Bioconjugation Techniques for Enhancing Stability and Targeting Efficiency of Protein and Peptide Therapeutics.

Bioconjugation techniques have emerged as powerful tools for enhancing the stability and targeting efficiency of protein and peptide therapeutics. This review provides a comprehensive analysis of the various bioconjugation strategies employed in the field. The introduction highlights the significance of bioconjugation techniques in addressing stability and targeting challenges associated with protein and peptide-based drugs. Chemical and enzymatic bioconjugation methods are discussed, along with crosslinking strategies for covalent attachment and site-specific conjugation approaches. The role of bioconjugation in improving stability profiles is explored, showcasing case studies that demonstrate successful stability enhancement. Furthermore, bioconjugation techniques for ligand attachment and targeting are presented, accompanied by examples of targeted protein and peptide therapeutics. The review also covers bioconjugation approaches for prolonging circulation and controlled release, focusing on strategies to extend half-life, reduce clearance, and design-controlled release systems. Analytical characterization techniques for bioconjugates, including the evaluation of conjugation efficiency, stability, and assessment of biological activity and targeting efficiency, are thoroughly examined. In vivo considerations and clinical applications of bioconjugated protein and peptide therapeutics, including pharmacokinetic and pharmacodynamic considerations, as well as preclinical and clinical developments, are discussed. Finally, the review concludes with an overview of future perspectives, emphasizing the potential for novel conjugation methods and advanced targeting strategies to further enhance the stability and targeting efficiency of protein and peptide therapeutics.

Effective management Alopecia totalis by Ayurveda - A case report.

Alopecia areata (AA) is a T-cell-mediated autoimmune illness characterized by intermittent, non-scarring hair loss, Alopecia totalis(AT) is a type of AA characterized by total hair loss on the face and scalp. Unfortunately, it is projected that 10-15 % of people with AA will advance to total hair loss on the scalp (AT) or hair loss on the scalp and body Alopecia Universalis (AU) only 10 % of patients with AT/AU recover completely. Treatment for severe AA is often unsatisfactory. The most popular AT/AU therapy techniques were topical steroid application and oral steroid administration. We present a case of Alopecia totalis that was treated with cupping therapy and ayurvedic treatments such as Punarnava Mandoor, manjistadi Kashaya, asanadi gana Kashaya, purnachandrodaya rasa, a churna combo, and Malatyadi and Dhurdhurapatradi taila for external application over scalp. The treatment's effectiveness is due to the synergistic action of all the herbs and the immunostimulant activity of cupping.

The role of sound touch elastography in assessment of liver fibrosis in chronic liver disease keeping APRI as the reference standard.

PURPOSE: The study aims to determine the role of Sound Touch Elastography [STE] technique in staging liver fibrosis and predicting clinically significant gastro-esophageal varices among patients with chronic liver disease [CLD] keeping aspartate aminotransferase to platelet ratio index [APRI] as the reference standard. METHODS: A prospective short-term study including 60 eligible patients with CLD were staged as non-significant fibrosis [NSF], significant fibrosis [SF] and cirrhosis [C] based on APRI values. STE was performed on each patient obtaining multiple readings as per pre-defined standards. The intra-observer reliability between each measurement and its association with APRI staging was evaluated using relevant statistical variables. Further, Youden's index was used to define the optimum cut-off values on STE in differentiating the stages of fibrosis and in predicting clinically significant gastro-esophageal varices. RESULTS: Based on APRI cut-off values, 41.7% [n = 25] of the study population had cirrhosis, while 45% [n = 27] had significant fibrosis and 13.3% [n = 8] had NSF. The STE values in kPa showed a positive correlation with APRI values [(rs) = 0.837, p < 0.001]. The intra-class correlation estimates based on a mean rating [k = 5] was found to be 0.97 [0.95-0.99], implying an excellent agreement between the measurements. Optimum cut-off values in staging SF and C were 7.26 kPa [J = 0.73, sensitivity-85.19%, specificity-87.5%; 95% CI] and 13.79 kPa [J = 0.84, sensitivity-96.0%, specificity-88.89%; 95% CI]. The AUROC for each of these stages were 0.926 [0.785-0.987] and 0.976 [0.890-0.999], respectively. 23.3% [n = 14] of the study population had clinically significant gastro-esophageal varices with a value above 18.84 kPa [J = 0.88] showing a sensitivity of 92.85% and a specificity of 95.65% in predicting the same. CONCLUSION: The novel STE technique shows good accuracy in staging liver fibrosis as determined by APRI values and in prediction of clinically significant gastro-esophageal varices with excellent reliability. It shows promising prospects and can be integrated widely in clinical practice for assessment and staging of fibrosis in CLD.

Novel COVID-19 Pneumonia: CT Manifestations and Pattern of Evolution.

Background This study aims to provide a better knowledge of COVID-19 that will aid in the formulation of future health policy by detailing the pathophysiology, case detection, and treatment, as well as management and prevention activities. Methodology A cross-sectional, prospective study was conducted at the Department of Radio-Diagnosis and Imaging, Shri B.M. Patil Medical College, Vijayapura. A total of 90 patients who presented with clinical features of COVID-19 and patients above the age of 18 years suspected of COVID-19 who were referred to the Department of Radio-Diagnosis and Imaging were included in the study. Results The classical findings which are observed on CT imaging in patients with COVID-19 include the presence of ground-glass opacities which are bilateral in distribution predominantly affecting the lower lobes with a posterior predilection. Overall, more than 33% of the patients who recovered from severe COVID-19 had lung abnormalities resembling fibrosis on follow-up imaging performed within two weeks of the commencement of the disease. These individuals were older and had more severe sicknesses during the acute period. Conclusions Chest CT can detect COVID-19 progression or secondary cardiopulmonary problems such as acute respiratory distress syndrome, pulmonary embolism, superimposed pneumonia, or heart failure. Future research into the prognostic value of chest CT in COVID-19 is required.

Needleless electrospun phytochemicals encapsulated nanofibre based 3-ply biodegradable mask for combating COVID-19 pandemic.

The emergence of COVID-19 pandemic has severely affected human health and world economies. According to WHO guidelines, continuous use of face mask is mandatory for personal protection for restricting the spread of bacteria and virus. Here, we report a 3-ply cotton-PLA-cotton layered biodegradable face-mask containing encapsulated phytochemicals in the inner-filtration layer. The nano-fibrous PLA filtration layer was fabricated using needleless electrospinning of PLA & phytochemical-based herbal-extracts. This 3-layred face mask exhibits enhanced air permeability with a differential pressure of 35.78 Pa/cm2 and superior bacterial filtration efficiency of 97.9% compared to conventional face masks. Close-packed mesh structure of the nano-fibrous mat results in effective adsorption of particulate matter, aerosol particles, and bacterial targets deep inside the filtration layer. The outer hydrophobic layer of mask exhibited effective blood splash resistance up to a distance of 30 cm, ensuring its utilization for medical practices. Computational analysis of constituent phytochemicals using the LibDock algorithm predicted inhibitory activity of chemicals against the protein structured bacterial sites. The computational analysis projected superior performance of phytochemicals considering the presence of stearic acid, oleic acid, linoleic acid, and Arachidic acid exhibiting structural complementarity to inhibit targeted bacterial interface. Natural cotton fibers and PLA bio-polymer demonstrated promising biodegradable characteristics in the presence of in-house cow-dung based biodegradation slurry. Addition of jaggery to the slurry elevated the biodegradation performance, resulting in increment of change of weight from 07% to 12%. The improved performance was attributed to the increased sucrose content in biodegradation slurry, elevating the bacterial growth in the slurry. An innovative face mask has shown promising results for utilization in day-to-day life and medical frontline workers, considering the post-pandemic environmental impacts.

CNNAI: A Convolution Neural Network-Based Latent Fingerprint Matching Using the Combination of Nearest Neighbor Arrangement Indexing.

Automatic fingerprint identification systems (AFIS) make use of global fingerprint information like ridge flow, ridge frequency, and delta or core points for fingerprint alignment, before performing matching. In latent fingerprints, the ridges will be smudged and delta or core points may not be available. It becomes difficult to pre-align fingerprints with such partial fingerprint information. Further, global features are not robust against fingerprint deformations; rotation, scale, and fingerprint matching using global features pose more challenges. We have developed a local minutia-based convolution neural network (CNN) matching model called "Combination of Nearest Neighbor Arrangement Indexing (CNNAI)." This model makes use of a set of "n" local nearest minutiae neighbor features and generates rotation-scale invariant feature vectors. Our proposed system doesn't depend upon any fingerprint alignment information. In large fingerprint databases, it becomes very difficult to query every fingerprint against every other fingerprint in the database. To address this issue, we make use of hash indexing to reduce the number of retrievals. We have used a residual learning-based CNN model to enhance and extract the minutiae features. Matching was done on FVC2004 and NIST SD27 latent fingerprint databases against 640 and 3,758 gallery fingerprint images, respectively. We obtained a Rank-1 identification rate of 80% for FVC2004 fingerprints and 84.5% for NIST SD27 latent fingerprint databases. The experimental results show improvement in the Rank-1 identification rate compared to the state-of-art algorithms, and the results reveal that the system is robust against rotation and scale.

End-to-End Automated Latent Fingerprint Identification With Improved DCNN-FFT Enhancement.

Automatic Latent Fingerprint Identification Systems (AFIS) are most widely used by forensic experts in law enforcement and criminal investigations. One of the critical steps used in automatic latent fingerprint matching is to automatically extract reliable minutiae from fingerprint images. Hence, minutiae extraction is considered to be a very important step in AFIS. The performance of such systems relies heavily on the quality of the input fingerprint images. Most of the state-of-the-art AFIS failed to produce good matching results due to poor ridge patterns and the presence of background noise. To ensure the robustness of fingerprint matching against low quality latent fingerprint images, it is essential to include a good fingerprint enhancement algorithm before minutiae extraction and matching. In this paper, we have proposed an end-to-end fingerprint matching system to automatically enhance, extract minutiae, and produce matching results. To achieve this, we have proposed a method to automatically enhance the poor-quality fingerprint images using the "Automated Deep Convolutional Neural Network (DCNN)" and "Fast Fourier Transform (FFT)" filters. The Deep Convolutional Neural Network (DCNN) produces a frequency enhanced map from fingerprint domain knowledge. We propose an "FFT Enhancement" algorithm to enhance and extract the ridges from the frequency enhanced map. Minutiae from the enhanced ridges are automatically extracted using a proposed "Automated Latent Minutiae Extractor (ALME)". Based on the extracted minutiae, the fingerprints are automatically aligned, and a matching score is calculated using a proposed "Frequency Enhanced Minutiae Matcher (FEMM)" algorithm. Experiments are conducted on FVC2002, FVC2004, and NIST SD27 latent fingerprint databases. The minutiae extraction results show significant improvement in precision, recall, and F1 scores. We obtained the highest Rank-1 identification rate of 100% for FVC2002/2004 and 84.5% for NIST SD27 fingerprint databases. The matching results reveal that the proposed system outperforms state-of-the-art systems.

A rare case of type X dual left anterior descending coronary artery.

A dual left anterior descending (LAD) coronary artery is a rare, and benign congenital anomaly. In this anomaly, there is the presence of two LADs in the anterior inter ventricular sulcus (AIVS). One of the LADs is a short one that ends high in the AIVS. The other longer one enters the distal AIVS and feeds the apex. To date, 9 types of dual LAD variants, and one novel type X has been reported. Herein, we report a case of type X dual LAD with a literature review. .

Successful device retrieval using simple balloon method during cardiac procedures.

OBJECTIVES: Although rare, incidents of broken/dislodged fragment of various angioplasty hardwares, including catheters, guidewires, angioplasty balloons, and stents, are being increasingly reported in recent years. Since these broken fragments may cause life-threatening consequences for a patient, it is vital for an interventional cardiologist to be acquainted with different retrieval techniques. Here, we are reporting our observations of several incidents of device dislodgement/fracture during cardiac interventions and their retrieval using simple balloon method. METHODS: We present a study of eight patients in whom we attempted to retrieve dislodged/fractured cath-lab hardwares during cardiac interventions, using simple balloon method. These cases include two cases of balloon, three cases of stent, and three cases of guidewire dislodgement/fracture. RESULTS: Fractured/dislodged cath-lab hardwares were successfully retrieved using a simple balloon method in six out of eight cases (75%), without any need of other retrieval hardwares. We observed no major complications in any patient. CONCLUSIONS: The balloon-assisted retrieval method is a simple, safe, and cost-effective way to avoid complications of endothelial injury, myocardial infarction, emergency coronary artery bypass graft, and sudden cardiac death. This study, particularly the context of retrieval technique used in each case, will offer valuable information to fellow interventional cardiologists.

Percutaneous Stenting for Unprotected Left Main Chronic Total Occlusion.

PCI of a left main coronary artery chronic total occlusion followed by PCI of the right coronary artery was performed in a patient refusing CABG surgery.

Tough, but not impossible - Retrieval of large atrial septal occluder devices embolized to left atrium.

Atrial septal defect (ASD) is a congenital heart defect that is being increasingly treated using percutaneous interventions. However, these techniques are not devoid of complications. One such complication is device embolization. Removal of such closure device poses tremendous risk and consequent complications both by percutaneous retrieval and surgical removal. Herein, we present two cases of ASDs that were closed using atrial septal occluder, but the devices were subsequently embolized into left atrium. These devices were then percutaneously retrieved without any further complication or injury.

Coronary stent concertina in proximal left anterior descending artery: An unusual case.

Since the emergence of stents, there has been persistent improvement in flexibility and deliverability of stents with modifications in its design and number of connectors. This has unfortunately created negative effect on longitudinal strength of stent resulting into a recently recognized and unaccustomed complication, longitudinal stent deformation (LSD). It is an abrupt shortening of the stent along its longitudinal axis, usually after deployment, due to various reasons. We present a case of LSD in Promus Element stent implanted at proximal left anterior descending artery. The stent shortening was about 25%-30% of its actual length. As this led to exposure of a part of lesion, it was successfully managed by overlapping another stent.

Aortoiliac reconstruction in the setting of in-stent restenosis.

Complex iliac artery obstructions, particularly bilateral stenosis or total iliac artery occlusions, are usually treated with aortofemoral or aortobifemoral graft surgery. However, surgical treatment is associated with 3% mortality rate and significant morbidity such as intestinal ischemia, spinal cord injury, and ureteral damage. Percutaneous interventions of aortic bifurcation offer a promising alternative to surgery with potentially lower morbidity and mortality risk. We report a case of peripheral artery disease who had underwent right transfemoral iliac angioplasty with femoropopliteal bypass presented again with bilateral lower limb ischemia, who was successfully treated with stent implantation with the kissing balloon technique.

Regional Comparison of Multiphase Computed Tomographic Angiography and Computed Tomographic Perfusion for Prediction of Tissue Fate in Ischemic Stroke.

BACKGROUND AND PURPOSE: Within different brain regions, we determine the comparative value of multiphase computed tomographic angiography (mCTA) and computed tomographic perfusion (CTP) in predicting follow-up infarction. METHODS: Patients with M1-middle cerebral artery occlusions were prospectively included in this multicenter study. Regional analysis was performed for each patient within Alberta Stroke Program Early CT Score regions M2 to M6. Regional pial vessel filling was assessed on mCTA in 3 ways: (1) Washout of contrast within pial vessels; (2) Extent of maximal pial vessel enhancement compared with contralateral hemisphere; (3) Delay in maximal pial vessel enhancement compared with contralateral hemisphere. Cerebral blood flow, cerebral blood volume, and Tmax data were extracted within these Alberta Stroke Program Early CT Score regions. Twenty-four- to 36-hour magnetic resonance imaging/CT was assessed for infarct in each Alberta Stroke Program Early CT Score region (defined as >20% infarction within that region). Mixed effects logistic regression models were used to compare mCTA and CTP parameters when predicting brain infarction. Area under the receiver operating characteristics was used to assess discriminative value of statistical models. RESULTS: Seventy-seven patients were included. mCTA parameter washout and CTP parameter Tmax were significantly associated with follow-up infarction in all models (P<0.05). The area under the receiver operating characteristic for mCTA models ranged from 92% to 94% and was not different compared with all CTP models (P>0.05). Mean Tmax and cerebral blood volume values were significantly different between each washout score (P<0.01) and each delay score category (P<0.01). Mean Tmax, cerebral blood flow, and cerebral blood volume values were significantly different between each extent score category (P<0.05). CONCLUSIONS: Similar to CTP, multiphase CTA can be used to predict tissue fate regionally in acute ischemic stroke patients.

Percutaneous Coronary Intervention of Hidden Coronary Artery-Unusual Type of Isolated Single Coronary Artery.

Single coronary artery is a rare congenital coronary artery anomaly, the incidence of which is 0.024-0.066% as described in literature. Report of cases having single coronary artery along with acute myocardial infarction are scanty and reports of percutaneous intervention in such a situation are even fewer, technically challenging and potentially cataclysmic. As single coronary artery supplies the entire myocardium, occlusion of this can result in significant ischemic insult, resulting in severe biventricular dysfunction. Percutaneous Coronary Intervention (PCI) of single coronary artery is technically challenging and carries high risk which may be equated to left main intervention. We report a rare interesting case of L1 variety of single coronary artery which presented as acute inferoposterior myocardial infarction with successful rescue PCI to Left Circumflex Artery (LCx).

Unusual non progressive idiopathic giant ascending aortic aneurysm-A rarity.

INTRODUCTION: Ascending aortic aneurysm is the second most common aortic aneurysm to abdominal aortic aneurysm. Most ascending aortic aneurysm is diagnosed in sixth or seventh decade of life. Majority of patients of ascending aortic aneurysm do not have any clinical manifestations. CASE PRESENTATION: 45year old female patient presented with Dyspnoea on exertion (NYHA class II-III), palpitation and vague chest pain since 2 years. Patient had worsening of symptoms NYHA IV dyspnoea since last 1 month and the patient managed with medications since the patient was not willing for surgery. Patient is on regular follow up on medications since last 2 years. DISCUSSION: Aneurysms are usually dilation of an arterial segment. It involves extensive area of the aorta and is a challenging surgical procedure especially when it involves aortic root. Computed Tomography (CT), and especially multi-detector CT (MDCT), is the most popular radiological modality for evaluating aortic aneurysms. CONCLUSION: Aortic aneurysms are localized dilation of the wall of aorta. They can rupture or dissect involving the pericardium, aortic valve. Open surgical repair remains the standard approach to treating most large aortic aneurysm and results are believed to be more predictable and satisfactory.

Clinical, angiographic profile and percutaneous endovascular management of Takayasu's arteritis - A single centre experience.

OBJECTIVE: Aim of the study was to evaluate clinical, angiographic profile and percutaneous endovascular management of Takayasu's arteritis. BACKGROUND: Takayasu's arteritis is a chronic inflammatory vasculitis affecting the aorta and its major branches. Although it is more prevalent in Asia, the distribution of the disease is worldwide with different vascular involvement patterns and clinical manifestations. METHODS: In this prospective study a total of 50 consecutive patients who were reported as having Takayasu's arteritis between January 2010 and April 2016 were evaluated. Detailed clinical presentation and angiograms of all patients were analysed. RESULTS: 50 patients were analysed during study period. Among 50 patients, 43(86%) were female and 7 (14%) were male. Average age of presentation was 26.92years. Most common clinical presentation was claudication (74%) followed by, musculoskeletal symptoms (48%), fatigue (46%), weight loss (22%), headache (22%), visual disturbances (16%), syncope (10%), dyspnoea (20%). Most common features were absent/diminished pulses (80%), difference in blood pressure (80%), followed by bruit (70%)hypertension (64%), cerebrovascular accident (8%),heart failure (8%) and aortic regurgitation (4%). According to the new angiographic classification, angiographic type I (40%) was encountered most frequently, followed by type III (30%), type V (16%), type IIb (8%), type IIa (2%), and type IV is (4%). Angioplasty was the main stay of treatment in 66% of the patients, remaining 34% of them were treated medically either with corticosteroids or methotrexate. CONCLUSION: Takayasu's arteritis is a rare disease, affects mainly women, manifestations range from asymptomatic disease, found as a result of impalpable pulses or bruits, to catastrophic neurological impairment. Takayasu's arteritis is the common cause of renovascular hypertension. Angiography remains the gold standard for diagnosis. Angiographic evaluation and percutaneous transluminal angioplasty with stenting is useful in selected cases.

What constitutes the M1 segment of the middle cerebral artery?

Intravenous tissue plasminogen activator has limited efficacy in fibrinolysis of large proximal intracranial thrombi. Thus, recent endovascular acute stroke trials restricted their selection criteria to patients with proximal occlusions in the anterior circulation. Although the terminal internal carotid artery occlusion is relatively easy to identify, there is often a debate as to what constitutes a proximal (involving the M1 segment) versus a distal (involving the M2 segment and beyond) middle cerebral artery occlusion. In light of overwhelming evidence demonstrating superiority of endovascular treatment in patients with proximal occlusion, this distinction has significant practical implications in patient selection. Here we present a brief review of the proximal (M1) segment of the middle cerebral artery anatomy and provide practical methods to recognize and separate the M1 and M2 segments. In keeping with the belief that CT angiography (CTA) (preferably multiphase CTA) is the ideal screening test for patients with emergent large vessel occlusion, we have provided tips for expeditious and accurate vascular imaging interpretation.

Assessment of inferior vena cava diameter by echocardiography in normal Indian population: A prospective observational study.

BACKGROUND: The assessment of the IVC diameter is self explanatory for evaluation of the individuals' volume status. Studies regarding IVC diameter estimation in normal individuals are scarce. AIM: The present study aimed to define normal criteria of size and dynamics of the inferior vena cava (IVC) by M-mode echocardiography in normal individuals. METHODS: This was a prospective, single-center, observational study carried out at Sri Jayadeva Institute of Cardiovascular Sciences and Research between December 2011 and April 2014. A total of 4126 consecutive individuals were enrolled. Normal IVC diameter was measured both during inspiration and expiration by M-mode echocardiography in subcostal view. RESULTS: The IVC diameter varied from 0.46 to 2.26cm in the study individuals. The IVC diameter ranged from 0.97 to 2.26cm during expiration and from 0.46 to 1.54cm during inspiration. A strong correlation was observed between IVC diameter and height, weight and BMI of the individuals, calculated using Pearson correlation. The correlation coefficients for expiratory and inspiratory IVC diameters as a function of BMI were 0.686 and 0.7, respectively. CONCLUSIONS: Our findings corroborate the correlations between height, weight and BMI with IVC diameter. Future studies could be focused to bring about a steadfast formula for calculating IVC diameter based on demographic parameters of an individual.