New Amino Acid-Based Thiosemicarbazones and Hydrazones: Synthesis and Evaluation as Fluorimetric Chemosensors in Aqueous Mixtures.

Bearing in mind the interest in the development and application of amino acids/peptides as bioinspired systems for sensing, a series of new phenylalanine derivatives bearing thiosemicarbazone and hydrazone units at the side chain were synthesised and evaluated as fluorimetric chemosensors for ions. Thiosemicarbazone and hydrazone moieties were chosen because they are considered both proton-donor and proton-acceptor, which is an interesting feature in the design of chemosensors. The obtained compounds were tested for the recognition of organic and inorganic anions (such as AcO-, F-, Cl-, Br-, I-, ClO4-, CN-, NO3-, BzO-, OH-, H2PO4- and HSO4-) and of alkaline, alkaline-earth, and transition metal cations, (such as Na+, K+, Cs+, Ag+, Cu+, Cu2+, Ca2+, Cd2+, Co2+, Pb2+, Pd2+, Ni2+, Hg2+, Zn2+, Fe2+, Fe3+ and Cr3+) in acetonitrile and its aqueous mixtures in varying ratios via spectrofluorimetric titrations. The results indicate that there is a strong interaction via the donor N, O and S atoms at the side chain of the various phenylalanines, with higher sensitivity for Cu2+, Fe3+ and F- in a 1:2 ligand-ion stoichiometry. The photophysical and metal ion-sensing properties of these phenylalanines suggest that they might be suitable for incorporation into peptide chemosensory frameworks.

Influence of the Intramolecular Hydrogen Bond on the Fluorescence of 2-ortho-Aminophenyl Pyridines.

The dynamic nature of excited-state intramolecular proton transfer (ESIPT) and its effect on emission spectra is an attractive strategy to create multi-emissive dyes. Here we describe the behavior of a series of hydrogen-bonded triphenylpyridines with a set of donor-acceptor combinations that allowed us to perceive the influence of each substitution on the photophysical properties of the dyes. The susceptibility of these ESIPT moieties to pH variations was also studied, elucidating that the level of protonation had a significant effect on the emission color. The assignment of each emission band was made by using DFT and td-DFT calculations that were in agreement with the experimental results. This study emphasizes the versatility of triphenylpyridines that can be synthesized effortlessly with a logical and independent C-2, C-4 and C-6 substitution in order to have the desired ESIPT modulation and subsequent multi-emission response.

Locking the GFP Fluorophore to Enhance Its Emission Intensity.

The Green Fluorescent Protein (GFP) and its analogues have been widely used as fluorescent biomarkers in cell biology. Yet, the chromophore responsible for the fluorescence of the GFP is not emissive when isolated in solution, outside the protein environment. The most accepted explanation is that the quenching of the fluorescence results from the rotation of the aryl-alkene bond and from the Z/E isomerization. Over the years, many efforts have been performed to block these torsional rotations, mimicking the environment inside the protein ß-barrel, to restore the emission intensity. Molecule rigidification through chemical modifications or complexation, or through crystallization, is one of the strategies used. This review presents an overview of the strategies developed to achieve highly emissive GFP chromophore by hindering the torsional rotations.

Enhance Access to Pulmonary Rehabilitation with a Structured and Personalized Home-Based Program-reabilitAR: Protocol for Real-World Setting.

Home-based models represent one of the solutions to respond to the poor accessibility of pulmonary rehabilitation (PR) services in patients with chronic respiratory disease (CRD). The main goal of this protocol is to present the implementation of the first nationwide home-based PR program-reabilitAR-in Portugal and the strategies to assess its benefits in patients with CRD. The program consists of 2 phases: a 12-week intensive phase and a 40-week maintenance phase (total: 52 weeks, 1 year). The intervention in both phases is composed of presential home visits and phone-call follow ups, including exercise training and the self-management educational program Living Well with COPD. Dyspnea, impact of the disease, emotional status, and level of dyspnea during activities of daily living are used as patient-reported outcomes measures. A one-minute sit-to-stand test is used as a functional outcome, and the number of steps as a measure of physical activity. To ensure safety, fall risk and the cognitive function are assessed. Data are collected at baseline, at 12 weeks, at 26 weeks and at 52 weeks. This is the first nationwide protocol on enhancing access to PR, providing appropriate responses to CRD patients' needs through a structured and personalized home-based program in Portugal.

Tetracyclic Thioxanthene Derivatives: Studies on Fluorescence and Antitumor Activity.

Thioxanthones are bioisosteres of the naturally occurring xanthones. They have been described for multiple activities, including antitumor. As such, the synthesis of a library of thioxanthones was pursued, but unexpectedly, four tetracyclic thioxanthenes with a quinazoline-chromene scaffold were obtained. These compounds were studied for their human tumor cell growth inhibition activity, in the cell lines A375-C5, MCF-7 and NCI-H460. Photophysical studies were also performed. Two of the compounds displayed GI50 values below 10 µM for the three tested cell lines, and structure-activity relationship studies were established. Three compounds presented similar wavelengths of absorption and emission, characteristic of dyes with a push-pull character. The structures of two compounds were elucidated by X-ray crystallography. Two tetracyclic thioxanthenes emerged as hit compounds. One of the two compounds accumulated intracellularly as a bright fluorescent dye in the green channel, as analyzed by both fluorescence microscopy and flow cytometry, making it a promising theranostic cancer drug candidate.

Effects of a Home-Based Pulmonary Rehabilitation Program in Patients with Chronic Obstructive Pulmonary Disease in GOLD B Group: A Pilot Study.

Patients with chronic obstructive pulmonary disease (COPD) in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) B group can be included in pulmonary rehabilitation (PR) settings outside the hospitals. This study aimed to explore the feasibility of a home-based pulmonary rehabilitation (HBPR) program and assess its impact on patients with COPD in the GOLD B group. A real-world, pre-post intervention study was conducted with 12 weeks of HBPR (presential home visits and phone calls) using the self-management program Living Well with COPD. The 1-min sit-to-stand test (1MSTS), modified Medical Research Council Questionnaire (mMRC), COPD Assessment Test (CAT), Hospital Anxiety and Depression Scale (HADS), and London Chest Activity of Daily Living (LCADL) were used to assess the impact. Pre-post differences and correlations between changes in outcomes were calculated. In 30 patients (71.6 years, FEV1 (%) 52.8), significant improvements (p < 0.05) were observed on 1MSTS (Pre 17.2, Post 21.2), mMRC (Pre 2.0, Post 1.0), CAT (Pre 16.3, Post 9.9), HADS (Pre 14.4, Post 9.6), and LCADL (Pre 21.0, Post 15.8), with no adverse events reported. When significant, correlations between changes in outcomes were moderate or strong (0.48 ≤ ρ ≤ 0.66). HBPR can be feasible and safe, and it shows the potential to significantly improve outcomes of patients with COPD in the GOLD B group.

Undifferentiated embryonal sarcoma of the liver: A rare hepatic tumor and its related characteristic radiological features.

The undifferentiated embryonal sarcoma of the liver is a rare tumor with a poor prognosis, with improved outcomes being reported with more recently multimodality treatments. We report a case of a 6-year-old girl with an incidentally diagnosed and histologically proven localized undifferentiated embryonal sarcoma of the liver. The divergence between solid appearance at US and cystic-like appearance on CT/MRI, which has been attributed to the presence of myxoid component frequently described with this tumor, was crucial for the diagnosis and subsequent treatment.

Multicomponent Synthesis of Luminescent Iminoboronates.

A family of iminoboronates was prepared through a one-pot multicomponent reaction, starting from boronic acid, anthranilic acid, and different salicylaldehydes. Their synthesis was straightforward and the complexes were obtained in good to excellent yields. Their photophysical properties were assessed in a diluted solution, and the complexes proved to be faintly luminescent. These chelates demonstrated remarkable Aggregation-Induced Emission Enhancement, which was rationalized using crystal structures.

Malignant Solitary Fibrous Tumor of the Liver: AIRP Best Cases in Radiologic-Pathologic Correlation.

Editor's Note.-RadioGraphics continues to publish radiologic-pathologic case material selected from the American Institute for Radiologic Pathology (AIRP) "best case" presentations. The AIRP conducts a 4-week Radiologic Pathology Correlation Course, which is offered five times per year. On the penultimate day of the course, the best case presentation is held at the American Film Institute Silver Theater and Cultural Center in Silver Spring, Md. The AIRP faculty identifies the best cases, from each organ system, brought by the resident attendees. One or more of the best cases from each of the five courses are then solicited for publication in RadioGraphics. These cases emphasize the importance of radiologic-pathologic correlation in the imaging evaluation and diagnosis of diseases encountered at the institute and its predecessor, the Armed Forces Institute of Pathology (AFIP).

Non-canonical amino acids bearing thiophene and bithiophene: synthesis by an Ugi multicomponent reaction and studies on ion recognition ability.

Novel thienyl and bithienyl amino acids with different substituents were obtained by a multicomponent Ugi reaction between a heterocyclic aldehyde, an amine, an acid and an isocyanide. Due to the presence of the sulphur heterocycle at the side chain, these unnatural amino acids are highly emissive and bear extra electron donating atoms so they were tested for their ability to act as fluorescent probes and chemosensors in the recognition of biomedically relevant ions in acetonitrile and acetonitrile/water solutions. The results obtained from spectrophotometric/spectrofluorimetric titrations in the presence of organic and inorganic anions, and alkaline; alkaline-earth and transition metal cations indicated that the bithienyl amino acid bearing a methoxy group is a selective colorimetric chemosensor for Cu2+, while the other (bi)thienyl amino acids act as fluorimetric chemosensors with high sensitivity towards Fe3+ and Cu2+ in a metal-ligand complex with 1:2 stoichiometry. The photophysical and ion sensing properties of these amino acids confirm their potential as fluorescent probes suitable for incorporation into peptidic frameworks with chemosensory ability.

Bilateral Congenital Agenesis of the Long Head of the Biceps Tendon: The Beginning.

The biceps brachii muscle is prone to variants but absence of the long head of the biceps (LHB) tendon is an exceptionally rare anomaly. This report concerns the fourth case of bilateral congenital absence of the LHB tendon and presents the ultrasonography (US) and magnetic resonance (MR) findings. Our case has the peculiarity of being the first in which bilateral LHB tendon agenesis is not associated with rotator cuff or labral tears.

Pleuroparenchymal fibroelastosis: role of high-resolution computed tomography (HRCT) and CT-guided transthoracic core lung biopsy.

OBJECTIVES: Pleuroparenchymal fibroelastosis (PPFE) is a rare idiopathic interstitial pneumonia (IIP) with variable clinical and radiological features. Diagnosis is based on histology obtained by surgical lung biopsy, which is associated with significant mortality and morbidity. This study aims to briefly review PPFE and discuss the role of CT-guided transthoracic core lung biopsy (TTB) in its diagnosis. MATERIALS/METHODS: Four cases of PPFE diagnosed at our institution with TTB are reported and discussed. RESULTS: Clinical, radiological and histological features are in agreement with the previous literature cases. TTB provided the diagnosis in all cases. Iatrogenic pneumothorax was the main complication in all patients. Placement of a chest tube was needed in three patients. An overlap between PPFE and other interstitial lung diseases (ILD) was documented. CONCLUSION: PPFE is an underdiagnosed IIP, so radiologist awareness of it needs to be widespread in patients with fibrosis with apical-caudal distribution. Coexistence of different lung diseases strengthens the idea of a predisposing factor. TTB proved to be a good diagnostic tool and can be considered the first choice for invasive assessment of these patients. PFFE has a variable course with no established therapeutic options; therefore a multidisciplinary team is crucial in the approach to patients with ILD. MAIN MESSAGES/TEACHING POINTS: • PPFE should be considered in the differential diagnosis of fibrosis with apical-caudal distribution. • CT-guided TTB can be considered the first choice for invasive assessment of PPFE. • Site of biopsy has to be chosen carefully in order not to miss PPFE. • Coexistence of different lung diseases strengthens the idea of a predisposing factor. • A multidisciplinary team is crucial in the approach to patients with ILD.

Ring-shaped lateral meniscus with hypoplasic anterior cruciate ligament.

Knee joint lesions can be solitary or occur concomitantly with other lower limb abnormalities. Ring-shaped lateral meniscus (RSM) and hypoplasic anterior cruciate ligament (ACL) are two rare malformations. The therapeutic management of such abnormalities is not consensual, and highly depends on clinical symptomatology. We report a case of a 25-year-old girl with progressive knee pain whose MRI demonstrated a continuous segment of lateral meniscus situated along the medial aspect of the lateral compartment, continuous with the otherwise normal-appearing lateral meniscus, compatible with an RSM. This anatomic variant can be mistaken by a displaced meniscal fragment, like a bucket-handle tear, a central tear of a discoid meniscus, or incomplete discoid meniscus, as previously reported. Her MRI examination also showed a thinned ACL with anomalous lateral course. This abnormality may be mistaken for an ACL rupture and/or a meniscofemoral ligament with agenesis of ACL. Multiple images in different planes as well as following the course of meniscal and ligaments are critical clues to avoid misdiagnosis. As a result, the diagnosis of an RSM along with hypoplasic ACL with abnormal attachment was assumed based on MRI and confirmed during arthroscopy. The patient was treated conservatively with clinical outcome improvement.

Novel highly emissive non-proteinogenic amino acids: synthesis of 1,3,4-thiadiazolyl asparagines and evaluation as fluorimetric chemosensors for biologically relevant transition metal cations.

Highly emissive heterocyclic asparagine derivatives bearing a 1,3,4-thiadiazolyl unit at the side chain, functionalised with electron donor or acceptor groups, were synthesised and evaluated as amino acid-based fluorimetric chemosensors for metal cations, such as Cu²(+), Zn²(+), Co²(+) and Ni²(+). The results suggest that there is a strong interaction through the donor heteroatoms at the side chain of the various asparagine derivatives, with high sensitivity towards Cu²(+) in a ligand-metal complex with 1:2 stoichiometry. Association constants and detection limits for Cu²(+) were calculated. The photophysical and metal ion sensing properties of these asparagine derivatives confirm their potential as fluorimetric chemosensors and suggest that they can be suitable for incorporation into chemosensory peptidic frameworks.