Computational choreography: dissecting the dance of hydrogen bonding and π-π stacking in the fluorescence discrimination mechanism of ciprofloxacin with supramolecular assembly.

The detailed binding insight between the fluorophore and analyte plays a pivotal role in the design of an efficient chemosensor for water pollution. In this study, we designed a picolinic acid-functionalized calix[4]pyrrole ligand (PCACP). When testing out the fluorescence study with selected antibiotics, we observed remarkable enhancement of fluorescence spectra in the presence of ciprofloxacin, singling out the PCACP_Ciprofloxacin complex. The detailed binding mechanism is explored via computational methods including molecular docking and dynamics, DFT (density functional theory) and NBO (Natural Bonding Orbital) analysis. The result of this study provides the comprehensive insight into the involvement of functionalized group of PCACP and ciprofloxacin antibiotic. The results of the computational findings are further explored through NMR complexation study, which corroborate the computational findings. With the limit of detection calculated at 18 µM, we carried out the water sample analysis, which shows promising results. The outcome of this research provides a new, effortless fluorescence approach to monitor the presence of ciprofloxacin in water.In the presence of the ciprofloxacin antibiotic, the fluorescence spectra of PCACP experience remarkable enhancements. This complexation phenomenon is studied through different computational and experimental methods.Communicated by Ramaswamy H. Sarma.

Illuminating Bacterial Contamination in Water Sources: The Power of Fluorescence-Based Methods.

Bacterial contamination of water sources is a significant public health concern, and therefore, it is important to have accurate and efficient methods for monitoring bacterial concentration in water samples. Fluorescence-based methods, such as SYTO 9 and PI staining, have emerged as a promising approach for real-time bacterial quantification. In this review, we discuss the advantages of fluorescence-based methods over other bacterial quantification methods, including the plate count method and the most probable number (MPN) method. We also examine the utility of fluorescence arrays and linear regression models in improving the accuracy and reliability of fluorescence-based methods. Overall, fluorescence-based methods offer a faster, more sensitive, and more specific option for real-time bacterial quantification in water samples.

Propyl-phthalimide Cyclotricatechylene-Based Chemosensor for Sulfosulfuron Detection: Hybrid Computational and Experimental Approach.

The detection of trace amounts of sulfosulfuron, a pesticide of increasing importance, has become a pressing issue, prompting the development of effective chemosensors. In this study, we functionalized cyclotricatechylene (CTC) with propyl-phthalimide due to the presence of electronegative oxygen and nitrogen binding sites. Our optimized ligand displayed the highest docking score with sulfosulfuron, and experimental studies confirmed a significant fluorescence enhancement upon its interaction with sulfosulfuron. To gain a deeper understanding of the binding mechanism, we introduced density functional theory (DFT) studies. We carried out binding constant, Job's plot, and limit of detection (LOD) calculations to establish the effectiveness of our chemosensor as a selective detector for sulfosulfuron. These findings demonstrate the potential of our chemosensor for future applications in the field of pesticide detection.

Host-guest interaction of tryptophane with acid-functionalized calix[4]pyrrole: a fluorescence-based study.

Functionalized calix[4]pyrroles are at forefront of host-guest aided molecular sensors. They offer unique platform for flexible functionalization to develop receptors suitable for different applications. In this context, calix[4]pyrrole derivative (TACP) was functionalized with an acidic group to investigate its binding behavior with different amino acids. The acid functionalization facilitated host-guest interactions through hydrogen bonding and increase the solubility of ligand in 90% aqueous media. The results indicated that TACP exhibited significant fluorescence enhancement in the presence of tryptophan while no considerable changes were observed with other amino acids. The other complexation properties such as LOD and LOQ were determined to be 25 µM and 22 µM respectively with 1:1 stoichiometry. In addition, the proposed binding phenomena were further confirmed through computational docking studies and NMR complexation study. Overall, this work highlights the potential of acid functionalization in developing molecular sensors for amino acid detection using calix[4]pyrrole derivatives.Communicated by Ramaswamy H. Sarma.

Predictors of need for endovascular intervention in hepatic trauma.

PURPOSE: Non-operative management of hepatic trauma with adjunctive hepatic arterial embolization (HAE) is widely accepted. Despite careful patient selection utilizing CTA, a substantial proportion of angiograms are negative for arterial injury and no HAE is performed. This study aims to determine which CT imaging findings and clinical factors are associated with the presence of active extravasation on subsequent angiography in patients with hepatic trauma. MATERIALS AND METHODS: The charts of 243 adults who presented with abdominal trauma and underwent abdominal CTA followed by conventional angiography were retrospectively reviewed. Of these patients, 49 had hepatic injuries on CTA. Hepatic injuries were graded using the American association for the surgery of trauma (AAST) CT classification, and CT images were assessed for active contrast extravasation, arterial pseudoaneurysm, sentinel clot, hemoperitoneum, laceration in-volving more than 2 segments, and laceration involving specific anatomic landmarks (porta hepatis, hepatic veins, and gallbladder fossa). Medical records were reviewed for pre- and post-angiography blood pressures, hemoglobin levels, and transfusion requirements. Angiographic images and reports were reviewed for hepatic arterial injury and performance of HAE. RESULTS: In multivariate analysis, AAST hepatic injury grade was significantly associated with increased odds of HAE (Odds ratio: 2.5, 95% CI 1.1, 7.1, p = 0.049). Univariate analyses demonstrated no significant association between CT liver injury grade, CT characteristics of liver injury, or pre-angiographic clinical data with need for HAE. CONCLUSION: In patients with hepatic trauma, prediction of need for HAE based on CT findings alone is challenging; such patients require consideration of both clinical factors and imaging findings.

Venous Malformations.

Venous malformations, the most common type of vascular malformation, are slow-flow lesions resulting from disorganized angiogenesis. The International Society for the Study of Vascular Anomalies (ISSVA) classification offers a categorization scheme for venous malformations based on their genetic landscapes and association with congenital overgrowth syndromes. Venous malformations present as congenital lesions and can have broad physiologic and psychosocial sequelae depending on their size, location, growth trajectory, and tissue involvement. Diagnostic evaluation is centered around clinical examination, imaging evaluation with ultrasound and time-resolved magnetic resonance imaging, and genetic testing for more complex malformations. Interventional radiology has emerged as first-line management of venous malformations through endovascular treatment with embolization, while surgery and targeted molecular therapies offer additional therapeutic options. In this review, an updated overview of the genetics and clinical presentation of venous malformations in conjunction with key aspects of diagnostic imaging and treatment are discussed.

Combined whole-lesion radiomic and iodine analysis for differentiation of pulmonary tumors.

Quantitative radiomic and iodine imaging features have been explored for diagnosis and characterization of tumors. In this work, we invistigate combined whole-lesion radiomic and iodine analysis for the differentiation of pulmonary tumors on contrast-enhanced dual-energy CT (DECT) chest images. 100 biopsy-proven solid lung lesions on contrast-enhanced DECT chest exams within 3 months of histopathologic sampling were identified. Lesions were volumetrically segmented using open-source software. Lesion segmentations and iodine density volumes were loaded into a radiomics prototype for quantitative analysis. Univariate analysis was performed to determine differences in volumetric iodine concentration (mean, median, maximum, minimum, 10th percentile, 90th percentile) and first and higher order radiomic features (n = 1212) between pulmonary tumors. Analyses were performed using a 2-sample t test, and filtered for false discoveries using Benjamini-Hochberg method. 100 individuals (mean age 65 ± 13 years; 59 women) with 64 primary and 36 metastatic lung lesions were included. Only one iodine concentration parameter, absolute minimum iodine, significantly differed between primary and metastatic pulmonary tumors (FDR-adjusted p = 0.015, AUC 0.69). 310 (FDR-adjusted p = 0.0008 to p = 0.0491) radiomic features differed between primary and metastatic lung tumors. Of these, 21 features achieved AUC ≥ 0.75. In subset analyses of lesions imaged by non-CTPA protocol (n = 72), 191 features significantly differed between primary and metastatic tumors, 19 of which achieved AUC ≥ 0.75. In subset analysis of tumors without history of prior treatment (n = 59), 40 features significantly differed between primary and metastatic tumors, 11 of which achieved AUC ≥ 0.75. Volumetric radiomic analysis provides differentiating capability beyond iodine quantification. While a high number of radiomic features differentiated primary versus metastatic pulmonary tumors, fewer features demonstrated good individual discriminatory utility.

In Silico Studies and Design of Scrupulous Novel Sensor for Nitro Aromatics Compounds and Metal Ions Detection.

A Novel calix[4]pyrrole system bearing carboxylic acid functionality [ABuCP] has been synthesized and its interaction towards various nitroaromatics compounds [NACs] were investigated. ABuCP showed significant color change with 1,3-dinitro benzene (1,3-DNB) in comparison to the solution of other nitroaromatic compounds such as 2,3-dinitro toluene (2,3-DNT), 2,4-dinitro toluene (2,4-DNT), 2,6-dinitro toluene (2,6-DNT), 4-NBB (4-nitrobenzyl bromide) and 4-nitro toluene (4-NT). The ABuCP-1,3-DNB complex produces a red shift in absorption spectra based on charge transfer mediated recognition. Additionally, the density functional theory calculation confirmed the possible mechanism for the binding of 1,3-DNB as a guest is well supported by the calculation of other parameters such as hardness, stabilization energy, softness, electrophilicity index and chemical potential. The TDDFT calculation facilitates the understanding of the proper binding mechanism in reference to experimental results. Additionally we have also developed its derivative which acts as a new fluorescent sensor which can selectively recognize Sr(II) ions. In this view its aminoanthraquinone derivative of calix[4]pyrrole i.e. ABuCPTAA is synthesized which also results in generation of high fluorescence capability sensor.

A versatile enrichment of functionalized calixarene as a facile sensor for amino acids.

Amino acids are the most important part of the human biological system due to their role in living processes. The role of amino acids stretches beyond their traditional role as a building block for proteins, and deficiency of amino acids could lead to decreased immunity, digestive problems, depression, fertility issues, lower mental alertness, slowed growth in children, and many other health issues. The acute detection of amino acids is necessary to determine the human health domain. Here, in this review, we summarize and study the calixarenes as complexes that are of immeasurable value and their utilization for amino acid detection. Key factors such as noncovalent forces, limit of detection, and the supramolecular chemistry of calixarenes with amino acids have been well described. This study presents the most recent efforts made towards the development of potential and highly efficient calixarene-based sensors for the detection of amino acids.

Functionalized Silver Nanoparticles as Colorimetric and Fluorimetric Sensor for Environmentally Toxic Mercury Ions: An Overview.

Nanoscience is a multifaceted field which encompasses metal nanoparticles (MNPs) having novel and size-related optical properties significantly different from the bulk level as well as at the atomic level. Amongst noble MNPs, the silver nanoparticles (AgNPs) have unique properties for metal interaction. Presently, there have been expedite reports which are taken under the review in virtue of sensing the mercury ions in aqueous media. Mercury dissemination in various forms contaminates the ecosystem. Globally mercury is ranked as the most toxic element and an urgent threat to humans since it causes major health issues. Employing MNPs, especially AgNPs for the detection of mercury ions is the economic, handy and apt method in contrast to time-consuming methods that use expensive instrumentations. The review highlights a study of colorimetric and fluorimetric detection of the level of Hg (II) ions in aqueous media selectively with high sensitivity in different courses of conditions using AgNPs synthesized by various approaches. Graphical abstract.

Essentials of Insulinoma Localization with Selective Arterial Calcium Stimulation and Hepatic Venous Sampling.

Insulinomas are the most common functional pancreatic neuroendocrine tumor. Most insulinomas can be localized non-invasively with cross-sectional and nuclear imaging. Selective arterial calcium stimulation and hepatic venous sampling is an effective and safe minimally-invasive procedure for insulinoma localization that may be utilized when non-invasive techniques are inconclusive. The procedure's technical success and proper interpretation of its results is dependent on the interventional radiologist's knowledge of normal and variant pancreatic arterial perfusion. Accurate pre-operative localization aids in successful surgical resection. Technical and anatomic considerations of insulinoma localization with selective arterial calcium stimulation and hepatic venous sampling are reviewed.

Symptomatic Management of Gastroparesis.

Gastroparesis is a chronic and debilitating neuromuscular disorder of the upper gastrointestinal tract. Symptoms of gastroparesis include nausea, vomiting, epigastric pain, early satiety, and weight loss. Treating gastroparesis can be difficult. Dietary changes may improve symptoms in patients with mild disease. A variety of medications can be used to treat symptoms of nausea and vomiting, although most have not been subjected to randomized controlled trials and only one is approved by the Food and Drug Administration (metoclopramide). Pain management is essential, as nearly 90% of patients report symptoms of epigastric pain. This article reviews treatment options for symptoms of gastroparesis.

Hyperbaric oxygen therapy is well tolerated and effective for ulcerative colitis patients hospitalized for moderate-severe flares: a phase 2A pilot multi-center, randomized, double-blind, sham-controlled trial.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) markedly increases tissue oxygen delivery. Case series suggest it may have a potential therapeutic benefit in ulcerative colitis (UC). We investigated the therapeutic potential of HBOT as an adjunct to steroids for UC flares requiring hospitalization. METHODS: The study was terminated early due to poor recruitment with 18 of the planned 70 patients enrolled. UC patients hospitalized for moderate-severe flares (Mayo score ≥6, endoscopic sub-score ≥2) were block randomized to steroids + daily HBOT (n = 10) or steroids + daily sham hyperbaric air (n = 8). Patients were blinded to study assignment, and assessments were performed by a blinded gastroenterologist. Primary outcome was the clinical remission rate at study day 5 (partial Mayo score ≤2 with no sub-score >1). Key secondary outcomes were: clinical response (reduction in partial Mayo score ≥2, rectal bleeding sub-score of 0-1) and progression to second-line therapy (colectomy or biologic therapy) during the hospitalization. RESULTS: A significantly higher proportion of HBOT-treated patients achieved clinical remission at study day 5 and 10 (50 vs. 0%, p = 0.04). HBOT-treated patients less often required progression to second-line therapy during the hospitalization (10 vs. 63%, p = 0.04). The proportion requiring in-hospital colectomy specifically as second-line therapy for medically refractory UC was lower in the HBOT group compared to sham (0 vs. 38%, p = 0.07). There were no serious adverse events. CONCLUSION: In this small, proof-of-concept, phase 2A trial, the use of HBOT as an adjunctive therapy to steroids for UC patients hospitalized for moderate-severe flares resulted in higher rates of clinical remission, and a reduction in rates of progression to second-line therapy during the hospitalization. Larger well-powered trials are needed, however, to provided definitive evidence of therapeutic benefit.

Rome Criteria and a Diagnostic Approach to Irritable Bowel Syndrome.

Functional gastrointestinal disorders (FGIDs) account for at least 40% of all referrals to gastroenterologists. Of the 33 recognized adult FGIDs, irritable bowel syndrome (IBS) is the most prevalent, with a worldwide prevalence estimated at 12%. IBS is an important health care concern as it greatly affects patients' quality of life and imposes a significant economic burden to the health care system. Cardinal symptoms of IBS include abdominal pain and altered bowel habits. The absence of abdominal pain makes the diagnosis of IBS untenable. The diagnosis of IBS can be made by performing a careful review of the patient's symptoms, taking a thoughtful history (e.g., diet, medication, medical, surgical, and psychological history), evaluating the patient for the presence of warning signs (e.g., "red flags" of anemia, hematochezia, unintentional weight loss, or a family history of colorectal cancer or inflammatory bowel disease), performing a guided physical examination, and using the Rome IV criteria. The Rome criteria were developed by a panel of international experts in the field of functional gastrointestinal disorders. Although initially developed to guide researchers, these criteria have undergone several revisions with the intent of making them clinically useful and relevant. This monograph provides a brief overview on the development of the Rome criteria, discusses the utility of the Rome IV criteria, and reviews how the criteria can be applied clinically to diagnose IBS. In addition, a diagnostic strategy for the cost-effective diagnosis of IBS will be reviewed.

Gastroparesis: Medical and Therapeutic Advances.

Gastroparesis is a chronic, bothersome, and often disabling neuromuscular disorder of the upper gastrointestinal tract. The most frequently reported symptoms of gastroparesis include nausea, vomiting, epigastric pain, early satiety, and unintentional weight loss. Etiologies of gastroparesis include diabetes, connective tissue disorders, prior infection, mesenteric ischemia, and post-surgical complications. The largest category of gastroparesis patients is comprised of those in whom no definitive cause can be identified (idiopathic gastroparesis). The individual and societal burden of gastroparesis is substantial. It considerably reduces patients' quality of life accompanied by a significant negative impact to the healthcare system. The current treatments of gastroparesis are less than ideal. Dietary modification may improve symptoms in patients with mild disease. Metoclopramide is the only medication currently approved for the treatment of gastroparesis; however, it is associated with adverse effects in a sizable proportion of patients. Other medications are frequently employed to treat symptoms of nausea and vomiting, although technically all are used off-label since they are not FDA approved for the treatment of gastroparesis. These data highlight the need to identify novel, more effective treatment options for this disabling disease. This review will provide a brief synopsis on the epidemiology, etiology, and impact of gastroparesis, discussing new therapeutic advances.

Essential role for Stat5a/b in myeloproliferative neoplasms induced by BCR-ABL1 and JAK2(V617F) in mice.

STAT5 proteins are constitutively activated in malignant cells from many patients with leukemia, including the myeloproliferative neoplasms (MPNs) chronic myeloid leukemia (CML) and polycythemia vera (PV), but whether STAT5 is essential for the pathogenesis of these diseases is not known. In the present study, we used mice with a conditional null mutation in the Stat5a/b gene locus to determine the requirement for STAT5 in MPNs induced by BCR-ABL1 and JAK2(V617F) in retroviral transplantation models of CML and PV. Loss of one Stat5a/b allele resulted in a decrease in BCR-ABL1-induced CML-like MPN and the appearance of B-cell acute lymphoblastic leukemia, whereas complete deletion of Stat5a/b prevented the development of leukemia in primary recipients. However, BCR-ABL1 was expressed and active in Stat5-null leukemic stem cells, and Stat5 deletion did not prevent progression to lymphoid blast crisis or abolish established B-cell acute lymphoblastic leukemia. JAK2(V617F) failed to induce polycythemia in recipients after deletion of Stat5a/b, although the loss of STAT5 did not prevent the development of myelofibrosis. These results demonstrate that STAT5a/b is essential for the induction of CML-like leukemia by BCR-ABL1 and of polycythemia by JAK2(V617F), and validate STAT5a/b and the genes they regulate as targets for therapy in these MPNs.

Vertebral artery anatomy: a review of two hundred fifty magnetic resonance imaging scans.

STUDY DESIGN: The aim of this study is to characterize the anatomy of vertebral arteries using magnetic resonance imaging scans of 250 consecutive patients. OBJECTIVES: To document the prevalence of midline vertebral artery (VA) migration in a subgroup of patients presenting with neck pain, radiculopathy, or myelopathy and to identify the course of the VA through the TFs. SUMMARY OF BACKGROUND DATA: Knowledge of VA anomalies and their respective prevalence may help surgeons decrease the incidence of iatrogenic injury to this artery. METHODS: In this retrospective review of 281 consecutive patients, who had an magnetic resonance imaging for axial neck pain, radiculopathy, or myelopathy, anatomic measurements were obtained from C2 to C7. RESULTS: The observed VA anomalies can be classified into following 3 main groups: (1) intraforaminal anomalies-midline migration, (2) extraforaminal anomalies, and (3) arterial anomalies. Midline migration of the VA was identified in 7.6% (19/250) of patients. The etiology can be degenerative or traumatic. It is important to note that the pattern of medial migration was clockwise rotation from caudal to cephalad and was present in all of our patients with anomalous arteries. Additionally, at C6, only 92% (460/500) of VAs were located within their respective transverse foramens and hypoplastic VAs were identified in 10% (25/250) of patients. CONCLUSION: Anomalies that must be considered before surgery include interforamenal anomalies, extraforamenal anomalies, and arterial anomalies. The intraforaminal anomalies involve midline migration, which places the VA at direct risk during corpectomy. Extraforaminal anomalies are related to VAs entering the transverse foramen at a level other than C6, which can increase the risk of injury during the anterior approach to the cervical spine. Arterial anomalies can be fenestrated, hypoplastic, or absent. These raise concern with the ability to maintain cerebral perfusion in the setting of damage to one of the VAs with the presence of contralateral arterial abnormality.

Suppression of E-protein activity interferes with the development of BCR-ABL-mediated myeloproliferative disease.

E-proteins are a class of helix-loop-helix (HLH) proteins, which play multiple roles throughout lymphoid development. The DNA binding activities of the E-proteins are regulated by a distinct class of antagonistic HLH proteins, named Id1-4. Here we demonstrate that Id2 deficient mice in a C57BL/6 genetic background exhibit increased cellularity in the granulocyte/myeloid progenitor compartment and show significantly higher numbers of maturing neutrophils. Within 6 months of age, Id2 deficient mice succumbed from overwhelming granulocytosis. The disease closely mimicked the distinctive features of human chronic myeloid leukemia: leukocytosis with maturing neutrophils, splenomegaly, hepatomegaly, and myeloid infiltration into peripheral tissues, including spleen, liver, and lungs. Strikingly, forced Id2 expression in murine bone marrow cells substantially delayed the onset of myeloproliferative disease (MPD). Collectively, these studies show that suppression of E-protein activity interferes with the development of BCR-ABL-mediated MPD.