Ultrasound evaluation of scar thickness for prediction of uterine dehiscence in term women with previous caesarean sections

Objective: To determine the role of ultrasound in evaluation of scar thickness for prediction of uterine dehiscence.Method: This retrospective cross-sectional study was conducted in the Radiology department of Aga Khan University Hospital from 1st July to 31st December 2021 after approval from the University Ethic Committee. In this study pregnant women 18 to 40 years with a live singleton fetus with vertex presentation, at term, with history of prior caesarean section and availability of medical record were included. Using a curvilinear ultrasound transducer with optimally distended urinary bladder, the myometrial thickness was measured in the sagittal plane. The intraoperative visual findings of the lower uterine segment outcome at the time of C-section were recorded and categorized into two groups i.e., with and without dehiscence for statistical analysis.Results: A total of 126 women were included. The mean age of the study participants was 29.8±4.1. The median gestational age was 35 (34-37) weeks. The highest AUC 0.58 was recorded for the scar thickness of ≤2.5mm with a sensitivity, specificity, PPV and NPV of 80.9%, 36.4%, 36.3% and 80.8% respectively. Similarly, the AUC for the scar thickness of ≤2mm was 0.55 with a sensitivity, specificity, PPV and NPV of 93%, 18.2%, 18.2% and 93% respectively.Conclusion: Transabdominal Sonography is a safe technique to determine the LUS thickness during antenatal ultrasound at term. A cutoff value of ≤2mm showed a high sensitivity and negative predictive value of 93% for evaluating the risk of uterine dehiscence

Evaluation of ThT Augmentation and RLS Inner Filter Effect Caused by Highly Fluorescent Coumarin Derivative and Establishing It as True Inhibitor of Amyloid Fibrillation

Screening of inhibitors that slow down or suppress amyloid fibrils formation relies on some simple but sensitive spectroscopy techniques. Thioflavin T (ThT) fluorescence assay is one of the most common, amyloid specific and sensitive method. However, if an inhibitor is itself fluorescent in the ThT fluorescence range, its screening becomes complicated and require complementary assays. One of such molecules, 6, 7-dihydroxycoumarin (6, 7-DHC, also known as aesculetin, esculetin, and cichorigenin) is fluorescent in the ThT emission range and absorbs in the ThT excitation range. Therefore, it can produce a subtractive effect attributed to primary inner filter effect and/or additive effect due to its self-fluorescence in ThT assay. Our study shows that 6, 7-DHC produces an additive effect in ThT fluorescence, which is minimized at high concentration of ThT and decrease in ThT fluorescence is solely due to its inhibitory effect against HSA fibrillation. These ThT fluorescence-based results are verified through other complementary assays, such as Rayleigh and dynamic light scattering and amyloid-specific Congo red binding assay. Furthermore, hydrophobicity reduction is studied through Nile red (NR) and kinetics through far-UV circular dichroism (far-UV CD) in place of the most commonly employed ThT assay owing to extremely high fluorescence of 6, 7-DHC during initial incubation period

Implementation of a clinical breast exam and referral program in a rural district of Pakistan

Background: The role of clinical breast examination (CBE) for early detection of breast cancer is extremely important in lower-middle-income countries (LMICs) where access to breast imaging is limited. Our study aimed to describe the outcomes of a community outreach breast education, home CBE and referral program for early recognition of breast abnormalities and improvement of breast cancer awareness in a rural district of Pakistan.Methods: Eight health care workers (HCW) and a gynecologist were educated on basic breast cancer knowledge and trained to create breast cancer awareness and conduct CBE in the community. They were then deployed in the Dadu district of Pakistan where they carried out home visits to perform CBE in the community. Breast cancer awareness was assessed in the community using a standardized questionnaire and standard educational intervention was performed. Clinically detectable breast lesions were identified during home CBE and women were referred to the study gynecologist to confirm the presence of clinical abnormalities. Those confirmed to have clinical abnormalities were referred for imaging. Follow-up home visits were carried out to assess reasons for non-compliance in patients who did not follow-through with the gynecologist appointment or prescribed imaging and re-enforce the need for follow-up.Results: Basic breast cancer knowledge of HCWs and study gynecologist improved post-intervention. HCWs conducted home CBE in 8757 women. Of these, 149 were warranted a CBE by a physician (to avoid missing an abnormality), while 20 were found to have a definitive lump by HCWs, all were referred to the study gynecologist (CBE checkpoint). Only 50% (10/20) of those with a suspected lump complied with the referral to the gynecologist, where 90% concordance was found between their CBEs. Follow-up home visits were conducted in 119/169 non-compliant patients. Major reasons for non-compliance were a lack of understanding of the risks and financial constraints. A significant improvement was observed in the community\u27s breast cancer knowledge at the follow-up visits using the standardized post-test.Conclusions: Basic and focused education of HCWs can increase their knowledge and dispel myths. Hand-on structured training can enable HCWs to perform CBE. Community awareness is essential for patient compliance and for early-detection, diagnosis, and treatmen

Molecular Basis of the Inhibition and Disaggregation of Thermally-induced Amyloid Fibrils of Human Serum Albumin by an Anti-Parkinson\u27s Drug, Benserazide Hydrochloride

This study summarises the results of multifactorial analysis of the inhibition/destabilization of human serum albumin (HSA) amyloid fibrils by an anti-Parkinson\u27s drug, benserazide hydrochloride (BH). Different biophysical techniques have been utilized for this purpose. Rayleigh light scattering (RLS) and dynamic light scattering (DLS) confirmed the formation of aggregates, that were identified as amyloid fibrils by the thioflavin T (ThT) and Congo Red (CR) fluorescent dye binding assays. Formation of amyloid fibrils and their inhibition/disaggregation was further characterized by transmission electron microscopy (TEM). The cytoprotective role of BH was examined by cytotoxicity assay performed on the SH-SY5Y neuronal cells. The deviation from linearity in the Stern Volmer plot indicated the presence of static and dynamic quenching of the HSA intrinsic fluorescence by BH. The value of Kd obtained by Scatchard plot was 4.5 × 10−4 M. The changes in the Trp microenvironment caused by the BH binding were further characterized by the synchronous fluorescence spectroscopy. Circular dichroism (CD) and differential scanning calorimetry (DSC) indicated increased HSA stability when bound to BH. Multiple binding sites in human serum albumin (HSA) for BH were found by binding and docking analysis, which revealed the involvement of hydrophobic and hydrogen bonding in the HSA-BH complex formation. Further, the negativity of the binding free energy suggested the spontaneity of the BH-HSA interaction. Overall, our study indicated that BH can serve as an efficient inhibitor/destabilizer of amyloid fibrils and the possible mechanism of this efficiency includes stabilization of HSA in the presence of BH. Therefore, BH can be used in treatment of systemic amyloidoses, since this drug cannot cross blood brain barrier (BBB)

A Multiparametric Analysis of the Synergistic Impact of Anti-Parkinson\u27s Drugs on the Fibrillation of Human Serum Albumin

Protein aggregation have been associated with several human neurodegenerative diseases, such as Parkinson\u27s and Alzheimer\u27s diseases. There are several small molecules that can reduce aggregation of proteins. The present study aimed to test the hypothesis that the application of more than one inhibitor either simultaneously or consecutively may result in more efficient inhibition of protein aggregation. To this end, the anti-amyloidogenic behaviour of benserazide hydrochloride (BH) and levodopa (LD) individually and in combination (BH + LD) was investigated using various biophysical, microscopic, and computational techniques. BH, LD, and BH + LD treatments showed inhibitory effects on protein aggregation and had the ability to minimise the amyloid-induced cytotoxicity in human neuroblastoma cell line (SH-SY5Y). The two drugs in combination showed synergism (combination index, CI \u3c 1) between them. These drugs also destabilised the preformed fibrils of human serum albumin (HSA). Our studies consistently showed that the BH + LD treatment showed highest efficacy towards inhibition and disaggregation of amyloid fibrils in comparison to treatment with BH and LD individually. Therefore, application of drugs in combination against fibrillogenesis may represent a new route for development of means for prevention or delaying of the aggregation-related diseases

Computational Studies on Phylogeny and Drug Designing Using Molecular Simulations for COVID-19

Since the first appearance of a novel coronavirus pneumonia (NCP) caused by a novel human coronavirus, and especially after the infection started its rapid spread over the world causing the COVID-19 (coronavirus disease 2019) pandemics, a very substantial part of the scientific community is engaged in the intensive research dedicated to finding of the potential therapeutics to cure this disease. As repurposing of existing drugs represents the only instant solution for those infected with the virus, we have been working on utilization of the structure-based virtual screening method to find some potential medications. In this study, we screened a library of 646 FDA approved drugs against the receptor-binding domain of the SARS-CoV-2 spike (S) protein and the main protease of this virus. Scoring functions revealed that some of the anticancer drugs (such as Pazopanib, Irinotecan, and Imatinib), antipsychotic drug (Risperidone), and antiviral drug (Raltegravir) have a potential to interact with both targets with high efficiency. Further we performed molecular dynamics simulations to understand the evolution in protein upon interaction with drug. Also, we have performed a phylogenetic analysis of 43 different coronavirus strains infecting 12 different mammalian species