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 with quantum yields over 50 %.

Migrated tubal sterilisation clip presenting as a subcutaneous gluteal foreign body 24 years later: a case report and literature review.

BACKGROUND: The incidence of sterilisation clip migration is reportedly 25%. However, less than 1% of those who experience clip migration will present with pain, an abscess, or spontaneous extrusion. Here we present a rare case of sterilisation clip migration through the entire pelvic floor. CASE PRESENTATION: A 66-year-old female was referred from community to the Surgical Emergency Unit with a possible metallic foreign body under the skin following an attempted routine gluteal cyst excision. The patient first noticed a lump under the skin 2 years ago which gradually became more apparent and tender over the previous 2 months. The patient denied recent trauma, had no co-morbidities and had a sterilisation procedure 24 years prior. Examination revealed a non-mobile solid structure just beneath the skin 5 cm laterally from the anal verge. Inflammatory markers were normal and an ultrasound confirmed a 15 × 7 mm foreign body in the subcutaneous tissues. The foreign body was excised easily under local anaesthesia, revealing a closed Filshie sterilisation clip. The wound was closed primarily, and recovery was uncomplicated. CONCLUSIONS: This was a case of sterilisation clip migration to the subcutaneous gluteal region. A literature review revealed 34 case reports of sterilisation clip migration, mostly to the bladder. Patients with a previous sterilisation procedure and suspected subcutaneous foreign body without trauma should elicit a high index of suspicion for migrated sterilisation clips. These clips can migrate through multiple layers of muscle and fascia, including the pelvic floor.

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.

Mitochondrial transcription factor A (TFAM) has 5'-deoxyribose phosphate lyase activity in vitro.

Mitochondrial DNA (mtDNA) plays a key role in mitochondrial and cellular functions. mtDNA is maintained by active DNA turnover and base excision repair (BER). In BER, one of the toxic repair intermediates is 5'-deoxyribose phosphate (5'dRp). Human mitochondrial DNA polymerase γ has weak dRp lyase activities, and another known dRp lyase in the nucleus, human DNA polymerase ß, can also localize to mitochondria in certain cell and tissue types. Nonetheless, whether additional proteins have the ability to remove 5'dRp in mitochondria remains unknown. Our prior work on the AP lyase activity of mitochondrial transcription factor A (TFAM) has prompted us to examine its ability to remove 5'dRp residues in vitro. TFAM is the primary DNA-packaging factor in human mitochondria and interacts with mitochondrial DNA extensively. Our data demonstrate that TFAM has the dRp lyase activity with different DNA substrates. Under single-turnover conditions, TFAM removes 5'dRp residues at a rate comparable to that of DNA polymerase (pol) ß, albeit slower than that of pol λ. Among the three proteins examined, pol λ shows the highest single-turnover rates in dRp lyase reactions. The catalytic effect of TFAM is facilitated by lysine residues of TFAM via Schiff base chemistry, as evidenced by the observation of dRp-lysine adducts in mass spectrometry experiments. The catalytic effect of TFAM observed here is analogous to the AP lyase activity of TFAM reported previously. Together, these results suggest a potential role of TFAM in preventing the accumulation of toxic DNA repair intermediates.

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.

The role of dietary vitamin A in mechanisms of cataract development in the teleost lumpfish (Cyclopterus lumpus L).

Lumpfish (Cyclopterus lumpus L) are highly prone to cataract development in the wild and in culture. There is evidence that cataract in farmed fish is related to nutrition. However, both the nutrients and the mechanisms involved in cataract development in lumpfish are not clear. Here we investigated the mechanisms involved and the role of dietary vitamin A in cataract development in a cultured lumpfish population. Cultured lumpfish were fed three diets differing only in vitamin A supplementation level (5000, 15,000 and 120,000 IU/kg) over an 18-month period, and fish weight, cataract frequencies and severities were determined. Western blotting and immunohistochemistry were performed on lens tissue to measure the levels of oxidative stress, and apoptosis. The lowest levels of vitamin A significantly reduced cataract frequencies in adult lumpfish and resulted in less severe cataract and increased weight in males. Oxidative stress levels in the lens were positively correlated with vitamin A intake. Apoptosis was observed at high levels in lenses with severe cataract. Oxidative stress and apoptosis levels were the highest in regions of the lens with severe, advanced cataract pathology when compared to regions with no visible pathology. These results suggest that higher vitamin A intake contributes to cataract development through an oxidative stress pathway, and that both oxidative stress and apoptosis are involved in advanced stages of cataract in lumpfish.

Oxidative DNA damage on the VEGF G-quadruplex forming promoter is repaired via long-patch BER.

In response to oxidative damage, base excision repair (BER) enzymes perturb the structural equilibrium of the VEGF promoter between B-form and G4 DNA conformations, resulting in epigenetic-like modifications of gene expression. However, the mechanistic details remain enigmatic, including the activity and coordination of BER enzymes on the damaged G4 promoter. To address this, we investigated the ability of each BER factor to conduct its repair activity on VEGF promoter G4 DNA substrates by employing pre-steady-state kinetics assays and in vitro coupled BER assays. OGG1 was able to initiate BER on double-stranded VEGF promoter G4 DNA substrates. Moreover, pre-steady-state kinetics revealed that compared to B-form DNA, APE1 repair activity on the G4 was decreased ~two-fold and is the result of slower product release as opposed to inefficient strand cleavage. Interestingly, Pol ß performs multiple insertions on G4 substrates via strand displacement DNA synthesis in contrast to a single insertion on B-form DNA. The multiple insertions inhibit ligation of the Pol ß products, and hence BER is not completed on the VEGF G4 promoter substrates through canonical short-patch BER. Instead, repair requires the long-patch BER flap-endonuclease activity of FEN1 in response to the multiple insertions by Pol ß prior to ligation. Because the BER proteins and their repair activities are a key part of the VEGF transcriptional enhancement in response to oxidative DNA damage of the G4 VEGF promoter, the new insights reported here on BER activity in the context of this promoter are relevant toward understanding the mechanism of transcriptional regulation.

Upadacitinib in Crohn's disease: real-world experience.

Small molecule therapy in inflammatory bowel disease has recently gained momentum. One such agent that was recently approved for use in Crohn's disease is upadacitinib. Even though clinical trials support the use of this agent and efficacy is impressive, real-world data remains limited and scattered in the current literature. This article aims to summarize the real-world data published so far about using upadacitinib in Crohn's disease.

Metastatic Plasmacytoid Urothelial Carcinoma Masquerading as a Primary Signet Ring Cell Carcinoma of the Duodenum.

Plasmacytoid urothelial carcinoma can histologically mimic gastrointestinal signet ring cell carcinoma, a potential diagnostic pitfall resulting in improper clinical management. We present a rare case of a malignant duodenal ulcer due to metastasis from plasmacytoid urothelial carcinoma. Only by histological and retrospective immunohistochemical comparison with the primary bladder tumor was this revealed as a metastasis from a plasmacytoid urothelial carcinoma. This case report highlights the importance of clinical correlation and comparison with any previous pathology specimens, the limitations of immunohistochemical staining, and the utilization of both old and new immunohistochemical tools when differentiating signet ring cell carcinomas of primary sites versus potential metastases.

Modern Treatment of Neurogenic Thoracic Outlet Syndrome: Pathoanatomy, Diagnosis, and Arthroscopic Surgical Technique.

Compressive pathology in the supraclavicular and infraclavicular fossae is broadly termed "thoracic outlet syndrome," with the large majority being neurogenic in nature. These are challenging conditions for patients and physicians and require robust knowledge of thoracic outlet anatomy and scapulothoracic kinematics to elucidate neurogenic versus vascular disorders. The combination of repetitive overhead activity and scapular dyskinesia leads to contracture of the scalene muscles, subclavius, and pectoralis minor, creating a chronically distalized and protracted scapular posture. This decreases the volume of the scalene triangle, costoclavicular space, and retropectoralis minor space, with resultant compression of the brachial plexus causing neurogenic thoracic outlet syndrome. This pathologic cascade leading to neurogenic thoracic outlet syndrome is termed pectoralis minor syndrome when primary symptoms localize to the infraclavicular area. Making the correct diagnosis is challenging and requires the combination of complete history, physical examination, advanced imaging, and ultrasound-guided injections. Most patients improve with nonsurgical treatment incorporating pectoralis minor stretching and periscapular and postural retraining. Surgical decompression of the thoracic outlet is reserved for compliant patients who fail nonsurgical management and respond favorably to targeted injections. In addition to prior exclusively open procedures with supraclavicular, infraclavicular, and/or transaxillary approaches, new minimally invasive and targeted endoscopic techniques have been developed over the past decade. They involve the endoscopic release of the pectoralis minor tendon, with additional suprascapular nerve release, brachial plexus neurolysis, and subclavius and interscalene release depending on the preoperative work-up.

Uretero-Jejunal Fistula: A Rare Cause of Acute Pyelonephritis.

Penetrating peptic ulcers often lead to severe complications. The development of uretero-enteric fistulas is rare and can be challenging to diagnose and treat. Here, we present the case of a 41-year-old patient who previously underwent gastrojejunostomy for superior mesenteric artery syndrome and developed a peptic jejunal ulcer, leading to a uretero-jejunal fistula and finally causing acute pyelonephritis. The patient was managed with a multidisciplinary approach including medical therapy and endoscopic and radiologic interventions.

Autologous blood transfusion reduces the requirement for perioperative allogenic blood transfusion in patients undergoing major hepatopancreatobiliary surgery: a retrospective cohort study.

INTRODUCTION: Major hepatopancreatobiliary surgery is associated with a risk of major blood loss. The authors aimed to assess whether autologous transfusion of blood salvaged intraoperatively reduces the requirement for postoperative allogenic transfusion in this patient cohort. MATERIALS AND METHODS: In this single centre study, information from a prospective database of 501 patients undergoing major hepatopancreatobiliary resection (2015-2022) was analysed. Patients who received cell salvage ( n =264) were compared with those who did not ( n =237). Nonautologous (allogenic) transfusion was assessed from the time of surgery to 5 days postsurgery, and blood loss tolerance was calculated using the Lemmens-Bernstein-Brodosky formula. Multivariate analysis was used to identify factors associated with allogenic blood transfusion avoidance. RESULTS: 32% of the lost blood volume was replaced through autologous transfusion in patients receiving cell salvage. Although the cell salvage group experienced significantly higher intraoperative blood loss compared with the noncell salvage group (1360 ml vs. 971 ml, P =0.0005), they received significantly less allogenic red blood cell units (1.5 vs. 0.92 units/patient, P =0.03). Correction of blood loss tolerance in patients who underwent cell salvage was independently associated with avoidance of allogenic transfusion (Odds ratio 0.05 (0.006-0.38) P =0.005). In a subgroup analysis, cell salvage use was associated with a significant reduction in 30-day mortality in patients undergoing major hepatectomy (6 vs. 1%, P =0.04). CONCLUSION: Cell salvage use was associated with a reduction in allogenic blood transfusion and a reduction in 30-day mortality in patients undergoing major hepatectomy. Prospective trials are warranted to understand whether the use of cell salvage should be routinely utilised for major hepatectomy.

Colonic Lymphangiomatosis.

Lymphangiomas are benign malformations of the lymphatic vessels which can be primary or secondary in etiology. Colonic involvement is rare, and the diagnosis is mostly incidental. Sometimes, the initial endoscopic appearance can be misleading. We present a case of colonic lymphangiomatosis presenting with free air under the diaphragm requiring surgical removal of the involved portion of the colon. The diagnosis was confirmed by the pathology of the resected specimen and its correlation with prior clinical information. The patient recovered well with an uneventful postoperative course and follow-up. This case demonstrates a rare complication of colonic lymphangiomatosis prompting definitive treatment by surgical resection.

Using machine learning to predict factors affecting academic performance: the case of college students on academic probation.

This study aims to employ the supervised machine learning algorithms to examine factors that negatively impacted academic performance among college students on probation (underperforming students). We used the Knowledge Discovery in Databases (KDD) methodology on a sample of N = 6514 college students spanning 11 years (from 2009 to 2019) provided by a major public university in Oman. We used the Information Gain (InfoGain) algorithm to select the most effective features and ensemble methods to compare the accuracy with more robust algorithms, including Logit Boost, Vote, and Bagging. The algorithms were evaluated based on the performance evaluation metrics such as accuracy, precision, recall, F-measure, and ROC curve, and then validated using 10-folds cross-validation. The study revealed that the main identified factors affecting student academic achievement include study duration in the university and previous performance in secondary school. Based on the experimental results, these features were consistently ranked as the top factors that negatively impacted academic performance. The study also indicated that gender, estimated graduation year, cohort, and academic specialization significantly contributed to whether a student was under probation. Domain experts and other students were involved in verifying some of the results. The theoretical and practical implications of this study are discussed.

Intramedullary Metacarpal Fracture Fixation: A Biomechanical Study of Screw Diameter and Comparison With Intramedullary Wire Stabilization.

PURPOSE: Interest in intramedullary metacarpal fracture fixation (IMFF) with screws is increasing. However, the optimal screw diameter for fracture fixation is not yet established. In theory, larger screws should be more stable, but there is concern about long-term sequelae of larger metacarpal head defects and extensor mechanism injury created during insertion as well as implant cost. Therefore, the purpose of this study was to compare different diameter screws for IMFF to a popular and more cost-effective alternative of intramedullary wiring. METHODS: Thirty-two cadaveric metacarpals were used in a transverse metacarpal shaft fracture model. Treatment groups consisted of IMFF with 3.0 × 60 mm, 3.5 x 60 mm, and 4.5 x 60 mm screws as well as 4 1.1-mm intramedullary wires. Cyclic cantilever bending was performed with the metacarpals mounted at 45° to simulate physiologic loading. Cyclical loading at 10, 20, and 30 N was performed to determine fracture displacement, stiffness, and ultimate force. RESULTS: At 10, 20, and 30 N of cyclical loading, all screw diameters tested provided similar stability as measured by fracture displacement and were superior to the wire group. However, ultimate force under load to failure testing was similar between the 3.5- and 4.5-mm screws and superior to 3.0-mm screws and wires. CONCLUSIONS: For IMFF, 3.0, 3.5, and 4.5-mm diameter screws provide adequate stability for early active motion and are superior to wires. When comparing the different screw diameters, 3.5- and 4.5-mm diameter screws offer similar construct stability and strength superior to the 3.0-mm diameter screw. Therefore, to minimize metacarpal head morbidity, smaller screw diameters may be preferable. CLINICAL RELEVANCE: This study suggests that IMFF with screws is biomechanically superior to wires in cantilever bending strength in the transverse fracture model. However, smaller screws may be sufficient to permit early active motion while minimizing metacarpal head morbidity.

Variation in scapulohumeral rhythm on dynamic radiography in pathologic shoulders: a novel diagnostic tool.

HYPOTHESIS: The purpose of this study was to analyze the SHR of patients diagnosed with small (SRCTs) and massive rotator cuff tears (MRCTs), adhesive capsulitis (AC), and glenohumeral osteoarthritis (GH-OA) and compare their measurements to those of patient controls with healthy shoulders using DDR. We hypothesize that various diagnoses will vary with regards to SHR. METHODS: The sequences of pulsed radiographs collated in DDR to create a moving image were prospectively analyzed during humeral abduction in normal controls and in 4 distinct shoulder pathology groups: SRCT, MRCT, AC, and GH-OA. GH and ST joint angles were measured at 0°-30°, 30°-60°, 60°-90°, and maximal coronal plane humeral abduction. SHR was defined as the ratio of the change in humeral abduction over the change in scapula upward rotation during humeral abduction and was calculated within the above angle intervals. RESULTS: A total of 121 shoulders were analyzed. Forty normal controls were compared to 13 SRCTs, 29 MRCTs, 16 AC, and 23 GH-OA. SHR during humeral abduction differed significantly in patients with MRCT (1.91 ± 0.72), AC (1.55 ± 0.37), and GH-OA (2.31 ± 1.01) compared to controls (3.39 ± 0.79). When analyzed across 30° intervals of abduction, there was a significantly lower SHR found at 0°-30°, 30°-60°, and 60°-90° in MRCT, AC, and GH-OA across each motion range compared to controls. Control patients had an arc of abduction of 103° ± 32°, which was significantly larger than all other pathologies (MRCT: 76° ± 23°, SRCT: 81° ± 21°, AC: 65° ± 27°, GH-OA: 71° ± 35°) and an average scapular abduction of 33° ± 14°, which was significantly less than patients with an MRCT (46° ± 10°) and AC (65° ± 27°). CONCLUSION: SHR remained significantly lower throughout shoulder abduction in MRCT (43.65%), AC (-54.29%), and GH-OA (32.01%) compared to controls. When isolating for humeral and scapular motion, all 4 pathologies had decreased GH abduction, whereas AC and MRCT had an increased scapular compensatory motion compared to controls. Quantifying kinematic patterns like SHR using DDR can be implemented as a novel, safe, and cost-effective method to diagnose shoulder pathology and to monitor response to treatment.

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.