Olifan Zewdie, Aboyans, Victor, Abraha, Haftom Niguse, Abrham, Aklilu Roba, Abu-Raddad, Laith Jamal, Abu-Rmeileh, Niveen Me, Abyu, Gebre Y, Accrombessi, Manfred Mario Kokou, Acharya, Dilaram, Acharya, Pawan, Adamu, Abdu A, Adebayo, Oladimeji M, Adedeji, Isaac Akinkunmi, Adedoyin, Rufus Adesoji, Adekanmbi, Victor, Adetokunboh, Olatunji O, Adhena, Beyene Meressa, Adhikari, Tara Ballav, Adib, Mina G, Adou, Arsène Kouablan, Adsuar, Jose C, Afarideh, Mohsen, Afshari, Mahdi, Afshin, Ashkan, Agarwal, Gina, Aghayan, Sargis Aghasi, Agius, Dominic, Agrawal, Anurag, Agrawal, Sutapa, Ahmadi, Alireza, Ahmadi, Mehdi, Ahmadieh, Hamid, Ahmed, Muktar Beshir, Ahmed, Sayem, Akalu, Temesgen Yihunie, Akanda, Ali S, Akbari, Mohammad Esmaeil, Akibu, Mohammed, Akinyemi, Rufus Olusola, Akinyemiju, Tomi, Akseer, Nadia, Alahdab, Fares, Al-Aly, Ziyad, Alam, Khurshid, Alam, Tahiya, Albujeer, Ammar, Alebel, Animut, Alene, Kefyalew Addis, Al-Eyadhy, Ayman, Alhabib, Samia, Ali, Raghib, Alijanzadeh, Mehran, Alizadeh-Navaei, Reza, Aljunid, Syed Mohamed, Alkerwi, Ala'a, Alla, François, Allebeck, Peter, Allen, Christine A, Almasi, Ali, Al-Maskari, Fatma, Al-Mekhlafi, Hesham M, Alonso, Jordi, Al-Raddadi, Rajaa M, Alsharif, Ubai, Altirkawi, Khalid, Alvis-Guzman, Nelson, Amare, Azmeraw T, Amenu, Kebede, Amini, Erfan, Ammar, Walid, Anber, Nahla Hamed, Anderson, Jason A, Andrei, Catalina Liliana, Androudi, Sofia, Animut, Megbaru Debalkie, Anjomshoa, Mina, Ansari, Hossein, Ansariadi, Ansariadi, Ansha, Mustafa Geleto, Antonio, Carl Abelardo T, Anwari, Palwasha, Appiah, Lambert Tetteh, Aremu, Olatunde, Areri, Habtamu Abera, Ärnlöv, Johan, Arora, Monika, 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Subjects: GENDER-DIFFERENCES, SUICIDE, Medicine (all), Burden of Disease Study 2017, SDG, CONSUMPTION, 11 Medical And Health Sciences, GBD, Sustainable Development Goals, PREVENTION, ALCOHOL-USE, CARDIOVASCULAR-DISEASE, SMOKING PREVALENCE, General & Internal Medicine, factors risk, Medicine and Health Sciences, Human medicine, CESSATION, PERSPECTIVE, TRANSITION
Abstract: Background Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of "leaving no one behind", it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health -related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990-2017, projected indicators to 2030, and analysed global attainment. Methods We measured progress on 41 health-related S DG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health related SDG index, we transformed the value for each indicator on a scale of 0-100, with 0 as the 2.5th percentile and 100 as the 97.5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings The global median health-related SDG index in 2017 was 59.4 (IQR 35.4-67.3), ranging from a low of 11.6 (95% uncertainty interval 9.6-14.0) to a high of 84.9 (83.1-86.7). SDG index values in countries assessed at the subnational level varied substantially particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attaimnent by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation The GBD study offers a unique, robust platform for monitoring the health -related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health -related SDG indicators, NCDs, NCD-related risks, and violence -related indicators will require a concerted shift away from what might have driven past gains curative interventions in the case of NCDs towards multisectoral, prevention -oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the S DGs. What is clear is that our actions or inaction today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030. Copyright (C) 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
Published: 2018

5. Identification of the drug/metabolite transporter 1 as a marker of quinine resistance in a NF54×Cam3.II P. falciparum genetic cross.

Author: Kanai M, Mok S, Yeo T, Shears MJ, Ross LS, Jeon JH, Narwal S, Haile MT, Tripathi AK, Mlambo G, Kim J, Gil-Iturbe E, Okombo J, Fairhurst KJ, Bloxham T, Bridgford JL, Sheth T, Ward KE, Park H, Rozenberg FD, Quick M, Mancia F, Lee MCS, Small-Saunders JL, Uhlemann AC, Sinnis P, and Fidock DA
Abstract: The genetic basis of Plasmodium falciparum resistance to quinine (QN), a drug used to treat severe malaria, has long been enigmatic. To gain further insight, we used FRG-NOD human liver-chimeric mice to conduct a P. falciparum genetic cross between QN-sensitive and QN-resistant parasites, which also differ in their susceptibility to chloroquine (CQ). By applying different selective conditions to progeny pools prior to cloning, we recovered 120 unique recombinant progeny. These progeny were subjected to drug profiling and QTL analyses with QN, CQ, and monodesethyl-CQ (md-CQ, the active metabolite of CQ), which revealed predominant peaks on chromosomes 7 and 12, consistent with a multifactorial mechanism of resistance. A shared chromosome 12 region mapped to resistance to all three antimalarials and was preferentially co-inherited with pfcrt . We identified an ATP-dependent zinc metalloprotease (FtsH1) as one of the top candidates and observed using CRISPR/Cas9 SNP-edited lines that ftsh1 is a potential mediator of QN resistance and a modulator of md-CQ resistance. As expected, CQ and md-CQ resistance mapped to a chromosome 7 region harboring pfcrt . However, for QN, high-grade resistance mapped to a chromosome 7 peak centered 295kb downstream of pfcrt . We identified the drug/metabolite transporter 1 (DMT1) as the top candidate due to its structural similarity to PfCRT and proximity to the peak. Deleting DMT1 in QN-resistant Cam3.II parasites significantly sensitized the parasite to QN but not to the other drugs tested, suggesting that DMT1 mediates QN response specifically. We localized DMT1 to structures associated with vesicular trafficking, as well as the parasitophorous vacuolar membrane, lipid bodies, and the digestive vacuole. We also observed that mutant DMT1 transports more QN than the wild-type isoform in vitro . Our study demonstrates that DMT1 is a novel marker of QN resistance and a new chromosome 12 locus associates with CQ and QN response, with ftsh1 is a potential candidate, suggesting these genes should be genotyped in surveillance and clinical settings.
Published: 2024
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6. A Plasmodium falciparum genetic cross reveals the contributions of pfcrt and plasmepsin II/III to piperaquine drug resistance.

Author: Kane J, Li X, Kumar S, Button-Simons KA, Vendrely Brenneman KM, Dahlhoff H, Sievert MAC, Checkley LA, Shoue DA, Singh PP, Abatiyow BA, Haile MT, Nair S, Reyes A, Tripura R, Peto TJ, Lek D, Mukherjee A, Kappe SHI, Dhorda M, Nkhoma SC, Cheeseman IH, Vaughan AM, Anderson TJC, and Ferdig MT
Subjects: Malaria, Falciparum parasitology, Malaria, Falciparum drug therapy, Humans, Alleles, Cambodia, Mutation, Piperazines, Plasmodium falciparum genetics, Plasmodium falciparum drug effects, Protozoan Proteins genetics, Protozoan Proteins metabolism, Drug Resistance genetics, Antimalarials pharmacology, Quinolines pharmacology, Aspartic Acid Endopeptidases genetics, Aspartic Acid Endopeptidases metabolism, Membrane Transport Proteins genetics
Abstract: Piperaquine (PPQ) is widely used in combination with dihydroartemisinin as a first-line treatment against malaria. Multiple genetic drivers of PPQ resistance have been reported, including mutations in the Plasmodium falciparum chloroquine resistance transporter ( pfcrt ) and increased copies of plasmepsin II/III ( pm2/3 ). We generated a cross between a Cambodia-derived multidrug-resistant KEL1/PLA1 lineage isolate (KH004) and a drug-susceptible Malawian parasite (Mal31). Mal31 harbors a wild-type (3D7-like) pfcrt allele and a single copy of pm2/3 , while KH004 has a chloroquine-resistant (Dd2-like) pfcrt allele with an additional G367C substitution and multiple copies of pm2/3 . We recovered 104 unique recombinant parasites and examined a targeted set of progeny representing all possible combinations of variants at pfcrt and pm2/3 . We performed a detailed analysis of competitive fitness and a range of PPQ susceptibility phenotypes with these progenies, including PPQ survival assay, area under the dose response curve, and a limited point IC 50 . We find that inheritance of the KH004 pfcrt allele is required for reduced PPQ sensitivity, whereas copy number variation in pm2/3 further decreases susceptibility but does not confer resistance in the absence of additional mutations in pfcrt . A deep investigation of genotype-phenotype relationships demonstrates that progeny clones from experimental crosses can be used to understand the relative contributions of pfcrt , pm2/3 , and parasite genetic background to a range of PPQ-related traits. Additionally, we find that the resistance phenotype associated with parasites inheriting the G367C substitution in pfcrt is consistent with previously validated PPQ resistance mutations in this transporter.IMPORTANCEResistance to piperaquine, used in combination with dihydroartemisinin, has emerged in Cambodia and threatens to spread to other malaria-endemic regions. Understanding the causal mutations of drug resistance and their impact on parasite fitness is critical for surveillance and intervention and can also reveal new avenues to limiting the evolution and spread of drug resistance. An experimental genetic cross is a powerful tool for pinpointing the genetic determinants of key drug resistance and fitness phenotypes and has the distinct advantage of quantifying the effects of naturally evolved genetic variation. Our study was strengthened since the full range of copies of KH004 pm2/3 was inherited among the progeny clones, allowing us to directly test the role of the pm2/3 copy number on resistance-related phenotypes in the context of a unique pfcrt allele. Our multigene model suggests an important role for both loci in the evolution of this multidrug-resistant parasite lineage., Competing Interests: The authors declare no conflict of interest.
Published: 2024
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7. A Plasmodium falciparum genetic cross reveals the contributions of pfcrt and plasmepsin II/III to piperaquine drug resistance.

Author: Kane J, Li X, Kumar S, Button-Simons KA, Brenneman KMV, Dahlhoff H, Sievert MAC, Checkley LA, Shoue DA, Singh PP, Abatiyow BA, Haile MT, Nair S, Reyes A, Tripura R, Peto T, Lek D, Kappe SHI, Dhorda M, Nkhoma SC, Cheeseman IH, Vaughan AM, Anderson TJC, and Ferdig MT
Abstract: Piperaquine (PPQ) is widely used in combination with dihydroartemisinin (DHA) as a first-line treatment against malaria parasites. Multiple genetic drivers of PPQ resistance have been reported, including mutations in the Plasmodium falciparum chloroquine resistance transporter ( pfcrt ) and increased copies of plasmepsin II/III ( pm2/3 ). We generated a cross between a Cambodia-derived multi-drug resistant KEL1/PLA1 lineage isolate (KH004) and a drug susceptible parasite isolated in Malawi (Mal31). Mal31 harbors a wild-type (3D7-like ) pfcrt allele and a single copy of pm2/3, while KH004 has a chloroquine-resistant (Dd2-like ) pfcrt allele with an additional G367C substitution and four copies of pm2/3 . We recovered 104 unique recombinant progeny and examined a targeted set of progeny representing all possible combinations of variants at pfcrt and pm2/3 for detailed analysis of competitive fitness and a range of PPQ susceptibility phenotypes, including PPQ survival assay (PSA), area under the dose-response curve (AUC), and a limited point IC 50 (LP-IC 50 ). We find that inheritance of the KH004 pfcrt allele is required for PPQ resistance, whereas copy number variation in pm2/3 further enhances resistance but does not confer resistance in the absence of PPQ-R-associated mutations in pfcrt . Deeper investigation of genotype-phenotype relationships demonstrates that progeny clones from experimental crosses can be used to understand the relative contributions of pfcrt, pm2/3, and parasite genetic background, to a range of PPQ-related traits and confirm the critical role of the PfCRT G367C substitution in PPQ resistance.
Published: 2023
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8. Predictors of obesity among school-age children in Debre Berhan City, Ethiopia.

Author: Ayele AN, Mekonen AG, Seid A, Mitikie EG, Abayneh AD, and Haile MT
Abstract: Background: Obesity causes a serious diet-related chronic disease, including type-2 diabetes, cardiovascular disease, hypertension, osteoarthritis, and certain forms of cancer. In Sub- Saharan Africa including Ethiopia, most nutritional interventions mainly focused on a child undernutrition and ignored the impacts of obesity among children. In Ethiopia, the magnitude and associated factors of obesity among school-age children were not clearly described. Therefore this study assesses the predictors of obesity among school- age children in Debre Berhan City, Ethiopia, 2022., Methods: A cross-sectional study design was conducted from June to July, 2022. Participants were selected by using multistage sampling method. Data were collected using pre-tested and structured questions. Data were coded and entered in Epi-data version 4.6 and exported and analyzed using SPSS version 25., Result: A total of 600 children were participating in the study. The prevalence of obesity was 10.7% (95% CI: 8.3, 13.2). In this study, attending at private school (AOR = 4.24, 95% CI: 1.58, 11.32), children aged between 10-12years (AOR = 2.67, 95% CI: 1.30, 5.48), soft drink available in home (AOR = 2.27, 95% CI: 1.25,18.13), Loneliness (AOR = 1.67 95% CI: 1.12, 3.15) and mothers with occupational status of daily labour (AOR = 8.54 95% CI: 1.12, 65.39) were significantly associated with childhood obesity., Conclusion: In this study, the overall magnitude of childhood obesity was (10.7%) which means one in eleven children and relatively high as compare to the EDHS survey. Therefore, more attention should be given to strengthening physical activities, providing nutritional education, and creating community awareness about healthy diets as well as other preventive measures., Competing Interests: The authors declare that they have no competing interests exist., (Copyright: © 2023 Ayele et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Published: 2023
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9. Chloroquine resistance evolution in Plasmodium falciparum is mediated by the putative amino acid transporter AAT1.

Author: Amambua-Ngwa A, Button-Simons KA, Li X, Kumar S, Brenneman KV, Ferrari M, Checkley LA, Haile MT, Shoue DA, McDew-White M, Tindall SM, Reyes A, Delgado E, Dalhoff H, Larbalestier JK, Amato R, Pearson RD, Taylor AB, Nosten FH, D'Alessandro U, Kwiatkowski D, Cheeseman IH, Kappe SHI, Avery SV, Conway DJ, Vaughan AM, Ferdig MT, and Anderson TJC
Subjects: Humans, Amino Acid Transport Systems metabolism, Drug Resistance genetics, Plasmodium falciparum genetics, Plasmodium falciparum metabolism, Protozoan Proteins metabolism, Chloroquine metabolism, Chloroquine pharmacology, Malaria, Falciparum parasitology
Abstract: Malaria parasites break down host haemoglobin into peptides and amino acids in the digestive vacuole for export to the parasite cytoplasm for growth: interrupting this process is central to the mode of action of several antimalarial drugs. Mutations in the chloroquine (CQ) resistance transporter, pfcrt, located in the digestive vacuole membrane, confer CQ resistance in Plasmodium falciparum, and typically also affect parasite fitness. However, the role of other parasite loci in the evolution of CQ resistance is unclear. Here we use a combination of population genomics, genetic crosses and gene editing to demonstrate that a second vacuolar transporter plays a key role in both resistance and compensatory evolution. Longitudinal genomic analyses of the Gambian parasites revealed temporal signatures of selection on a putative amino acid transporter (pfaat1) variant S258L, which increased from 0% to 97% in frequency between 1984 and 2014 in parallel with the pfcrt1 K76T variant. Parasite genetic crosses then identified a chromosome 6 quantitative trait locus containing pfaat1 that is selected by CQ treatment. Gene editing demonstrated that pfaat1 S258L potentiates CQ resistance but at a cost of reduced fitness, while pfaat1 F313S, a common southeast Asian polymorphism, reduces CQ resistance while restoring fitness. Our analyses reveal hidden complexity in CQ resistance evolution, suggesting that pfaat1 may underlie regional differences in the dynamics of resistance evolution, and modulate parasite resistance or fitness by manipulating the balance between both amino acid and drug transport., (© 2023. The Author(s).)
Published: 2023
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10. Early life adversity impaired dorsal striatal synaptic transmission and behavioral adaptability to appropriate action selection in a sex-dependent manner.

Author: de Carvalho G, Khoja S, Haile MT, and Chen LY
Abstract: Early life adversity (ELA) is a major health burden in the United States, with 62% of adults reporting at least one adverse childhood experience. These experiences during critical stages of brain development can perturb the development of neural circuits that mediate sensory cue processing and behavioral regulation. Recent studies have reported that ELA impaired the maturation of dendritic spines on neurons in the dorsolateral striatum (DLS) but not in the dorsomedial striatum (DMS). The DMS and DLS are part of two distinct corticostriatal circuits that have been extensively implicated in behavioral flexibility by regulating and integrating action selection with the reward value of those actions. To date, no studies have investigated the multifaceted effects of ELA on aspects of behavioral flexibility that require alternating between different action selection strategies or higher-order cognitive processes, and the underlying synaptic transmission in corticostriatal circuitries. To address this, we employed whole-cell patch-clamp electrophysiology to assess the effects of ELA on synaptic transmission in the DMS and DLS. We also investigated the effects of ELA on the ability to update action control in response to outcome devaluation in an instrumental learning paradigm and reversal of action-outcome contingency in a water T-maze paradigm. At the circuit level, ELA decreased corticostriatal glutamate transmission in male but not in female mice. Interestingly, in DMS, glutamate transmission is decreased in male ELA mice, but increased in female ELA mice. ELA impaired the ability to update action control in response to reward devaluation in a context that promotes goal-directedness in male mice and induced deficits in reversal learning. Overall, our findings demonstrate the sex- and region-dependent effects of ELA on behavioral flexibility and underlying corticostriatal glutamate transmission. By establishing a link between ELA and circuit mechanisms underlying behavioral flexibility, our findings will begin to identify novel molecular mechanisms that can represent strategies for treating behavioral inflexibility in individuals who experienced early life traumatic incidents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 de Carvalho, Khoja, Haile and Chen.)
Published: 2023
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11. Conditional deletion of Neurexin-2 alters neuronal network activity in hippocampal circuitries and leads to spontaneous seizures.

Author: Haile MT, Khoja S, de Carvalho G, Hunt RF, and Chen LY
Subjects: Mice, Inbred C57BL, Animals, Mice, Mice, Knockout, Nerve Net metabolism, Male, Female, Homing Behavior, Sex Characteristics, Synaptic Transmission, Seizures genetics, Seizures metabolism, Hippocampus metabolism
Abstract: Neurexins (Nrxns) have been extensively studied for their role in synapse organization and have been linked to many neuropsychiatric disorders, including autism spectrum disorder (ASD), and epilepsy. However, no studies have provided direct evidence that Nrxns may be the key regulator in the shared pathogenesis of these conditions largely due to complexities among Nrxns and their non-canonical functions in different synapses. Recent studies identified NRXN2 mutations in ASD and epilepsy, but little is known about Nrxn2's role in a circuit-specific manner. Here, we report that conditional deletion of Nrxn2 from the hippocampus and cortex (Nrxn2 cKO) results in behavioral abnormalities, including reduced social preference and increased nestlet shredding behavior. Electrophysiological recordings identified an overall increase in hippocampal CA3→CA1 network activity in Nrxn2 cKO mice. Using intracranial electroencephalogram recordings, we observed unprovoked spontaneous reoccurring electrographic and behavioral seizures in Nrxn2 cKO mice. This study provides the first evidence that conditional deletion of Nrxn2 induces increased network activity that manifests into spontaneous recurrent seizures and behavioral impairments., (© 2023. The Author(s).)
Published: 2023
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12. Advances in neurexin studies and the emerging role of neurexin-2 in autism spectrum disorder.

Author: Khoja S, Haile MT, and Chen LY
Abstract: Over the past 3 decades, the prevalence of autism spectrum disorder (ASD) has increased globally from 20 to 28 million cases making ASD the fastest-growing developmental disability in the world. Neurexins are a family of presynaptic cell adhesion molecules that have been increasingly implicated in ASD, as evidenced by genetic mutations in the clinical population. Neurexins function as context-dependent specifiers of synapse properties and critical modulators in maintaining the balance between excitatory and inhibitory transmission (E/I balance). Disrupted E/I balance has long been established as a hallmark of ASD making neurexins excellent starting points for understanding the etiology of ASD. Herein we review neurexin mutations that have been discovered in ASD patients. Further, we discuss distinct synaptic mechanisms underlying the aberrant neurotransmission and behavioral deficits observed in different neurexin mouse models, with focus on recent discoveries from the previously overlooked neurexin-2 gene ( Nrxn2 in mice and NRXN2 in humans). Hence, the aim of this review is to provide a summary of new synaptic insights into the molecular underpinnings of ASD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Khoja, Haile and Chen.)
Published: 2023
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13. Pf SRPK1 Regulates Asexual Blood Stage Schizogony and Is Essential for Male Gamete Formation.

Author: Kumar S, Baranwal VK, Leeb AS, Haile MT, Oualim KMZ, Hertoghs N, Vaughan AM, and Kappe SHI
Subjects: Animals, Female, Humans, Male, Arginine, Crystalloid Solutions, Germ Cells, Nucleotides, Cyclic, Protein Kinases, RNA Splicing Factors, Malaria, Falciparum parasitology, Plasmodium falciparum genetics, Protein Serine-Threonine Kinases genetics, Protozoan Proteins genetics
Abstract: Serine/arginine-rich protein kinases (SRPKs) are cell cycle-regulated serine/threonine protein kinases and are important regulators of splicing factors. In this study, we functionally characterize SRPK1 of the human malaria parasite Plasmodium falciparum. P. falciparum SRPK1 ( PfSRPK1 ) was expressed in asexual blood-stage and sexual-stage gametocytes. Pfsrpk1 - parasites formed asexual schizonts that generated far fewer merozoites than wild-type parasites, causing reduced replication rates. Pfsrpk1 - parasites also showed a severe defect in the differentiation of male gametes, causing a complete block in parasite transmission to mosquitoes. RNA sequencing (RNA-seq) analysis of wild-type Pf NF54 and Pfsrpk1 - stage V gametocytes suggested a role for Pf SRPK1 in regulating transcript splicing and transcript abundance of genes coding for (i) microtubule/cilium morphogenesis-related proteins, (ii) proteins involved in cyclic nucleotide metabolic processes, (iii) proteins involved in signaling such as Pf MAP2, (iv) lipid metabolism enzymes, (v) proteins of osmophilic bodies, and (vi) crystalloid components. Our study reveals an essential role for Pf SRPK1 in parasite cell morphogenesis and suggests this kinase as a target to prevent malaria transmission from humans to mosquitoes. IMPORTANCE Plasmodium sexual stages represent a critical bottleneck in the parasite life cycle. Gametocytes taken up in an infectious blood meal by female anopheline mosquito get activated to form gametes and fuse to form short-lived zygotes, which transform into ookinetes to infect mosquitoes. In the present study, we demonstrate that Pf SRPK1 is important for merozoite formation and critical for male gametogenesis and is involved in transcript homeostasis for numerous parasite genes. Targeting Pf SRPK1 and its downstream pathways may reduce parasite replication and help achieve effective malaria transmission-blocking strategies.
Published: 2022
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14. Malaria parasites utilize two essential plasma membrane fusogens for gamete fertilization.

Author: Kumar S, Valansi C, Haile MT, Li X, Flyak K, Dwivedy A, Abatiyow BA, Leeb AS, Kennedy SY, Camargo NM, Vaughan AM, Brukman NG, Podbilewicz B, and Kappe SHI
Subjects: Animals, Cell Membrane, Female, Fertilization, Germ Cells metabolism, Humans, Male, Plasmodium falciparum genetics, Malaria, Parasites
Abstract: Cell fusion of female and male gametes is the climax of sexual reproduction. In many organisms, the Hapless 2 (HAP2) family of proteins play a critical role in gamete fusion. We find that Plasmodium falciparum, the causative agent of human malaria, expresses two HAP2 proteins: PfHAP2 and PfHAP2p. These proteins are present in stage V gametocytes and localize throughout the flagellum of male gametes. Gene deletion analysis and genetic crosses show that PfHAP2 and PfHAP2p individually are essential for male fertility and thereby, parasite transmission to the mosquito. Using a cell fusion assay, we demonstrate that PfHAP2 and PfHAP2p are both authentic plasma membrane fusogens. Our results establish nonredundant essential roles for PfHAP2 and PfHAP2p in mediating gamete fusion in Plasmodium and suggest avenues in the design of novel strategies to prevent malaria parasite transmission from humans to mosquitoes., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
Published: 2022
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15. A genetically engineered Plasmodium falciparum parasite vaccine provides protection from controlled human malaria infection.

Author: Murphy SC, Vaughan AM, Kublin JG, Fishbauger M, Seilie AM, Cruz KP, Mankowski T, Firat M, Magee S, Betz W, Kain H, Camargo N, Haile MT, Armstrong J, Fritzen E, Hertoghs N, Kumar S, Sather DN, Pinder LF, Deye GA, Galbiati S, Geber C, Butts J, Jackson LA, and Kappe SHI
Subjects: Animals, Humans, Plasmodium falciparum genetics, Sporozoites genetics, Vaccines, Attenuated, Insect Bites and Stings chemically induced, Malaria prevention & control, Malaria Vaccines, Malaria, Falciparum parasitology, Malaria, Falciparum prevention & control, Parasites
Abstract: Genetically engineered live Plasmodium falciparum sporozoites constitute a potential platform for creating consistently attenuated, genetically defined, whole-parasite vaccines against malaria through targeted gene deletions. Such genetically attenuated parasites (GAPs) do not require attenuation by irradiation or concomitant drug treatment. We previously developed a P. falciparum (Pf) GAP with deletions in P52 , P36 , and SAP1 genes (PfGAP3KO) and demonstrated its safety and immunogenicity in humans. Here, we further assessed safety, tolerability, and immunogenicity of the PfGAP3KO vaccine and tested its efficacy against controlled human malaria infection (CHMI) in malaria-naïve subjects. The vaccine was delivered by three ( n = 6) or five ( n = 8) immunizations with ~200 PfGAP3KO-infected mosquito bites per immunization. PfGAP3KO was safe and well tolerated with no breakthrough P. falciparum blood stage infections. Vaccine-related adverse events were predominately localized urticaria related to the numerous mosquito bites administered per vaccination. CHMI via bites with mosquitoes carrying fully infectious Pf NF54 parasites was carried out 1 month after the last immunization. Half of the study participants who received either three or five PfGAP3KO immunizations remained P. falciparum blood stage negative, as shown by a lack of detection of Plasmodium 18 S rRNA in the blood for 28 days after CHMI. Six protected study participants received a second CHMI 6 months later, and one remained completely protected. Thus, the PfGAP3KO vaccine was safe and immunogenic and was capable of inducing protection against sporozoite infection. These results warrant further evaluation of PfGAP3KO vaccine efficacy in dose-range finding trials with an injectable formulation.
Published: 2022
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16. Pf ARID Regulates P. falciparum Malaria Parasite Male Gametogenesis and Female Fertility and Is Critical for Parasite Transmission to the Mosquito Vector.

Author: Kumar S, Baranwal VK, Haile MT, Oualim KMZ, Abatiyow BA, Kennedy SY, Vaughan AM, and Kappe SHI
Subjects: Animals, Female, Fertility, Gametogenesis genetics, Humans, Male, Mosquito Vectors parasitology, Plasmodium falciparum physiology, Anopheles parasitology, Malaria parasitology, Malaria, Falciparum parasitology, Parasites
Abstract: Sexual reproduction of Plasmodium falciparum parasites is critical to the spread of malaria in the human population. The factors that regulate gene expression underlying formation of fertilization-competent gametes, however, remain unknown. Here, we report that P. falciparum expresses a protein with an AT-rich interaction domain (ARID) which, in other organisms, is part of chromatin remodeling complexes. P. falciparum ARID ( Pf ARID) localized to the parasite nucleus and is critical for the formation of male gametes and fertility of female gametes. Pf ARID gene deletion ( Pfarid - ) gametocytes showed downregulation of gene expression important for gametogenesis, antigenic variation, and cell signaling and for parasite development in the mosquito. Our study identifies Pf ARID as a critical nuclear protein involved in regulating the gene expression landscape of mature gametocytes. This establishes fertility and also prepares the parasite for postfertilization events that are essential for infection of the mosquito vector. IMPORTANCE Successful completion of the Plasmodium life cycle requires formation of mature gametocytes and their uptake by the female Anopheles mosquito vector in an infected blood meal. Inside the mosquito midgut the parasite undergoes gametogenesis and sexual reproduction. In the present study, we demonstrate that Pf ARID is essential for male gametogenesis and female fertility and, thereby, transmission to the mosquito vector. Pf ARID possibly regulates the chromatin landscape of stage V gametocytes and targeting Pf ARID function may provide new avenues into designing interventions to prevent malaria transmission.
Published: 2022
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17. A Malaria Parasite Cross Reveals Genetic Determinants of Plasmodium falciparum Growth in Different Culture Media.

Author: Kumar S, Li X, McDew-White M, Reyes A, Delgado E, Sayeed A, Haile MT, Abatiyow BA, Kennedy SY, Camargo N, Checkley LA, Brenneman KV, Button-Simons KA, Duraisingh MT, Cheeseman IH, Kappe SHI, Nosten F, Ferdig MT, Vaughan AM, and Anderson TJC
Subjects: Animals, Crosses, Genetic, Culture Media, Gene Frequency, Mice, Quantitative Trait Loci, Malaria, Falciparum parasitology, Plasmodium falciparum genetics, Plasmodium falciparum growth & development
Abstract: What genes determine in vitro growth and nutrient utilization in asexual blood-stage malaria parasites? Competition experiments between NF54, clone 3D7, a lab-adapted African parasite, and a recently isolated Asian parasite (NHP4026) reveal contrasting outcomes in different media: 3D7 outcompetes NHP4026 in media containing human serum, while NHP4026 outcompetes 3D7 in media containing AlbuMAX, a commercial lipid-rich bovine serum formulation. To determine the basis for this polymorphism, we conducted parasite genetic crosses using humanized mice and compared genome-wide allele frequency changes in three independent progeny populations cultured in media containing human serum or AlbuMAX. This bulk segregant analysis detected three quantitative trait loci (QTL) regions [on chromosome (chr) 2 containing aspartate transaminase AST ; chr 13 containing EBA-140; and chr 14 containing cysteine protease ATG4 ] linked with differential growth in serum or AlbuMAX in each of the three independent progeny pools. Selection driving differential growth was strong ( s = 0.10 - 0.23 per 48-hour lifecycle). We conducted validation experiments for the strongest QTL on chr 13: competition experiments between ΔEBA-140 and 3D7 wildtype parasites showed fitness reversals in the two medium types as seen in the parental parasites, validating this locus as the causative gene. These results (i) demonstrate the effectiveness of bulk segregant analysis for dissecting fitness traits in P. falciparum genetic crosses, and (ii) reveal intimate links between red blood cell invasion and nutrient composition of growth media. Use of parasite crosses combined with bulk segregant analysis will allow systematic dissection of key nutrient acquisition/metabolism and red blood cell invasion pathways in P. falciparum., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kumar, Li, McDew-White, Reyes, Delgado, Sayeed, Haile, Abatiyow, Kennedy, Camargo, Checkley, Brenneman, Button-Simons, Duraisingh, Cheeseman, Kappe, Nosten, Ferdig, Vaughan and Anderson.)
Published: 2022
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18. A Plasmodium falciparum ATP-binding cassette transporter is essential for liver stage entry into schizogony.

Author: Goswami D, Kumar S, Betz W, Armstrong JM, Haile MT, Camargo N, Parthiban C, Seilie AM, Murphy SC, Vaughan AM, and Kappe SHI
Abstract: Plasmodium sporozoites invade hepatocytes and transform into liver stages within a parasitophorous vacuole (PV). The parasites then grow and replicate their genome to form exoerythrocytic merozoites that infect red blood cells. We report that the human malaria parasite Plasmodium falciparum (Pf) expresses a C-type ATP-binding cassette transporter, Pf ABCC2, which marks the transition from invasive sporozoite to intrahepatocytic early liver stage. Using a humanized mouse infection model, we show that Pf ABCC2 localizes to the parasite plasma membrane in early and mid-liver stage parasites but is not detectable in late liver stages. Pf abcc2 - sporozoites invade hepatocytes, form a PV, and transform into liver stage trophozoites but cannot transition to exoerythrocytic schizogony and fail to transition to blood stage infection. Thus, Pf ABCC2 is an expression marker for early phases of parasite liver infection and plays an essential role in the successful initiation of liver stage replication., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)
Published: 2022
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19. A Putative Plasmodium RNA-Binding Protein Plays a Critical Role in Female Gamete Fertility and Parasite Transmission to the Mosquito Vector.

Author: Kumar S, Abatiyow BA, Haile MT, Oualim KMZ, Leeb AS, Vaughan AM, and Kappe SHI
Abstract: Plasmodium falciparum sexual stage gametocytes are critical for parasite transmission from the human host to the mosquito vector. Mature gametocytes generate fertile male (micro-) or female (macro-) gametes upon activation inside the mosquito midgut. While a number of parasite genes have been described that are critical for P. falciparum gametogenesis and fertility, no parasite gene has been shown to have a unique function in macrogametes. The genome of P. falciparum encodes numerous RNA-binding proteins. We identified a novel protein containing a putative RNA-binding domain, which we named Macrogamete-Contributed Factor Essential for Transmission (MaCFET). This protein is expressed in the asexual and sexual stages. Parasites that carry a deletion of MaCFET ( Pfmacfet¯ ), developed normally as asexual stages, indicating that its function is not essential for the asexual proliferation of the parasite in vitro . Furthermore, Pfmacfet¯ male and female gametocytes developed normally and underwent activation to form microgametes and macrogametes. However, by utilizing genetic crosses, we demonstrate that Pfmacfet¯ parasites suffer a complete female-specific defect in successful fertilization. Therefore, Pf MaCFET is a critical female-contributed factor for parasite transmission to the mosquito. Based on its putative RNA-binding properties, Pf MaCFET might be in involved in the regulation of mRNAs that encode female-specific functions for fertilization or female-contributed factors needed post fertilization., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kumar, Abatiyow, Haile, Oualim, Leeb, Vaughan and Kappe.)
Published: 2022
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20. Optimizing bulk segregant analysis of drug resistance using Plasmodium falciparum genetic crosses conducted in humanized mice.

Author: Brenneman KV, Li X, Kumar S, Delgado E, Checkley LA, Shoue DA, Reyes A, Abatiyow BA, Haile MT, Tripura R, Peto T, Lek D, Button-Simons KA, Kappe SHI, Dhorda M, Nosten F, Nkhoma SC, Cheeseman IH, Vaughan AM, Ferdig MT, and Anderson TJC
Abstract: Classical malaria parasite genetic crosses involve isolation, genotyping, and phenotyping of progeny parasites, which is time consuming and laborious. We tested a rapid alternative approach-bulk segregant analysis (BSA)-that utilizes sequencing of bulk progeny populations with and without drug selection for rapid identification of drug resistance loci. We used dihydroartemisinin (DHA) selection in two genetic crosses and investigated how synchronization, cryopreservation, and the drug selection regimen impacted BSA success. We detected a robust quantitative trait locus (QTL) at kelch13 in both crosses but did not detect QTLs at four other candidate loci. QTLs were detected using synchronized, but not unsynchronized progeny pools, consistent with the stage-specific action of DHA. We also successfully applied BSA to cryopreserved progeny pools, expanding the utility of this approach. We conclude that BSA provides a powerful approach for investigating the genetic architecture of drug resistance in Plasmodium falciparum ., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)
Published: 2022
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21. Plasmodium falciparum Calcium-Dependent Protein Kinase 4 is Critical for Male Gametogenesis and Transmission to the Mosquito Vector.

Author: Kumar S, Haile MT, Hoopmann MR, Tran LT, Michaels SA, Morrone SR, Ojo KK, Reynolds LM, Kusebauch U, Vaughan AM, Moritz RL, Kappe SHI, and Swearingen KE
Subjects: Animals, Calcium Signaling, Calcium-Calmodulin-Dependent Protein Kinases genetics, Culicidae, Gametogenesis genetics, Germ Cells metabolism, Life Cycle Stages, Malaria, Falciparum parasitology, Malaria, Falciparum transmission, Male, Phosphorylation, Plasmodium falciparum genetics, Protozoan Proteins genetics, Calcium-Calmodulin-Dependent Protein Kinases metabolism, Gametogenesis physiology, Mosquito Vectors, Plasmodium falciparum enzymology, Plasmodium falciparum metabolism
Abstract: Gametocytes of the malaria parasite Plasmodium are taken up by the mosquito vector with an infectious blood meal, representing a critical stage for parasite transmission. Calcium-independent protein kinases (CDPKs) play key roles in calcium-mediated signaling across the complex life cycle of the parasite. We sought to understand their role in human parasite transmission from the host to the mosquito vector and thus investigated the role of the human-infective parasite Plasmodium falciparum CDPK4 in the parasite life cycle. P. falciparum cdpk4 - parasites created by targeted gene deletion showed no effect in blood stage development or gametocyte development. However, cdpk4 - parasites showed a severe defect in male gametogenesis and the emergence of flagellated male gametes. To understand the molecular underpinnings of this defect, we performed mass spectrometry-based phosphoproteomic analyses of wild-type and Plasmodium falciparum cdpk4 - late gametocyte stages to identify key CDPK4-mediated phosphorylation events that may be important for the regulation of male gametogenesis. We further employed in vitro assays to identify these putative substrates of Plasmodium falciparum CDPK4. This indicated that CDPK4 regulates male gametogenesis by directly or indirectly controlling key essential events, such as DNA replication, mRNA translation, and cell motility. Taken together, our work demonstrates that PfCDPK4 is a central kinase that regulates exflagellation and thereby is critical for parasite transmission to the mosquito vector. IMPORTANCE Transmission of the malaria parasite to the mosquito vector is critical for the completion of the sexual stage of the parasite life cycle and is dependent on the release of male gametes from the gametocyte body inside the mosquito midgut. In the present study, we demonstrate that PfCDPK4 is critical for male gametogenesis and is involved in phosphorylation of proteins essential for male gamete emergence. Targeting PfCDPK4 and its substrates may provide insights into achieving effective malaria transmission-blocking strategies.
Published: 2021
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22. Emotional responses and perceived stressors of frontline medical staffs in case of COVID-19 treatment centers and obstetrics emergency in Ethiopia.

Author: Kebede MA, Demissie DB, Guddu DK, Haile MT, Bitew ZW, and Muleta MB
Subjects: Adult, Cross-Sectional Studies, Ethiopia, Female, Humans, Medical Staff, Pregnancy, SARS-CoV-2, Obstetrics, Pregnancy Complications, Infectious, Psychological Distress, COVID-19 Drug Treatment
Abstract: Background: the rapid spread of COVID-19, its lethality in severe cases and the absence of specific medicine poses a huge threat to human life and health, as well as huge impact on the mental health. Facing this critical situation, health care workers on the front line who are directly involved in the diagnosis, treatment, and care of patients with COVID-19 are at risk of developing psychological distress and other mental health symptoms including emotional disturbance., Objective: the aim of this study will be to assess the current state of emotional responses and perceived stressors of frontline medical staffs in case of Addis Ababa COVID-19 Treatment Centers and obstetrics emergency and abortion care, Ethiopia 2020., Methods: Hospital based comparative cross-section study design was conducted by using self-administered questionnaire survey from June 1st to 30th of 2020 among 133 and 266 frontline medical staffs from obstetric emergency and abortion care clinic and COVID-19 treatment centers respectively. The data were collected after getting written consent from each participant and it entered into the computer using Epi-data version 7, then exported to SPSS version 20 for further analysis. Descriptive analysis was done using frequencies & percent. All independent determinants with P-value < 0.05 were used to identify important predictors of emotional responses and perceived stressors., Result: A total of 399 frontline medical staffs were included in the study. The mean age of the respondents of those who were working in obstetrics emergency and abortion care clinic was 27.47 (SD, 3.46) years and it was 28.12 (SD, 4.09) years for the other groups. This study revealed that, 72.9 and 5.6% of the study participant from obstetrics emergency and abortion clinic and COVID-19 treatment centers had a positive emotional response, respectively. Factors such as having a low level of motivational factors (AOR 2.78, 95% CI (1.13, 6.84)), being a nurse (AOR 10.53, 95% CI (1.31, 85.26)) and working at triage (AOR 8.61, 95% CI (1.15, 64.81))) had statistically significant association with negative emotional response., Conclusion: The current study revealed that a high proportion of front line a negative emotional responses had negative emotional response. Further, almost all of the medical staffs working in COVID-19 treatment centers and at obstetrics emergency and abortion care unit had perceived the outbreak related stressors. So, providing comprehensive psychological support is warranted for health care providers working in such kinds of department or units.
Published: 2021
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23. The power and promise of genetic mapping from Plasmodium falciparum crosses utilizing human liver-chimeric mice.

Author: Button-Simons KA, Kumar S, Carmago N, Haile MT, Jett C, Checkley LA, Kennedy SY, Pinapati RS, Shoue DA, McDew-White M, Li X, Nosten FH, Kappe SH, Anderson TJC, Romero-Severson J, Ferdig MT, Emrich SJ, Vaughan AM, and Cheeseman IH
Subjects: Animals, Genetic Association Studies, Hepatocytes transplantation, Humans, Mice, Transplantation Chimera, Chromosome Mapping methods, Crosses, Genetic, Hepatocytes parasitology, Plasmodium falciparum genetics
Abstract: Genetic crosses are most powerful for linkage analysis when progeny numbers are high, parental alleles segregate evenly and numbers of inbred progeny are minimized. We previously developed a novel genetic crossing platform for the human malaria parasite Plasmodium falciparum, an obligately sexual, hermaphroditic protozoan, using mice carrying human hepatocytes (the human liver-chimeric FRG NOD huHep mouse) as the vertebrate host. We report on two genetic crosses-(1) an allopatric cross between a laboratory-adapted parasite (NF54) of African origin and a recently patient-derived Asian parasite, and (2) a sympatric cross between two recently patient-derived Asian parasites. We generated 144 unique recombinant clones from the two crosses, doubling the number of unique recombinant progeny generated in the previous 30 years. The allopatric African/Asian cross has minimal levels of inbreeding and extreme segregation distortion, while in the sympatric Asian cross, inbred progeny predominate and parental alleles segregate evenly. Using simulations, we demonstrate that these progeny provide the power to map small-effect mutations and epistatic interactions. The segregation distortion in the allopatric cross slightly erodes power to detect linkage in several genome regions. We greatly increase the power and the precision to map biomedically important traits with these new large progeny panels.
Published: 2021
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24. Incidence Density Rate of Neonatal Mortality and Predictors in Sub-Saharan Africa: A Systematic Review and Meta-Analysis.

Author: Bitew ZW, Alemu A, Ayele EG, Jember DA, Haile MT, and Worku T
Abstract: Background: Neonatal mortality in Sub-Saharan countries is remarkably high. Though there are inconsistent studies about the incidence density rate of neonatal mortalities (IDR) and predictors in Sub-Saharan Africa, they are inconclusive to policymakers and program planners. In this study, the IDR of neonatal mortalities and predictors was determined., Methods: Electronic databases (Web of Science, PubMed, EMBASE (Elsevier), Scopus, CINAHL (EBSCOhost), World Cat, Google Scholar, and Google) were explored. 20 out of 818 studies were included in this study. The IDRs and predictors of neonatal mortality were computed from studies conducted in survival analysis. Fixed and random effect models were used to compute pooled estimates. Subgroup and sensitivity analyses were performed., Results: Neonates were followed for a total of 1,095,611 neonate-days; 67142 neonate-days for neonates treated in neonatal intensive care units and 1,028,469 neonate-days for community-based studies. The IDRs of neonatal mortalities in neonatal intensive care units and in the community were 24.53 and 1.21 per 1000 person-days, respectively. The IDRs of early and late neonatal mortalities neonatal intensive care units were 22.51 and 5.09 per 1000 neonate-days, respectively. Likewise, the IDRs of early and late neonatal mortalities in the community were 0.85 and 0.31, respectively. Not initiating breastfeeding within one hour, multiple births, rural residence, maternal illness, low Apgar score, being preterm, sepsis, asphyxia, and respiratory distress syndrome were independent predictors of time to neonatal mortality in neonatal intensive care units and male gender, perceived small size, multiple births, and ANC were predictors of neonatal mortality in the community., Conclusion: The incidence density rate of neonatal mortality in Sub-Saharan Africa is significantly high. Multiple factors (neonatal and maternal) were found to be independent predictors. Strategies must be designed to address these predictors, and prospective studies could reveal other possible factors of neonatal mortalities., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020 Zebenay Workneh Bitew et al.)
Published: 2020
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25. Modern contraceptive utilization and associated factors among married pastoralist women in Bale eco-region, Bale Zone, South East Ethiopia.

Author: Belda SS, Haile MT, Melku AT, and Tololu AK
Subjects: Adolescent, Adult, Contraception methods, Contraception psychology, Cross-Sectional Studies, Ethiopia epidemiology, Female, Health Knowledge, Attitudes, Practice, Humans, Marriage, Middle Aged, Spouses ethnology, Surveys and Questionnaires, Young Adult, Contraception statistics & numerical data, Contraception Behavior statistics & numerical data, Family Planning Services statistics & numerical data, Health Services Accessibility statistics & numerical data, Islam psychology, Spouses psychology
Abstract: Background: Women who live in remote rural areas encounter different challenges against contraception and often deny the use of modern contraceptive methods. The predictors of modern contraceptive utilization by pastoralist women in the Bale eco-region could be specific and are not well known. Therefore, this study aims to assess modern contraceptive utilization and its determinants among married pastoralist women in Bale eco-region, Oromia regional state, South East Ethiopia., Methods: A community-based cross-sectional study was conducted from 20th November 2015 to 30th February 2016. A structured questionnaire was used to interview 549 married pastoralist women who were selected by multistage sampling technique. The data were analyzed by SPSS - 21 software, multivariate logistic regression analysis was used to identify predictors of modern contraceptive use at (P-value <0.05), and odds ratios with 95% confidence interval were used to assess the strength of associations between variables., Results: The current modern contraceptive method use by married pastoralist women was (20.8%). Among the total users, (78.1%) use the injectable method. The common reasons for non-use of modern contraceptive methods includes: religious-opposition (55.9%), desire for more children (28.3%), fear of side effects (25.5%), and husband's opposition (17.5%). Couple discussion (AOR = 4.63, 95%CI: 2.15, 9.98), perceived husband's approval (AOR = 8.00, 95% CI: 3.52, 18.19), discussion with health extension worker (AOR = 5.99, 95% CI: 1.81, 19.85), and perceived cultural acceptability (AOR = 2.10, 95% CI: 1.09, 4.03) were the independent predictors of modern contraceptive use by married pastoralist women in Bale eco-region., Conclusion: The study identified lower modern contraceptive method utilization by pastoralist women, and the majority of the contraceptive users rely on short- acting contraceptive methods. The uncomplimentary perceptions towards religious and cultural acceptability of modern contraceptive method were among the major reasons for lesser utilization of the methods. Family planning programs should be tailored to actively involve pastoralist women, husbands, and religious leaders in pastoralist communities.
Published: 2017
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25 results on '"Haile MT"'

1. Outcome of Diabetic Keto Acidosis Treatment and Associated Factors Among Adult Patients Admitted to Emergency and Medical Wards at St. Paul’s Hospital, Addis Ababa Ethiopia, 2023: A Cross-Sectional Study

2. The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

3. The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017

4. Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017

5. Identification of the drug/metabolite transporter 1 as a marker of quinine resistance in a NF54×Cam3.II P. falciparum genetic cross.

6. A Plasmodium falciparum genetic cross reveals the contributions of pfcrt and plasmepsin II/III to piperaquine drug resistance.

7. A Plasmodium falciparum genetic cross reveals the contributions of pfcrt and plasmepsin II/III to piperaquine drug resistance.

8. Predictors of obesity among school-age children in Debre Berhan City, Ethiopia.

9. Chloroquine resistance evolution in Plasmodium falciparum is mediated by the putative amino acid transporter AAT1.

10. Early life adversity impaired dorsal striatal synaptic transmission and behavioral adaptability to appropriate action selection in a sex-dependent manner.

11. Conditional deletion of Neurexin-2 alters neuronal network activity in hippocampal circuitries and leads to spontaneous seizures.

12. Advances in neurexin studies and the emerging role of neurexin-2 in autism spectrum disorder.

13. Pf SRPK1 Regulates Asexual Blood Stage Schizogony and Is Essential for Male Gamete Formation.

14. Malaria parasites utilize two essential plasma membrane fusogens for gamete fertilization.

15. A genetically engineered Plasmodium falciparum parasite vaccine provides protection from controlled human malaria infection.

16. Pf ARID Regulates P. falciparum Malaria Parasite Male Gametogenesis and Female Fertility and Is Critical for Parasite Transmission to the Mosquito Vector.

17. A Malaria Parasite Cross Reveals Genetic Determinants of Plasmodium falciparum Growth in Different Culture Media.

18. A Plasmodium falciparum ATP-binding cassette transporter is essential for liver stage entry into schizogony.

19. A Putative Plasmodium RNA-Binding Protein Plays a Critical Role in Female Gamete Fertility and Parasite Transmission to the Mosquito Vector.

20. Optimizing bulk segregant analysis of drug resistance using Plasmodium falciparum genetic crosses conducted in humanized mice.

21. Plasmodium falciparum Calcium-Dependent Protein Kinase 4 is Critical for Male Gametogenesis and Transmission to the Mosquito Vector.

22. Emotional responses and perceived stressors of frontline medical staffs in case of COVID-19 treatment centers and obstetrics emergency in Ethiopia.

23. The power and promise of genetic mapping from Plasmodium falciparum crosses utilizing human liver-chimeric mice.

24. Incidence Density Rate of Neonatal Mortality and Predictors in Sub-Saharan Africa: A Systematic Review and Meta-Analysis.

25. Modern contraceptive utilization and associated factors among married pastoralist women in Bale eco-region, Bale Zone, South East Ethiopia.

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