Norbornadiene-Quadricyclane Photoswitches with Enhanced Solar Spectrum Match.

Herein, we report monomeric and dimeric norbornadiene-quadricyclane molecular photoswitch systems intended for molecular solar thermal applications. A series of six new norbornadiene derivatives conjugated with benzothiadiazole as the acceptor unit and dithiafulvene as the donor unit were synthesized and fully characterized. The photoswitches were evaluated by experimentally and theoretically measuring optical absorption profiles and thermal conversion of quadricyclane to norbornadiene. Computational insight by density functional theory calculations at the M06-2X/def2-SVPD level of theory provided geometries, storage energies, UV-vis absorption spectra and HOMO-LUMO levels, that are used to describe the function of the molecular systems. The studied molecules exhibit absorption onset ranging from 416 nm to 595 nm due to a systemic change in their donor-acceptor character. This approach was advantageous due to the introduction of benzothiadiazole and the dimeric nature of molecular structures. The best-performing system has a half-life of 3 days.

Pyrene Functionalized Norbornadiene-Quadricyclane Fluorescent Photoswitches: Characterization of their Spectral Properties and Application in Imaging of Amyloid Beta Plaques.

This study presents the synthesis and characterization of two fluorescent norbornadiene (NBD) photoswitches, each incorporating two conjugated pyrene units. Expanding on the limited repertoire of reported photoswitchable fluorescent NBDs, we explore their properties with a focus on applications in bioimaging of amyloid beta (Aß) plaques. While the fluorescence emission of the NBD decreases upon photoisomerization, aligning with what has been previously reported, for the first time we observed luminescence after irradiation of the quadricyclane (QC) isomer. We deduce how the observed emission is induced by photoisomerization to the excited state of the parent isomer (NBD) which is then the emitting species. Thorough characterizations including NMR, UV-Vis, fluorescence, X-ray structural analysis and density functional theory (DFT) calculations provide a comprehensive understanding of these systems. Notably, one NBD-QC system exhibits exceptional durability. Additionally, these molecules serve as effective fluorescent stains targeting Aß plaques in situ, with observed NBD/QC switching within the plaques. Molecular docking simulations explore NBD interactions with amyloid, unveiling novel binding modes. These insights mark a crucial advancement in the comprehension and design of future photochromic NBDs for bioimaging applications and beyond, emphasizing their potential in studying and addressing protein aggregates.

Synthesis and Characterization of Carbon-Based Heterogeneous Catalysts for Energy Release of Molecular Solar Thermal Energy Storage Materials.

Molecular solar thermal energy storage (MOST) systems are rapidly becoming a feasible alternative to energy storage and net-zero carbon emission heating. MOST systems involve a single photoisomerization pair that incorporates light absorption, storage, and heat release processes in one recurring cycle. Despite significant recent advancements in the field, the catalytic back-reaction from MOST systems remains relatively unexplored. A wide range of applications is possible, contingent on the energy densities of the specific photoisomers. Here, we report platinum-, copper-, and nickel-based heterogeneous catalysts screened in batch conditions for the back-conversion reaction on the cyano-3-(4-methoxyphenyl)-norbornadiene/quadricyclane pair. Catalyst reactivities are investigated using structural characterization, imaging techniques, and spectroscopic analysis. Finally, the thermal stability is also explored for our best-performing catalysts.

Case of split notochord syndrome: a neonate with thoracic neuroenteric cyst, abdominal duodenal duplication cyst, malrotation and vertebral anomalies.

The authors describe a case of a male neonate with split notochord syndrome presenting with cervico-thoracic deformity, thoracic neuroenteric cyst, separate abdominal duodenal duplication cyst and concurrent intestinal malrotation. This combination of abnormalities is very rare. When these lesions are suspected, patients must be investigated carefully.This case is presented not only to recount an infrequent combination of structural abnormalities but also to raise awareness of the signs that should point to clinical suspicion and prompt diagnosis.Following surgical excision of the thoracic neuroenteric cyst, the patient has made a good recovery.

Synthesis of Dioxa-1,7-naphthicorrole and Its Oxidized Porphyrinoid as a Potential Built-In Linker for Biomolecules.

The first aromatic benzicorrole termed naphthicorrole was synthesized with a carbon donor containing more than six members. Its oxidized (enedione-embedded) porphyrinoid was also obtained using different meso-aryl substitutions under sequential oxidation conditions. The resulting enedione motif of the nonaromatic porphyrinoid was regioselective to the C2 position for S or N nucleophiles. Thus, the oxidized porphyrinoid was tested as a built-in linker for biomolecules. The progress of the reaction was visually monitored due to their different conjugation pathways.

o-(2-Thienyl)vinylarene as an Alternative Synthetic Motif for Porphyrinoids: o-Arene-Connected Porphyrinoids.

o-Arene-connected porphyrinoids were synthesized with o-(2-thienyl)vinylarene motif as a new building block for porphyrinoids. This motif can replace meso-aryl-substituted dipyrromethene and serve as a command key arranging o-connectivity of porphyrinoid. While 6a (benzene version) is very weak, 6b (pyridine version) shows a substantial amount of diatropic ring current due to reduced steric hindrance (without H23) and rigidified Pd-6a became more aromatic than 6b.

Carbaporphyrin Dimers That Bear a Rigid Naphthalene Motif as an Internal Strap.

The first fully connected aromatic carbaporphyrin dimer (6) and its bis-Pd complex (6-Pd2) that bear a rigid naphthalene motif as an internal strap were synthesized. These dimers consisted of two aromatic carbaporphyrins that shared a naphthalene motif. The π-electron conjugation of the obtained macrocycles was proposed to have two separated local 22 π-electron pathways and a 34 π-electron pathway. Their weak aromaticity was fully supported by 1H NMR spectroscopy, NICS values, ACID calculations, and ICSS plots.

Comprehensive strategies to minimize radiation exposure during Interventional electrophysiology procedures: state-of-the-art review.

INTRODUCTION: Cardiac electrophysiology (EP) procedures are frequently performed in patients with cardiac arrhythmias, chronic heart failure, and sudden cardiac death. Most EP procedures involve fluoroscopy, which results in radiation exposure to physicians, patients, and EP lab staff. Accumulated radiation exposure is a known health detriment to patients and physicians. AREA COVERED: This review will summarize radiation exposure, dose metrics, complications of radiation exposure, factors affecting radiation exposure, minimizing radiation exposure, zero or near-zero fluoroscopy strategies, and up-to-date research in the area of reducing radiation exposure and best practices. EXPERT COMMENTARY: Comprehensive strategies should be implemented in EP laboratories to minimize radiation exposure with standard fluoroscopy. There are routine techniques that can mitigate significant amounts of radiation exposure using standard equipment within the EP lab. The operators need to emphasize that EP practices routinely incorporate non-ionizing radiation sources for cardiac imaging (e.g. magnetic resonance imaging, advanced electroanatomical mapping systems, intracardiac ultrasonography) in addition to other novel technologies to mitigate radiation exposure to patients and physicians.

Beware the Innocent Presentation of a Spontaneous Perforated Meckel Diverticulum: A Rare Case and Review of the Literature.

Perforation of a Meckel diverticulum in a preterm neonate is very rare. To our knowledge, only 7 cases of spontaneous Meckel perforation in a preterm neonate have previously been described in the literature. The etiology is uncertain. We present the case of a 30-week preterm female twin with a spontaneous Meckel diverticulum perforation discovered on day 3 of life and review the published cases. A possible etiological explanation for this rare entity at this age group is also suggested.

Synthetic Anion Transporters as Endoplasmic Reticulum (ER) Stress Inducers.

Cl--ion transporters (2a-2h) were synthesized based on the binding motifs of prodigiosin. Transporter 2e clearly displays Cl--ion transportation activity across both model and live cell membranes. Furthermore, 2e can disrupt Ca2+ homeostasis and increase the intracellular concentration of Ca2+ in the DLD-1 cell. This disruption can lead to Caspase-dependent apoptosis supported by CHOP expression (a marker of ER stress) and the appearance of the cleaved forms of Caspase 3 and PARP.

The Cambridge experience with buried bumpers.

AIM: Buried Bumper (BB) is a complication of percutaneous endoscopic gastrostomy (PEG) that leads to tube dysfunction and major morbidity. Although many techniques have been described to manage BB, none are universally adopted, and laparotomy remains the mainstay. We introduce a novel endoscopic technique in paediatric surgery that avoids laparotomy. METHODS: A retrospective review of medical records of patients who presented with BB to Cambridge University Hospital, UK, between January 2012 and June 2018 was done. Data collected included: demographics, tube size and type, interval between insertion and diagnosis of BB, hospital stay, technique used, and postoperative complications. The technique involved using an endoscopic snare passed from inside the stomach lumen through the PEG lumen to the outside, guided if required by a stiff nylon thread if no part of the PEG was visible, grasping the PEG tube externally after cutting it short, followed by a retrograde pull to remove the buried tube via the mouth. MAIN RESULTS: Fifteen BBs were found in ten patients. Median patient age was 5.25 years (1.2-16.6). Median time between gastrostomy insertion and diagnosis of BB was 9 months (1-32). Twelve BBs were removed endoscopically with no postoperative complications. Patients had a replacement inserted through the original track and were discharged within 24 h. Two underwent laparotomies performed by surgeons unfamiliar with endoscopic technique, and one was converted to laparotomy owing to inability to transverse an encrusted and closed PEG tube lumen. CONCLUSION: Endoscopic retrograde BB removal is a safe, easy, and quick technique with minimal complications. We strongly advocate widespread adoption of the technique before considering a laparotomy. LEVEL OF EVIDENCE: Treatment study: Level IV.

Factors affecting prognosis in locoregional recurrence of oral squamous cell carcinoma.

BACKGROUND: Recurrence of oral squamous cell carcinoma (rOSCC) after primary treatment is associated with poor survival outcomes. Salvage treatment with further surgery, radiotherapy and chemotherapy has high morbidity, making patient selection crucial. However, in the recurrence setting, reliable stratification data are scarce. Decision-making in this context is consequently complex. We investigated factors influencing overall survival after rOSCC. METHODS: Retrospective cohort study of patients with rOSCC (n = 83) at the Queen Elizabeth Hospital Birmingham, UK between 2006 and 2016. Associations with overall survival were analysed using univariate and multivariate analyses to identify important clinical prognostic indicators. RESULTS: Overall survival at 1 year was 32.5% and at 5 years was 18.1% after a median follow-up of 7.4 months. Multivariate analysis identified four independent predictors of overall survival following rOSCC: size of primary tumour (HR 2.077; 95% CI 1.034-4.172), extent of recurrent disease (HR 3.286; 95% CI 1.545-6.991), history of moderate alcohol consumption (HR 0.351; 95% CI 0.162-0.763), and close or positive margins at primary resection (HR 1.955; 95% CI 1.063-3.595). CONCLUSIONS: We identified four key factors that help prognostication and risk stratification of rOSCC. Given the high morbidity associated with salvage treatment, we recommend that the multidisciplinary team (MDT) and the patient weigh these factors carefully when considering further treatment. Further investigation of the biology underlying these oncophenotypes may contribute to better patient stratification.

Bond Rotation in an Aromatic Carbaporphyrin: Allyliporphyrin.

Allyliporphyrin is a carbaporphyrin that has replaced one pyrrole with an allyl group. Dynamic behavior (bond rotation) was observed by variable temperature 1 H NMR and 2D-NOESY NMR spectroscopy and theoretically examined by DFT calculations. These studies revealed that well-defined bond rotation was first observed in the limited space of the carbaporphyrin from 2 through cis-2 and the calculated rotational barrier was low enough, with the relative energy level of cis-2 only 0.65 kcal mol-1 higher than 2. The synthesized allyliporphyrin (2) is a strongly aromatic macrocycle as indicated by the chemical shifts of its inner NH and CH signals. However, its palladium complex displayed reduced aromaticity due to the tilted thiophene of Pd-2.

Synthesis of a Phlorin from a Meso-Fused Anthriporphyrin by a Diels-Alder Strategy.

An anthracene-containing meso-fused carbaporphyrin, which has extended π-conjugation pathways as compared to the corresponding naphthalene-containing carbaporphyrin, has been synthesized. The weak global aromaticity of the anthriporphyrin also allowed its use as the diene for a Diels-Alder reaction with dimethyl acetylenedicarboxylate (DMAD). The resulting phlorin contains an interesting bicyclic structure. Moreover, to the best of our knowledge, this phlorin is the first Diels-Alder adduct of a diene forming part of the global π-conjugation pathway of an aromatic porphyrinoid.

2-(Naphthalen-1-yl)thiophene as a New Motif for Porphyrinoids: Meso-Fused Carbaporphyrin.

The first synthesis of meso-fused carbaporphyrin via a premodification method was accomplished by substituting two pyrrole moieties and one meso-carbon with 2-(naphthalen-1-yl)thiophene. The obtained global π-conjugation pathway of the macrocycle noticeably disturbs the 10π local aromaticity of naphthalene, and its aromatic nature was supported by NMR spectroscopy together with nucleus-independent chemical shift, anisotropy of the induced current density, and harmonic oscillator stabilization energy calculations. In addition, the meso-fused carbaporphyrin also allowed the formation of a square planar Pd(II) complex.

Features and prognostic utility of biopsy in oral squamous cell carcinoma.

BACKGROUND: Traditional approaches in oral squamous cell carcinoma (OSCC) management utilize biopsy tissue for diagnostic purposes only. Adverse prognostic features, such as the tumor depth, are usually determined from final resection specimens, but are seldom studied in biopsy tissue. METHODS: A preliminary study of 139 consecutive biopsies compared biopsy size with T classification, tumor site, and operator grade, and biopsy tumor depth with the true tumor depth. RESULTS: This study demonstrated that biopsy size is independent of T classification (p = .44), subsite (p = .86), and operator grade (p = .10). The biopsy tumor depth significantly underrepresented true tumor depth (2.5 mm, 95% confidence interval [CI] = 2.4-2.9 vs 8.2 mm, 95% CI = 6.5-9.9; p < .001), confirming the limited prognostic utility of biopsies in OSCC. CONCLUSION: A future clinical trial will compare the routine biopsy technique with standardized deeper biopsy techniques using punch biopsy to sample invasive fronts and investigate opportunities for up-front staging using a combination of histological features and epithelial and stromal molecular biomarkers in OSCC. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1857-E1862, 2016.

Congenital lung lesions: preoperative three-dimensional reconstructed CT scan as the definitive investigation and surgical management.

AIM OF STUDY: The aim of this study was to review our experience of postnatal investigations and management of congenital lung lesions. METHODS: All children with antenatal diagnosis undergoing surgical management were identified from hospital records. Antenatal diagnosis and serial antenatal ultrasound findings were noted, postnatal chest X-ray (CXR) and computed tomographic (CT) scan were reviewed. Pearson correlation coefficient (r) was used to look into relation between CT scan and per-operative findings. Surgical management and outcome of these lesions were assessed. RESULTS: A total of 38 children were identified between January 2000 and December 2011; 22 were males and 16 were females. The mean gestational age at diagnosis was 21 weeks (range 18 to 26 weeks). Five children showed complete resolution antenatally. Four children were symptomatic at birth. Postnatal CXR showed an abnormality in only 17 infants. CT scan with three-dimensional (3D) reconstructions was performed at the mean age of 7.7 months (range 1 day to 42 months). CT scan correlated well with per-operative findings and provided adequate anatomical information r = 0.98. Open thoracotomy and lobectomy/excision was performed in 23, and 15 had thoracoscopic lobectomy/excision. The mean age of operation was 18 months (range 2 days to 96 months). Twenty patients had signs of recurrent preoperative infection with pleural adhesions and hilar thickening resulting in conversion of 10 thoracoscopic cases to open surgery. Histology confirmed 26 congenital cystic adenomatoid malformations, 2 hybrid lesions, 7 sequestrations, and 3 bronchopulmonary malformations. CONCLUSIONS: Antenatal resolution and normal postnatal CXR are not reliable indicators of resolution of the lesion. Early postnatal CT scan preferably with 3D reconstruction and early surgical treatment are suggested, as delaying the operation may result in repeated infection making thoracoscopic approach more difficult.

Identification of novel genes in Hirschsprung disease pathway using whole genome expression study.

AIM: This study aims to identify new genes not described previously that may be relevant in the etiology or pathophysiology of patients with Hirschsprung disease (HD). This was done by identifying differences in gene expression between normal and abnormal segments of bowel in HD patients compared with controls. METHODS: Full-thickness colonic tissue samples were taken from HD patients, both from the diseased (Ds) and normal segment of the colon (Nr), and from controls (Ct). Samples were further dissected into mucosa (MUC) and muscle (MUS). RNA was extracted and analyzed on Affymetrix Gene Chip Human Gene 1.0 ST arrays. Statistical analyses using ANOVA with a fold change cut off of 2 was applied to detect a number of differentially expressed genes. Selected genes were revalidated by quantitative real-time reverse transcriptase polymerase chain reaction. RESULTS: Thirty-four samples (18 MUS and 16 MUC) were analyzed. MUC (1.64 ± 0.46 µg/mg) and MUS (0.83 ± 0.48 µg/mg) showed good RNA extraction yield and quality. Of the 24,987 filtered on expression genes, MUS showed 220 genes with expression difference of 2-fold, out of which 120 genes were significant with P ≤ .05. Similarly, MUC demonstrated 206 genes with 2-fold changes and 9 had P ≤ .05. Some genes showing differential expression between groups and therefore subject to further analysis were RELN, GAL, GAP43, NRSN1, and GABRG2. CONCLUSION: Analyzed data showed significant differences in expression of above sets of genes with up- and down-regulation, which has not been described before in HD and could have a role in pathogenesis of this condition.