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Scrutinizing Deleterious Nonsynonymous SNPs and Their Effect on Human POLD1 Gene
- Md. Nazmul Islam Bappy, Anindita Roy, Md Gulam Rabbany Rabbi, Nusrat Jahan, Fahmida Akther Chowdhury, Syeda Farjana Hoque, Emran Hossain Sajib, Parvez Khan, Ferdaus Mohd Altaf Hossain, Kazi Md. Ali Zinnah, Giuseppe Damante
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- Journal:
- Genetics Research / Volume 2022 / 2022
- Published online by Cambridge University Press:
- 01 January 2024, e61
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POLD1 (DNA polymerase delta 1, catalytic subunit) is a protein-coding gene that encodes the large catalytic subunit (POLD1/p125) of the DNA polymerase delta (Polδ) complex. The consequence of missense or nonsynonymous SNPs (nsSNPs), which occur in the coding region of a specific gene, is the replacement of single amino acid. It may also change the structure, stability, and/or functions of the protein. Mutation in the POLD1 gene is associated with autosomal dominant predisposition to colonic adenomatous polyps, colon cancer, endometrial cancer (EDMC), breast cancer, and brain tumors. These de novo mutations in the POLD1 gene also result in autosomal dominant MDPL syndrome (mandibular hypoplasia, deafness, progeroid features, and lipodystrophy). In this study, genetic variations of POLD1 which may affect the structure and/or function were analyzed using different types of bioinformatics tools. A total of 17038 nsSNPs for POLD1 were collected from the NCBI database, among which 1317 were missense variants. Out of all missense nsSNPs, 28 were found to be deleterious functionally and structurally. Among these deleterious nsSNPs, 23 showed a conservation scale of >5, 2 were predicted to be associated with binding site formation, and one acted as a posttranslational modification site. All of them were involved in coil, extracellular structures, or helix formation, and some cause the change in size, charge, and hydrophobicity.
Association of recent respiratory illness and influenza with acute myocardial infarction among the Bangladeshi population: A case–control study
- Mohammad Abdul Aleem, C. Raina Macintyre, Bayzidur Rahman, A. K. M. Monwarul Islam, Zubair Akhtar, Fahmida Chowdhury, Firdausi Qadri, Abrar Ahmad Chughtai
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- Journal:
- Epidemiology & Infection / Volume 151 / 2023
- Published online by Cambridge University Press:
- 30 November 2023, e204
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Current evidence suggests that recent acute respiratory infections and seasonal influenza may precipitate acute myocardial infarction (AMI). This study examined the potential link between recent clinical respiratory illness (CRI) and influenza, and AMI in Bangladesh. Conducted during the 2018 influenza season at a Dhaka tertiary-level cardiovascular (CV) hospital, it included 150 AMI cases and two control groups: 44 hospitalized cardiac patients without AMI and 90 healthy individuals. Participants were matched by gender and age groups. The study focused on self-reported CRI and laboratory-confirmed influenza ascertained via quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) within the preceding week, analyzed using multivariable logistic regression. Results showed that cases reported CRI, significantly more frequently than healthy controls (27.3% vs. 13.3%, adjusted odds ratio (aOR): 2.21; 95% confidence interval (CI): 1.05–4.06), although this was not significantly different from all controls (27.3% vs. 22.4%; aOR: 1.19; 95% CI: 0.65–2.18). Influenza rates were insignificantly higher among cases than controls. The study suggests that recent respiratory illnesses may precede AMI onset among Bangladeshi patients. Infection prevention and control practices, as well as the uptake of the influenza vaccine, may be advocated for patients at high risk of acute CV events.
Alarming prevalence of Candida auris among critically ill patients in intensive care units in Dhaka City, Bangladesh
- Fahmida Chowdhury, Kamal Hussain, Sanzida Khan Khan, Dilruba Ahmed, Debashis Sen, Zakiul Hassan, Mahmudur Rahman, Sajeda Prema, Alex Jordan, Shawn Lockhart, Meghan Lyman, Syeda Mah-E-Muneer
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- Journal:
- Antimicrobial Stewardship & Healthcare Epidemiology / Volume 3 / Issue S2 / June 2023
- Published online by Cambridge University Press:
- 29 September 2023, p. s11
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Background: Candida auris is a multidrug-resistant yeast capable of invasive infection with high mortality and healthcare-associated outbreaks globally. Due to limited labratory capacity, the burden of C. auris is unknown in Bangladesh. We estimated the extent of C. auris colonization and infection among patients in Dhaka city intensive care units. Methods: During August 2021–September 2022 at adult intensive care units (ICUs) and neonatal intensive care units (NICUs) of 1 government and 1 private tertiary-care hospital, we collected skin swabs from all patients and blood samples from sepsis patients on admission, mid-way through, and at the end of ICU or NICU stays. Skin swab and blood with growth in blood-culture bottle were inoculated in CHROMagar, and identification of isolates was confirmed by VITEK-2. Patient characteristics and healthcare history were collected. We performed descriptive analyses, stratifying by specimen and ICU type. Results: Of 740 patients enrolled, 59 (8%) were colonized with C. auris, of whom 2 (0.3%) later developed a bloodstream infection (BSI). Among patients colonized with C. auris, 27 (46%) were identified in the ICU and 32 (54%) were identified from the NICU. The median age was 55 years for C. auris–positive ICU patients and 4 days for those in the NICU. Also, 60% of all C. auris patients were male. Among 366 ICU patients, 15 (4%) were positive on admission and 12 (3%) became colonized during their ICU stay. Among 374 NICU patients, 19 (5%) were colonized on admission and 13 (4%) became colonized during their NICU stay. All units identified C. auris patients on admission and those who acquired it during their ICU or NICU stay, but some differences were observed among hospitals and ICUs (Figure). Among patients colonized on admission to the ICU, 11 (73%) were admitted from another ward, 3 (20%) were admitted from another hospital, and 1 (7%) were admitted from home. Of patients colonized on admission to the NICU, 4 (21%) were admitted from the obstetric ward, 9 (47%) were admitted from another hospital, and 6 (32%) were admitted from home. In addition, 18 patients with C. auris died (12 in the ICU and 6 in the NICU); both patients with C. auris BSIs died. Conclusions: In these Bangladesh hospitals, 8% of ICU or NICU patients were positive for C. auris, including on admission and acquired during their ICU or NICU stay. This high C. auris prevalence emphasizes the need to enhance case detection and strengthen infection prevention and control. Factors contributing to C. auris colonization should be investigated to inform and strengthen prevention and control strategies.
Disclosure: None
Antibiotic use among SARI patients according to the AWaRe classification before and during the COVID-19 pandemic in Bangladesh
- Md Ariful Islam, Md. Zakiul Hassan, Mohammad Abdul Aleem, Zubair Akhtar, Tanzir Ahmed Shuvo, Md Kaousar Ahmmed, Syeda Mah-E-Muneer, Md Abdullah Al Jubayer Biswas, Ayesha Afrin, Probir Kumar Ghosh, Fahmida Chowdhury
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- Journal:
- Antimicrobial Stewardship & Healthcare Epidemiology / Volume 3 / Issue S2 / June 2023
- Published online by Cambridge University Press:
- 29 September 2023, p. s28
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Background: Irrational antibiotic use among hospitalized patients can lead to antibiotic resistance. For rational use, the WHO introduced the Access, Watch, and Reserve (AWaRe) classification of antibiotics. We explored antibiotic use according to the AWaRe classification among patients hospitalized with severe acute respiratory infection (SARI) between the prepandemic and COVID-19 pandemic periods in Bangladesh. Methods: From June 2017 to November 2022, we analyzed SARI inpatient data from the hospital-based influenza surveillance platform at 9 tertiary-level hospitals in Bangladesh. We defined June 2017–February 2020 as the prepandemic period and March 2020–November 2022 as the pandemic period. Physicians identified inpatients meeting the WHO SARI case definition and recorded patient demographics, clinical characteristics, and antibiotics received during hospitalization. We used descriptive statistics to summarize the data. Results: We enrolled 20,640 SARI patients (median age, 20 years; IQR, 1.6–50; 63% male); and among them, 18,197 (88%) received antibiotics (26% of those received >1 different course of antibiotics). Compared to the prepandemic period, the proportion of antibiotic use among SARI patients was higher during the pandemic: 93% (9,887 of 10,655) versus 83% (8,310 of 9,985) (P < .001). According to AWaRe classification, Access, Watch, and Reserve groups accounted for 32% (n = 2,623), 86% (n = 7,158), and 0.05% (n = 4), respectively, before the pandemic and 32% (n = 3,194), 90% (n = 8,850), and 0.08% (n = 8), respectively, during the pandemic (Fig.). The most common antibiotic prescribed for children aged <5 years during the prepandemic was ceftriaxone (n = 1,940, 74%), followed by amikacin (n = 325, 13%) and flucloxacillin (n = 300, 12%); similarly, during the pandemic, most common antibiotic prescribed was ceftriaxone (n = 3,097, 79%), followed by amikacin (n = 723, 18%) and flucloxacillin (n = 348, 9%). The most common antibiotic prescribed for patients aged ≥5 years during the prepandemic period was ceftriaxone (n = 3,174, 54%), followed by amoxicillin-clavulanic acid (n = 1,304, 22%) and azithromycin (n = 1,038, 18%). During the pandemic, the most common antibiotic prescribed for patients aged ≥5 years was ceftriaxone (n = 3,793, 64%), followed by amoxicillin-clavulanic acid (n = 1,327, 22%) and clarithromycin (n = 797, 13%). Among children aged <5 years, use of the Watch group of antibiotics during the prepandemic and pandemic periods was similar: 94% (n = 3,688) versus 95% (n = 2,347) (P = .099). However, among patients aged ≥5 years, the use of Watch antibiotics was higher during the pandemic compared to the prepandemic period: 87% (n = 5,163) versus 82% (n = 4,811) (P < .001). Conclusions: Use of antibiotics in the Watch group was predominant among SARI patients both before and during the COVID-19 pandemic, and it increased among SARI patients aged ≥5 years during the pandemic period in Bangladesh. Promoting antibiotic stewardship programs for physicians, including in-service training on antibiotic use, could reduce irrational antibiotic use, which might contribute to mitigating antibiotic resistance in the country.
Financial support: This study was funded by the CDC.
Disclosures: None
Assessment of standard precaution related to infection prevention readiness of healthcare facilities in Bangladesh: Findings from a national cross-sectional survey
- Md Abdullah Al Jubayer Biswas, Md Zakiul Hassan, Mohammad Riashad Monjur, Md Saiful Islam, Aninda Rahman, Zubair Akhtar, Fahmida Chowdhury, Sayera Banu, Nusrat Homaira
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- Journal:
- Antimicrobial Stewardship & Healthcare Epidemiology / Volume 1 / Issue 1 / 2021
- Published online by Cambridge University Press:
- 09 December 2021, e52
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Background:
Baseline assessment of standard precaution relating to infection prevention and control (IPC) preparedness to fight health crisis within healthcare facilities at different levels and its associated factors in Bangladesh remains unknown.
Methods:We analyzed the nationally representative Bangladesh health facility survey (BHFS) data conducted by the Ministry of Health and Family Welfare (MoHFW) during July–October 2017. We used the World Health Organization (WHO) Service Availability and Readiness Assessment (SARA) manual to determine the standard precautions related to the IPC readiness index. Using a conceptual framework and multivariable linear regression, we identified the factors associated with the readiness index.
Results:We analyzed data for 1,524 surveyed healthcare facilities. On average, only 44% of the standard precaution elements were available in all facilities. Essential elements, such as guidelines for standard precautions (30%), hand-washing soap (29%), and pedal bins (38%), were not readily available in all facilities. The tuberculosis service area was least prepared, with 85% of elements required for standard precaution deficient in all facilities. Significantly lower readiness indexes were observed in the rural healthcare facilities (mean difference, −13.2), healthcare facilities administered by the MoHFW (mean difference, −7.8), and private facilities (mean difference, −10.1) compared to corresponding reference categories.
Conclusions:Our study revealed a severe lack of standard precaution elements in most healthcare facilities, particularly in rural health centers. These data can provide a baseline from which to measure improvement in infection prevention and control (IPC) in these facilities and to identify areas of gaps for targeted interventions to improve IPC strategies that can improve the Bangladesh health system.
Working with Respiratory Illness: Presenteeism Among Healthcare Personnel at Tertiary-Care Hospitals in Bangladesh, 2008–2016
- Syeda Mah-E-Muneer, Md. Zakiul Hassan, Mejbah Uddin Bhuiyan, Kamal Hussain, Zubair Akhtar, Mustafizur Rahman, A. Danielle Iuliano, Eduardo Azziz-Baumgartner, Fahmida Chowdhury
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- Journal:
- Antimicrobial Stewardship & Healthcare Epidemiology / Volume 1 / Issue S1 / July 2021
- Published online by Cambridge University Press:
- 29 July 2021, p. s76
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Background: Healthcare personnel (HCP) in crowded and resource-poor countries (eg Bangladesh), might be at risk of exposure to and transmission of respiratory illnesses to coworkers, patients, and caregivers. The infection control practices in public hospitals are inadequate in Bangladesh. We estimated the incidence of respiratory illness episodes among HCP, and proportion of HCP who worked during respiratory illnesses, including influenza virus infection, at 2 tertiary-care public hospitals in Bangladesh. Methods: From May 2008 to February 2016, HCP (defined as physicians, nurses, interns, patient care assistant, cleaners, and administrative staff working in adult and pediatric medicine wards) were asked to self-report to study physicians when they experienced new onset of cough, rhinorrhea, difficulty breathing, or fever during the April–September influenza epidemic period each year. Study physicians followed HCP throughout their respiratory illness episodes and recorded respiratory symptoms, onset dates, duration of illness, and days of presenteeism and absenteeism during illness. Nasopharyngeal and oropharyngeal swabs were collected after informed written consent and were tested for influenza by rRT-PCR. We used hospital records to enumerate total HCP working in the study wards during influenza season and multiplied by 6-months follow-up per year to calculate person-time contribution for estimating respiratory illness incidence. Results: HCP self-reported 107 episodes of respiratory illness during 656 person years of follow-up, for an estimated incidence of 16.3 per 100 person years (95% CI, 13–20). Of 107 episodes, 33 (31%) included fever and cough. The mean illness length was 3.9 days (SD, ±1.8). HCP worked an average of 3.4 days (SD, ±1.4) while ill. HCP missed work for a median of 1 day (IQR, 1–2) during 29 (27%) of 107 illness episodes. HCP consented to collect swabs during 56 (52%) episodes, and among them 8 (14%) of 56 tested positive for influenza (flu-A, n = 5; flu-B, n = 3). Also, 63% of HCP with influenza reported fever and cough. HCP experiencing either respiratory illness or influenza worked for similar periods of days while ill: mean, 4 (SD, ±2.2) versus mean, 3.3 (SD, ±1.4) (P = .257). HCP worked during 105 (98%) of 107 respiratory illness and 7 (88%) of 8 influenza episodes. Conclusions: Most HCP in Bangladesh, including those with influenza, worked during respiratory illnesses. The potential value of stay-at-home policies, compensation for sick days, and influenza vaccination in reducing HCP-associated respiratory pathogen transmission could be assessed in Bangladesh and similar settings.
Funding: No
Disclosures: None
Chapter 11 - Hippocampal Sclerosis as a Cause of Medication-Resistant Epilepsy
- Edited by John M. Stern, Raman Sankar, Michael Sperling
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- Medication-Resistant Epilepsy
- Published online:
- 20 August 2020
- Print publication:
- 10 September 2020, pp 87-99
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Summary
Hippocampal sclerosis (HS) is the most frequent aetiology for medically refractory epilepsy [1]. It was first described by Bouchet and Cazauvielh in 1825 on pathological examination of a patient who had died following seizures [2]. In 1880, Sommer studied pathological samples from over 90 patients with chronic epilepsy, and reported gliosis and pyramidal cell loss in the hippocampus, predominantly in the CA1 region, originally known as Sommer’s sector. He proposed that these abnormalities were the cause of the epilepsy. In 1889, Jackson associated focal lesions in the hippocampus with the clinical symptoms of temporal lobe seizures. In addition to the loss of pyramidal cells, the loss of hilar interneurons was recognized as an important feature [3] and is dominant in the type of pathology that came to be described as end-folium sclerosis [4]. Loss of both inhibitory gamma-aminobutyric acid (GABA) neurons and excitatory mossy cells in the hilus reduces their control of the dentate granule cells, and such loss of neurons in the hilus (sometimes included as part of CA4) is one of the most consistent findings in TLE [5,6]. The International League Against Epilepsy has proposed a classification of the distinct patterns of HS to correlate the type of pathological changes to post-surgical outcome [7]. In the 1950s with the development of electroencephalography, HS was linked to electrophysiologic temporal lobe seizures.
Chapter 69 - Bacterial meningitis and pyogenic abscess in adults
- from Section 3 - Symptomatic epilepsy
- Edited by Simon D. Shorvon, Frederick Andermann, Renzo Guerrini
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- The Causes of Epilepsy
- Published online:
- 05 March 2012
- Print publication:
- 14 April 2011, pp 482-491
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Summary
Congenital Arachnoid cysts (AC) have been reported to account for roughly 1% of atraumatic intracranial mass lesions. Sylvian fissure cysts can manifest clinically at any age, but they become symptomatic more frequently in children and adolescents than in adults, and in most series infants and toddlers account for about a quarter of the cases. The incidence of epilepsy in AC patients has been reported to be between 7.5% and 42.4%; conversely MRI screening studies in epileptic patients have showed that AC are incidentally found in up to 2% of the cases. Single photon emission computed tomography (SPECT) studies proved more sensitive than increased intracranial pressure (ICP) monitoring in children with unspecific clinic radiologic correlation. Open cyst marsupialization is considered the preferable surgical procedure. Cyst extrathecal diversions are obviously safer, but are accompanied by a high incidence of additional surgical procedures and the stigma of lifelong shunt dependency.
Contributors
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- By Jane E. Adcock, Yahya Aghakhani, A. Anand, Eva Andermann, Frederick Andermann, Alexis Arzimanoglou, Sandrine Aubert, Nadia Bahi-Buisson, Carman Barba, Agatino Battaglia, Geneviève Bernard, Nadir E. Bharucha, Laurence A. Bindoff, William Bingaman, Francesca Bisulli, Thomas P. Bleck, Stewart G. Boyd, Andreas Brunklaus, Harry Bulstrode, Jorge G. Burneo, Laura Canafoglia, Laura Cantonetti, Roberto H. Caraballo, Fernando Cendes, Kevin E. Chapman, Patrick Chauvel, Richard F. M. Chin, H. T. Chong, Fahmida A. Chowdhury, Catherine J. Chu-Shore, Rolando Cimaz, Andrew J. Cole, Bernard Dan, Geoffrey Dean, Alessio De Ciantis, Fernando De Paolis, Rolando F. Del Maestro, Irissa M. Devine, Carlo Di Bonaventura, Concezio Di Rocco, Henry B. Dinsdale, Maria Alice Donati, François Dubeau, Michael Duchowny, Olivier Dulac, Monika Eisermann, Brent Elliott, Bernt A. Engelsen, Kevin Farrell, Natalio Fejerman, Rosalie E. Ferner, Silvana Franceschetti, Robert Friedlander, Antonio Gambardella, Hector H. Garcia, Serena Gasperini, Lorenzo Genitori, Gioia Gioi, Flavio Giordano, Leif Gjerstad, Daniel G. Glaze, Howard P. Goodkin, Sidney M. Gospe, Andrea Grassi, William P. Gray, Renzo Guerrini, Marie-Christine Guiot, William Harkness, Andrew G. Herzog, Linda Huh, Margaret J. Jackson, Thomas S. Jacques, Anna C. Jansen, Sigmund Jenssen, Michael R. Johnson, Dorothy Jones-Davis, Reetta Kälviäinen, Peter W. Kaplan, John F. Kerrigan, Autumn Marie Klein, Matthias Koepp, Edwin H. Kolodny, Kandan Kulandaivel, Ruben I. Kuzniecky, Ahmed Lary, Yolanda Lau, Anna-Elina Lehesjoki, Maria K. Lehtinen, Holger Lerche, Michael P. T. Lunn, Snezana Maljevic, Mark R. Manford, Carla Marini, Bindu Menon, Giulia Milioli, Eli M. Mizrahi, Manish Modi, Márcia Elisabete Morita, Manuel Murie-Fernandez, Vivek Nambiar, Lina Nashef, Vincent Navarro, Aidan Neligan, Ruth E. Nemire, Charles R. J. C. Newton, John O'Donavan, Hirokazu Oguni, Teiichi Onuma, Andre Palmini, Eleni Panagiotakaki, Pasquale Parisi, Elena Parrini, Liborio Parrino, Ignacio Pascual-Castroviejo, M. Scott Perry, Perrine Plouin, Charles E. Polkey, Suresh S. Pujar, Karthik Rajasekaran, R. Eugene Ramsey, Rahul Rathakrishnan, Roberta H. Raven, Guy M. Rémillard, David Rosenblatt, M. Elizabeth Ross, Abdulrahman Sabbagh, P. Satishchandra, Swati Sathe, Ingrid E. Scheffer, Philip A. Schwartzkroin, Rod C. Scott, Frédéric Sedel, Michelle J. Shapiro, Elliott H. Sherr, Michael Shevell, Simon D. Shorvon, Adrian M. Siegel, Gagandeep Singh, S. Sinha, Barbara Spacca, Waney Squier, Carl E. Stafstrom, Bernhard J. Steinhoff, Andrea Taddio, Gianpiero Tamburrini, C. T. Tan, Raymond Y. L. Tan, Erik Taubøll, Robert W. Teasell, Mario Giovanni Terzano, Federica Teutonico, Suzanne A. Tharin, Elizabeth A. Thiele, Pierre Thomas, Paolo Tinuper, Dorothée Kasteleijn-Nolst Trenité, Sumeet Vadera, Pierangelo Veggiotti, Jean-Pierre Vignal, J. M. Walshe, Elizabeth J. Waterhouse, David Watkins, Ruth E. Williams, Yue-Hua Zhang, Benjamin Zifkin, Sameer M. Zuberi
- Edited by Simon D. Shorvon, Frederick Andermann, Renzo Guerrini
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- Book:
- The Causes of Epilepsy
- Published online:
- 05 March 2012
- Print publication:
- 14 April 2011, pp ix-xvi
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Electrical Engineering
- Edited by Marla Parker, SunSoft
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- She Does Math!
- Published by:
- Mathematical Association of America
- Published online:
- 05 June 2012
- Print publication:
- 01 June 1995, pp 102-105
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Summary
I was born in Bangladesh, and went to all-girls schools where it never occured to anyone that girls were not supposed to be good at mathematics and science. In ninth grade, we had to choose a “track”—either science or humanities. Once you chose a track, you couldn't switch back to the other track, because you would have missed too many courses and there was no way of making them up.
The science track included advanced mathematics, physics, inorganic and organic chemistry, biology, calculus, statics, and dynamics. Both tracks taught algebra and geometry, but the science students took more of both. In eleventh and twelfth grades, science students chose between advanced geography and biology. To go to medical school, you had to take biology. However, by that time I had decided to be an electrical engineer, so I chose geography.
Although my childhood dream was to become a writer or painter, or both, I thought that the safest bet was to become an engineer. At that time, the job market in Bangladesh guaranteed that an engineering degree would lead to a decent job (alas, it is not so any more.) Besides, I thought that as an engineer, I could still write or paint in my spare time, but just try to be a full-time writer and do engineering on the side!
Of course, at that time almost no women went into engineering, particularly electrical.