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Background: In this report, we describe an uncommon instance of fungating synovial sarcoma affecting the posterior aspect of the neck. Although the existing literature has documented a limited number of cases, this particular case contributes to the knowledge about it, which is scarce., Case Presentation: A total of 5 months before the examination, a Pakistani-Asian male, age 20 years, complained of a malodorous fungating swelling on the posterior aspect of his neck. An examination revealed a foul-smelling, 10 × 13 cm fungating enlargement surrounded by maggots and hemorrhaging at the site of the incision. A hemoglobin level of 6 and a total leukocyte count (TLC) of 23,000 indicated the patient's disoriented and pallid appearance. He was expeditiously admitted, and preoperatively, the general well-being of the patient was optimized. After a comprehensive discussion with the medical team, a strategy for marginal excision and coverage with a latissimus dorsi (LD) flap and grafting was devised. The tumor was successfully excised, and an LD flap with graft was conducted on the patient during surgery; however, the infection caused the failure of half of the graft. Following that, the lesion was debrided, and re-grafting was performed. The patient was subsequently administered 5 cycles of chemotherapy and 32 cycles of radiotherapy. He was diagnosed with pulmonary metastasis 2 years later. Sadly, the patient died during a follow-up visit 3.5 years later., Conclusions: The patient's unfavorable prognosis after surgical intervention, radiotherapy, and chemotherapy, despite undergoing all-encompassing treatments, underscores the importance of early detection and intervention in fungating tumor cases., (© 2024. The Author(s).)

Objective: To assess the factors affecting the transition of dental students from pre-clinical to clinical courses in an outcome-based curriculum., Methods: This cross-sectional study surveyed dental students in the third and fourth academic years of the Bachelor of Dental and Oral Surgery (BDS) program at the College of Dentistry, Jouf University. Ethically approved and powered by the G Power software, the study employed a modified questionnaire validated through a pilot test to assess five domains. Likert scale responses were analyzed using SPSS v.25, revealing insights into clinical workload, patient interaction, and learning experiences. Multiple regression analysis was used to assess the impact of clinical skill application, workload, transition to clinics, and patient interaction on learning experience as well as CGPA. The Mann-Whitney U test compared the ranks of two independent samples, making it less sensitive to outliers and more suitable for data with non-normal distributions., Results: In this study, the response rate of the participants was 70%. A total of 44 dental students in their third and fourth years of the program completed the survey. The multiple regression analysis showed that the predictors collectively explained 36.1% of the variance in the learning experience (Adjusted R 2 = 0.361). "Transition to Clinics" had a significant positive effect on learning experience (β = 0.292, p = 0.012), "Workload" (β = -0.203, p = 0.393) and "Patient Interaction" (β = 0.443, p = 0.168) were not significant predictors. The Mann-Whitney U test revealed no significant gender differences in transition to clinics, workload, patient interaction, application of clinical skills, and learning experience (U = 33.09 to -40.33, p > 0.05), but a significant difference in transition to clinics between third- and fourth-year students (U = 31.56 to -43.24, p < 0.05)., Conclusion: The results of this study demonstrate that the transition to clinical training can be intricate, and that multiple elements have an impact on this process. It is crucial to have support systems that facilitate the transition into the clinical learning environment., Competing Interests: The authors declare that they have no competing interests., (© 2024 Khattak et al.)

In the present study, we investigated the interaction of alpha-2-macroglobulin (α2M) with naringenin using multi-spectroscopic, molecular docking, and molecular simulation approaches to identify the functional changes and structural variations in the α2M structure. Our study suggests that naringenin compromised α2M anti-proteinase activity. The results of absorption spectroscopy and fluorescence measurement showed that naringenin-α2M formed a complex with a binding constant of (k b )∼10 4 , indicative of moderate binding. The value of ΔG° in the binding indicates the process to be spontaneous and the major force responsible to be hydrophobic interaction. The findings of FRET reveal the binding distance between naringenin and the amino acids of α2M was 2.82 nm. The secondary structural analysis of α2M with naringenin using multi-spectroscopic methods like synchronous fluorescence, red-edge excitation shift (REES), FTIR, and CD spectra further confirmed the significant conformational alterations in the protein. Molecular docking approach reveals the interactions between naringenin and α2M to be hydrogen bonds, van der Waals forces, and pi interactions, which considerably favour and stabilise the binding. Molecular dynamics modelling simulations also supported the steady binding with the least RMSD deviations. Our study suggests that naringenin interacts with α2M to alter its confirmation and compromise its activity.Communicated by Ramaswamy H. Sarma.

Tylophora indica (Burm f.) Merrill, belong to family Asclepiadaceae, is considered to be a natural remedy with high medicinal benefits. The objective of this work is to assess the metabolomic profile of T. indica leaves enriched in alkaloids, as well as to evaluate the in vitro cytotoxicity of these leaves using the MTT assay on human breast MCF-7 and liver HepG2 cancer cell lines. Dried leaves of T. indica were extracted by sonication, using methanol containing 2 % (v/v) of acetic acid and obtained fraction was characterized by HPTLC and UPLC-MS. The UPLC-MS study yielded a preliminary identification of 32 metabolites, with tylophorine, tylophorine B, tylophorinine, and tylophorinidine being the predominant metabolites. The cytotoxicity of the extract of T. indica was evaluated on HepG2 and MCF-7 cell lines, yielding inhibitory concentration (IC 50 ) values of 75.71 μg/mL and 69.60 μg/mL, respectively. Data suggested that the phytochemical screening clearly showed presence of numerous secondary metabolites with moderate cytotoxic efficacy. In conclusion, the future prospects of T. indica appear promising for the advancement of phytopharmaceutical-based anticancer medications, as well as for the design of contemporary pharmaceuticals in the field of cancer chemotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We present a hybrid machine learning and flow analysis feature detection method, RipViz, to extract rip currents from stationary videos. Rip currents are dangerous strong currents that can drag beachgoers out to sea. Most people are either unaware of them or do not know what they look like. In some instances, even trained personnel such as lifeguards have difficulty identifying them. RipViz produces a simple, easy to understand visualization of rip location overlaid on the source video. With RipViz, we first obtain an unsteady 2D vector field from the stationary video using optical flow. Movement at each pixel is analyzed over time. At each seed point, sequences of short pathlines, rather a single long pathline, are traced across the frames of the video to better capture the quasi-periodic flow behavior of wave activity. Because of the motion on the beach, the surf zone, and the surrounding areas, these pathlines may still appear very cluttered and incomprehensible. Furthermore, lay audiences are not familiar with pathlines and may not know how to interpret them. To address this, we treat rip currents as a flow anomaly in an otherwise normal flow. To learn about the normal flow behavior, we train an LSTM autoencoder with pathline sequences from normal ocean, foreground, and background movements. During test time, we use the trained LSTM autoencoder to detect anomalous pathlines (i.e., those in the rip zone). The origination points of such anomalous pathlines, over the course of the video, are then presented as points within the rip zone. RipViz is fully automated and does not require user input. Feedback from domain expert suggests that RipViz has the potential for wider use.

Medical and dental professionals should continue to adhere to preventive measures after COVID-19 vaccination due to their increased risk of exposure to the virus, particularly as new variants emerge that may heighten their risk perception and susceptibility. Therefore, this study aimed to explore the effects of COVID-19 vaccination on complacency to adherence to COVID-19 preventive behavioral measures and mental health among medical and dental professionals. In this cross-sectional study 410 medical and dental professionals were recruited from different medical and dental hospitals in Islamabad, Pakistan. The data was collected using a valid and reliable questionnaire comprising of three sections (socio-demographic, information of preventive behaviors performance against COVID-19 after vaccination, mental health status). A chi-square test and ordinal logistic regression were used for analysis. Post COVID-19 vaccination there was decrease in the frequency of use of hand washing, sanitizers (70.2%), and social distancing (60.5%), however greeting with a handshake (58.8%) and use of public transport (45.9%) seen upward trend among participants. Only face mask usage post-vaccination was statistically significant ( p  < .05) in association with age, marital status, and years of working Experience. The greatest decrease in the usage of masks after COVID-19 vaccination was seen in age group of 10-30 (41.7%) and working experience group of 0-5 years (39.7%). All the preventive behaviors are statistically significant ( p  < .05) associated with the mental status of the participants except online shopping and use of public transport. These results indicate the presence of vaccination-induced complacency in adherence to COVID-19 preventive behavioral measures among healthcare professionals.

Background: Echocardiography is widely used to evaluate left ventricular (LV) diastolic function in patients suspected of heart failure. For patients in sinus rhythm, a combination of several echocardiographic parameters can differentiate between normal and elevated LV filling pressure with good accuracy. However, there is no established echocardiographic approach for the evaluation of LV filling pressure in patients with atrial fibrillation. The objective of the present study was to determine if a combination of several echocardiographic and clinical parameters may be used to evaluate LV filling pressure in patients with atrial fibrillation., Results: In a multicentre study of 148 atrial fibrillation patients, several echocardiographic parameters were tested against invasively measured LV filling pressure as the reference method. No single parameter had sufficiently strong association with LV filling pressure to be recommended for clinical use. Based on univariate regression analysis in the present study, and evidence from existing literature, we developed a two-step algorithm for differentiation between normal and elevated LV filling pressure, defining values ≥ 15 mmHg as elevated. The parameters in the first step included the ratio between mitral early flow velocity and septal mitral annular velocity (septal E/e'), mitral E velocity, deceleration time of E, and peak tricuspid regurgitation velocity. Patients who could not be classified in the first step were tested in a second step by applying supplementary parameters, which included left atrial reservoir strain, pulmonary venous systolic/diastolic velocity ratio, and body mass index. This two-step algorithm classified patients as having either normal or elevated LV filling pressure with 75% accuracy and with 85% feasibility. Accuracy in EF ≥ 50% and EF < 50% was similar (75% and 76%)., Conclusions: In patients with atrial fibrillation, no single echocardiographic parameter was sufficiently reliable to be used clinically to identify elevated LV filling pressure. An algorithm that combined several echocardiographic parameters and body mass index, however, was able to classify patients as having normal or elevated LV filling pressure with moderate accuracy and high feasibility., (© 2024. The Author(s).)

Background: Although the conventional replacement for lost teeth has been partial or full dentures, the need for a fixed, esthetic, and functional restoration makes dental implants a reliable alternative., Aim: To evaluate the initial and final stability of platelet rich fibrin coated implants using resonance frequency analyzer., Method: ology: Thirteen patients with two or more missing teeth were informed about the procedure, and a consent form was obtained after cone beam computer tomography evaluation. Blood was drawn from the anticubital area of the patient, which was centrifuged to obtain platelet-rich fibrin. In all, 26 implants were placed, among which 13 were platelet-rich fibrin-coated (test group) and 13 were without platelet-rich fibrin (control group), and implant stability quotient values were recorded., Results: The mean age of the patients was 34.4 (SD = 4.28). Majority of the patients were males (9; 69.2%) whereas there were only four (30.8%) female patients. When comparison between overall primary implant stability with and without PRF was done, the mean difference was 5.12 and this difference was not statistically significant (p = 0.221) whereas a statistically significant difference (p = 0.019) was found when comparison between overall secondary implant stability was done with and without PRF. The primary and secondary stability values for the control group were 69.18 ± 7.45 and 73.84 ± 8.21 respectively, and the primary and secondary stability values for the test group were 64.06 ± 12.66 and 81.49 ± 7.61 respectively, which showed statistically significant differences among the groups. The difference in these values signify that primary stability is more in control group whereas secondary stability is more in case group. This signifies that PRF enhances the stability of implant., Conclusion: Implants coated with platelet-rich fibrin exhibited better osseointegration than implants without platelet-rich fibrin., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Nickel is a heavy metal that is regarded as a possible hazard to living organisms due to its toxicity and carcinogenicity. Nickel chloride (NiCl 2 ), an inorganic divalent Ni compound, has been shown to cause oxidative stress in cells by altering the redox equilibrium. We have investigated the effect of NiCl 2 on isolated human erythrocytes under in vitro condition., Methods: Isolated erythrocytes were treated with different concentrations of NiCl 2 (25-500 µM) for 24 h at 37 ºC. Hemolysates were prepared and several biochemical parameters were analyzed in them., Results: Treatment of erythrocytes with NiCl 2 enhanced the intracellular generation of reactive oxygen species (ROS). A significant increase in hydrogen peroxide levels and oxidation of proteins and lipids was also seen. This was accompanied by a reduction in levels of nitric oxide, glutathione, free amino groups and total sulfhydryl groups. NiCl 2 treatment impaired both enzymatic and non-enzymatic defense systems, resulting in lowered antioxidant capacity and diminished ability of cells to quench free radicals and reduce metal ions. NiCl 2 exposure also had an inhibitory effect on the activity of enzymes involved in pathways of glucose metabolism (glycolytic and pentose phosphate shunt pathways). Increased level of methemoglobin, which is inactive in oxygen transport, was also seen. The rate of heme breakdown increased resulting in the release of free iron. Exposure to NiCl 2 led to considerable cell lysis, indicating damage to the erythrocyte membrane. This was supported by the inhibition of membrane bound enzymes and increase in the osmotic fragility of NiCl 2 treated cells. NiCl 2 treatment caused severe morphological alterations with the conversion of normal discocytes to echinocytes. All changes were seen in a NiCl 2 concentration-dependent manner., Conclusion: NiCl 2 generates cytotoxic ROS in human erythrocytes which cause oxidative damage that can decrease the oxygen carrying capacity of blood and also lead to anemia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Objective: To compare high-para and low-para women with respect to haematological findings, determinants, and consequences secondary to anaemia., Study Design: Descriptive cohort study. Place and Duration of the Study: Maternity and Child Hospital, Hail, Saudi Arabia and Specialist Care Hospital (private), Islamabad, Pakistan, from April 2022 to April 2023., Methodology: The study population comprised of pregnant women in the last trimester, with the exception of those women who had more than one fetus and history of haematological disease. Purposive non-probability sampling technique was adopted. Hospital data were retrieved retrospectively for the past obstetrical, contraception usage, and supplement history. Blood parameters, type of delivery, and maternofetal complications were noted down. For qualitative-variable and quantitative-variable comparisons, Chi-square test and t-test were applied, respectively. Significance level was kept at p ≤0.05., Results: The frequency of severe anaemia in high-para was 52%. High parity and anaemia had a significant dose-response relationship (p <0.05). There was a significant difference (p <0.05) in blood parameters between high-para and low-para groups. Main determinants identified for anaemia were lack of intake of iron-rich food (36%) followed by inadequate intake of oral iron (25%). Preterm birth (68%) and post-partum haemorrhage (96%) were significantly associated (p <0.05) with high parity. There was a significantly high proportion (83%) of high-para women with more than 3 cesarean deliveries and admissions in ICU., Conclusion: High parity and anaemia had a significant dose-response relationship. High parity was the main determinant of maternal and fetal admissions in ICU., Key Words: Parity, Comparison, Maternal anaemia, Haematological findings, Diet, Contraception, Cost-effective.

Cancer is the primary and one of the most prominent causes of the rising global mortality rate, accounting for nearly 10 million deaths annually. Specific methods have been devised to cure cancerous tumours. Effective therapeutic approaches must be developed, both at the cellular and genetic level. Immunotherapy offers promising results by providing sustained remission to patients with refractory malignancies. Genetically modified T‑lymphocytic cells have emerged as a novel therapeutic approach for the treatment of solid tumours, haematological malignancies, and relapsed/refractory B‑lymphocyte malignancies as a result of recent clinical trial findings; the treatment is referred to as chimeric antigen receptor T‑cell therapy (CAR T‑cell therapy). Leukapheresis is used to remove T‑lymphocytes from the leukocytes, and CARs are created through genetic engineering. Without the aid of a major histocompatibility complex, these genetically modified receptors lyse malignant tissues by interacting directly with the carcinogen. Additionally, the outcomes of preclinical and clinical studies reveal that CAR T‑cell therapy has proven to be a potential therapeutic contender against metastatic breast cancer (BCa), triple‑negative, and HER 2+ve BCa. Nevertheless, unique toxicities, including (cytokine release syndrome, on/off‑target tumour recognition, neurotoxicities, anaphylaxis, antigen escape in BCa, and the immunosuppressive tumour microenvironment in solid tumours, negatively impact the mechanism of action of these receptors. In this review, the potential of CAR T‑cell immunotherapy and its method of destroying tumour cells is explored using data from preclinical and clinical trials, as well as providing an update on the approaches used to reduce toxicities, which may improve or broaden the effectiveness of the therapies used in BCa.

2,4-Dibromophenol (DBP) has several industrial applications, including as a wood preservative and flame retardant. This study investigated the interaction between DBP and human hemoglobin (Hb) using spectroscopic, molecular docking and molecular dynamic techniques. The UV-visible spectra showed ground-state complex formation between DBP and Hb. Fluorescence studies revealed that DBP binding caused significant quenching of Hb fluorescence by the static quenching mechanism. The binding of DBP to Hb is a spontaneous process that involves van der Waals forces and hydrogen bonds. There is one DBP binding site on each Hb molecule that is located at the α 1 β 2 interface of Hb. DBP binding did not alter the microenvironment of tyrosine and tryptophan residues in Hb. Circular dichroism studies revealed that DBP increased the α-helical content of Hb. The intrinsic esterase activity of Hb was inhibited by DBP in a concentration-dependent manner. Molecular docking showed that DBP binds to Hb via hydrogen bonds, hydrophobic, van der Waals and π - π interactions. Molecular dynamics simulation confirmed that the Hb-DBP complex is stable. Overall, the results of this study clearly show that DBP induces structural changes and interferes with the function of Hb. This can have important implications for human health.Communicated by Ramaswamy H. Sarma.

Background and aim: The presence of mechanical dyssynchrony on echocardiography is associated with reverse remodelling and decreased mortality after cardiac resynchronization therapy (CRT). Contrarily, myocardial scar reduces the effect of CRT. This study investigated how well a combined assessment of different markers of mechanical dyssynchrony and scarring identifies CRT responders. Methods: In a prospective multicentre study of 170 CRT recipients, septal flash (SF), apical rocking (ApRock), systolic stretch index (SSI), and lateral-to-septal (LW-S) work differences were assessed using echocardiography. Myocardial scarring was quantified using cardiac magnetic resonance imaging (CMR) or excluded based on a coronary angiogram and clinical history. The primary endpoint was a CRT response, defined as a ≥15% reduction in LV end-systolic volume 12 months after implantation. The secondary endpoint was time-to-death. Results: The combined assessment of mechanical dyssynchrony and septal scarring showed AUCs ranging between 0.81 (95%CI: 0.74-0.88) and 0.86 (95%CI: 0.79-0.91) for predicting a CRT response, without significant differences between the markers, but significantly higher than mechanical dyssynchrony alone. QRS morphology, QRS duration, and LV ejection fraction were not superior in their prediction. Predictive power was similar in the subgroups of patients with ischemic cardiomyopathy. The combined assessments significantly predicted all-cause mortality at 44 ± 13 months after CRT with a hazard ratio ranging from 0.28 (95%CI: 0.12-0.67) to 0.20 (95%CI: 0.08-0.49). Conclusions: The combined assessment of mechanical dyssynchrony and septal scarring identified CRT responders with high predictive power. Both visual and quantitative markers were highly feasible and demonstrated similar results. This work demonstrates the value of imaging LV mechanics and scarring in CRT candidates, which can already be achieved in a clinical routine.

Verticillium wilt is a disastrous disease caused by Verticillium dahliae that severely damages the production of cotton in China. Even under homogeneous conditions, the same cotton cultivar facing V. dahliae tends to either stay healthy or become seriously ill and die. This binary outcome may be related to the interactions between microbiome assembly and plant health. Understanding how the rhizosphere microbiome responds to V. dahliae infection is vital to controlling Verticillium wilt through the manipulation of the microbiome. In this study, we evaluated the healthy and diseased rhizosphere microbiome of two upland cotton cultivars that are resistant to V. dahliae , Zhong 2 (resistant) and Xin 36 (susceptible), using 16S rRNA and ITS high-throughput sequencing. The results showed that the healthy rhizosphere of both resistant cultivar and susceptible cultivar had more unique bacterial ASVs than the diseased rhizosphere, whereas fewer unique fungal ASVs were found in the healthy rhizosphere of resistant cultivar. There were no significant differences in alpha diversity and beta diversity between the resistant cultivar and susceptible cultivar. In both resistant cultivar and susceptible cultivar, bacterial genera such as Pseudomonas and Acidobacteria bacterium LP6 , and fungal genera such as Cephalotrichum and Mortierella were both highly enriched in the diseased rhizosphere, and Pseudomonas abundance in diseased rhizospheres was significantly higher than that in the healthy rhizosphere regardless of the cultivar type. However, cultivar and V. dahliae infection can cause composition changes in the rhizosphere bacterial and fungal communities, especially in the relative abundances of core microbiome members, which varied significantly, with different responses in the two cotton cultivars. Analysis of co-occurrence networks showed that resistant cultivar has a more complex network relationship than susceptible cultivar in the bacterial communities, and V. dahliae has a significant impact on the bacterial community structure. These findings will further broaden the understanding of plant-rhizosphere microbiome interactions and provide an integrative perspective on the cotton rhizosphere microbiome, which is beneficial to cotton health and production., 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 Tie, Wang, Chen, Tang, Yu, Liu, Zhao, Khan, Zhang and Xi.)

Objectives: C5 inhibitors such as eculizumab and ravulizumab are the first-line treatment in the management of paroxysmal nocturnal hemoglobinuria (PNH). However, some patients develop novel symptoms as part of their treatment with eculizumab, and the disease is termed as eculizumab refractory PNH. The aim of this study was to conduct a systematic review on the available treatment modalities for the management of eculizumab refractory PNH., Methods: Two authors independently searched two databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 70 studies were obtained: 4 out 70 studies were found to meet the inclusion criteria., Results: Four studies were found to meet the inclusion criteria of our study. Two studies were published in 2021 and two studies were published in 2020. All four studies were multicenter clinical trials. Two studies were phase III clinical trials, one study was a phase II clinical trial, and one study was a phase I clinical trial. Two studies were about pegcetacoplan, one was about danicopan, and one was about iptacopan., Conclusion: Based upon the findings of our systematic review, we recommend an individualized treatment plan based on the mechanism of eculizumab refractoriness and the mechanism of PNH breakthrough. This recommendation is subject to the available resources and clinical expertise available at different hospitals. More studies using study designs such as randomized controlled trials comparing multiple drugs should be performed to accurately assess the different medications and aid in designing guidelines of the management of eculizumab refractory PNH., Level of Evidence: Level I., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article., (© The Author(s) 2023.)

Alpha-2-macroglobulin (α 2 M) is an essential antiproteinase that is widely distributed in human plasma. The present study was aimed at investigating the binding of a potential therapeutic dietary flavonol, morin, with human α 2 M using a multi-spectroscopic and molecular docking approach. Recently, flavonoid-protein interaction has gained significant attention, because a majority of dietary bioactive components interact with proteins, thereby altering their structure and function. The results of the activity assay exhibited a 48% reduction in the antiproteolytic potential of α 2 M upon interaction with morin. Fluorescence quenching tests unequivocally confirmed quenching in the fluorescence of α 2 M in the presence of morin, conforming complex formation and demonstrating that the binding mechanism involves a dynamic mode of interaction. Synchronous fluorescence spectra of α 2 M with morin showed perturbation in the microenvironment around tryptophan residues. Furthermore, structural changes were observed through CD and FT-IR, showing alterations in the secondary structure of α 2 M induced by morin. FRET further supports the results of the dynamic mode of quenching. Moderate interaction is shown by binding constant values using Stern-Volmer's fluorescence spectroscopy. Morin binds to α 2 M at 298 K with a binding constant of 2.7 × 10 4  M -1 , indicating the strength of the association. The α 2 M-morin system was found to have negative ΔG values, which suggests that the binding process was spontaneous. Molecular docking also reveals the different amino acid residues involved in this binding process, revealing that the binding energy is -8.1 kcal/mol., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives: The study was conducted in a tertiary educational hospital based in Riyadh to explore faculty's perception of using simulation-based teaching as part of the Cardiovascular Diploma Program (CDP) to improve patients' safety. The study, also aimed to identify the benefits and challenges of utilizing simulation., Methods: Researchers used a qualitative approach. Semi-structured interviews were conducted online with ten faculty-members. The interviews were performed between July and September in the year 2019. Authors used convenient sampling techniques for recruitment. Data were transcribed and analyzed using a framework analysis approach., Result: Data analysis showed four emergent themes, i.e., the concept of simulation (it is a risk-free environment for training), simulation for patients' safety (students first learn on the simulators and deal with patients), simulation as a safe learning environment (gives idea basic things about the working environment, knowing the symptoms of the patients, catheterizing the patient, knowing preparations for the procedure and post care), and the challenges of utilizing simulation (identify gaps between the theoretical and practical parts)., Conclusion: Faculty has appreciated the role of simulation in improving patients' safety. Simulation was underutilized due to the limited time allotted for simulation and lack of adequate experienced faculty. It is recommended that simulation should be integrated into the CDP curriculum., Competing Interests: Conflict of interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)

Myricetin (MYR) is a bioactive secondary metabolite found in plants that is recognized for its nutraceutical value and is an essential constituent of various foods and beverages. It is reported to exhibit a plethora of activities, including antioxidant, antimicrobial, antidiabetic, anticancer, and anti-inflammatory. Alpha-2-macroglobulin (α2M) is a major plasma anti-proteinase that can inhibit proteinases of both human and non-human origin, regardless of their specificity and catalytic mechanism. Here, we explored the interaction of MYR-α2M using various biochemical and biophysical techniques. It was found that the interaction of MYR brings subtle change in its anti-proteolytic potential and thereby alters its structure and function, as can be seen from absorbance and fluorescence spectroscopy. UV spectroscopy of α2M in presence of MYR indicated the occurrence of hyperchromism, suggesting complex formation. Fluorescence spectroscopy reveals that MYR reduces the fluorescence intensity of native α2M with a shift in the wavelength maxima. At 318.15 K, MYR binds to α2M with a binding constant of 2.4 × 10 3  M -1 , which indicates significant binding. The ΔG value was found to be - 7.56 kcal mol -1 at 298.15 K, suggesting the interaction to be spontaneous and thermodynamically favorable. The secondary structure of α2M does not involve any major change as was confirmed by CD analysis. The molecular docking indicates that Asp-146, Ser-172, Glu-174, and Tyr-180 were the key residues involved in α2M-MYR complex formation. This study contributes to our understanding of the function and mechanism of protein and flavonoid binding by providing a molecular basis of the interaction between MYR and α2M., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Coronavirus disease-2019 (COVID-19) is pro-inflammatory disorder characterized by acute respiratory distress syndrome. Interleukin-6, a cytokine secreted by macrophages, which mediates an inflammatory response, is frequently increased and associated with the severity in COVID-19 patients. The differential expression of IL6 cytokine in COVID-19 patients may be associated with the presence of single nucleotide polymorphisms (SNPs) in regulatory region of cytokine genes. The aim of this study is to investigate the role of two promoter polymorphisms of the IL6 gene (-597G > A and -174G > C) with the severity of COVID-19. The study included 242 patients, out of which 97 patients with severe symptoms and 145 patients with mild symptoms of COVID-19. Genotyping of two selected SNPs, rs1800795 (-174G > C) and rs1800797 (-597G > A) of promoter region of IL6 gene, was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In our study, individuals with GC genotypes of IL6 (-174G > C) polymorphism showed significantly higher risk of severity [adjusted odds (OR) 3.86, p <.001] but we did not observe any association of COVID-19 severity with rs1800797 (-597G > A) polymorphism. The COVID-19 severity was significantly higher in individuals having 'C' allele of IL6 (-174G > C) polymorphism (p = .014). Linkage disequilibrium between rs1800795 (-174G > C) and rs1800797 (-597G > A) showed that individuals having AC* haplotype significantly association with COVID-19 severity (p = .034). Our results suggest that 'C' allele of rs1800795 (-174G > C) polymorphism of IL6 may be the risk allele for severity of COVID-19 in North Indian population., (© 2022 John Wiley & Sons Ltd.)

In the context of the global increase in the rate of cesarean deliveries, with an associated higher morbidity and mortality, this study aimed to investigate the role of maternal age and parity in the cesarean section rate among women in the Hail Region of Saudi Arabia. This retrospective cohort study used data collected from the labor ward of the Maternity and Child Health Hospital, Hail, over a period of 8 months, forming a cohort of 500 women. Women were categorized into four different parity classes. The results revealed that there was no significant relationship between cesarean deliveries and maternal age ( p -value, 0.07). There was no significant difference in the mode of delivery between the study's parity cohort group. A significant increase in cesarean deliveries was noticed among obese women with a BMI between 35-39.9 (52.14%). This increase was even greater among those with a BMI above 40 (63.83%). Fetal distress, malpresentation and abruptio placenta were the most significant indications for CS among all age groups ( p -value 0.000, 0.021, and 0.048, respectively). Conclusions: The number of cesarean deliveries has no association with parity or age. However, there was a statistically significant association with BMI, a perineal tear after previous vaginal delivery, and a history of diabetes mellitus and gestational diabetes. The most reported reasons for CS were fetal distress, malpresentation, and abruptio placenta among all age groups.

The extensive production and use of harmful pesticides in agriculture to improve crop yield has raised concerns about their potential threat to living components of the environment. Pesticides cause serious environmental and health problems both to humans and animals. Carbendazim (CBZ) is a broad spectrum fungicide that is used to control or effectively kill pathogenic microorganisms. CBZ is a significant contaminant found in food, soil and water. It exerts immediate and delayed harmful effects on humans, invertebrates, aquatic animals and soil microbes when used extensively and repeatedly. CBZ is a teratogenic, mutagenic and aneugenic agent that imparts its toxicity by enhancing generation of reactive oxygen species generation. It elevates the oxidation of thiols, proteins and lipids and decreases the activities of antioxidant enzymes. CBZ is cytotoxic causing hematological abnormalities, mitotic spindle deformity, inhibits mitosis and alters cell cycle events which lead to apoptosis. CBZ is known to cause endocrine-disruption, embryo toxicity, infertility, hepatic dysfunction and has been reported to be one of the leading causes of neurodegenerative disorders. CBZ is dangerous to human health, the most common side effects upon chronic exposure are thyroid gland dysfunction and oxidative hepato-nephrotoxicity. In mammals, CBZ has been shown to disrupt the antioxidant defense system. In this review, CBZ-induced toxicity in different cells, tissues and organisms, under in vitro and in vivo conditions, has been systematically discussed., (© 2022 Wiley Periodicals LLC.)

Open de-gloving hand injuries with exposed tendons and bones require coverage by a flap. Conventionally used groin or abdominal flaps are cumbersome to patients due to extensive dressing and prolonged passive positioning of the hand until pedicle division. Superficial circumflex iliac artery (SCIA) flap is evolved from a traditional groin flap, and because of its thinness, pliability, and concealed donor site, it is an ideal option for single-stage reconstruction of traumatic hand defects avoiding discomforting passive hand position, joint stiffness, and unexpected flap avulsion which were associated with traditional groin flap. All patients with exposed bones or tendons due to traumatic hand injuries who opted for free flap coverage during the year 2018 to 2020 were enrolled in our study. After initial debridement, the wound was covered with a free SCIA flap. Duration of hospital stay, days out of work, the number of dressings required, postoperative complications, and any secondary procedures for flap readjustment were noted till six months postoperatively. A total of eight patients were included in the study. The mechanism of injury was road traffic accidents in a single patient and occupational injury in eight patients. The average duration of hospital stay was six days after reconstructive surgery. The average number of dressings a patient had was 18, and only two patients required flap thinning. Only one patient had a postoperative infection which was managed with dressings and antibiotics. One patient had peripheral flap necrosis. We had zero flap re-exploration. Therefore, we conclude that hand defects coverage with SCIA flap leads to a smaller number of working days lost and rarely requires secondary procedures., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Hussain et al.)

High parity is associated with the risk of fetomaternal complications such as gestational diabetes mellitus, hypertensive disorders, maternal anemia, preterm labor, miscarriage, postpartum hemorrhage, and perinatal and preterm mortality. The objective of the study was to compare fetomaternal complications in women of high parity with women of low parity. This involved a cohort study on a sample size of 500 women who had singleton births. Data were collected from the Maternity and Child Hospital, Ha'il, Kingdom of Saudi Arabia. Participants were classified into two groups according to parity, i.e., women of low parity and women of high parity. Socio-demographic data and pregnancy complications, such as gestational diabetes, hypertension, preeclampsia, intrauterine growth restriction, etc., were retrieved from participants' files. Participants were followed in the postnatal ward until their discharge. The results revealed that women of high parity mostly (49%) were married before 20 years of age, less educated, obese, and were of un-booked cases. Premature babies and fetal mortality are significantly high (0.000) in this group. There is a significant difference between the two groups with respect to maternal anemia, gestational diabetes mellitus, joint pain, perineal tear, miscarriage, postpartum hemorrhage, preeclampsia, vaginal tear, and cesarean section. Determinants responsible for high parity should be identified via evidence-based medicine. Public health education programs targeting couples, weight control, nutrition, and contraception would be a cost-effective strategy for reducing the risk of possible fetomaternal complications.

The lung microbiome plays an essential role in maintaining healthy lung function, including host immune homeostasis. Lung microbial dysbiosis or disruption of the gut-lung axis can contribute to lung carcinogenesis by causing DNA damage, inducing genomic instability, or altering the host's susceptibility to carcinogenic insults. Thus far, most studies have reported the association of microbial composition in lung cancer. Mechanistic studies describing host-microbe interactions in promoting lung carcinogenesis are limited. Considering cancer as a multifaceted disease where epigenetic dysregulation plays a critical role, epigenetic modifying potentials of microbial metabolites and toxins and their roles in lung tumorigenesis are not well studied. The current review explains microbial dysbiosis and epigenetic aberrations in lung cancer and potential therapeutic opportunities., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

5-Fluorouracil (5-FU) is a well-recognized anticancer drug used in the treatment of tumors of head, neck and breast. Drug pharmacokinetics is affected upon binding with protein, thus, making drug-protein interactions imperative to study. Present work investigates the interaction between 5-FU and human major antiproteinase-alpha-2-macroglobulin (α 2 M) by multi-spectroscopic, calorimetric and molecular docking techniques. UV/Visible absorption, intrinsic fluorescence and circular dichroism (CD) spectroscopic methods have been employed to unveil the mode and mechanism of 5-FU-α 2 M interaction. Synchronous fluorescence showed alteration in the microenvironment of tryptophan and tyrosine residues of protein. Far UV-CD spectra suggest slight alterations in the secondary structure of α 2 M by 5-FU. Thermodynamic parameters determined by fluorescence quenching experiments and isothermal titration calorimetry (ITC) suggested the involvement of hydrogen bonds and hydrophobic interactions. Moreover, ITC corroborate the spontaneous and exothermic nature of the interaction process. Molecular docking illustrates that 5-FU binds with moderate affinity and Asp953, Tyr1264, Lys1236, Thr1232, Tyr1323 and Leu951 were the main residues involved. Molecular dynamics simulation studies suggested that 5-FU was stabilizing the α 2 M structure and forming a stable complex. It was concluded that 5-FU lower the antiproteolytic activity of α 2 M significantly and causes disruption in the native structure and conformation of α 2 M.Communicated by Ramaswamy H. Sarma.

Exosomes are 30 to 150 nm-diameter lipid bilayer-enclosed extracellular vesicles that enable cell-to-cell communication through secretion and uptake. The exosomal cargoes contain RNA, lipids, proteins, and metabolites which can be delivered to recipient cells in vivo. In a healthy lung, exosomes facilitate interaction between adaptive and innate immunity and help maintain normal lung physiology. However, tumor-derived exosomes in lung cancer (LC) can, on the other hand, restrict immune cell proliferation, cause apoptosis in activated CD8+ T effector cells, reduce natural killer cell activity, obstruct monocyte differentiation, and promote proliferation of myeloid-derived suppressor and regulatory T cells. In addition, exosomes in the tumor microenvironment may also play a critical role in cancer progression and the development of drug resistance. In this review, we aim to comprehensively examine the current updates on the role of exosomes in lung carcinogenesis and their potential application as a diagnostic, prognostic, and therapeutic tool in lung cancer., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Miniaturized accelerometers incorporated in pacing leads attached to the myocardium, are used to monitor cardiac function. For this purpose functional indices must be extracted from the acceleration signal. A method that automatically detects the time of aortic valve opening (AVO) and aortic valve closure (AVC) will be helpful for such extraction. We tested if deep learning can be used to detect these valve events from epicardially attached accelerometers, using high fidelity pressure measurements to establish ground truth for these valve events., Method: A deep neural network consisting of a CNN, an RNN, and a multi-head attention module was trained and tested on 130 recordings from 19 canines and 159 recordings from 27 porcines covering different interventions. Due to limited data, nested cross-validation was used to assess the accuracy of the method., Result: The correct detection rates were 98.9% and 97.1% for AVO and AVC in canines and 98.2% and 96.7% in porcines when defining a correct detection as a prediction closer than 40 ms to the ground truth. The incorrect detection rates were 0.7% and 2.3% for AVO and AVC in canines and 1.1% and 2.3% in porcines. The mean absolute error between correct detections and their ground truth was 8.4 ms and 7.2 ms for AVO and AVC in canines, and 8.9 ms and 10.1 ms in porcines., Conclusion: Deep neural networks can be used on signals from epicardially attached accelerometers for robust and accurate detection of the opening and closing of the aortic valve.

Ifosfamide is an active alkylating chemotherapeutic drug chemically related to nitrogen mustard. The pharmacokinetics of drugs is affected upon binding with protein, making the studies on drug-protein interaction promising. The present study investigates the interaction between ifosfamide and human antiproteinase-alpha-2-macroglobulin (α 2 M) by using multi-spectroscopic and in silico techniques. The UV-visible absorption, intrinsic fluorescence and circular dichroism (CD) spectroscopic methods were employed to unveil the mode and mechanism of ifosfamide-α 2 M interaction. Fluorescence quenching studies performed at three different temperatures indicated that ifosfamide-α 2 M complex formation involves static quenching. Far UV-CD spectra revealed a minor alteration in the secondary structure of α 2 M instigated by ifosfamide. The thermodynamic parameters determined by fluorescence quenching experiment and isothermal titration calorimetry (ITC) suggested that the complex between ifosfamide and α 2 M involves hydrogen bonding and hydrophobic interactions. Molecular docking illustrates that ifosfamide binds with moderate affinity to Lys1240, Asn173, Ser957, Leu955, Asp953, Lys1216 and Thr1236 residues during the interaction. Molecular dynamic (MD) simulation suggested that the ifosfamide forms a stable complex with α 2 M. Communicated by Ramaswamy H. Sarma.

Background: Full-thickness defects on the dorsum of the hand requires thin, soft, and pliable skin for which there are limited locoregional flaps. The reverse posterior interosseous artery (PIA) flap based on the communicating artery fulfills all above requirements and can reach upto the fingers. However, there has been discrepancy in the surface marking of the flap and the anatomical position of the vessel pedicle. We share our alteration with the marking and ease of harvesting this flap., Method and Material: This is a prospective study conducted at a private teaching hospital in Karachi, over a period of 2 years from November 2017 to December 2019. After taking consent and ensuring confidentiality of all patients who had PIA flap reconstruction, we collected patient's demographic details, mode of injury, and flap surface area. We altered the described skin marking and took measures to prevent venous congestion and noted the outcomes in term of flap congestion and flap loss., Results: Twenty-eight patients with a mode age of 32 years were operated during this period. The majority (64.2%) had a motor vehicle accident and machine injuries. The mean surface area of flaps was 6 × 10 cm 2 , and 11 (39.2%) flaps had venous supercharging. All patients had a 10-20° wrist extension splint for 2 weeks. The mean follow-up of the patients was 14 ± 5 days, and 6 (21.4%) flaps developed a minimal marginal flap loss, which was managed conservatively., Conclusion: By minimally altering our surface marking, we experienced a easy and quick harvesting of this flap. However, one has to be vigilant and take all described precautions for venous congestion., Competing Interests: All authors declare that they have no conflict of interests., (© 2022 The Authors.)

Human race has survived several outbreak of pandemics in the past and their impact was long lasting. Some of the recent pandemics have been caused by a viruses known as Coronaviruses (CoVs) which are diverse, complex, adaptable viruses that have a significant impact on human health and animal productivity. The novel coronavirus that emerged in Wuhan, China (SARS-CoV-2) in 2019 has quickly spread throughout the world. Human coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV) and 2019 novel coronavirus (2019-nCoV, also known as SARS-CoV-2), have led to a global epidemic with high morbidity and mortality. Human pathogenic coronaviruses, SARS-CoV and SARS-CoV-2, bind to their target cells through angiotensin-converting enzyme 2 (ACE2), which is expressed by epithelial cells of the lung, intestine, kidneys, and blood vessels. The efforts to contain the virus are undergoing throughout the world, given the many uncertainties regarding pathogen transmissibility and virulence. Thus, the ongoing studies to promote the understanding of HCoVs will help to avoid or/and minimize the impact of anticipated pandemics in future.

Background: Deltamethrin (DLM) is a commercial insecticide of the synthetic pyrethroid family that is used to control disease-causing insects and vectors. When humans are exposed to the fumes or aerosols of DLM, it enters the body via cuticular absorption and reacts with proteins and other biomolecules., Objective: Alpha-2-macroglobulin (α 2 M) is a serum proteinase inhibitor that also carries out receptor- mediated endocytosis of extracellular substances. This study was done to decipher the structural and functional alterations of α 2 M by DLM., Methods: Various spectroscopic techniques, including UV absorption and fluorescence spectroscopy, binding studies, and molecular docking, were used to characterize the interaction of DLM with α 2 M. The affinity constant was calculated from the Stern-Volmer equation using fluorescence data., Results: The UV-Vis and fluorescence spectral studies indicated the formation of a complex between α 2 M and DLM. Thermodynamically, the interaction was found to be spontaneous with ΔG = -4.23 kcal/mol. CD spectra suggested a change in the secondary structure of the protein from β to α helical content with increasing concentration of DLM. The molecular docking study by Autodock Vina established the interaction of DLM with Glu-926, Ala-1103, Ala-1108, Val-1116, Asn-1159, Glu-1220, Leu-1261, Thr-1272, Ile-1390, Pro-1391, Lys-1393, Val-1396, Lys-1397, Thr-1408, Glu-1409, Val-1410, Ser-1411, Ser-1412, and Asn-1413 with an improved docking score of -6.191 kcal/mol. The binding was carried out in the vicinity of the receptor-binding domain at the C-terminal of α 2 M., Conclusion: The decrease in the functional activity and structural changes of protein after binding with DLM has a significant effect on human α 2 M. The information may be useful for exploring the role of DLM in a clinical chemistry laboratory., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aims: The aim of this study is to investigate determinants of left atrial (LA) reservoir and pump strain and if these parameters may serve as non-invasive markers of left ventricular (LV) filling pressure., Methods and Results: In a multicentre study of 322 patients with cardiovascular disease of different aetiologies, LA strain and other echocardiographic parameters were compared with invasively measured LV filling pressure. The strongest determinants of LA reservoir and pump strain were LV global longitudinal strain (GLS) (r-values 0.64 and 0.51, respectively) and LV filling pressure (r-values -0.52 and -0.57, respectively). Left atrial volume was another independent, but weaker determinant of both LA strains. For both LA strains, association with LV filling pressure was strongest in patients with reduced LV ejection fraction. Left atrial reservoir strain <18% and LA pump strain <8% predicted elevated LV filling pressure better (P < 0.05) than LA volume and conventional Doppler parameters. Accuracy to identify elevated LV filling pressure was 75% for LA reservoir strain alone and 72% for pump strain alone. When combined with conventional parameters, accuracy was 82% for both LA strains. In patients with normal LV systolic function by GLS, LA pump strain >14% identified normal LV filling pressure with 92% accuracy., Conclusion: Left atrial reservoir and pump strain are determined predominantly by LV GLS and filling pressure. Accuracy of LA strains to identify elevated LV filling pressure was best in patients with reduced LV systolic function. High values of LA pump strain, however, identified normal LV filling pressure with good accuracy in patients with normal systolic function., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Human papillomaviruses (HPV) infection is a major causative agent and strongly associated with the development of cervical cancer. Understanding the mechanisms of HPV-induced cervical cancer is extremely useful in therapeutic strategies for primary prevention (HPV vaccines) and secondary prevention (screening and diagnosis of precancerous lesions). However, due to the lack of proper implementation of screening programs in developing countries, cervical cancer is usually diagnosed at advanced stages that result in poor treatment responses. Nearly half of the patients will experience disease recurrence within two years post treatment. Therefore, it is vital to identify new tools for early diagnosis, prognosis, and treatment prediction. MicroRNAs (miRNAs) are small non-coding RNAs, implicated in posttranscriptional regulation of gene expression. Growing evidence has shown that abnormal miRNA expression is associated with cervical cancer progression, metastasis, and influences treatment outcomes. In this review, we provide comprehensive information about miRNA and their potential utility in cervical cancer diagnosis, prognosis, and clinical management to improve patient outcomes., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background: Bangladesh experienced a sudden, large influx of forcibly displaced persons from Myanmar in August 2017. A cholera outbreak occurred in the displaced population during September-December 2019. This study aims to describe the epidemiologic characteristics of cholera patients who were hospitalized in diarrhea treatment centers (DTCs) and sought care from settlements of Forcibly Displaced Myanmar Nationals (FDMN) as well as host country nationals during the cholera outbreak., Methods: Diarrhea Treatment Center (DTC) based surveillance was carried out among the FDMN and host population in Teknaf and Leda DTCs hospitalized for cholera during September-December 2019., Results: During the study period, 147 individuals with cholera were hospitalized. The majority, 72% of patients reported to Leda DTC. Nearly 65% sought care from FDMN settlements. About 47% of the cholera individuals were children less than 5 years old and 42% were aged 15 years and more. Half of the cholera patients were females. FDMN often reported from Camp # 26 (45%), followed by Camp # 24 (36%), and Camp # 27 (12%). Eighty-two percent of the cholera patients reported watery diarrhea. Some or severe dehydration was observed in 65% of cholera individuals. Eighty-one percent of people with cholera received pre-packaged ORS at home. About 88% of FDMN cholera patients reported consumption of public tap water. Pit latrine without water seal was often used by FDMN cholera individuals (78%)., Conclusion: Vigilance for cholera patients by routine surveillance, preparedness, and response readiness for surges and oral cholera vaccination campaigns can alleviate the threats of cholera., Competing Interests: The authors have declared that no competing interests exist.

In this review, we present an elaborate account of coronavirus in context to Covid-19 focusing on its origin, genome, life cycle, and immunology with a basic understanding of the disease and its cause. Further, the transmission, prevention and advances in therapeutics have also been discussed anticipating the possible outcomes in the near future. Moreover, the recently emerged unconventional approaches to this viral disease like drug repurposing, plasma therapy, nasal spray, and other preventive measures worldwide are studied for a long-term impact and relevance. Hence, this account on coronavirus and the ongoing pandemic serves a purpose of spreading awareness and to pass on relevant knowledge for a better chance to combat such unfortunate health crisis in future.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become a global health issue and develops into a broad range of illnesses from asymptomatic to fatal respiratory diseases. SARS-CoV-2 infection is associated with oxidative stress that triggers cytokine production, inflammation, and other pathophysiological processes. Glutathione-S-transferase (GST) is an important enzyme that catalyzes the conjugation of glutathione (GSH) with electrophiles to protect the cell from oxidative damage and participates in the antioxidant defense mechanism in the lungs. Thus, in this study, we investigated the role of GSTM1 and GSTT1 gene polymorphism with COVID-19 susceptibility, as well as its outcome. The study included 269 RT-PCR confirmed COVID-19 patients with mild (n = 149) and severe (n = 120) conditions. All subjects were genotyped for GSTM1 and GSTT1 by multiplex polymerase chain reaction (mPCR) followed by statistical analysis. The frequency of GSTM1 -/- , GSTT1 -/- and GSTM1 -/- /GSTT1 -/- was higher in severe COVID-19 patients as compared to mild patients but we did not observe a significant association. In the Cox hazard model, death was significantly 2.28-fold higher in patients with the GSTT1 -/- genotype (p = 0.047). In combination, patients having GSTM1 +/+ and GSTT1 -/- genotypes showed a poor survival rate (p = 0.02). Our results suggested that COVID-19 patients with the GSTT1 -/- genotype showed higher mortality., (© 2021 Wiley Periodicals LLC.)

Background Complex wounds of hands and feet have always been a challenge for reconstructive surgeon. We aim to share our experience of reconstruction of such defects using free fibula osteocutaneous flaps. Materials and methods This is a retrospective study over a period of six years which was conducted at a tertiary care teaching hospital in Karachi. All patients, who were included and had reconstruction with this flap, agreed to participate in this study. Hospital records were retrieved for patient's demographic details, mode of injury, size of the defect, number of bone loss in the defect, dimensions of flap, size and number of bony segments in each flap. Outcomes were recorded in terms of flap survival and secondary procedures, with post-operative radiographs. Results In 14 patients, 25 (80.5%) metacarpals and 6 (19.5%) metatarsals defects were reconstructed. K-wires were used for bony stabilization and were removed at 8 weeks post-operatively. Only two flaps were re-explored due to venous congestion. Minor wound dehiscence was noted in two flaps which were managed conservatively. Conclusion Proper planning and meticulous flap dissection and inset using free fibula flap can save many hand and foot from amputations., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Khan et al.)