Cytogenetic profile of Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia in Northern Pakistan.

Objective: To determine the frequencies of different cytogenetic abnormalities in patients of Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia in Northern Pakistan. Methods: It was descriptive cross-sectional study conducted in Hematology Department of a Tertiary care referral institute from June 2015 to July 2017. All newly diagnosed cases of Acute Leukemia were analyzed. Cytogenetic analysis was performed on bone marrow aspirate samples using Giemsa-trypsin banding technique. Karyotypes were identified and interpreted according to ISCN criteria. Results: A total of 355 newly diagnosed patients of Acute Leukemia were analyzed. Out of these, 180 patients had AML and 175 had ALL. In Acute Myeloid Leukemia chromosomal abnormalities were detected in 28.2 % cases. Of these the common ones included t(8;21),t(15;17),+8, Inversion 16 and Monosomy 7. Other abnormalities included Complex karyotype, Down's syndrome related AML, Hyperdiploidy, del 16q,-8,+Y and t(3p;17q)del 10. In Acute Lymphoblastic Leukemia chromosomal abnormalities were detected in 40% cases. Common ones included Hyperdiploidy, Tetraploidy and t(9;22). Other abnormalities included t(1;19) and t(2;8)t(8;14). Conclusion: Cytogenetically favorable abnormalities are commonest occurring chromosomal defects in both Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia in Northern Pakistan, i.e., t(8;21) in AML and Hyperdiploidy in ALL.

Thiadiazine thione derivatives as anti-leishmanial agents: synthesis, biological evaluation, structure activity relationship, ADMET, molecular docking and molecular dynamics simulation studies.

During last decades, 3,5-disubstituted-tetrahydro-2H-thiadiazine-2-thione scaffold remains the center of interest due to their ease of preparation, diverse range substituents at N-3 and N-5 positions, and profound biological activities. In the current study, a series of 3,5-disubstituted-tetrahydro-2H-thiadiazine-2-thiones were synthesized in good to excellent yield, and the structure of the compounds were confirmed by various spectroscopic techniques such as FTIR, 1H-NMR, 13C-NMR and Mass spectrometry, and finally evaluated against Leishmania major. Whereas, all the evaluated compounds (1-33), demonstrate potential leishmanicidal activities with IC50 values in the range of (1.30- 149.98 uM). Among the evaluated compounds such as 3, 4, 6, and 10 exhibited excellent leishmanicidal activities with IC50 values of (2.17 µM), (2.39 µM), (2.00 µM), and (1.39 µM), respectively even better than the standard amphotericin B (IC50 = 0.50) and pentamidine (IC50 = 7.52). In order to investigate binding interaction of the most active compounds, molecular docking study was conducted with Leishmania major. Further molecular dynamic simulation study was also carried out to assess the stability and correct binding of the most active compound 10, within active site of the Leishamania major. Likewise, the physiochemical properties, drug likeness, and ADMET of the most active compounds were investigated, it was found that none of the compounds violate Lipiniski's rule of five, which show that this class of compounds had enough potential to be used as drug candidate in near future.Communicated by Ramaswamy H. Sarma.

Dihydropyrazole Derivatives Act as Potent α-Amylase Inhibitors and Free Radical Scavengers: Synthesis, Bioactivity Evaluation, Structure-Activity Relationship, ADMET, and Molecular Docking Studies.

Dihydropyrazole (1-22) derivatives were synthesized from already synthesized chalcones. The structures of all of the synthesized compounds were confirmed by elemental analysis and various spectroscopic techniques. Furthermore, the synthesized compounds were screened against α amylase as well as investigated for antioxidant activities. The synthesized compounds demonstrate good to excellent antioxidant activities with IC50 values ranging between 30.03 and 913.58 µM. Among the 22 evaluated compounds, 11 compounds exhibit excellent activity relative to the standard ascorbic acid IC50 = 287.30 µM. Interestingly, all of the evaluated compounds show good to excellent α amylase activity with IC50 values lying in the range between 0.5509 and 810.73 µM as compared to the standard acarbose IC50 = 73.12 µM. Among the investigated compounds, five compounds demonstrate better activity compared to the standard. In order to investigate the binding interactions of the evaluated compounds with amylase protein, molecular docking studies were conducted, which show an excellent docking score as compared to the standard. Furthermore, the physiochemical properties, drug likeness, and ADMET were investigated, and it was found that none of the compounds violate Lipiniski's rule of five, which shows that this class of compounds has enough potential to be used as a drug candidate in the near future.

Detection of asymptomatic Leishmania donovani in healthy voluntary blood donors.

OBJECTIVE: To check incidence of Asymptomatic Leishmania donovani reporting to Armed Forces Institute of Transfusion Rawalpindi. MATERIAL AND METHODS: Two thousand (n = 2000) consecutive healthy voluntary blood donors were tested for 18 s rRNA by Real time Polymerase chain reaction. One thousand (n = 1000) subject's permanent resident of Azad Kashmir along with a thousand (n = 1000) healthy voluntary blood donors from rest of Pakistan were included. The study was carried out over a period of three months Jun - Aug 2020. RESULTS: Total of 2000 blood donors were enrolled in the study, all were males with age ranging from 16 to 60 years. Stratification based on residence, 1000 (50 %) resided in the Azad kashmir, 349 (17.45 %) were from Islamabad and Rawalpindi, 541 (27.05 %) from Punjab mainly residing in Lahore and Multan, 110 (5.5 %) were from other cities of Pakistan. Grouping on the basis of age, 55.25 % (n = 1105) of the donors were 16-25 years old, 19.45 % (n = 389) were in age range of 26-40 years old, 15.55 % (n = 311) were 41-50 years old and 9.75 % (n = 195) 51-60 years old. No donor was diagnosed as an asymptomatic carrier. CONCLUSION: Screening of blood donors for Leishmania donovani is not recommended.

Bacillus subtilis: As an Efficient Bacterial Strain for the Reclamation of Water Loaded with Textile Azo Dye, Orange II.

The azo dye orange II is used extensively in the textile sector for coloring fabrics. High concentrations of it are released into aqueous environments through textile effluents. Therefore, its removal from textile wastewater and effluents is necessary. Herein, initially, we tested 11 bacterial strains for their capabilities in the degradation of orange II dye. It was revealed in the preliminary data that B. subtilis can more potently degrade the selected dye, which was thus used in the subsequent experiments. To achieve maximum decolorization, the experimental conditions were optimized whereby maximum degradation was achieved at: a 25 ppm dye concentration, pH 7, a temperature of 35 °C, a 1000 mg/L concentration of glucose, a 1000 mg/L urea concentration, a 666.66 mg/L NaCl concentration, an incubation period of 3 days, and with hydroquinone as a redox mediator at a concentration of 66.66 mg/L. The effects of the interaction of the operational factors were further confirmed using response surface methodology, which revealed that at optimum conditions of pH 6.45, a dye concentration of 17.07 mg/L, and an incubation time of 9.96 h at 45.38 °C, the maximum degradation of orange II can be obtained at a desirability coefficient of 1, estimated using the central composite design (CCD). To understand the underlying principles of degradation of the metabolites in the aliquot mixture at the optimized condition, the study steps were extracted and analyzed using GC-MS(Gas Chromatography Mass Spectrometry), FTIR(Fourier Transform Infrared Spectroscopy), 1H and carbon 13 NMR(Nuclear Magnetic Resonance Spectroscopy). The GC-MS pattern revealed that the original dye was degraded into o-xylene and naphthalene. Naphthalene was even obtained in a pure state through silica gel column isolation and confirmed using 1H and 13C NMR spectroscopic analysis. Phytotoxicity tests on Vigna radiata were also conducted and the results confirmed that the dye metabolites were less toxic than the parent dye. These results emphasize that B. subtilis should be used as a potential strain for the bioremediation of textile effluents containing orange II and other toxic azo dyes.

Biodegradation of Azo Dye Methyl Red by Pseudomonas aeruginosa: Optimization of Process Conditions.

Water pollution due to textile dyes is a serious threat to every life form. Bacteria can degrade and detoxify toxic dyes present in textile effluents and wastewater. The present study aimed to evaluate the degradation potential of eleven bacterial strains for azo dye methyl red. The optimum degradation efficiency was obtained using P. aeruginosa. It was found from initial screening results that P. aeruginosa is the most potent strain with 81.49% degradation activity and hence it was subsequently used in other degradation experiments. To optimize the degradation conditions, a number of experiments were conducted where only one variable was varied at a time and where maximum degradation was observed at 20 ppm dye concentration, 1666.67 mg/L glucose concentration, 666.66 mg/L sodium chloride concentration, pH 9, temperature 40 °C, 1000 mg/L urea concentration, 3 days incubation period, and 66.66 mg/L hydroquinone (redox mediator). The interactive effect of pH, incubation time, temperature, and dye concentration in a second-order quadratic optimization of process conditions was found to further enhance the biodegradation efficiency of P. aeruginosa by 88.37%. The metabolites of the aliquot mixture of the optimized conditions were analyzed using Fourier transform infrared (FTIR), GC-MS, proton, and carbon 13 Nuclear Magnetic Resonance (NMR) spectroscopic techniques. FTIR results confirmed the reduction of the azo bond of methyl red. The Gas Chromatography-Mass Spectrometry (GC-MS) results revealed that the degraded dye contains benzoic acid and o-xylene as the predominant constituents. Even benzoic acid was isolated from the silica gel column and identified by 1H and 13C NMR spectroscopy. These results indicated that P. aeruginosa can be utilized as an efficient strain for the detoxification and remediation of industrial wastewater containing methyl red and other azo dyes.

Celebrating 60 Years of Accomplishments of the Armed Forces Radiobiology Research Institute1.

Chartered by the U.S. Congress in 1961, the Armed Forces Radiobiology Research Institute (AFRRI) is a Joint Department of Defense (DoD) entity with the mission of carrying out the Medical Radiological Defense Research Program in support of our military forces around the globe. In the last 60 years, the investigators at AFRRI have conducted exploratory and developmental research with broad application to the field of radiation sciences. As the only DoD facility dedicated to radiation research, AFRRI's Medical Radiobiology Advisory Team provides deployable medical and radiobiological subject matter expertise, advising commanders in the response to a U.S. nuclear weapon incident and other nuclear or radiological material incidents. AFRRI received the DoD Joint Meritorious Unit Award on February 17, 2004, for its exceptionally meritorious achievements from September 11, 2001 to June 20, 2003, in response to acts of terrorism and nuclear/radiological threats at home and abroad. In August 2009, the American Nuclear Society designated the institute a nuclear historic landmark as the U.S.'s primary source of medical nuclear and radiological research, preparedness and training. Since then, research has continued, and core areas of study include prevention, assessment and treatment of radiological injuries that may occur from exposure to a wide range of doses (low to high). AFRRI collaborates with other government entities, academic institutions, civilian laboratories and other countries to research the biological effects of ionizing radiation. Notable early research contributions were the establishment of dose limits for major acute radiation syndromes in primates, applicable to human exposures, followed by the subsequent evolution of radiobiology concepts, particularly the importance of immune collapse and combined injury. In this century, the program has been essential in the development and validation of prophylactic and therapeutic drugs, such as Amifostine, Neupogen®, Neulasta®, Nplate® and Leukine®, all of which are used to prevent and treat radiation injuries. Moreover, AFRRI has helped develop rapid, high-precision, biodosimetry tools ranging from novel assays to software decision support. New drug candidates and biological dose assessment technologies are currently being developed. Such efforts are supported by unique and unmatched radiation sources and generators that allow for comprehensive analyses across the various types and qualities of radiation. These include but are not limited to both 60Co facilities, a TRIGA® reactor providing variable mixed neutron and γ-ray fields, a clinical linear accelerator, and a small animal radiation research platform with low-energy photons. There are five major research areas at AFRRI that encompass the prevention, assessment and treatment of injuries resulting from the effects of ionizing radiation: 1. biodosimetry; 2. low-level and low-dose-rate radiation; 3. internal contamination and metal toxicity; 4. radiation combined injury; and 5. radiation medical countermeasures. These research areas are bolstered by an educational component to broadcast and increase awareness of the medical effects of ionizing radiation, in the mass-casualty scenario after a nuclear detonation or radiological accidents. This work provides a description of the military medical operations as well as the radiation facilities and capabilities present at AFRRI, followed by a review and discussion of each of the research areas.

Profile of Asphyxial Deaths in Faisalabad: A 10-Year Study.

OBJECTIVE: To determine the frequency of violent asphyxial deaths in Faisalabad over a span of a decade; and assessing the age and gender vulnerability. STUDY DESIGN: Descriptive cross-sectional study. PLACE AND DURATION OF STUDY: Department of Forensic Medicine and Toxicology, Punjab Medical College, Faisalabad, from January 2007 to December 2016. METHODOLOGY: Cases identified as violent asphyxial deaths according to police inquests and findings of the medico-legal examiners were computed. Age, gender, and cause of asphyxia recorded in predesigned proformas and analysed by SPSS version 12.0. RESULTS: Asphyxial deaths accounted for 7.66% (259 / 3,381) of the medico-legal deaths during the 10-year span. Majority (28.57%) victims belonged to the 20-29 year age group, followed by the 10-19 year age group (20.07%). Male victims (56%) outnumbered the females (44%) by ratio of 1.3:1. Ligature strangulation was the cause of asphyxia in majority of the victims (40.93%), followed by hanging (28.96%). CONCLUSION: Young population between 20-29 years were the predominant victims of violent asphyxial deaths. Homicide due to ligature strangulation was the commonest form of violent asphyxial deaths.

Categorization of Putative Factors Against Rhopalosiphum padi (L.) (Heteroptera: Aphididae).

The bird cherry-oat aphid, Rhopalosiphum padi (L.) (Heteroptera: Aphididae), causes heavy losses to wheat crops worldwide by direct damage and virus transmission. This study was conducted to identify putative resistance mechanisms in four wheat varieties (Bobtail, Ladd, Stephens, and Skiles) and one advanced line (YS434)where R. padi was subjected to choice and no-choice tests. Antixenosis, antibiosis and tolerance studies were conducted in controlled environmental conditions at temperature of 20±5°C, 50­65% RH, and a photoperiod of 14:10 (L:D) h. Based on the antixenosis test, the variety Skiles was found susceptible to R. padi, while the line YS434 showed a significant level of resistance; the varieties Bobtail, Ladd, and Stephens showed intermediate response. In the antibiosis experiment, R. padi produced less progeny on the variety Skiles as compared with other varieties, but the developmental time for nymphs was also significantly shorter on Skiles and recorded higher intrinsic rate of natural increase (r(m)) values as compared with the varieties YS434, Bobtail, and Ladd. In the tolerance tests, the variety Ladd showed significantly lower tolerance index value than YS434, followed by Skiles, Bobtail, and Stephens. The plant resistance index value was greater for the variety Ladd, followed by Stephens, YS434, and Bobtail. In conclusion, this study provides baseline information that will contribute to the identification of putative resistance factors for a future breeding program against this aphid.

SENSITIVITY PATTERNS OF PSEUDOMONAS AERUGINOSA ISOLATES OBTAINED FROM CLINICAL SPECIMENS IN PESHAWAR.

BACKGROUND: Pseudomonas aeruginosa (P. aeruginosa) is a highly virulent opportunistic pathogen and a leading cause of nosocomial infections. Affected patients are often hospitalized in an intensive care unit, and are immuno-compromised as a result of disease and treatment. Suspected P. aeruginosa require timely, adequate and empirical antibiotic therapy to ensure improved outcomes. The purpose of the study was to find the sensitivity and resistance pattern of P. aeruginosa to various groups of drugs, in clinical isolates collected from two major tertiary care hospitals of Peshawar. METHODS: Different clinical isolate were taken from patients admitted in various wards of Khyber Teaching Hospital and Lady Reading Hospital Peshawar. RESULTS: A total of 258 clinical isolates were positive for P. aeruginosa out of 2058 clinical isolates. Pseudomonas showed high degree of resistance to third generation Cephalosporins (Ceftazidime, and Ceftriaxone) and moderate degree of resistance to Quinolones and Aminoglycosides (Ofloxacin, Ciprofloxacin, Levofloxacin and Amikacin). Low resistance was observed to different combinations (Cefoperazone+Sulbactum, Piperacillin+Tazobactum). Meropenem and Imipenem had negligible resistance. CONCLUSION: There is growing resistance to different classes of antibiotics. Combination drugs are useful approach for empirical treatment in suspected Pseudomonas infection. Imipenem and Meropenem are extremely effective but should be in reserve.

RATE AND INDICATIONS OF ELECTIVE AND EMERGENCY CAESAREAN SECTION; A STUDY IN A TERTIARY CARE HOSPITAL OF PESHAWAR.

BACKGROUND: The study was conducted to determine the rate and clinical indications for emergency and elective caesarean section. METHODS: This was a cross-sectional descriptive study conducted from December 2010 to January 2011 in Gynaecology unit-A of Lady Reading Hospital Peshawar. Consecutive patients who gave birth in the hospital during the study period were included in the study. There were a total of 966 patients. Mode of delivery and basic demographics of the patients who underwent elective and emergency caesarean section were noted down. Clinical indications were recorded. RESULTS: Out of 966 patients, 210 underwent caesarean section. Therefore, the rate of caesarean section was 21.7 per 100. Among those 78% (n=164) were emergency caesarean sections and others were elective caesarean sections. Top six indicators for caesarean sections were foetal distress 17.1% (n=36), obstructive labour/failure to progress 16.1% (n=34), previous caesarean section 15.2% (n=32), breech presentation 9.5% (n=20), cephalopelvic disproportion 6.1% (n=13), failed induction 5.7% (n=12) and pregnancy induced hypertension (PIH) 5.7% (n=12). CONCLUSION: The rate of caesarean section was only slightly higher than recommended by the WHO. Most of caesarean sections were emergency caesarean sections.

Percutaneous CT-guided drainage of a postoperative intra-abdominal abscess in a combat environment.

Combat medical care results in limited resource availability, which can prompt creativity in treatment of otherwise common conditions. A postoperative intra-abdominal abscess is not an uncommon occurrence following traumatic hollow viscous injury in the deployed environment, but treatment is often limited to surgical drainage only. Herein, we describe a novel use of a dual-lumen central venous catheter to obtain percutaneous drainage of a postoperative intra-abdominal abscess.

Patient communication in radiology: current status of breaking bad news among radiologists and radiology trainees in Pakistan.

Breaking bad news can be an intimidating task for any physician. The aim of this study was to record the practices of breaking bad news to the patients by Pakistani radiologists and trainees. The radiologists and trainees attending the 26th National Radiological Conference in October 2010 in Karachi, Pakistan, were surveyed. The response rate was 76%. The respondents included residents (51%), private practicing radiologists (28%), academic radiologists (13%), and other trainees (8%). Most of the academic radiologists communicated with their patients. The daily frequency of breaking bad news by residents was noted, which was highest in the public teaching hospitals (71%). For severe abnormalities such as malignancy, 50% residents, 55% of the academic radiologists and 74% of the private practicing radiologists were very uncomfortable in disclosure of results. Differences in frequency of communication with patients were noticed with both different training levels, and different settings of practice in a developing country.

An accurate retrieval of leaf water content from mid to thermal infrared spectra using continuous wavelet analysis.

Leaf water content determines plant health, vitality, photosynthetic efficiency and is an important indicator of drought assessment. The retrieval of leaf water content from the visible to shortwave infrared spectra is well known. Here for the first time, we estimated leaf water content from the mid to thermal infrared (2.5-14.0 µm) spectra, based on continuous wavelet analysis. The dataset comprised 394 spectra from nine plant species, with different water contents achieved through progressive drying. To identify the spectral feature most sensitive to the variations in leaf water content, first the Directional Hemispherical Reflectance (DHR) spectra were transformed into a wavelet power scalogram, and then linear relations were established between the wavelet power scalogram and leaf water content. The six individual wavelet features identified in the mid infrared yielded high correlations with leaf water content (R(2)=0.86 maximum, 0.83 minimum), as well as low RMSE (minimum 8.56%, maximum 9.27%). The combination of four wavelet features produced the most accurate model (R(2)=0.88, RMSE=8.00%). The models were consistent in terms of accuracy estimation for both calibration and validation datasets, indicating that leaf water content can be accurately retrieved from the mid to thermal infrared domain of the electromagnetic radiation.

Cataract: trends in surgical procedures and visual outcomes; a study in a tertiary care hospital.

OBJECTIVE: To determine the current procedures in practice and visual outcome following a cataract surgery. METHODS: The study was conducted from January 7 to April 7, 2011 in the Eye Unit of the Lady Reading Hospital, Peshawar, involving 181 patients. Basic demographics of the patients as well as the type of cataract surgery were noted. Risk factors like diabetes mellitus and glaucoma were also noted for each patient. A pre-operative visual acuity was determined. The patient was examined after two months to determine the visual improvement. RESULTS: Out of 181 patients, 117 were males and 64 were females. Age ranged from 5 years to 83 years with a median age of 60. Most common procedure performed (60.2%) was extra capsular cataract extraction with posterior chamber intraocular lense (ECCE), followed by Phacoemulsification (24.3%). Visual outcome was good in 88.3%, borderline in 8.3% and poor in 3.3% patients. The main reasons for poor visual outcomes were diabetic retinopathy 42.8%, glaucoma-related vision loss 19.0%, history of trauma with retinal detachment 9.5%, and age-related macular degeneration 9.5%. Poor visual outcome was found in diabetic and Glaucoma patients. Surgical complications (3.8%) were rare. CONCLUSION: Overall a good visual outcome was noted in cataract surgery, which was similar to World Health Organisation guidelines. Extra capsular cataract extraction was the most common procedure followed by Phacoemulsification.

Factors associated with low hepatitis B vaccination; a user and provider perspective study in Peshawar.

Hepatitis B is a major burden in Pakistan. A cross-sectional study was conducted in Peshawar, from 9th June to 19th June 2010. Cluster random sampling was done. Confidence level of 95% and confidence interval of 5 was used to derive sample size. Parents of 506 children were asked about their hepatitis B immunization status who were aged 4 years or under. Questions on demographics, income, education, accessibility and occupation, knowledge and views on immunization were asked. Forty health personnel were interviewed for their views. In all, 62.2% children were completely vaccinated. Reasons for not being immunized included unawareness, busy schedule, long distance to the centre and various misconceptions. Education, mothers' knowledge and views on immunization, income, closer accessibility, were the main factors associated with immunization. Health personnel thought lack of awareness among people, low accessibility and poor incentives as the shortcomings in immunization. It is recommended that effective steps should be taken to ensure better coverage.

Intrathecal anti-tetanus human immunoglobulin in the treatment of neonatal tetanus.

OBJECTIVE: To determine the outcome of tetanus in neonates treated with intrathecal tetanus immunoglobulin in terms of mortality and hospital stay. STUDY DESIGN: Experimental study. PLACE AND DURATION OF STUDY: Paediatric Unit I, Bahawal Victoria Hospital, Bahawalpur, from April 2004 to December 2007. METHODOLOGY: Seventy neonates with diagnosis of neonatal tetanus were included in the study. The neonates with fits due to causes other than tetanus were excluded. Thirty five patients received intrathecal immunoglobulin in addition to standard treatment (group A) while, the other 35 patients received only standard treatment (group B). The mortality and duration of hospital stay in 2 groups were recorded. RESULTS: In group A, mean duration of hospital stay was 10 days while, in group B it was 13 days (p < 0.001). One patient from group A and 8 patients from group B expired (p = 0.026). The occurrence of refractory fits, repeated apnoeic episodes and high grade fever did not show any statistically significant difference in the 2 groups. CONCLUSION: Intrathecal anti-tetanus immunoglobulin in addition to the standard improved the outcome of neonatal tetanus in terms of mortality and hospital stay.