Inexpensive water soluble methyl methacrylate-functionalized hydroxyphthalimide: variations of the mycophenolic acid core for selective live cell imaging of free cysteine.

Evident from numerous studies, cysteine plays a crucial role in cellular function. Reactions with analyte also enables for molecular recognition to adhere to molecular therapeutic potential; integration between synthetic probes therefore allows for a potentially deep therapy-related interogation of biological systems (theranostics). The development of molecular cysteine probes with extremely accurate detection is still a key challenge for the field. The development of water-soluble organic molecular fluorescent probes able to efficiently distinguish common biothiols such as cysteine (Cys), homocysteine (Hcy) and glutathione (GSH) by chemical recognition means i.e. by (binding, cleavage) in biological systems is a greatly sought research challenge due to the similarity of the small sulfhydryl-containing species. Herein, we have developed a water-soluble and highly cell viable fluorescent organic molecule (log P = 0.82) for the selective detection of cysteine. The probe (Myco-Cys) shows a "turn-on" response with the cleavage ester linkage of the methacrylate as cysteine is encountered in solution. The probe shows strong fluorescence enhancement (16.5-fold) when treated with Cys (1 equiv., 10 µM) compared to closely related species such as amino acids, including HCy/GSH, and the limit of detection was determined as 45.0 nM. DFT calculations helped confirm the photomechanism of Myco-Cys. Furthermore, the sensing ability of the probe was demonstrated by living cell assays through the use of confocal fluorescence microscopy. Myco-Cys could selectively detect cysteine among biothiols. Myco-Cys was able to monitor the cysteine level, apart from the oxidative stress present in the form of H2O2 in A549 cells.

Solvent Effects on the Phosphorescence of Gold(III) Complexes Chelated by ß-Multisubstituted Corroles.

A set of gold corrole complexes containing four different ß-substituent groups (Br/I/CF3), namely, 4Br-Au, 4I-Au, and 4CF3-Au, were investigated; all showed room temperature phosphorescence. The phosphorescence quantum yields of the corroles were determined using tetraphenylporphyrin as a reference: Φph (4I-Au, 0.75%) > Φph (4Br-Au, 0.64%) > Φph (4CF3-Au, 0.38%). 4CF3-Au exhibited near-IR emission (858 nm, aerobic); absorbance intensity for the Q-band was higher than that for the Soret band. Complex 4I-Au showed a longer phosphorescence lifetime (82 µs) compared to those of 4Br-Au (53 µs) and 4CF3-Au (28 µs; N2, tol). Thermally activated delayed fluorescence (TADF) emission of 4I/Br-Au complexes was observed: stronger emission intensity correlated with increasing temperature. Good negative correlations for 4I/Br-Au were observed between the Soret band absorption energy and the solvent polarizability: excited states of 4I/Br-Au are more polar than their ground states. TD-DFT calculations revealed very fast intersystem crossing (ISC) rate constants, 2.20 × 1012 s-1 (4CF3-Au) > 1.96 × 1011 s-1 (4Br-Au) > 1.15 × 1011 s-1 (4I-Au), and importantly, the reverse intersystem crossing (rISC) rate constants are determined as 1.68 × 107 s-1 (4I-Au) > 2.40 × 103 s-1 (4Br-Au) ≫ 8.09 × 10-8 s-1 (4CF3-Au). The exceptionally low rISC rate constant of 4CF3-Au is attributed to its more steric and deformed structure bearing a larger energy gap between the S1 and T1 states.

Clean Ar-Me conversion to Ar-aldehyde with the aid of carefully designed metallocorrole photocatalysts.

Toluene, p-xylene and mesitylene were cleanly converted to their corresponding monoaldehydes via mild photooxygenation utilizing transition metal and main group ß-CF3-substituted corroles. Aldehyde yield increased as more electron-donating CH3 groups are present on the substrate. 4-P was most efficient (TON ∼ 1072, mesitylene) via the singlet oxygen vis the superoxide mechanism.

Aqueous Red-Emissive Probe for the Selective Fluorescent Detection of Cysteine by Deprotection/Cyclization Cascade Resulting in Large Stokes' Shift.

Cysteine plays a crucial role in cellular functions and in human pathologies. However, the development of cysteine probes with extremely accurate detection is still a key challenge for the field. Herein, we have fully characterized and developed a novel selective fluorescent probe: red emission, aqueous detection and large Stokes' shift for cysteine (Reals-C). Key in the probe synthesis is a Michael addition onto an acroylate group and subsequent intramolecular cyclization. The probe exhibits analyte detection via an intricate role set up by the leaving groups so to discriminate and form the red-emissive analyte sensing platform (λex =471 nm, λem =637 nm) through a chemical cascade pathway. Furthermore, the sensing ability of the probe was demonstrated by both in vitro and in vivo assays. This probe enables for successfully endogenous cysteine sensing in HaCaT human keratinocytes through comparison with a commercial thiol-sensitive probe; Reals-C shows excellent in vivo cysteine detection in a drug-induced animal liver injury model.

Associations of mental health and sleep duration with menstrual cycle irregularity: a population-based study.

This study aimed to examine whether the characteristics of mental health and sleep duration, alone or in combination, are associated with menstrual cycle irregularity. This population-based, cross-sectional study analyzed the data from 4445 women aged 19-49 years, who participated in the Korea National Health and Nutrition Examination Survey 2010-2012. A structured questionnaire was used to assess mental health characteristics, sleep duration, and menstrual cycle irregularity. A multivariable logistic regression analysis was performed. High stress, depressive mood, and suicidal ideation were associated with increased risk of menstrual cycle irregularity after adjusting for confounding variables (odds ratio [95% confidence interval] = 1.33 [1.07-1.65], 1.56 [1.17-2.07], and 1.37 [1.01-1.87], respectively). Short sleep duration (≤ 5 h a day) was significantly associated with higher odds of severe menstrual cycle irregularity with menstrual interval of greater than 3 months (2.67 [1.35-5.27]). Participants with sleep duration of ≤ 5 h a day with psychological stress, depressive mood, or suicidal ideation had higher odds of menstrual cycle irregularity (1.96 [1.26-3.05], 2.86 [1.50-5.44], and 2.25 [1.18-4.29]). This study suggests positive associations of mental health problems and short sleep duration with menstrual cycle irregularity among Korean female adults. Therefore, strategies to deal with psychological stress, depressive mood, and sleep duration are needed for improving the reproductive health of women suffering from menstrual disturbances.

Evaluation of coblation lingual tonsil removal technique for obstructive sleep apnea in Asians: preliminary results of surgical morbidity and prognosticators.

Retroglossal obstruction is one of the etiologies causing obstructive sleep apnea (OSA) and can be addressed by removing some tissues of the tongue base. However, because of its deep-seated location, its surgical removal is still challenging. Although coblation technique has been introduced, its efficacy and morbidity need further evaluation, particularly in Asians. This study aimed to assess its safety and effectiveness and to identify outcome prognosticators. Forty-seven OSA patients who underwent coblation lingual tonsil removal were included. Retroglossal obstruction was confirmed by drug-induced sleep videofluoroscopy. Attended full-night polysomnography was performed twice; before and 6 months after surgery in 27 patients. The tongue base was fully exposed with three deep-seated traction sutures, visualized with a 30° or 70° endoscope, and ablated using a coblator. Surgical success was defined with postoperative apnea hypopnea index (AHI) <20 and reduction >50 %. Postoperative morbidities were evaluated. Demographic and polysomnographic parameters between success and failure groups were compared. None of the patients had immediate postoperative hemorrhage. Postoperatively, one patient had delayed hemorrhage and one patient severe respiratory difficulty. Taste loss, tongue dysmotility, dental injury or severe oropharyngeal stricture were absent. A mean AHI decreased from 37.7 ± 18.6 to 18.7 ± 14.8/h (P < 0.001). The success rate was 55.6 %. Their mean minimal oxygen saturation was significantly lower (P = 0.004) in the failure group. Coblation lingual tonsil removal technique showed minimal morbidity and favorable outcome in Koreans. The surgical outcome might be associated with the severity of single respiratory events.

Digital Templating of Hip Arthroplasty Using Microsoft PowerPoint: A Pilot Study with Technical Details.

Templating is essential in hip arthroplasty preparation, facilitating implant size prediction and surgical rehearsal. It ensures the selection of suitable implants according to patient anatomy and disease, aiming to minimize post-operative complications. Various templating methods exist, including traditional acetate templating on both analog and digital images, alongside digital templating on digital images, which is categorized into 2D and 3D approaches. Despite the popularity of acetate templating on digital images, challenges such as the requirement for physical templates and result preservation persist. To address these limitations, digital templating with software like OrthoSize and Orthoview has been suggested, although not universally accessible. This technical note advocates for Microsoft PowerPoint as an effective alternative for 2D digital templating, highlighting its user-friendly features for image manipulation without needing specialized software. The described method involves scanning acetate templates, adjusting the images in PowerPoint 365 for size, position, and calibration on patient radiographs, and demonstrating reliability through preliminary assessments, with intraclass correlation coefficient (ICC) values indicating a high level of agreement for cup and stem size (ICC = 0.860, 0.841, respectively) but moderate for neck length (ICC = 0.592). We have introduced a method for performing 2D digital templating in the clinical field without the need for specialized software dedicated to digital templating. We believe this method significantly improves the accessibility to 2D digital templating, which was previously limited by the need for digital templating software. Additionally, it enables surgeons to easily establish arthroplasty plans and share them, overcoming the limitations of acetate templates.

Post-tonsillectomy hemorrhage in children: a single surgeon's experience with coblation compared to diathermy.

The aim of this study was to compare coblation and diathermy techniques with respect to secondary post-tonsillectomy hemorrhage (PTH). A total of 1,397 children underwent tonsillectomies with or without adenoidectomy by a single surgeon in a single center from June 2005 through December 2011. A diathermy tonsillectomy was performed on 315 patients for the first 2 years, while a coblation tonsillectomy was performed on 1,082 for the next 5 years. All patients were followed-up within 28 days of surgery by the same surgeon. The characteristics of primary and secondary PTH were analyzed with a retrospective chart review. Primary PTH did not occur in both surgical technique groups. Secondary PTH occurred in 9 patients (2.9 %) in the diathermy group and in 30 patients (2.8 %) in the coblation group. The secondary PTH rates were 1.2, 2.5, 3.8, 3.1 and 4.5 % in the first, second, third, fourth and fifth years after employment of the coblation tonsillectomy, respectively (P = 0.243). Sex, age, tonsil size and severity of tonsillar embedding were not significant factors for PTH. The coblation technique was associated more with late secondary PTH than diathermy technique (odds ratio 9.14, P = 0.049). Analysis of the time of onset of PTH showed that secondary PTH occurred most commonly between 6 p.m. and 6 a.m. In summary, coblation technique has similar secondary PTH rate with diathermy technique although it has increased late secondary PTH rate in children. Coblation technique can be a good alternative to the diathermy technique.

Phosphinate-benzoindocyanin fluorescent probe for endogenous mitochondrial peroxynitrite detection in living cells and gallbladder access in inflammatory zebrafish animal models.

Potent oxidants such as peroxynitrite (ONOO-) play important roles in the regulation of different physiopathological processes; their overproduction is thought to potentially cause several diseases in living organisms. Hence, the precise and selective monitoring of ONOO- is imperative for elucidating its interplay and roles in pathological and physiological processes. Herein, we present a novel diphenyl phosphinate-masked benzoindocyanin "turn-on" fluorogenic probe to help detect mitochondrial ONOO- in living cells and zebrafish models. A pale yellow color solution of BICBzDP turns rose-red upon the addition of ONOO-, selectively, contrary to that of other competitive bioactive molecules. BICBzDP displays an ultra-sensitivity detection limit (47.8 nM) with outstanding selectivity and sensitivity towards mitochondrial ONOO- and possesses a notable 68-fold fluorescence enhancement involving a large redshift of 91 nm. Importantly, further biological experimental investigations with BICBzDP indicate specific sensitivity and reliability of the probe to track the ONOO- level, not only in live cells, but also demonstrates dynamic fluctuations in the inflammatory zebrafish animal models. Thus, BICBzDP could be employed as a future potential biological tool for exploiting the role of ONOO- in a variety of different physiological systems.

Minding our P-block and Q-bands: paving inroads into main group corrole research to help instil broader potential.

Main group chemistry is often considered less "dynamic" than transition metal (TM) chemistry because of predictable VSEPR-based central atom geometries, relatively slower redox switching and lack of electronic d-d transitions. However, we delineate what has been made possible with main group chemistry to give it its proper due and up-to-date treatment. The huge untapped potential regarding photophysical properties and functioning hereby spurred us to review a range of corrole reports addressing primarily photophysical trends, synthetic aspects, and important guidelines regarding substitution and inorganic principles. We also look at Ag and Au systems and also consider substitutions such as CF3, halogens, additives and also counterions. Throughout, as well as at the end of this review, we suggest various future directions; further future industrial catalytic and health science research is encouraged.

A Transformative Gold Patterning through Selective Laser Refining of Cyanide.

Gold is an essential noble metal for electronics, and its application area is increasing continuously through the introduction of gold nanoparticle ink that enables rapid prototyping and direct writing of gold electrodes on versatile substrates at a low temperature. However, the synthesis of gold nanoparticles has certain limitations involving high cost, long synthesis time, large waste of material, and frequent use of chemicals. In this study, we suggest simultaneous laser refining of gold cyanide and selective fabrication of gold electrodes directly on the substrate without a separate synthesis step. Gold cyanide is commonly the first product of gold from the primitive ore, and the gold can be extracted directly from the rapid photothermal decomposition of gold cyanide by the laser. It was confirmed that laser-induced thermocapillary force plays an important role in creating the continuous gold patterns by aligning the refined gold. The resultant gold electrodes exhibited a low resistivity analogous to the conventional direct writing method using nanoparticles, and the facile repair process of a damaged electrode was demonstrated as the proof-of-concept. The proposed transformative approach for gold patterning, distinguished from the previous top-down and bottom-up approaches, has the potential to replace the well-known techniques and provide a new branch of electrode manufacturing scheme.

Didactic approach recounting advances and limitations in novel glutathione and cysteine detection (reduced GSH probe) with mixed coumarin, aldehyde, and phenyl-selenium chemistry.

We describe the pertinent research steps and analysis, many of which are chemical, to achieve a novel molecular probe for glutathione (GSH) which has been published and patented based on two recent articles: "Exceptional time response, stability and selectivity in doubly-activated phenyl selenium-based glutathione-selective platform" and "Enhanced Doubly Activated Dual Emission Fluorescent Probes for Selective Imaging of Glutathione or Cysteine in Living Systems" (Kim et al., 2015; Mulay et al., 2018). The papers involve coumarin probes. Reaction/detection unfolds with aminothiol attack at an electrophilic ring carbon position. An adjacent -CHO group is heavily involved in resonance aspects of the C-Se position, as well as the binding of the pendant N-group; the coumarin lactone carbonyl also allows for resonance to be achieved (vide infra). The leaving group, -SePh, while precedented in some systems, depends on electronic tuning (Fig. 1). For 1, the response times with GSH was ~100ms; a 100-fold fluorescence increase is observed (Compound 1). The probe also reacts with cysteine (Cys) and homocysteine (Hcy), albeit differently. For glutathione probing, the greater wavelength maxima (1: 550nm, DACP-1: 555nm, DACP-2: 590nm) enabled eventual cell studies (confocal microscopy) and animal studies. The limits of detection (LOD, 1: 270nM DACP-1: 10.1nM DACP-2: 17.0nM), as measured using the 3σ/k method. We provide a didactic presentation from probe conception to probe in vivo testing, etc., with additional considerations presented; a variety of factors/issues (2.1-2.28) help maintain a realistic sequence, a flow from wider to narrower, of the factors that go into developing medical, biological and neurodegenerative disease-related probes, meant to help other researchers follow our intention, gain perspective, and overcome current limitations.

Associations between Living Alone and Smoking and Alcohol Consumption in Korean Adults.

BACKGROUND: Recently, single-person households have increased in Korea and this trend may have potential public health implications and affect various health behaviors. This study investigated the associations between living alone and health behaviors such as smoking and alcohol consumption among Korean adults. METHODS: We used data from the 6th Korea National Health and Nutrition Examination Survey between 2013 and 2015 and a total of 17,088 adults were included. We performed a multivariable logistic regression analysis and calculated odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Single-person households accounted for about 10% of the total participants. The proportions of currently smoking and heavy alcohol consumption were higher among individuals living alone than those living together among younger women and middle-aged and elderly men and women. In the multivariable logistic regression analysis, living alone was associated with increased odds of currently smoking compared to living together among middle-aged men and women (OR, 7.37; 95% CI, 2.33-23.32 in men and OR, 2.36; 95% CI, 1.04-5.36 in women) after adjusting for confounding variables. CONCLUSION: From this nationwide, population-based study, we found that living alone is associated with increased odds of currently smoking, especially in middle-aged people. Public health concerns may be warranted for middle-aged single-person households to reduce health risks related to smoking.

Diels-Alder and Stille Coupling Approach for the Short Protecting-Group-Free Synthesis of Mycophenolic Acid, Its Phenylsulfenyl and Phenylselenyl Analogues, and Reactive Oxygen Species (ROS) Probing Capacity in Water.

A short, protecting-group-free synthesis is achieved. The synthesis is step-efficient and general. A Diels-Alder and Stille cross-coupling approach includes key transformations, allowing for a competitive synthesis which involves a rare halophenol Stille cross-coupling study. The phenylselenyl and phenylsulfenyl analogues were prepared as novel compounds in good overall yield. The applicability of one of the intermediates as a potential probe for reactive oxygen species (ROS) in water is investigated.

Interrater reliability of sleep videofluoroscopy for airway obstruction in obstructive sleep apnea.

OBJECTIVES/HYPOTHESIS: Sleep videofluoroscopy (SVF) has been introduced to identify upper airway obstruction. This study was aimed to determine the interrater reliability of SVF in patients with obstructive sleep apnea (OSA). STUDY DESIGN: A retrospective analysis. METHODS: On the basis of apnea-hypopnea index in full-night attended polysomnography, 374 consecutive OSA patients who underwent SVF were enrolled in this study. The SVF was evaluated by three independent reviewers. Interrater reliabilities were assessed by evaluating agreement of the obstructive anatomic structures (soft palate, tongue base, tonsils, and epiglottis) and airway levels (velopharynx, oropharynx, and hypopharynx) between the reviewers. RESULTS: In a comparison between an unblinded and a blinded well-experienced sleep surgeons, the interrater reliability for the presence of obstruction was the highest for the soft palate at the level of the velopharynx (Cohen's kappa value, 0.919) and the lowest for the soft palate at the level of the oropharynx (Cohen's kappa value, 0.757). In a blind comparison between a well-experienced and less-experienced sleep surgeons, the interrater reliability for the presence of obstruction was also the highest for the soft palate at the level of the velopharynx (Cohen's kappa value, 0.938) and the lowest for the palatine tonsils at the level of the oropharynx (Cohen's kappa value, 0.635). CONCLUSION: This study showed that SVF was a diagnostic modality that can be used to evaluate upper airway obstruction without significant interrater disagreements.

Regrowth of the adenoids after coblation adenoidectomy: cephalometric analysis.

OBJECTIVES/HYPOTHESIS: To analyze the prevalence of adenoid regrowth at 1 year after coblation adenoidectomy using cephalometric radiography. STUDY DESIGN: Retrospective analysis. METHODS: One hundred eighty-eight children who underwent adenoidectomy from June 2006 through September 2010 were included. Demographic data, preoperative size of palatine tonsils, presence of allergic rhinitis, concurrent operation of recurrent middle ear effusion, and preoperative and postoperative Korean version of Obstructive Sleep Apnea-18 (KOSA-18) scores were analyzed. The size of the adenoids was measured three times in all the children by lateral cephalometry; preoperatively, at 1 month after adenoidectomy to observe adenoid residual; and at 1 year after surgery to observe adenoid regrowth. RESULTS: The adenoid regrowth at 1 year after adenoidectomy was observed in 25 children (13.3%), and the adenoid residual at 1 month after surgery was observed in 11 children (5.9%) in the cephalometry. Seven of the 11 children with residual disease (63.6%) had adenoid regrowth at 1 year. The regrowth group was significantly younger than no regrowth group, and the preoperative adenoids were larger in regrowth group than in no regrowth group. The symptoms of sleep disordered breathing recurred in two patients and they had revision adenoidectomy. CONCLUSION: The regrowth rate of the adenoids at 1 year was not low. However, most of the patients were asymptomatic. The adenoid residual at 1 month contributed to regrowth at 1 year, and the risk factors of the adenoid regrowth were younger age and larger initial size of the adenoids. LEVEL OF EVIDENCE: 2b.

Mortality of patients with obstructive sleep apnea in Korea.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with diverse health risks, including death. However, the role of OSA as a risk factor for death has never been studied in Asians. This study is aimed at evaluating the influence of OSA on the mortality in Korean sleep clinic population. METHODS: A total of 2,240 patients who underwent in-laboratory full-night polysomnography due to snoring or sleep apnea were included. The patients were categorized based on apnea-hypopnea index (AHI)/hour. Death records were provided from the Statistics Korea. A Cox-proportional hazard regression model and Kaplan-Meier survival curve were used for analysis and demonstration of the all-cause mortality and cardiovascular mortality. RESULTS: The all-cause mortality risk adjusted for age, sex, body mass index, diabetes, hypertension, cardiovascular diseases, and previous history of stroke was significantly associated with the increased severity of OSA. The adjusted hazard ratio (HR) for all-cause mortality in the severe OSA group (AHI ≥ 30) vs. reference group (5 < AHI) was 2.47 (95% confidence interval [CI], 1.09-5.57) and the adjusted HR for cardiovascular mortality was 4.66 (CI 1.03-21.08). After adjusting for whether the patients were treated or untreated, the HR for all-cause and cardiovascular mortality in the severe OSA group vs. reference group were 2.14 (p = 0.079) and 4.19 (p = 0.076), respectively. CONCLUSIONS: The present study showed that the increased mortality was also associated with the increased severity of OSA in Koreans as shown in the studies performed in the Western countries.

Establishment of a rabbit model of obstructive sleep apnea by paralyzing the genioglossus.

IMPORTANCE: This study presents an innovative method for developing a neuromuscular model of obstructive sleep apnea (OSA). OBJECTIVE: To establish a new OSA animal model simulating real upper airway conditions during sleep. DESIGN AND SETTING: In vivo animal study at an academic tertiary referral center. SUBJECTS: A total of 27 New Zealand white male rabbits were used. INTERVENTION: Sleep was induced by intramuscular injection of 0.3 mL/kg of tiletamine hydrochloride plus zolazepam hydrochloride and 0.2 mL/kg of xylazine. Upper airway obstruction was induced by injecting botulinum toxin type A (2.5 U in 8 rabbits, 5.0 U in 10 rabbits, and 7.5 U in 1 rabbit) into the genioglossus. Eight rabbits were injected with normal saline as a control. MAIN OUTCOMES AND MEASURES: Drug-induced sleep was evaluated using a portable polysomnography device for electroencephalography, electrooculography, chin electromyography, nasal airflow, breathing efforts, and pulse oxymetry. Respiratory events (apneas or hypopneas) during sleep were evaluated using a sleep-screening tool. RESULTS: All the rabbits showed no apneas or hypopneas before injection of botulinum toxin type A. In the control rabbits injected with normal saline, apneas or hypopneas were not found. The respiratory events were observed in 5 of 8 rabbits injected with 2.5 U of botulinum toxin type A, whereas they were observed in 7 of 10 rabbits injected with 5.0 U of botulinum toxin type A. The median (interquartile range) apnea hypopnea index was 9.6 (5.3-14.8) per hour and 45.6 (21.5-70.5) per hour in the rabbits injected with 2.5 U and 5.0 U of botulinum toxin type A, respectively (P = .03). CONCLUSIONS AND RELEVANCE: An animal model of OSA could be developed by paralyzing the genioglossus in rabbits. This model may contribute to identifying the pathogenesis of upper airway obstruction in OSA and to developing new diagnostic or treatment devices targeting specific obstruction sites.