Exploration of novel cationic amino acid-enriched short peptides: design, SPPS, biological evaluation and in silico study.

Antimicrobial resistance (AMR) represents a critical challenge worldwide, necessitating the pursuit of novel approaches to counteract bacterial and fungal pathogens. In this context, we explored the potential of cationic amino acid-enriched short peptides, synthesized via solid-phase methods, as innovative antimicrobial candidates. Our comprehensive evaluation assessed the antibacterial and antifungal efficacy of these peptides against a panel of significant pathogens, including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pyogenes, Candida albicans, and Aspergillus niger. Utilizing molecular docking techniques, we delved into the molecular interactions underpinning the peptides' action against these microorganisms. The results revealed a spectrum of inhibitory activities, with certain peptide sequences displaying pronounced effectiveness across various pathogens. These findings underscore the peptides' potential as promising antimicrobial agents, with molecular docking offering valuable insights into their mechanisms of action. This study enriches antimicrobial peptide (AMP) research by identifying promising candidates for further refinement and development toward therapeutic application, highlighting their significance in addressing the urgent issue of AMR.

Synthesis and Evaluation of Biological Activities for a Novel 1,2,3,4-Tetrahydroisoquinoline Conjugate with Dipeptide Derivatives: Insights from Molecular Docking and Molecular Dynamics Simulations.

Peptide synthesis has opened new frontiers in the quest for bioactive molecules with limitless biological applications. This study presents the synthesis of a series of novel isoquinoline dipeptides using advanced spectroscopic techniques for characterization. These compounds were designed with the goal of discovering unexplored biological activities that could contribute to the development of novel pharmaceuticals. We evaluated the biological activities of novel compounds including their antimicrobial, antibacterial, and antifungal properties. The results show promising activity against Escherichia coli and potent antibacterial activity against MTCC 443 and MTCC 1688. Furthermore, these compounds demonstrate strong antifungal activity, outperforming existing standard drugs. Computational binding affinity studies of tetrahydroisoquinoline-conjugated dipeptides against E. coli DNA gyrase displayed significant binding interactions and binding affinity, which are reflected in antimicrobial activities of compounds. Our integrative significant molecular findings from both wet and dry laboratories would help pave a path for the development of antimicrobial therapeutics. The findings suggest that these isoquinoline-conjugated dipeptides could be excellent candidates for drug development, with potential applications in the fight against bacterial and fungal infections. This research represents an exciting step forward in the field of peptide synthesis and its potential to discover novel bioactive molecules with significant implications for human health.

A Rare Case of Pembrolizumab Associated Encephalopathy.

We present a unique case of a 55-year-old man with confusion thought to be due to pembrolizumab which he was receiving for renal cell carcinoma. His workup for other possible etiologies for encephalopathy was negative. He was treated with high dose intravenous methylprednisolone followed by prednisone taper and intravenous immunoglobulin with gradual improvement in his mentation.

A Rare Case of Idiopathic Systemic Capillary Leak Syndrome.

Idiopathic systemic capillary leak syndrome (SCLS) is characterized by an increased capillary hyperpermeability with subsequent hemoconcentration, hypoproteinemia, and hypovolemia. Patients present with diffuse swelling, weight gain, low blood pressure, and shock. We present our case of idiopathic SCLS in a 50-year-old man presenting with prodromal flu-like illness associated with shock that was complicated by compartment syndrome requiring four limb fasciotomies, disseminated intravascular coagulation, acute kidney injury requiring dialysis, and cardiac arrest.

Acute Portal Vein Thrombosis during COVID-19 Convalescent Phase.

Acute portal vein thrombosis represents a less common type of venous thromboembolism, even among the prothrombotic complications of coronavirus disease 2019 (COVID-19). Such complications are primarily reported during the active phase of infection. The case here describes acute portal vein thrombosis following resolution of COVID-19 in a 44-year-old male who presented with abdominal pain. Abdominal imaging identified portal and other splanchnic vein thromboses. Studies for hypercoagulable conditions were negative. Polymerase chain reaction was negative for severe acute respiratory syndrome coronavirus-2; however, IgG serology was positive. The case highlights the importance of considering thrombotic complications, particularly splanchnic vein thromboses, in patients with recent COVID-19.

Seroprevalence of anti-SARS-CoV-2 of IgG antibody by ELISA: Community-based, cross-sectional study from urban area of Malegaon, Maharashtra.

BACKGROUND: Given the high incidence of asymptomatic or subclinical SARS-CoV-2 infection, reported cases likely underestimate the overall prevalence and infectivity of COVID-19. Serological test for IgG can provide a better measure of disease activity by identifying asymptomatic or subclinical infection. This study was conducted to estimate the seroprevalence of SARS-CoV-2 infection and to the determinants of SARS-CoV-2 infection in the hotspot area of COVID-19. METHOD: It was a community-based, cross-sectional study using multistage sampling with a sample size of 360. After informed consent, the demographic information, past history of SARI/ILI, contact, COVID-19 status were collected. The blood samples were taken from one family member for anti-SARS-CoV-2 IgG antibody by ELISA testing kit. RESULTS: Majority of the study subjects had no history of SARI (86%) or any contact with COVID-19 case (98%). Overall seroprevalence of anti-SARS-CoV-2 of IgG antibody was 40% (95% CI 35-45%), infection fatality rate (IFR) was 0.7%. Seroprevalence varied significantly depending on religious background; with Muslims (53%) seroprevalence compared to other religious groups. Seroprevalence of homemaker/unemployed (49%) and laborer (55%) was significantly higher compared to business (30%) and service occupation (21%). Subjects with overcrowding conditions and poor ventilation was significantly associated with higher seroprevalence with odds ratio of 2.5 and 2.3, respectively. CONCLUSION: The antibody testing detects a large number of asymptomatic cases or previously infected cases which would have been missed by clinical history. Thus, the number of undiagnosed cases was found significantly higher even with rigorous implementation of lockdown.

Colorectal Services in Covid-19 Times: Minimally Invasive Surgery and Enhanced Recovery, the Need of the Hour.

The health services across the world have been deeply impacted by the ongoing COVID-19 pandemic which has resulted in diversion of resources to testing, isolating and treating COVID-19 patients. This meant cutting down resources and manpower away of various healthcare facilities and severely hampering the functioning of various cancer services across the world. It is however, important to understand, cancer itself is a life-threatening condition, and there is a need to continue running cancer care services, at least for those who needed the most. Various clinical societies have put forward guidelines and protocols to help continue surgical services during the pandemic. The role of minimally invasive surgery (MIS) was initially questioned at the start of the pandemic, however gradually increasing evidence favored MIS as it reduced hospital stay and complication. Enhanced recovery programs which have been introduced to various fields of surgery to improve outcomes and reduce hospital stay. It plays an essential role in times like this, where the optimal usage of minimal resources is essential. We embraced these methods to ensure safety of our patients and staff and at the same time provide the highest standards of care. Here we are presenting our experience of running a colorectal surgical unit during these difficult times with emphasis on promotion of minimally invasive surgery, at the epicenter of the pandemic in India.

The Technique and Justification for Minimally Invasive Surgery in COVID-19 Pandemic: Laparoscopic Anterior Resection for Near Obstructed Rectal Carcinoma.

Introduction: The recent COVID-19 pandemic outbreak has made surgeons change and take on newer strategies and safe exercises. All elective cases have been put off, but oncology cases need to be done to prevent progression of the disease. There is concern about minimally invasive surgery due to aerosol formation. Here we discuss how we have dealt with this in our colorectal surgery department taking into account current evidence about the danger of viral transmission during laparoscopic surgery. Discussion: We report a case of 28 years old female patient with carcinoma rectum. The patient had near total intestinal obstruction. She was operated on utilizing laparoscopic anterior resection. The air seal (CONMED, Utica, NY) and high-efficiency particulate air (HEPA) filter was utilized for safe gas evacuation. There is no evidence against laparoscopic surgery, which suggest viral transmission. One should take utmost precautions using N95 masks and personal protective equipment (PPE). Air filtration products like aerosol, HEPA filters will be of great aid in safe evacuation of gases. Conclusion: At present, there is no solid evidence to suggest viral transmission through surgical smoke. We believe due to effective smoke containment, less blood loss, and less postoperative stay, laparoscopy will be a non-inferior option than open surgical procedure. We advise taking all precautions for operating room staff to lessen the danger of transmission.

Enantioselective synthesis of tetrahydrocarbazoles via trienamine catalysis and their anxiolytic-like activity.

The first study about the anxiolytic activity of two chiral tetrahydrocarbazoles is presented. This new chiral compounds were prepared through an organocatalytic strategy via trienamine activation. The in situ ortho-quinodimethane species, formed by the condensation of the N-protected 2-methylindole acrylaldehyde with a sterically hindred diarylsilylprolinol ether derivative as catalyst, easily participate in a Diels-Alder reaction with the ethyl cyanophenyl acrylate as dienophile, in good yields and excellent stereoselectivity. These compounds showed activity against anxiety and mood disorders that can possibly contribute in the discovery of new drugs. In addition, the use of N-protected 2-methylindole acrylaldehyde will set a new base for the synthesis of medically and pharmacologically important tetrahydrocarbazoles via trienamine catalysis.

BODIPY as electron withdrawing group for the activation of double bonds in asymmetric cycloaddition reactions.

In this work we have found that a BODIPY can be used as an electron withdrawing group for the activation of double bonds in asymmetric catalysis. The synthesis of cyclohexyl derivatives containing a BODIPY unit can easily be achieved via trienamine catalysis. This allows a new different asymmetric synthesis of BODIPY derivatives and opens the door to future transformation of this useful fluorophore. In addition, the Quantum Chemistry calculations and mechanistic studies provide insights into the role of BODIPY as an EWG.

Video Assisted Thoracoscopic Surgical Enucleation of a Giant Esophageal Leiomyoma Presenting with Persistent Cough.

Esophageal leiomyoma is a relatively rare tumor of esophagus but it is the most common benign neoplasm of the esophagus. Small esophageal leiomyoma can be observed but larger ones and those producing symptoms should be excised. As observed for other esophageal tumors, dysphagia is its main symptom. Traditionally, open thoracotomy and enucleation are its main treatment but in the last few years video assisted thoracoscopic surgical (VATS) enucleation is gaining recognition with proven advantages of minimally invasive surgery. Herein we present our experience with patient presenting with cough rather than dysphagia as a main symptom, who was diagnosed to be having giant esophageal leiomyoma. VATS guided enucleation was accomplished successfully. Size of lesion was 16 × 4 × 3 cm. Postoperative recovery was uneventful and patient is not having any signs of recurrence, after three years during follow-up period.

Wound healing complications in brain tumor patients on Bevacizumab.

Bevacizumab (BEV) is commonly used for treating recurrent glioblastoma (GBM), and wound healing is a well-established adverse event. Retrospective analysis of GBM patients with and without wound healing complications while on BEV treatment is reported. 287 patients identified, majority were males (60 %) with median age of 52.5 years. 14 cases identified with wound healing problems, related to either craniotomy (n = 8) or other soft tissue wounds (n = 6). Median duration of BEV treatment to complication was 62 days (range 6-559). Majority received 10 mg/kg (n = 11) and nine (64.3 %) were on corticosteroids, with median daily dose of 6 mg (range 1-16 mg) for median of 473 days before starting BEV. For dehisced craniotomy wounds, median time for starting BEV from last surgery was 29 days (range 27-345). Median time from starting BEV to developing wound complication was 47 days (range 16-173). Seven (87.5 %) had infected wounds requiring antibiotics, hospitalization. Four (50 %) required plastic surgery. BEV stopped and safely resumed in 6 (75 %) patients; median delay was 70 days (range 34-346). Soft tissue wounds included decubitus ulcer, dehisced striae, herpes simplex, trauma to hand and back, and abscess. Median time from starting BEV to wound issues was 72 days (range 6-559). Five (83.3 %) were infected, requiring antibiotics. While three (50 %) required hospitalization, none required plastic surgery. Treatment stopped in five (83.3 %) and restarted in two (median delay 48 days, range 26-69). Wound healing complications are uncommon but associated with significant morbidity. Identifying those at risk and contributing factors warrants further investigation.

Venous thromboembolism (VTE) and glioblastoma.

The risk of venous thromboembolism (VTE) is high for patients with brain tumors (11-20 %). Glioblastoma (GBM) patients, in particular, have the highest risk of VTE (24-30 %). The Khorana scale is the most commonly used clinical scale to evaluate the risk of VTE in cancer patients but its efficacy in patients with GBM remains unclear. The aim of this study is to estimate the frequency of VTE in GBM patients and identify potential risk factors for the development of VTE during adjuvant chemotherapy. Furthermore, we intend to examine whether the Khorana scale accurately predicts the risk of VTE in GBM patients. We retrospectively reviewed the medical records of GBM patients treated at MD Anderson during the years 2005-2011. The study cohort included 440 patients of which 64 (14.5 %) developed VTE after the start of adjuvant treatment. The median time to develop VTE was 6.5 months from the start of adjuvant treatment. On multivariate analysis male sex, BMI ≥ 35, KPS ≤ 80, history of VTE and steroid therapy were significantly associated with the development of VTE. The Khorana scale was found to be an invalid VTE predictive model in GBM patients due to poor specificity. Of the 64 patients who developed a VTE, 36 were treated with anticoagulation, 2 with an IVC filter, and 21 with both. Complications (intracranial hemorrhage, bleeding in other organs and thrombocytopenia) secondary to anticoagulation were reported in 16 % (n = 10). VTE is common in patients with GBM. Our results did not validate the Khorana scale in GBM patients. Additional studies identifying which GBM patients are at highest risk for VTE are needed to enable further evaluation of VTE preventive measures in this selected group.

Incidence rate, clinical correlates, and outcomes of AKI in patients admitted to a comprehensive cancer center.

BACKGROUND AND OBJECTIVES: Incidence of AKI in hospitalized patients with cancer is increasing, but reports are scant. The objective of this study was to determine incidence rate, clinical correlates, and outcomes of AKI in patients admitted to a cancer center. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Cross-sectional analysis of prospectively collected data on 3558 patients admitted to the University of Texas M.D. Anderson Cancer Center over 3 months in 2006. RESULTS: Using modified RIFLE (Risk, Injury, Failure, Loss, ESRD) criteria, 12% of patients admitted to the hospital had AKI, with severity in the Risk, Injury, and Failure categories of 68%, 21%, and 11%, respectively. AKI occurred in 45% of patients during the first 2 days and in 55% thereafter. Dialysis was required in 4% of patients and nephrology consultation in 10%. In the multivariate model, the odds ratio (OR) for developing AKI was significantly higher for diabetes (OR, 1.89; 95% confidence interval [CI], 1.51-2.36), chemotherapy (OR, 1.61; 95% CI, 1.26-2.05), intravenous contrast (OR, 4.55; 95% CI, 3.51-5.89), hyponatremia (OR, 1.97; 95% CI, 1.57-2.47), and antibiotics (OR, 1.52; 95% CI, 1.15-2.02). In patients with AKI, length of stay (100%), cost (106%), and odds for mortality (4.7-fold) were significantly greater. CONCLUSION: The rate of AKI in patients admitted to a comprehensive cancer center was higher than the rate in most noncancer settings; was correlated significantly with diabetes, hyponatremia, intravenous contrast, chemotherapy, and antibiotics; and was associated with poorer clinical outcomes. AKI developed in many patients after admission. Studies are warranted to determine whether proactive measures may limit AKI and improve outcomes.