Single-step antibiotic-mediated synthesis of kanamycin-conjugated gold nanoparticles for broad-spectrum antibacterial applications.

Widespread and irrational use of antibiotics results in the development of antibiotic-resistant bacteria. Thus, there is a need to develop novel antibacterial agents in order to replace conventional antibiotics and to increase the efficacy of already existing antibiotics by combining them with other materials. Herein, a single-step antibiotic-mediated synthesis of antibiotic-conjugated gold nanoparticles is reported. In this single-step method antibiotic Kanamycin, an aminoglycoside itself plays the role of reducing as well as capping agent by reducing gold salt into gold nanoparticles. The kanamycin-conjugated gold nanoparticles (Kan-AuNPs) were confirmed by UV-Visible spectroscopy and further physico-chemically characterized by various instrumental techniques. Synthesized Kan-AuNPs showed broad-spectrum antibacterial activity against Gram-positive Staphylococcus aureus as well as Gram-negative Escherichia coli bacterial strains. They are also found to be effective against Pseudomonas aeruginosa and pathogenic E. coli isolated from urinary tract infections (UTIs) patients, which are responsible to cause hospital-acquired infections like nosocomial, burn wound and UTIs. The minimum inhibitory concentration (MIC) of Kan-AuNPs is 50 µg ml-1 for S. aureus and E. coli, 125 µg ml-1 for P. aeruginosa and 100 µg ml-1 for E. coli isolated from UTIs patients. It is also evident that the MIC of Kan-AuNPs for antibacterial activity is lower as compared to antibiotic kanamycin alone for all bacterial strains. Hence, the one-step strategy of synthesis for Kan-AuNPs is a suitable strategy for fighting infectious bacterial strains in hospitals, healthcare and the pharmaceutical industry.

Screening of osmotic stress-tolerant bacteria for plant growth promotion in wheat (Triticum aestivum L.) and brinjal (Solanum melongena L.) under drought conditions.

Drought stress adversely affects plant growth and productivity. Therefore, the application of plant growth-promoting bacteria is a viable option for combating drought resistance in crops. In this study, 144 bacteria were isolated from the Kutch desert soil in Gujarat. Based on osmotic stress tolerance and PGP properties, two strains, Bacillus tequilensis (KS5B) and Pseudomonas stutzeri (KS5C) were tested for their effect on wheat (Triticum aestivum L.) and brinjal (Solanum melongena L.) under drought stress conditions. Inoculation with osmotic stress-tolerant bacteria showed 15·15-29·27% enhancement in root length of wheat and 15·27-32·59% in brinjal plants. Similarly, the enhancement of shoot length ranged from 14·72 to 37·70% for wheat and 59·39-95·94% for brinjal plants. Furthermore, the inoculated plants showed significant improvement in chlorophyll content and antioxidant properties such as proline, peroxidase and polyphenol oxidase activity compared to the control. Therefore, the bacterial strains identified in this study can be used to mitigate drought stress and enhance plant biomass.

Evolution of MET and NRAS gene amplification as acquired resistance mechanisms in EGFR mutant NSCLC.

EGFR mutant non-small cell lung cancer patients' disease demonstrates remarkable responses to EGFR-targeted therapy, but inevitably they succumb to acquired resistance, which can be complex and difficult to treat. Analyzing acquired resistance through broad molecular testing is crucial to understanding the resistance mechanisms and developing new treatment options. We performed diverse clinical testing on a patient with successive stages of acquired resistance, first to an EGFR inhibitor with MET gene amplification and then subsequently to a combination EGFR and MET targeted therapies. A patient-derived cell line obtained at the time of disease progression was used to identify NRAS gene amplification as an additional driver of drug resistance to combination EGFR/MET therapies. Analysis of downstream signaling revealed extracellular signal-related kinase activation that could only be eliminated by trametinib treatment, while Akt activation could be modulated by various combinations of MET, EGFR, and PI3K inhibitors. The combination of an EGFR inhibitor with a MEK inhibitor was identified as a possible treatment option to overcome drug resistance related to NRAS gene amplification.

Robust Protective Effect of COVID-19 Vaccination in India-Results of Survey in the Midst of Pandemic's Second Wave.

Introduction Our objective was to document the incidence of COVID-19 in vaccinated health care professionals and related personnel. Method We conducted an online survey to ascertain the incidence of COVID-19 symptoms, reverse transcriptase polymerase chain reaction (RT-PCR) positivity, effect on normal activity, need for anti-COVID-19 medication, hospitalization, and death among individuals who had completed both doses of COVID vaccination at least 2 weeks earlier. Results A total of 351 unique valid responses were received. Among the 340 people who had been vaccinated in India, 5% (17/340) had COVID-19 symptoms, 4.7% (16) became COVID-19 RT-PCR positive, 12 (3.5%) had sickness preventing normal daily activity, 2.65% (9) required anti-COVID-19 medication, and 1.18% (4) required hospitalization. Among family members living with the survey responders, the corresponding incidence was even lower. There was one death in this group. Discussion Being health care professionals, the responders would be at higher risk of daily exposure to COVID-19. Even in this high risk group, the vaccine efficacy is good. Vulture journalists should stop spreading fake news and misinformation that makes people hesitate taking the vaccine or be afflicted analysis paralysis. Every person who chooses to remain unvaccinated increases the risk for our entire community. We also need to follow universal precautions (wearing mask, physical distancing, handwashing) diligently without letting down our guard.

Conversion during off-pump coronary artery bypass graft surgery: A case-control study.

Objectives: Off pump coronary artery bypass (OPCAB) surgery is carried out as an alternative to conventional coronary artery bypass grafting using cardiopulmonary bypass (CPB). At times 'conversion' to CPB may be required to bail out a situation resulting from acute decompensation of the heart. It is reported that such conversion carries significant mortality risk. Since we conduct coronary revascularization by OPCAB technique as the preferred technique, we conducted this study with an aim to identify the markers of adverse outcome during conversion in Indian patients. Design: Case control retrospective study. Setting: Tertiary referral center. Participants: We conducted three thousand two hundred OPAB surgeries in the period between 2013 to16. Ninety patients (3.1%) required conversion to complete the revascularization (Con version group). Twice the number of patients who underwent OPCAB surgery without conver sion were chosen as controls (Control group). Intervention: OPCAB surgery Results: Mortality in the conversion group was 5.56% in contrast to 0.06% in the controls (P = 0.01). The conversion group had higher left ventricular end diastolic pressure, incidence of endarterectomy, and intra-aortic balloon counter pulsation requirement. Female gender was also predictive of conversion. The total chest drain, duration of ventilation, ICU stay and hospital stay were also higher in the conversion group. Conversion was associated with 9.47 times the odds for mortality. Conclusion: Conversion during OPCAB is associated with significantly increased mortality. Female gender, increased left ventricular end diastolic pressure and preoperative requirement of Intra-aortic balloon are markers of increased risk of mortality when converted.

Targeted therapies for ROS1-rearranged non-small cell lung cancer.

ROS1 gene fusions account for approximately 1-2% of all cases of non-small cell lung cancer (NSCLC). Similarly to anaplastic lymphoma kinase (ALK)-positive NSCLC, patients with ROS1+ NSCLC tend to have minimal smoking and be of the female sex. In most cases, adenocarcinoma is the dominant histology. The ROS1 gene has homology to ALK and this structural similarity formed the basis for utilizing ALK inhibitors for ROS1+ NSCLC. On the basis of impressive progression-free survival of 19.2 months from the PROFILE 1001 trial, crizotinib obtained Food and Drug Administration (FDA) approval as first-line therapy for treatment of ROS1+ NSCLC. Since then, there has been a growing appreciation of the incidence of brain metastases in ROS1+ NSCLC and rates of central nervous system progression on crizotinib. Additionally, appreciation of novel resistance mechanisms to crizotinib has led to the development of newer tyrosine kinase inhibitors (TKIs). In this review, we highlight known and emerging TKIs for the management of ROS1+ NSCLC.

New therapies for anaplastic thyroid cancer.

Anaplastic thyroid cancer is a rare but extremely aggressive type of thyroid cancer. Treatment typically consists of surgery, external beam radiotherapy and cytotoxic chemotherapy. However, available literature suggests only modest survival benefit for cytotoxic chemotherapy. Recent advances have suggested the combination of BRAF and MEK inhibition may have a profound and durable effect on patients with BRAFV600E-mutated anaplastic thyroid cancer, with a response rate of 69%. Other systemic treatments, including immunotherapies, have also shown promising but more limited results. Many clinical trials assessing the efficacy of kinase inhibitors and immunotherapies are currently ongoing.

Transesophageal echocardiography evaluation of the thoracic aorta.

Transesophageal echocardiography (TEE) can be used to identify risk factors such as aortic atherosclerosis [2] before any sort of surgical manipulations involving aorta and its related structures. TEE has become an important noninvasive tool to diagnose acute thoracic aortic pathologies. TEE evaluation of endoleaks helps early detection and immediate corrective interventions. TEE is an invaluable imaging modality in the management of aortic pathology. TEE has to a large extent improved the patient outcomes.

Cardiopulmonary bypass in conscious patients undergoing cardiac surgery.

This study was undertaken to evaluate the feasibility of thoracic epidural anesthesia as an alternative technique to general anesthesia in patients undergoing cardiac surgery under cardiopulmonary bypass. This prospective study was conducted in a tertiary referral hospital. Seventeen patients underwent cardiac surgical procedures requiring cardiopulmonary bypass without general anesthesia under thoracic epidural anesthesia from February to May 2004. An epidural catheter was inserted at any of intervertebral spaces from C7 to T2 on the day before surgery. Subsequently, cardiac surgery was performed under normothermic cardiopulmonary bypass, during which the patients remained conscious. The types of surgery included closure of atrial septal defects, valve replacements, and combined bypass surgery and valve replacements. Approach to the heart was obtained through midsternotomy. Anticoagulation was achieved with 300 units/kg of heparin. Normothermic cardiopulmonary bypass was initiated slowly during the course of 10 to 15 min. Nonpulsatile flow was administered using centrifugal pump and mean perfusion pressure was maintained in the range of 70-80 mmHg. The planned surgical procedure could be performed in all the patients. Soon after establishing cardiopulmonary bypass, the patients developed apnea, which reverted to normalcy a few minutes after disconnection of cardiopulmonary bypass. The mean time for cardiopulmonary bypass was 102 +/- 28 min, aortic cross clamp time was 58 +/- 28 min, and the total duration of surgery was 229 +/- 64 min. None of the patients required conversion to general anesthesia. There was no mortality or morbidity in this series and to our knowledge our series is the first such. Cardiac surgical procedures requiring cardiopulmonary bypass may be conducted under thoracic epidural anesthesia, without endotracheal general anesthesia.

Conscious off-pump coronary artery bypass surgery.

BACKGROUND: Cardiothoracic surgery has been previously performed successfully under thoracic epidural anesthesia alone. Between October 2001 and December 2003, we performed 123 conscious off-pump coronary artery bypass surgeries using epidural anesthesia as the sole anesthetic. This technique is an alternative to cardiothoracic surgery performed under general anesthesia. Certain modifications in the technique facilitate the process. METHODS AND RESULTS: There were 24 female patients and 99 male patients with mean age of 58.6 +/- 6.2 years; 12 patients underwent repeat coronary artery bypass surgery. All the patients underwent epidural catheterization on the evening before surgery. Out of the 123 patients scheduled for coronary artery bypass graft surgery, 120 underwent off-pump coronary artery bypass graft surgery successfully; 4 patients underwent off-pump surgery via left thoracotomy and the rest through mid sternotomy. These patients received 295 grafts in all (single graft in 26 patients, double in 42 patients, triple in 35 patients, and quadruple in 20 patients). Three patients required conversion to general anesthesia and one to cardiopulmonary bypass. There was no mortality in the group. CONCLUSIONS: Our experience suggests that by modifying the surgical techniques, we can accomplish conscious coronary artery bypass surgery.

Transesophageal echocardiography estimation of coronary sinus blood flow for the adequacy of revascularization in patients undergoing off-pump coronary artery bypass graft.

AIMS AND OBJECTIVES: Physiologically coronary sinus (CS) drains the left coronary artery (LCA) territory. Stenosis of the branches of LCA may decrease the coronary sinus blood flow (CSBF). Any intervention that aims at restoring the flow of the stenosed vessel increases coronary artery flow that should consequently increase the CSBF. Hence, this study was undertaken to assess the CSBF before and after each branch of LCA to determine the adequacy of surgical revascularization in patients undergoing elective off pump coronary artery bypass grafting (OPCAB) using transesophageal echocardiography (TEE). MATERIALS AND METHODS: Thirty consecutive patients scheduled for elective OPCAB were enrolled. CSBF was assessed before and after each branch of LCA revascularization using TEE. Left internal mammary artery (LIMA) Doppler was also obtained post LIMA to left anterior descending (LAD) grafting. RESULTS: Hemodynamic and echocardiographic variables were compared by means of Student's t-test for paired data before and after revascularization. The CSBF per beat (1.28 ± 0.71), CSBF per minute (92.59 ± 59.32) and total velocity time integral (VTI) (8.93 ± 4.29) before LAD grafting showed statistically significant increase to CSBF per beat (1.70 ± 0.89), CSBF per minute (130.72 ± 74.22) and total VTI (11.96 ± 5.68) after LAD revascularization. The CSBF per beat (1.67 ± 1.03), CSBF per minute (131.91 ± 86.59) and total VTI (11.00 ± 5.53) before obtuse marginal (OM) grafting showed statistically significant increase to CSBF per beat (1.91 ± 1.03), CSBF per min (155.20 ± 88.70) and total VTI (12.09 ± 5.43) after OM revascularization. In 9 patients, color flow Doppler of LIMA could be demonstrated which showed diastolic predominant blood flow after LIMA to LAD grafting. CONCLUSION: Demonstration of CSBF was simple and monitoring the trend of CSBF values before and after each graft of LCA territory will guide to determine the adequacy of surgical revascularization.

Osteopontin signaling upregulates cyclooxygenase-2 expression in tumor-associated macrophages leading to enhanced angiogenesis and melanoma growth via α9ß1 integrin.

Tumor-associated macrophages (TAMs) have multifaceted roles in tumor development, particularly linked with tumor angiogenesis and invasion, but the molecular mechanism underlying this association remains unclear. In this study, we report that lack of osteopontin (OPN) suppresses melanoma growth in opn(-/-) mice and macrophages are the crucial component responsible for OPN-regulated melanoma growth. In tumor microenvironment, OPN activates macrophages and influences angiogenesis by enhancing cyclooxygenase-2 (COX-2)-dependent prostaglandin E2 (PGE2) production in an autocrine manner. Furthermore, we identify α9ß1 integrin as a functional receptor for OPN that mediates its effect and activates ERK and p38 signaling, which ultimately leads to COX-2 expression in macrophages. The major role played by OPN and PGE2 in angiogenesis are further amplified by upregulation of MMP-9. OPN-activated macrophages promote the migration of endothelial and cancer cells via PGE2. These findings provide evidence that TAMs serve as source of key components such as OPN and COX-2-derived PGE2 and MMP-9 in melanoma microenvironment. Clinical specimens analyses revealed that increased infiltration of OPN-positive TAMs correlate with melanoma growth and angiogenesis. These data provide compelling evidence that OPN and COX-2 expressing macrophages are obligatory factors in melanoma growth. We conclude that OPN signaling is involved in macrophage recruitment into tumor, and our results emphasize the potential role of macrophage in modulation of tumor microenvironment via secretion of OPN, PGE2 and MMP-9, which trigger angiogenesis and melanoma growth. Thus, blockade of OPN and its regulated signaling network provides unique strategy to eradicate melanoma by manipulating TAMs.

Utility of pulmonary venous flow diastolic deceleration time in an adult patient undergoing surgical closure of atrial septal defect and coronary artery bypass grafting.

Acute left ventricular (LV) failure has been reported after surgical closure of atrial septal defect (ASD) in adult patients. We report acute LV failure in a 56 year old gentleman following coronary artery bypass grafting (CABG) and surgical closure of ASD. Transesophageal echocardiography examination of the patient following closure of ASD and CABG showed a residual ASD and a shunt (Qp :Qs = 1.5). The residual ASD was closed after re-institution of cardiopulmonary bypass (CPB) under cardioplegic cardiac arrest. However, the patient did not tolerate closure of the residual ASD. The CPB was re-established and under cardioplegic cardiac arrest residual ASD was reopened to create a fenestration. This time patient was weaned easily from CPB. Postoperatively, 16 hours after extubation, patient became hemodynamically unstable, the patient was electively put on ventilator and intra-aortic balloon pump. Later the patient was weaned off successfully from ventilator. Retrospective analysis of pulmonary venous flow diastolic deceleration time (PVDT D ) recorded during prebypass period measured 102 msec suggestive of high left atrial pressure which indicate possibility of LV failure after ASD closure.

Giant Sporadic Low Grade Malignant Peripheral Nerve Sheath (MPNST) of Left Thigh.

Malignant Peripheral Nerve Sheath Tumours (MPNST) are rare spindle- cell sarcomas which are derived from the schwann cells or the pleuripotent cells of the neural crest. MPNSTs are usually located in the peripheral nerve trunk roots, extremities and in the head and neck region. These tumours may arise as sporadic variants or in patients with neurofibromatosis1 (NF1). The estimated incidence of MPNSTs in the patients with NF1is 2-5% as compared to a 0.001% incidence in the general population. Herein, we are reporting a case of a giant sporadic (NF1 independent) low grade MPNST of the left thigh in 65 year female patient, which had a good prognosis.