A Cardiologist's Clinical Dilemma: An Incidental Finding of a Potentially High-Risk Anomalous Right Coronary Artery Origin.

Coronary artery anomalies may place patients at risk for various adverse events. We present a case of a 62-year-old male with a two-year history of intermittent chest pain. A computed tomography coronary angiogram revealed a rare finding of an anomalous right coronary artery (ARCA) originating from the left ascending aorta, with high-risk features. This case highlights the complexities in diagnosing and managing ARCA, underscoring the importance of individualized care and careful consideration of invasive intervention risks versus potential benefits.

Establishing a role for the oral microbiome in infectious complications following major oral cavity cancer surgery.

Surgery forms the backbone of treatment for most locoregional or advanced oral cavity squamous cell carcinoma. Unfortunately, infectious complications (including orocutaneous fistulas) are common following such extensive surgery and can afflict over half of patients. These complications can lead to delays in adjuvant treatment, prolonged hospitalization, reconstructive failure, and decreased quality of life. The frequency and morbidity associated with infectious complications has led to the search for pre-disposing risk factors; and, several have been identified, including both patient (e.g. diabetes) and surgical (e.g. operative time) factors. However, these findings are inconsistently reproduced, and risk factor modification has had a limited impact on rates of infectious complications. This is striking given that the likely contaminant-the oral microbiome-is a well-studied microbial reservoir. Because many oral cavity cancer surgeries involve violation of oral mucosa and the spillage of the oral microbiome into normally sterile areas (e.g. the neck), variance in oral microbiome composition and function could underly differences in infectious complications. The goal of this perspective is to highlight 1) this knowledge gap and 2) opportunities for studies in this domain. The implication of this line of thought is that the identification of oral microbial dysbiosis in patients undergoing surgery for oral cavity cancer could lead to targeted pre-operative therapeutic interventions, decreased infectious complications, and improved patient outcomes.

Using tele-paramedicine to conduct in-home fall risk reduction after emergency department discharge: Preliminary data.

BACKGROUND: Older adults discharged from our emergency department (ED) do not receive comprehensive fall risk evaluations. We conducted a quality improvement project using an existing Community Tele-Paramedicine (CTP) program to perform in-home fall risk assessment and mitigation after ED discharge. METHODS: High falls-risk patients, as defined by STEADI score >4, were referred for a CTP home visit by community paramedics supervised virtually by emergency physicians. Home hazards assessment, Timed Up and Go test (TUG), medication reconciliation, and psychosocial evaluation were used to develop fall risk mitigation plans. Outcomes assessed at 30 days post ED-discharge included: completed CTP visits, falls, ED revisits, hospital admissions, and referrals. RESULTS: Between November 2022 and June 2023, 104 (65%) patients were discharged and referred to CTP. The mean age of enrolled patients was 80 years, 66% were female, 63% White, 79% on Medicare or Medicaid, most lived with a family member (50%) or alone (38%). Sixty-one (59%) patients received an initial CTP visit, 48 (79%) a follow-up visit, and 12 (11%) declined a visit. Abnormal TUG tests (74%), home hazards (67%), high-risk medications (36%), or need for outpatient follow-up (49%) or additional home services (41%) were frequently identified. At 30 days, only one of the CTP patients reported a fall, one patient had a fall-related ED visit, and one patient was admitted secondary to a fall. CONCLUSIONS: A quality improvement initiative using CTP to perform fall risk reduction after ED discharge identified areas of risk mitigation in the home where most falls take place. Further controlled studies are needed to assess the impact of CTP on clinical outcomes important to patients and health systems.

Ni-kshay Poshan Yojana: receipt and utilization among persons with TB notified under the National TB Elimination Program in India, 2022.

BACKGROUND: Ni-kshay Poshan Yojana (NPY), a direct benefit transfer scheme under the National Tuberculosis Elimination Program (NTEP) in India, provides a monthly benefit of INR500 for nutritional support of persons with TB (PwTB). OBJECTIVES: To determine the proportion of PwTB receiving atleast one NPY instalment and pattern of utilisation; to ascertain factors associated with NPY non-receipt and association of NPY receipt with TB treatment outcome. METHODS: In our cross-sectional study, we used multi-stage sampling to select PwTB whose treatment outcome was declared between May 2022 and February 2023. A cluster-adjusted, generalized linear model was used to identify factors associated with the non-receipt of NPY and determine association between NPY receipt and TB treatment outcome. RESULTS: Among 3201 PwTB, 2888 (92.7%; 95% CI 89.8%, 94.8%) had received at least one NPY instalment, and 1903 (64.2%; 95% CI 58.9%, 69.2%) self-reported receipt of benefit. The median (IQR) time to receipt of first instalment was 105 (60,174) days. Non-receipt was significantly higher among PwTB from states with low TB score (aPR = 2.34; 95%CI 1.51, 3.62), who do not have bank account (aPR = 2.48; 95%CI 1.93, 3.19) and with unknown/missing diabetic status (aPR = 1.69; 95%CI 1.11, 2.55). Unfavorable treatment outcomes were associated with non-receipt of NPY (aPR 4.93; 95%CI 3.61,6.75) after adjusting for potential confounders. CONCLUSION: Majority of the PwTB received atleast one NPY instalment, but they experience significant delays. Most of the recipients utilised NPY for nutrition. Longitudinal follow-up studies are required to study the impact of NPY on treatment outcomes.

Main findings: Five years since implementation, almost ninety percent of persons with tuberculosis in India had received at least one benefit under Ni-kshay Poshan Yojana, most of whom utilise it for nutrition.Added knowledge: Persons with tuberculosis in India experience a median delay of over three months to receive the first instalment of the benefit.Global health impact for policy and action: Ensuring timely credit of benefits is crucial to enable its utilisation by persons with tuberculosis for better nutrition and favourable treatment outcomes.

Large-Scale Direct Growth of Monolayer MoS2 on Patterned Graphene for van der Waals Ultrafast Photoactive Circuits.

Two-dimensional (2D) van der Waals heterostructures combine the distinct properties of individual 2D materials, resulting in metamaterials, ideal for emergent electronic, optoelectronic, and spintronic phenomena. A significant challenge in harnessing these properties for future hybrid circuits is their large-scale realization and integration into graphene interconnects. In this work, we demonstrate the direct growth of molybdenum disulfide (MoS2) crystals on patterned graphene channels. By enhancing control over vapor transport through a confined space chemical vapor deposition growth technique, we achieve the preferential deposition of monolayer MoS2 crystals on monolayer graphene. Atomic resolution scanning transmission electron microscopy reveals the high structural integrity of the heterostructures. Through in-depth spectroscopic characterization, we unveil charge transfer in Graphene/MoS2, with MoS2 introducing p-type doping to graphene, as confirmed by our electrical measurements. Photoconductivity characterization shows that photoactive regions can be locally created in graphene channels covered by MoS2 layers. Time-resolved ultrafast transient absorption (TA) spectroscopy reveals accelerated charge decay kinetics in Graphene/MoS2 heterostructures compared to standalone MoS2 and upconversion for below band gap excitation conditions. Our proof-of-concept results pave the way for the direct growth of van der Waals heterostructure circuits with significant implications for ultrafast photoactive nanoelectronics and optospintronic applications.

Peer Assessment of Student Presentations: Key Takeaways and Lessons Learned.

Background Students' presentations are a teaching-learning tool where students not only study and understand a topic but also teach their peers, thereby learning the art and skill of effective presentation. Aims The study aimed to evaluate peer assessments in students' presentations and find their role and application in improving presentation skills among students through feedback and course correction. Methods A group of students every week from a class of 125 was assigned a topic to present to the rest of their batch students who evaluated their presentation on a rubric shared via a Google Form link. The number of students who gave responses was noted. The responses were also shared with the presenters. The evaluator faculty moderated and discussed the areas for possible improvement and course correction. The students also filled out a feedback form on the entire exercise after presentations from the entire batch. Results The quality of students' presentation skills improved with subsequent students over the period. The students learned about their areas of improvement. Through the feedback form, students shared their reasons not to give a presentation. However, most of them found the exercise beneficial. Conclusions Peer assessment can be a credible mode for improving presentation skills with the active participation of other students and provide a learning method based on others' performances. Peer responses provide for self-evaluation and self-reflection. This type of survey among different institutions will identify students' flaws, help them improve and self-evaluate, and add to the current literature.

Volvulus is Stressful: Stress-Induced Cardiomyopathy Secondary to Gastric Volvulus and Paraesophageal Hernia.

Stress-induced cardiomyopathy (SCM) is a cardiac systolic dysfunction caused by various stressful triggers. It is often transient and reversible upon the reversal of the underlying stressor. We present the case of a 70-year-old female with SCM in the setting of gastric volvulus and incarcerated para-esophageal hernia.

A Retrospective Analysis of BCR-ABL1 Kinase Domain Mutations in the Frontline Drug Intolerant or Resistant Chronic Myeloid Leukemia Patients: An Indian Experience from a High-End Referral Laboratory.

Atreye MajumdarSambit K. MohantyObjective This article identifies and evaluates the frequency of mutations in the BCR-ABL1 kinase domain (KD) of chronic myeloid leukemia (CML) patients who showed suboptimal response to their current tyrosine kinase inhibitor (TKI) regime and assesses their clinical value in further treatment decisions. Materials and Methods Peripheral and/or bone marrow were collected from 791 CML patients. Ribonucleic acid was extracted, reverse transcribed, and Sanger sequencing method was utilized to detect single-nucleotide variants (SNVs) in BCR-ABL1 KD. Results Thirty-eight different SNVs were identified in 29.8% ( n = 236/791) patients. T315I, E255K, and M244V were among the most frequent mutations detected. In addition, one patient harbored a novel L298P mutation. A subset of patients from the abovementioned harbored compound mutations (13.3%, n = 33/236). Follow-up data was available in 28 patients that demonstrated the efficacy of TKIs in correlation with mutation analysis and BCR-ABL1 quantitation. Molecular response was attained in 50% patients following an appropriate TKI shift. A dismal survival rate of 40% was observed in T315I-harboring patients on follow-up. Conclusion This study shows the incidence and pattern of mutations in one of the largest sets of Indian CML patients. In addition, our findings strengthen the prognostic value of KD mutation analysis among strategies to overcome TKI resistance.

Malignant Melanoma: An Overview, New Perspectives, and Vitamin D Signaling.

Melanoma, originating through malignant transformation of melanin-producing melanocytes, is a formidable malignancy, characterized by local invasiveness, recurrence, early metastasis, resistance to therapy, and a high mortality rate. This review discusses etiologic and risk factors for melanoma, diagnostic and prognostic tools, including recent advances in molecular biology, omics, and bioinformatics, and provides an overview of its therapy. Since the incidence of melanoma is rising and mortality remains unacceptably high, we discuss its inherent properties, including melanogenesis, that make this disease resilient to treatment and propose to use AI to solve the above complex and multidimensional problems. We provide an overview on vitamin D and its anticancerogenic properties, and report recent advances in this field that can provide solutions for the prevention and/or therapy of melanoma. Experimental papers and clinicopathological studies on the role of vitamin D status and signaling pathways initiated by its active metabolites in melanoma prognosis and therapy are reviewed. We conclude that vitamin D signaling, defined by specific nuclear receptors and selective activation by specific vitamin D hydroxyderivatives, can provide a benefit for new or existing therapeutic approaches. We propose to target vitamin D signaling with the use of computational biology and AI tools to provide a solution to the melanoma problem.

Beyond Cardiology: A Rare Encounter With Small Bowel Obstruction Disguised as Inferior Wall ST-Elevation Myocardial Infarction.

ST segment elevations (STEs) on an electrocardiogram (EKG) gravitate immediate attention to the heart. However, these EKG changes can sometimes be the result of noncardiac pathologies. Here, we present an interesting case of small bowel obstruction (SBO) masquerading as an inferior wall myocardial infarction. A 77-year-old woman with a history of aortic stenosis status postsurgical aortic valve replacement presented with chest pain. Workup revealed elevated high-sensitivity troponins and STE in the inferior leads. She subsequently underwent a left heart catheterization, which showed no critical plaques or stenosis. Persistent abdominal pain prompted further evaluation with a computed tomography scan of the abdomen, which demonstrated evidence of SBO. Conservative treatment with bowel decompression resulted in symptom improvement and complete resolution of the STEs on a follow-up EKG. This case underscores the importance of considering noncardiac etiologies, such as SBO, in the differential diagnosis of STE on EKG for accurate diagnosis and management.

Prophylactic Antibiotic Use in Reconstruction of Nasal Mohs Defects.

OBJECTIVE: To evaluate the effect of prophylactic antibiotics on outcomes and complications following surgical reconstructions of nasal Mohs defects in the outpatient setting. STUDY DESIGN: Retrospective cohort study. SETTING: Single tertiary care center, July 2021 to June 2023. METHODS: All adult patients who underwent reconstruction of nasal Mohs defects in an outpatient office setting were examined. Patient demographics, surgical details, prophylactic postprocedural antibiotic use, and postprocedural complications (infection, flap or graft necrosis, wound dehiscence) were collected. Outcomes and complications were compared between patients who received and did not receive prophylactic antibiotics using χ2, Kruskal-Wallis, and multivariable logistic regression. RESULTS: A total of 211 patients met inclusion criteria. A majority of reconstructions utilized a local flap (70%), followed by a skin or composite graft (22%), then an interpolated flap (8%). Over half of patients (55%) were prescribed prophylactic antibiotics. Postprocedural complications were documented in 16 patients (7.6%), including infection (3.3%) and flap or graft loss or necrosis (1.4%). The rate of complications did not differ based on receipt of antibiotics. The only factors independently associated with the development of complications were history of chemoradiation and reconstruction with skin or composite grafts. CONCLUSION: Prophylactic antibiotics after nasal Mohs reconstructions performed in the office setting were not associated with any differences in the rate of postprocedural complications, including surgical site infections.

Endoscopic Repair of Internal Carotid Artery Injury with a Lateral Tongue Muscle Patch Graft: Novel Technique and Literature Review.

Objectives Iatrogenic injury to the internal carotid artery (ICA) is one of the most catastrophic complications of endoscopic sinus and skull base surgery. Previous research has shown that packing with a crushed muscle graft at the injury site can be an effective management technique to control bleeding and prevent the need for ICA sacrifice. Here, we describe a novel and readily available repair donor site-an autologous lateral tongue muscle patch. Design Three representative cases of a successful repair of ICA injuries using a lateral tongue muscle patch are included in this study. The graft measured approximately 2 × 3 cm and was taken from the lateral intrinsic tongue musculature. We describe the harvest of the graft, its advantages, and the details of operative repair. Results The lateral tongue provides a large and readily accessible source of muscle within the surgical field that can be quickly harvested during an endoscopic procedure. For the first case, an expanding parasellar ICA pseudoaneurysm was managed with a tongue muscle patch and nasal packing. In the second case, a cavernous ICA injury was sustained during craniopharyngioma resection. Case three involved an ICA injury during endonasal debridement of invasive fungal rhinosinusitis. None of the patients required embolization or neurovascular stenting. Postoperative angiograms and serial computed tomography angiograms showed complete resolution of the pseudoaneurysm, and the patients continued to do well at least 1 year after repair. Conclusion Lateral tongue muscle graft is an effective and efficient method to manage ICA injuries during endoscopic endonasal surgery. Advantages include the speed of harvest, donor site being readily accessible in the surgical field, and low donor site morbidity. It should be added to the repertoire of possible donor sites for addressing catastrophic sinonasal bleeding.

Postoperative Cosmetic Scores and Revision Rates After Nasal Mohs Reconstructive Surgery.

OBJECTIVE: Few studies have examined the impact of preoperative and surgical factors on the change in cosmetic survey scores after nasal Mohs reconstruction using a subset of the 10-item Standardized Cosmesis and Health Nasal Outcomes Survey-Cosmesis (SCHNOS-C). We aim to determine preoperative and surgical factors that impact cosmetic outcomes following Mohs nasal reconstruction. STUDY DESIGN: Retrospective analysis. SETTING: Nasal Mohs reconstruction patients at a tertiary medical center. METHODS: All patients receiving Mohs reconstruction of any nasal subunit at a tertiary medical center were analyzed. Variables collected included demographic and Mohs defect/reconstruction characteristics. Primary outcomes were changes in cosmetic (SCHNOS-C) scores and revision rates. Multivariable analysis was used to identify independent predictors of cosmetic scores/revision. RESULTS: We included 296 patients for analysis. On multivariable logistic regression, factors contributing to better final cosmetic scores were receiving a skin/composite graft (odds ratio [OR]: 0.22, 95% confidence interval: 0.06-0.68, P = .014) compared to a local flaps. Women were more likely to have worsening cosmetic scores (OR: 2.27, 1.06-4.99, P = .037). Only initial cosmetic scores independently predicted receiving any revision (OR: 1.11, 1.03-1.20, P = .006). CONCLUSION: Average SCHNOS-C scores after nasal reconstruction of Mohs defects are low. Only worse patient reported SCHNOS-C scores predicted revision. It is important to understand preoperative and surgical factors that affect cosmetic outcomes to optimize patient counseling and reconstructive planning. Patient perception is a key factor in predicting revisions.

Need for operational simplicity and timely disbursal of benefits-a qualitative exploration of the implementation of a direct benefit transfer scheme for persons with tuberculosis in India.

BACKGROUND: Ni-kshay Poshan Yojana (NPY) is a direct benefit transfer scheme of the Government of India introduced in 2018 to support the additional nutritional requirements of persons with TB (PwTB). Our recent nationwide evaluation of implementation and utilization of NPY using programmatic data of PwTB from nine randomly selected Indian states, reported a 70% coverage and high median delay in benefit credit. We undertook a qualitative study between January and July 2023, to understand the detailed implementation process of NPY and explore the enablers and barriers to effective implementation and utilization of the NPY scheme. METHODS: We followed a grounded theory approach to inductively develop theoretical explanations for social phenomena through data generated from multiple sources. We conducted 36 in-depth interviews of national, district and field-level staff of the National Tuberculosis Elimination Programme (NTEP) and NPY beneficiaries from 30 districts across nine states of India, selected using theoretical sampling. An analytical framework developed through inductive coding of a set of six interviews, guided the coding of the subsequent interviews. Categories and themes emerged through constant comparison and the data collection continued until theoretical saturation. RESULTS: Stakeholders perceived NPY as a beneficial initiative. Strong political commitment from the state administration, mainstreaming of NTEP work with the district public healthcare delivery system, availability of good geographic and internet connectivity and state-specific grievance redressal mechanisms and innovations were identified as enablers of implementation. However, the complex, multi-level benefit approval process, difficulties in accessing banking services, perceived inadequacy of benefits and overworked human resources in the NTEP were identified as barriers to implementation and utilization. CONCLUSION: The optimal utilization of NPY is enabled by strong political commitment and challenged by its lengthy implementation process and delayed disbursal of benefits. We recommend greater operational simplicity in NPY implementation, integrating NTEP activities with the public health system to reduce the burden on the program staff, and revising the benefit amount more equitably.

Clinical journey for patients with aortic regurgitation: A retrospective observational study from a multicenter database.

BACKGROUND: Data using real-world assessments of aortic regurgitation (AR) severity to identify rates of Heart Valve Team evaluation and aortic valve replacement (AVR), as well as mortality among untreated patients, are lacking. The present study assessed these trends in care and outcomes for real-world patients with documented AR. METHODS: Using a deidentified data set (January 2018-March 2023) representing 1,002,853 patients >18 years of age from 25 US institutions participating in the egnite Database (egnite, Inc.) with appropriate permissions, patients were classified by AR severity in echocardiographic reports. Rates of evaluation by the Heart Valve Team, AVR, and all-cause mortality without AVR were examined using Kaplan-Meier estimates and compared using the log-rank test. RESULTS: Within the data set, 845,113 patients had AR severity documented. For moderate-to-severe or severe AR, respectively, 2-year rates (95% confidence interval) of evaluation by the Heart Valve Team (43.5% [41.7%-45.3%] and 65.4% [63.3%-67.4%]) and AVR (19.4% [17.6%-21.1%] and 46.5% [44.2%-48.8%]) were low. Mortality at 2 years without AVR increased with greater AR severity, up to 20.7% for severe AR (p < 0.001). In exploratory analyses, 2-year mortality for untreated patients with left ventricular end-systolic dimension index > 25 mm/m2 was similar for moderate (34.3% [29.2%-39.1%]) and severe (37.2% [24.9%-47.5%]) AR. CONCLUSIONS: Moderate or greater AR is associated with poor clinical outcomes among untreated patients at 2 years. Rates of Heart Valve Team evaluation and AVR were low for those with moderate or greater AR, suggesting that earlier referral to the Heart Valve Team could be beneficial.

Synergistic Manifestations in Cardiac Cysticercosis Complicated by Snake Bite: A Case Report and Literature Review.

Cysticercosis presents a prevalent issue on a global scale. Nevertheless, disseminated cysticercosis (DCC) is infrequent; even rarer is asymptomatic DCC. Here, we present a unique case of asymptomatic DCC involving the heart in a young male who came to medical attention following a fatal snake bite, ultimately leading to his demise. Despite the widespread dissemination of cysticercosis affecting multiple organs, the individual remained asymptomatic for the condition. We present a case of a 23-year-old male who was brought to the emergency department with a history of alleged snake bites. The patient was declared dead upon arrival at the All India Institute of Medical Sciences (AIIMS), Rishikesh, India. Autopsy findings revealed multiple significant cardiac abnormalities, including atheromatous changes with calcification in the root of the aorta and aortic valve, along with numerous collateral vessels originating from the left main coronary artery. Additionally, cystic nodules containing cysticercus larvae were identified within the myocardium, suggesting cardiac cysticercosis. The cause of death was determined to be complications related to the snakebite. This case emphasizes the importance of considering multiple potential etiologies in complex clinical presentations, especially in the tropics.

Biocidal efficacy of olefinic N-alkylamides against Aedes aegypti and Culex quinquefasciatus larvae.

Mosquito-borne diseases are a major public-health concern worldwide. The development of resistance in mosquitoes to the existing larvicides and the associated-risks necessitates the exploration of novel molecules to control vector-borne pathogens. This study demonstrates that N-alkylamides [2E,4E-N-isobutyl-undeca-2,4-diene-8,10-diynamide (1) and 2E,4E,8Z,10E-N-isobutyl-dodeca-2,4,8,10-tetraenamide (2)] of Acmella ciliata exhibit biocidal action against Aedes aegypti and Culex quinquefasciatus larvae. The LC50 for 1 and 2 were 44.19 and 18.28 ppm against Aedes larvae, and 30.89 and 11.75 ppm against Culex larvae, respectively. We further observed that the chain length, degree of unsaturation, and terminal methylation influence the larvicidal efficacy of N-alkylamides. HPLC-assisted quantification revealed that the content of both 1 (19.01 mg/g) and 2 (68.55 mg/g) was maximum in the flowers of A. ciliata. Thus, this study concludes that N-alkylamides are promising alternatives to control mosquito larvae and can be used as standard for quantitation in test samples.

Genetic dependencies associated with transcription factor activities in human cancer cell lines.

Transcription factors (TFs) are important mediators of aberrant transcriptional programs in cancer cells. In this study, we focus on TF activity (TFa) as a biomarker for cell-line-selective anti-proliferative effects, in that high TFa predicts sensitivity to loss of function of a given gene (i.e., genetic dependencies [GDs]). Our linear-regression-based framework identifies 3,047 pan-cancer and 3,952 cancer-type-specific candidate TFa-GD associations from cell line data, which are then cross-examined for impact on survival in patient cohorts. One of the most prominent biomarkers is TEAD1 activity, whose associations with its predicted GDs are validated through experimental evidence as proof of concept. Overall, these TFa-GD associations represent an attractive resource for identifying innovative, biomarker-driven hypotheses for drug discovery programs in oncology.

Redesigning the kinetics of lysozyme amyloid aggregation by cephalosporin molecules.

In lysozyme amyloidosis, fibrillar aggregates of lysozyme are associated with severe renal, hepatic, and gastrointestinal manifestations, with no definite therapy. Current drugs are now being tested in amyloidosis clinical trials as aggregation inhibitors to mitigate disease progression. The tetracycline group among antimicrobials in use is in phase II of clinical trials, whereas some macrolides and cephalosporins have shown neuroprotection. In the present study, two cephalosporins, ceftazidime (CZD) and cefotaxime (CXM), and a glycopeptide, vancomycin (VNC), are evaluated for inhibition of amyloid aggregation of hen egg white lysozyme (HEWL) under two conditions (i) 4 M guanidine hydrochloride (GuHCl) at pH 6.5 and 37° C, (ii) At pH 1.5 and 65 °C. Fluorescence quench titration and molecular docking methods report that CZD, CXM, and VNC interact more strongly with the partially folded intermediates (PFI) in comparison to the protein's natural state (N). However, only CZD and CXM proficiently inhibit the aggregation. Transmission electron microscopy, tinctorial assessments, and aggregation kinetics all support oligomer-level inhibition. Transition structures in CZD-HEWL and CXM-HEWL aggregation are shown by circular dichroism (CD). On the other hand, kinetic variables and soluble fraction assays point to a localized association of monomers. Intrinsic fluorescence (IF),1-Anilino 8-naphthalene sulphonic acid, and CD demonstrate structural and conformational modifications redesigning the PFI. GuHCl-induced unfolding and differential scanning fluorimetry suggested that the PFI monomers bound to CZD and CXM exhibited partial stability. Our results present two mechanisms that function in both solution conditions, creating a novel avenue for the screening of putative inhibitors for drug repurposing. We extend our proposed mechanisms in the designing of physical inhibitors of amyloid aggregation considering shorter time frames and foolproof methods.Communicated by Ramaswamy H. Sarma.

Drug repurposing has overcome failures in drug discovery and has reduced the overall time and cost of drug discovery and development.We examined the effect of screened antibiotics, ceftazidime (CZD), cefotaxime (CXM), and vancomycin (VNC) on lysozyme aggregation under two solution conditions.These antibiotics inhibit/modulate the aggregation reactions by strongly interacting with aggregation-prone intermediate and modulation of conformation and stability.Our study puts forward with caution two cephalosporins for aggregation inhibition studies.