Introduction A subset of individuals with COVID-19 can suffer from a severe form of the disease requiring breathing support for respiratory failure and even death due to disease complications. COVID-19 disease severity can be attributed to numerous factors, where several studies have associated changes in the expression of serum pro-inflammatory cytokines with disease severity. However, very few studies have associated the changes in expression of pro-inflammatory changes in the nasopharyngeal milieu with disease severity. Therefore, in the current study, we performed differential gene expression analysis of various pro-inflammatory cytokines in the nasopharyngeal milieu of mild & severe COVID-19 cases. Material and method For this retrospective, cross-sectional study, a total of 118 nasopharyngeal swab samples, previously collected from mild and severe (based on the WHO criteria) COVID-19 patients were used. A real-time qPCR was performed to determine the viral loads and also evaluate the mRNA expression of eight cytokines ( IL-1 , IL-2 , IL-4 , IL-6 , IL-10 , IFN-γ , TGF-β1 , and TNF-α ). Subsequently, an unpaired T-test was applied to compare the statistical difference in mean expression of viral loads and each cytokine between the mild and severe groups, while the Pearson correlation test was applied to establish a correlation between disease severity, viral load, and cytokines expression. Similarly, a multivariable logistic regression analysis was performed to assess the relationship between different variables from the data and disease severity. Results Out of 118 samples, 71 were mild, while 47 were severe. The mean viral load between the mild and severe groups was comparable (mild group: 27.07± 5.22; severe group: 26.37 ±7.89). The mRNA expression of cytokines IL-2 , IL-6 , IFN- γ , and TNF-α was significantly different in the two groups (p<0.05), where the Log 2 normalized expression of IL-2 , IL-6 , IFN- γ , and TNF-α was found to be 2.2–, 16–, 2.3–, and 1.73–fold less in the severe group as compared to the mild group. Furthermore, we also observed a significant positive correlation between all the cytokines in the severe group. The multivariate analysis showed a significant relationship between age, IL-6 , and disease severity. Conclusion This decreased expression of certain cytokines ( IL-2 , IL-6 , TNF-α , and IFN-γ ) in the nasopharyngeal milieu may be considered early biomarkers for disease severity in COVID-19 patients.
Background: Iron deficiency anaemia (IDA) is the prevalent form of anaemia which has become a major public health problem, globally. Women in the reproductive age group (15–49 years of age) are at increased risk, especially in the South Asian population. It is of paramount importance to identify these micronutrient deficiencies in this age group as it adversely affects the birth outcomes, but the mother and the child at risk of morbidity and mortality during pregnancy. Methods: A cross-sectional study was conducted at Civil Hospital, Karachi for 12 months i.e. October, 2018 to December, 2019. Data was prospectively collected from patients after obtaining written informed consent. 377 patients were included who met the diagnostic criteria. Descriptive statistics were used and qualitative data analysis; mean, standard deviation, frequency, and percentages were respectively calculated. Effect modifiers were controlled through stratification to see the effect of these on the outcome variable. For post-stratification, the chi-square test was applied with a p value of≤0.05.Results: A total of 377 patients with microcytic anaemia were enrolled from Civil Hospital, Karachi. Mean age, duration of anaemia, haemoglobin, height, weight and BMI in our study was 29.28±6.14 years, 1.41±0.26 months, 9.27±0.86 mg/dl, 26.72±1.56 kg/m2, 138±7.28 cm and 78.7±9.87 kg. Out of 377 patients with microcytic anaemia, 144 (38.2%) and 233 (61.8%) had and did not have iron deficiency anaemia. Conclusions: IDA is frequently found in microcytic anaemia patients. Thus, it is important to screen premenopausal in female patients for iron deficiency presenting with microcytic anaemia to prevent adverse outcomes.
Oral squamous cell carcinoma (OSCC) comprises most of head and neck neoplasms and is one of the highest-ranking and lethal cancers in Pakistan due to prevailing mouth habits. Several types of receptors act as prognostic markers and targets for therapy in some cancers, but their application in OSCC is largely unexplored. This study aimed to evaluate the expression of hormonal receptors and Her-2 in OSCC patients and correlate it with 10-year, overall and disease-free survival. To achieve this objective, immunohistochemistry for Her-2, AR, ER and PR was performed on 100 formalin-fixed paraffin-embedded primary OSCC specimens. Receptor expression was correlated with mouth habits and clinicopathological features and patient survival was analyzed using Kaplan-Meier method and Cox regression univariate analysis. We observed that in 100 patients, there were 57 males and 43 females. Immunopositive Her-2 expression was observed in 21% of patients, AR in 13%, ER in 3% and 0% for PR. Patients with betel quid/areca nut mouth habits had significantly absent Her-2 expression ( P = 0.035). Also, Her-2 negative patients were also negative for AR expression ( P = 0.002). Her-2 positive patients had poor 10-year survival ( P = 0.041). A trend of low survival and high recurrence rate was observed in AR positive patients, but this was not significant ( P = 0.072). No statistically relevant correlations were seen in the case of ER and PR. In conclusion, Her-2 may be a valuable marker for predicting long-term prognosis of OSCC patients.
Laboratory biosafety is currently a major global issue in clinical research and academic laboratories. To alleviate these concerns, subject-specific education of standardized laboratory practices is essential and should be delivered in a comprehensible, interactive, and appealing manner. The objective of the present study was to engage university-level students in laboratory biosafety and biosecurity related education through the Socratic method of learning. A pre/post-test model was implemented to assess the knowledge improvement after the workshop. Two workshops were conducted individually at a public and private educational institute in October 2019 and December 2019, respectively. Important concepts were delivered in an interactive engagement format to ensure substantive understanding. Pre- and post-training scores were computed, and a paired t-test was used to assess knowledge gain. Out of the 357 students from both institutes, 320 (90%) provided consent and completed the pre- and post-test questionnaires. The participants lacked a baseline knowledge of laboratory biosafety. A statistically significant increase (14% to 84%) in knowledge was reported among students, with a p-value of < 0.001. Scores improved in the post-test assessment, where 87% were high performers, and only 1% were low-performing students. The difference between the pre- and post-test mean scores was indicative of a substantial 70% improvement in education. Students exhibited high levels of satisfaction with the Socratic method of teaching style. The study highlighted the significance of the Socratic style of learning for engaging students and improving their knowledge and awareness of laboratory biosafety in academic settings in Pakistan.
Oral squamous cell carcinoma (OSCC) is one of the highest-ranking cancers among both genders in Pakistan. Obesity is linked to a much higher risk for developing multiple cancer types. Individuals with Diabetes mellitus (DM) face an increased risk for developing oral cancer. Hence, the objective of this study was to identify the effect of obesity and DM on the prognosis of OSCC patients.This retrospective cohort analysis was conducted on 386 patients diagnosed and treated for OSCC at The Aga Khan University Hospital, Karachi, Pakistan. Patient information was obtained from hospital medical records. Obesity was defined as having a body mass index (BMI) of ⩾25 kg/m2 according to the WHO Asian cut-offs for BMI. Patient BMI was correlated with diabetes status, clinicopathological features and overall survival. Kaplan-Meier survival analysis was performed, along with univariate and multivariate cox regression analysis to test the effect of obesity and diabetes on overall survival.In a set of 386 patients, there were 296 males (76.7%) and 90 females (23.3%). The mean BMI was 24.4 (SD ± 5.25) and 42.7% of patients were found to be obese (⩾25 BMI). 64 patients (16.6%) were diabetic. The risk of death was significantly higher in underweight patients (P = .035) compared with normal weight individuals. Diabetics had a higher mean BMI compared with non-diabetics. However, DM was not a statistically valid predictor of survival.Underweight OSCC patients were at a higher risk of death compared with normal weight OSCC patients.
The androgen receptor (AR) is a transcription factor that is dependent upon ligand activation and is a member of the nuclear receptor superfamily. AR has been found to have a role in cancers of the prostate, breast, ovarian, nasal cavity, and lung. It has been seen that AR plays a significant role in both the early and later stages of prostate cancer as AR is expressed in almost every primary prostate cancer. An evolving prognostic and therapeutic role of AR also exists in breast cancer as increased expression of AR has been linked to improved survival. In the case of OSCC, the role of hormonal therapy as a prognostic marker remains to be explored. Some reports have failed to identify the expression of AR in oral cavity cancers or any significant associations, while others have predicted AR-expressing tumours to have a worse prognosis. This review narrates the current research on AR and how it can be applied in future research.
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
HIV-1 and hepatitis B virus (HBV) share common routes of transmission and therefore co-infection is common. In 2019, an HIV-1 outbreak that resulted in >1000 children being infected, predominantly through nosocomial transmission, occurred in Sindh, Pakistan. We conducted a phylogenetic and drug resistance analysis of the HBV Reverse Transcriptase (RT) gene in children with HIV-1 and HBV co-infection.
Abstract Background Biotransformation by using microbial and plant cell cultures has been applied effectively for the production of fine chemicals on large scale. Inspired by the wealth of literature available on the biotransformation of steroids, we decided to investigate the biotransformation of ethynodiol diacetate ( 1 ) by using plant and microbial cultures. Results The biotransformation of ethynodiol diacetate ( 1 ) with Cunninghamella elegans and plant cell suspension cultures of Ocimum basilicum and Azadirachta indica is being reported here for the first time. Biotransformation of 1 with Cunninghamella elegans yielded three new hydroxylated compounds, characterized as 17α-ethynylestr-4-en-3β,17β-diacetoxy-6α-ol ( 2 ), 17α-ethynylestr-4-en-3β,17β-diacetoxy-6β-ol ( 3 ), and 17α-ethynylestr-4-en-3β,17β-diacetoxy-10β-ol ( 4 ) and a known metabolite, 17α-ethynyl-17β-acetoxyestr-4-en-3-one ( 5 ). The biotransformation of 1 with Ocimum basilicum included hydrolysis of the ester group, oxidation of alcohol into ketone, and rearrangement of the hydroxyl group. Thus four major known metabolites were characterized as 17α-ethynyl-17β-acetoxyestr-4-en-3-one ( 5 ), 17α-ethynyl-17β-hydroxyestr-4-en-3-one ( 6 ), 17α-ethynyl-3 β-hydroxy-17β-acetoxyestr-4-ene ( 7 ) and 17α-ethynyl-5α,17β-dihydroxyestr-3-ene ( 8 ). Biotransformation of 1 with Azadirachta indica culture yielded compounds 5 and 6 . Spectroscopic data of compound 8 is being reported for the first time. Structure of compound 6 was unambiguously deduced through single-crystal x-ray diffraction studies. Conclusion Biotransformation of an oral contraceptive, ethynodiol diacetate ( 1 ), by using microbial and plant cell cultures provides an efficient route to the synthesis of a library of new steroids with potential contraceptive properties. These methods can be employed in the production of such compounds with high stereoselectivity.
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