Everyday Violence: Immigration Enforcement, COVID-19, and Depression among Undocumented Young Adults in California.

Background: The immigration enforcement system has significant effects on the health of immigrants, their families, and society. Exposure to the immigration enforcement system is linked to adverse mental health outcomes, which may have been exacerbated by sustained immigration enforcement activities during the COVID-19 pandemic. Objectives: This study was conducted to investigate the association between exposure to immigration enforcement and the mental health of undocumented young adults in California during the COVID-19 pandemic. Methods: Data are from the COVID-19 BRAVE (Building Community Raising All Immigrant Voices for Health Equity) Study, a community-engaged cross-sectional survey of the impacts of the COVID-19 pandemic on undocumented immigrants in California. A total of 366 undocumented immigrants between 18 and 39 years of age completed the online survey, which was conducted between September 2020 and February 2021. Multivariable logistic regression models were fit to examine the association between immigration enforcement exposure and depression. Results: Almost all participants (91.4%) disclosed exposure to the immigration enforcement system, with most reporting an average of 3.52 (SD=2.06) experiences. Multivariate analyses revealed that an increase in the immigration enforcement exposure score was significantly associated with higher odds of depression (adjusted odds ratio [aOR]=1.24; 95% confidence interval [CI]: 1.10, 1.40), and women were 92% more likely to report depression than were men (aOR=1.92; 95% CI: 1.12, 3.31). Those who reported deportation fears were significantly more likely to be depressed (aOR=1.24; 95% CI: 1.10, 1.40). Conclusions: Researchers should consider the mental health implications of a punitive immigration enforcement system, and policymakers should examine the impacts of immigration policies on local communities.

AI-Generated Draft Replies Integrated Into Health Records and Physicians' Electronic Communication.

Importance: Timely tests are warranted to assess the association between generative artificial intelligence (GenAI) use and physicians' work efforts. Objective: To investigate the association between GenAI-drafted replies for patient messages and physician time spent on answering messages and the length of replies. Design, Setting, and Participants: Randomized waiting list quality improvement (QI) study from June to August 2023 in an academic health system. Primary care physicians were randomized to an immediate activation group and a delayed activation group. Data were analyzed from August to November 2023. Exposure: Access to GenAI-drafted replies for patient messages. Main Outcomes and Measures: Time spent (1) reading messages, (2) replying to messages, (3) length of replies, and (4) physician likelihood to recommend GenAI drafts. The a priori hypothesis was that GenAI drafts would be associated with less physician time spent reading and replying to messages. A mixed-effects model was used. Results: Fifty-two physicians participated in this QI study, with 25 randomized to the immediate activation group and 27 randomized to the delayed activation group. A contemporary control group included 70 physicians. There were 18 female participants (72.0%) in the immediate group and 17 female participants (63.0%) in the delayed group; the median age range was 35-44 years in the immediate group and 45-54 years in the delayed group. The median (IQR) time spent reading messages in the immediate group was 26 (11-69) seconds at baseline, 31 (15-70) seconds 3 weeks after entry to the intervention, and 31 (14-70) seconds 6 weeks after entry. The delayed group's median (IQR) read time was 25 (10-67) seconds at baseline, 29 (11-77) seconds during the 3-week waiting period, and 32 (15-72) seconds 3 weeks after entry to the intervention. The contemporary control group's median (IQR) read times were 21 (9-54), 22 (9-63), and 23 (9-60) seconds in corresponding periods. The estimated association of GenAI was a 21.8% increase in read time (95% CI, 5.2% to 41.0%; P = .008), a -5.9% change in reply time (95% CI, -16.6% to 6.2%; P = .33), and a 17.9% increase in reply length (95% CI, 10.1% to 26.2%; P < .001). Participants recognized GenAI's value and suggested areas for improvement. Conclusions and Relevance: In this QI study, GenAI-drafted replies were associated with significantly increased read time, no change in reply time, significantly increased reply length, and some perceived benefits. Rigorous empirical tests are necessary to further examine GenAI's performance. Future studies should examine patient experience and compare multiple GenAIs, including those with medical training.

How low can we go? A randomized controlled trial of low-quantity initial opioid prescriptions for shoulder surgery.

BACKGROUND: Orthopedic surgeons are the third most frequent prescribers of opioid medications. Given the current opioid addiction crisis, it is critical to limit opioid prescriptions to the lowest effective dose. In this study, we investigated how the initial opioid prescription after shoulder surgery affects maximum possible opioid consumption. We hypothesized that fewer pills in the initial opioid prescription would lead to less opioid consumption, a lower refill request rate, and fewer post-surgery office contacts for pain. METHODS: In this single-center, prospective, randomized controlled clinical trial, 74 adults who underwent shoulder arthroplasty, rotator cuff repair, or other arthroscopic shoulder procedures were enrolled from December 2020 to July 2022. Follow-up was completed by February 2023. Participants were randomly assigned to receive postoperative prescriptions of seven 5-mg oxycodone pills (n = 20), 15 pills (n = 29), or 23 pills (n = 25). The primary outcome was maximum possible opioid consumption within 2 weeks after surgery, calculated by assuming consumption of all pills in the initial prescription, as well as any refills. Secondary outcomes were the opioid prescription refill request rates, post-surgery pain-related telephone calls or messages to the provider's office ("office contacts") within 2 weeks after surgery, and American Shoulder and Elbow Surgeons pain scores 2 weeks after surgery. Baseline characteristics did not differ among groups except for mean age, which was younger in the 7-pill group (P = .047). RESULTS: Maximum possible opioid consumption increased with the number of pills initially prescribed, with means of 78 morphine milligram equivalents (MME) for the 7-pill group, 118 MME for the 15-pill group, and 199 MME for the 23-pill group (P < .001). None of the secondary outcome measures differed among groups. Refill request rates were 20% for the 7-pill group, 3.4% for the 15-pill group, and 12% for the 23-pill group (P = .20). The proportions of patients with at least 1 office contact were 35% in the 7-pill group, 45% in the 15-pill group, and 28% in the 23-pill group (P = .43). Mean American Shoulder and Elbow Surgeons pain scores were 49 in the 7-pill group, 44 in the 15-pill group, and 40 in the 23-pill group (P = .20). CONCLUSION: After shoulder surgery, an initial prescription of fewer opioid pills was associated with less maximum possible opioid consumption without an increase in the percentage of patients requesting opioid refills or contacting the provider's office for pain-related concerns. An initial postoperative prescription of fewer 5-mg oxycodone pills may be equally or more effective compared with larger quantities for most patients.

Mediating bio-fate of polymeric cholecalciferol nanoparticles through rational size control.

Whilst 10-200 nm polymeric nanoparticles hold enormous medical potential, successful clinical translation remains scarce. There is an inadequate understanding of how these nanoparticles could be fabricated with consistent particle architecture in this size range, as well as their corresponding biological performance. We seek to fill this important knowledge gap by employing Design of Experiment (DoE) to examine critical formulation and processing parameters of cholecalciferol (VitD3)-loaded nanoparticles by flash nanoprecipitation (FNP). Based on the regression analysis of the critical processing parameters, six VitD3 nanoparticle formulations with z-average particle sizes between 40 and 150 nm were successfully developed, possessing essentially the same particle shape and zeta potential. To evaluate the effect of particle size on the in vivo performance, not only VitD3 but also its active metabolites (25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3) were assayed in the biodistribution study. Results indicated that VitD3 nanoparticles with sizes ≤110 nm would achieve higher plasma retention. VitD3 nanoparticles with sizes of 40 nm and 150 nm were superior for lung deposition, while particle size had no major role in the brain uptake of VitD3 nanoparticles. The present study demonstrates the value of DoE for generating size-tunable nanoparticles with controlled particle properties in FNP and offers important insights into the particle size effect of nanoparticles <200 nm on their therapeutic potential.

Iridium(iii) polypyridine complexes with a disulfide linker as biological sensors and cytotoxic agents.

The synthesis, characterization, and photophysical properties of two novel cyclometalated iridium(iii) PEG complexes with a disulfide linkage [Ir(N^C)2(bpy-SS-PEG)](PF6) (bpy-SS-PEG = 4-(N-(2-((N-(2-(ω-methoxypoly(1-oxapropyl))ethyl)amino)cabonylethoxy)dithiolethoxy)carbonylamino)methyl-4'-methyl-2,2'-bipyridine; HN^C = methyl 2-phenyl-4-quinolinecarboxylate (pqe) (1a), 2-phenylquinoline (pq) (2a)), their PEG-free counterparts [Ir(N^C)2(bpy-SS-py)](PF6) (HN^C = pqe (1b), pq (2b)), their disulfide-free counterparts [Ir(N^C)2(bpy-CONH-PEG)](PF6) (bpy-CONH-PEG = 4-N-(2-(ω-methoxypoly-(1-oxapropyl))ethyl)aminocarbonyl)-4'-methyl-2,2'-bipyridine; (HN^C = pqe (1c), pq (2c)), and a bimetallic iridium(iii)-rhenium(i) complex [Ir(pqe)2(bpy-SS-py)Re(Me4-phen)(CO)3](PF6)(CF3SO3) (Me4-phen = 3,4,7,8-tetramethyl-1,10-phenathroline) (3) are reported. Upon irradiation, the complexes displayed intense green to red emission under ambient conditions. Complex 3 containing two communicating luminophores exhibited large spectral overlap and was found to have a theoretical FRET efficiency of 0.79. In the presence of GSH, the bimetallic disulfide-containing complex 3 would be cleaved which was followed by a 8-fold increase in emission intensity of the rhenium(i) moiety. The reaction was found to be specific toward Cys, GSH, and H2S compared to other biothiols. Cell-based assays on complex 1a demonstrated that the addition of GSH to induce cleavage of the disulfide linkage would provide a more cytotoxic agent due to the release of the appended PEG pendant. Cellular localization studies by laser-scanning confocal microscopy in live HeLa cells indicated that complexes 1a-c exhibited punctate staining in the mitochondria.

Correction: Iridium(iii) polypyridine complexes with a disulfide linker as biological sensors and cytotoxic agents.

Correction for 'Iridium(iii) polypyridine complexes with a disulfide linker as biological sensors and cytotoxic agents' by Steve Po-Yam Li et al., Dalton Trans., 2019, DOI: 10.1039/c9dt00793h.

Installing an additional emission quenching pathway in the design of iridium(III)-based phosphorogenic biomaterials for bioorthogonal labelling and imaging.

We report the synthesis, characterization, photophysical and electrochemical behaviour and biological labelling applications of new phosphorogenic bioorthogonal probes derived from iridium(III) polypyridine complexes containing a 1,2,4,5-tetrazine moiety. In contrast to common luminescent cyclometallated iridium(III) polypyridine complexes, these tetrazine complexes are almost non-emissive due to effective Förster resonance energy transfer (FRET) and/or photoinduced electron transfer (PET) from the excited iridium(III) polypyridine unit to the appended tetrazine moiety. However, they exhibited significant emission enhancement upon reacting with (1R,8S,9s)-bicyclo[6.1.0]non-4-yn-9-ylmethanol (BCN-OH) (ca. 19.5-121.9 fold) and BCN-modified bovine serum albumin (BCN-BSA) (ca. 140.8-1133.7 fold) as a result of the conversion of the tetrazine unit to a non-quenching pyridazine derivative. The complexes were applied to image azide-modified glycans in live cells using a homobifunctional crosslinker, 1,13-bis((1R,8S,9s)-bicyclo[6.1.0]non-4-yn-9-ylmethyloxycarbonylamino)-4,7,10-trioxatridecane (bis-BCN).

Synthesis and Electrochemical, Photophysical, and Self-Assembly Studies on Water-Soluble pH-Responsive Alkynylplatinum(II) Terpyridine Complexes.

A series of water-soluble pH-responsive alkynylplatinum(II) terpyridine complexes have been synthesized and characterized. The electronic absorption, emission, and electrochemical properties of the complexes have been studied. The self-assembly processes of representative complexes in aqueous media, presumably through Pt···Pt and/or π-π interactions, have been investigated by concentration- and temperature-dependent UV-vis absorption measurements and dynamic light scattering experiments. Interestingly, some of the complexes have been found to undergo induced self-assembly and disassembly in aqueous media through modulation of the pH value of the solutions, resulting in remarkable UV-vis absorption and emission spectral changes. The emission spectral changes have been rationalized by the change in the hydrophilicity of the complexes, electrostatic repulsion among the complex molecules, and/or the extent of photoinduced electron transfer (PET) quenching upon protonation/deprotonation of the pH-responsive groups on the complexes. By simple modifications of the chemical structures of the complexes, induced self-assembly/disassembly of the complexes can occur at different and/or multiple pH regions, thus allowing the probing of changes at the desired pH region by triplet metal-metal-to-ligand charge-transfer emission of the complexes in the near-infrared (NIR) region. Fixed-cell imaging experiments have further demonstrated the potential of this class of complexes as pH-responsive NIR luminescent probes in vitro, while the NIR emissions of the complexes from live cells have been found to show good differentiation of acidic organelles such as lysosomes from other cellular compartments.

A novel ultra performance liquid chromatography-tandem mass spectrometry method for the determination of sucrose octasulfate in dog plasma.

A novel, specific and sensitive bioanalytical method has been developed for the determination of sucrose octasulfate (SOS) in dog plasma and urine using ion-pair reversed-phase ultraperformance liquid chromatography coupled with electrospray triple quadruple mass spectrometry (IPRP-UPLC ESI MS/MS). (13)C-labeled sucrose octasulfate-(13)C12 sodium salt is used as the internal standard. 200 µL of plasma or serum sample is extracted using weak anion exchange solid phase cartridge. In this method, a polar amide column is employed for the liquid chromatograph (LC) separation while the diethylamine and formic acid buffer is used as the ion-pairing reagent. The low limitation of quantitation of sucrose octasulfate is 0.20 ng on the column with a signal to noise ratio larger than 50. Parameters such as linearity, accuracy and precision have been validated in full compliance with the FDA guidelines for the bioanalytical method development and validation. A linear regression model fit the calibration curve very well with R>0.99. The bias and coefficient of variation of all levels of QCs are within the range of 15%. The selectivity, matrix effect and stabilities of analytes in solution and matrix have also been evaluated and the results met the acceptance criteria according to the guidelines. Based on these results, the method has qualified to analyze sucrose octasulfate in dog plasma for clinic research. This method has been applied to 1000 preclinical samples.

The expanded amelogenin polyproline region preferentially binds to apatite versus carbonate and promotes apatite crystal elongation.

The transition from invertebrate calcium carbonate-based calcite and aragonite exo- and endoskeletons to the calcium phosphate-based vertebrate backbones and jaws composed of microscopic hydroxyapatite crystals is one of the great revolutions in the evolution of terrestrial organisms. To identify potential factors that might have played a role in such a transition, three key domains of the vertebrate tooth enamel protein amelogenin were probed for calcium mineral/protein interactions and their ability to promote calcium phosphate and calcium carbonate crystal growth. Under calcium phosphate crystal growth conditions, only the carboxy-terminus augmented polyproline repeat peptide, but not the N-terminal peptide nor the polyproline repeat peptide alone, promoted the formation of thin and parallel crystallites resembling those of bone and initial enamel. In contrast, under calcium carbonate crystal growth conditions, all three amelogenin-derived polypeptides caused calcium carbonate to form fused crystalline conglomerates. When examined for long-term crystal growth, polyproline repeat peptides of increasing length promoted the growth of shorter calcium carbonate crystals with broader basis, contrary to the positive correlation between polyproline repeat element length and apatite mineralization published earlier. To determine whether the positive correlation between polyproline repeat element length and apatite crystal growth versus the inverse correlation between polyproline repeat length and calcium carbonate crystal growth were related to the binding affinity of the polyproline domain to either apatite or carbonate, a parallel series of calcium carbonate and calcium phosphate/apatite protein binding studies was conducted. These studies demonstrated a remarkable binding affinity between the augmented amelogenin polyproline repeat region and calcium phosphates, and almost no binding to calcium carbonates. In contrast, the amelogenin N-terminus bound to both carbonate and apatite, but preferentially to calcium carbonate. Together, these studies highlight the specific binding affinity of the augmented amelogenin polyproline repeat region to calcium phosphates versus calcium carbonate, and its unique role in the growth of thin apatite crystals as they occur in vertebrate biominerals. Our data suggest that the rise of apatite-based biominerals in vertebrates might have been facilitated by a rapid evolution of specialized polyproline repeat proteins flanked by a charged domain, resulting in apatite crystals with reduced width, increased length, and tailored biomechanical properties.

Lyophilized platelet-rich fibrin (PRF) promotes craniofacial bone regeneration through Runx2.

Freeze-drying is an effective means to control scaffold pore size and preserve its composition. The purpose of the present study was to determine the applicability of lyophilized Platelet-rich fibrin (LPRF) as a scaffold for craniofacial tissue regeneration and to compare its biological effects with commonly used fresh Platelet-rich fibrin (PRF). LPRF caused a 4.8-fold±0.4-fold elevation in Runt-related transcription factor 2 (Runx2) expression in alveolar bone cells, compared to a 3.6-fold±0.2-fold increase when using fresh PRF, and a more than 10-fold rise of alkaline phosphatase levels and mineralization markers. LPRF-induced Runx2 expression only occurred in alveolar bone and not in periodontal or dental follicle cells. LPRF also caused a 1.6-fold increase in osteoblast proliferation (p<0.001) when compared to fresh PRF. When applied in a rat craniofacial defect model for six weeks, LPRF resulted in 97% bony coverage of the defect, compared to 84% for fresh PRF, 64% for fibrin, and 16% without scaffold. Moreover, LPRF thickened the trabecular diameter by 25% when compared to fresh PRF and fibrin, and only LPRF and fresh PRF resulted in the formation of interconnected trabeculae across the defect. Together, these studies support the application of lyophilized PRF as a biomimetic scaffold for craniofacial bone regeneration and mineralized tissue engineering.

Mitochondria-targeting cyclometalated iridium(III)-PEG complexes with tunable photodynamic activity.

We present a new class of phosphorescent cyclometalated iridium(III) polypyridine poly(ethylene glycol) (PEG) complexes [Ir(N(^)C)2(bpy-CONH-PEG)](PF6) (bpy-CONH-PEG = 4-(N-(2-(ω-methoxypoly-(1-oxapropyl))ethyl)aminocarbonyl)-4'-methyl-2,2'-bipyridine, number average molecular weight (Mn) = 5272.23, weight average molecular weight (Mw) = 5317.38, polydispersity index (PDI) = 1.009; HN(^)C = 2-phenylpyridine, Hppy (1a), 2-((1,1'-biphenyl)-4-yl)pyridine, Hpppy (2a), 2-phenylquinoline, Hpq (3a), 2-phenylbenzothiazole, Hbt (4a), 2-(1-naphthyl)benzothiazole, Hbsn (5a)). The photophysical, photochemical, and biological properties of these complexes have been compared with those of their PEG-free counterparts [Ir(N(^)C)2(bpy-CONH-Et)](PF6) (bpy-CONH-Et = 4-(N-ethylaminocarbonyl)-4'-methyl-2,2'-bipyridine; HN(^)C = Hppy (1b), Hpppy (2b), Hpq (3b), Hbt (4b), Hbsn (5b)). Upon irradiation, all the complexes exhibited intense and long-lived green to orange-red emission under ambient conditions. The emission was phosphorescence in nature and can be quenched by O2 with the generation of singlet oxygen ((1)O2). The quantum yields for (1)O2 production of the complexes in aerated DMSO (0.24-0.83) were found to be dependent on the excited-state lifetimes of the complexes, which can be altered using different cyclometalating ligands (N(^)C). Cell-based assays indicated that the PEG complexes were noncytotoxic in the dark (IC50 > 300 µM); however, most of them became significantly cytotoxic upon irradiation (IC50 = 3.4 - 23.2 µM). Laser-scanning confocal microscopy images revealed localization of complex 3a in the mitochondrial region of HeLa cells and the induction of rapid necrotic cell death upon light activation. Additionally, the lack of dark toxicity and potential application of the PEG complexes as a visualizing reagent have been demonstrated using zebrafish (Danio rerio) as an animal model.

Cyclometalated iridium(III) polypyridine dibenzocyclooctyne complexes as the first phosphorescent bioorthogonal probes.

We report the synthesis, photophysical behavior, and biological properties of new cyclometalated iridium(iii) polypyridine complexes appended with a dibenzocyclooctyne (DIBO) moiety; these complexes have been utilized as the first phosphorescent bioorthogonal probes for azide-modified biomolecules.

Airborne measurements of atmospheric methane column abundance using a pulsed integrated-path differential absorption lidar.

We report airborne measurements of the column abundance of atmospheric methane made over an altitude range of 3-11 km using a direct detection integrated-path differential-absorption lidar with a pulsed laser emitting at 1651 nm. The laser transmitter was a tunable, seeded optical parametric amplifier pumped by a Nd:YAG laser, and the receiver used a photomultiplier detector and photon-counting electronics. The results follow the expected changes with aircraft altitude, and the measured line shapes and optical depths show good agreement with theoretical calculations.

Emissive behavior, cytotoxic activity, cellular uptake, and PEGylation properties of new luminescent rhenium(I) polypyridine poly(ethylene glycol) complexes.

We report here a new class of biological reagents derived from luminescent rhenium(I) polypyridine complexes modified with a poly(ethylene glycol) (PEG) pendant. The PEG-amine complexes [Re(N(^)N)(CO)(3)(py-PEG-NH(2))](PF(6)) (py-PEG-NH(2) = 3-amino-5-(N-(2-(ω-methoxypoly(1-oxapropyl))ethyl)aminocarbonyl)pyridine, MW(PEG) = 5000 Da, PDI(PEG) < 1.08; N(^)N = 1,10-phenanthroline (phen) (1-PEG-NH(2)), 3,4,7,8-tetramethyl-1,10-phenanthroline (Me(4)-phen) (2-PEG-NH(2)), 4,7-diphenyl-1,10-phenanthroline (Ph(2)-phen) (3-PEG-NH(2))) and [Re(bpy-PEG)(CO)(3)(py-NH(2))](PF(6)) (bpy-PEG = 4-(N-(2-(ω-methoxypoly(1-oxapropyl))ethyl)aminocarbonyl)-4'-methyl-2,2'-bipyridine; py-NH(2) = 3-aminopyridine) (4-PEG-NH(2)) have been synthesized and characterized. The photophysical properties, lipophilicity, water solubility, cytotoxic activity, and cellular uptake properties of these complexes have been compared to those of their PEG-free counterparts [Re(N(^)N)(CO)(3)(py-Et-NH(2))](PF(6)) (py-Et-NH(2) = 3-amino-5-(N-(ethyl)aminocarbonyl)pyridine; N(^)N = phen (1-Et-NH(2)), Me(4)-phen (2-Et-NH(2)), Ph(2)-phen (3-Et-NH(2))) and [Re(bpy-Et)(CO)(3)(py-NH(2))](PF(6)) (bpy-Et = 4-(N-(ethyl)aminocarbonyl)-4'-methyl-2,2'-bipyridine) (4-Et-NH(2)). The PEG complexes exhibited significantly higher water solubility and lower cytotoxicity (IC(50) = 6.6 to 1152 µM) than their PEG-free counterparts (IC(50) = 3.6 to 159 µM), indicating that the covalent attachment of a PEG pendant to rhenium(I) polypyridine complexes is an effective way to increase their biocompatibility. The amine complexes 1-PEG-NH(2)-4-PEG-NH(2) have been activated with thiophosgene to yield the isothiocyanate complexes [Re(N(^)N)(CO)(3)(py-PEG-NCS)](PF(6)) (py-PEG-NCS = 3-isothiocyanato-5-(N-(2-(ω-methoxypoly(1-oxapropyl))ethyl)aminocarbonyl)pyridine; N(^)N = phen (1-PEG-NCS), Me(4)-phen (2-PEG-NCS), Ph(2)-phen (3-PEG-NCS)), and [Re(bpy-PEG)(CO)(3)(py-NCS)](PF(6)) (py-NCS = 3-isothiocyanatopyridine) (4-PEG-NCS) as a new class of luminescent PEGylation reagents. To examine their PEGylation properties, these isothiocyanate complexes have been reacted with a model substrate n-butylamine, resulting in the formation of the thiourea complexes [Re(N(^)N)(CO)(3)(py-PEG-Bu)](PF(6)) (py-PEG-Bu = 3-n-butylthioureidyl-5-(N-(2-(ω-methoxypoly(1-oxapropyl))ethyl)aminocarbonyl)pyridine; N(^)N = phen (1-PEG-Bu), Me(4)-phen (2-PEG-Bu), Ph(2)-phen (3-PEG-Bu)), and [Re(bpy-PEG)(CO)(3)(py-Bu)](PF(6)) (py-Bu = 3-n-butylthioureidylpyridine) (4-PEG-Bu). Additionally, bovine serum albumin (BSA) and poly(ethyleneimine) (PEI) have been PEGylated with the isothiocyanate complexes to yield bioconjugates 1-PEG-BSA-4-PEG-BSA and 1-PEG-PEI-4-PEG-PEI, respectively. Upon irradiation, all the PEGylated BSA and PEI conjugates exhibited intense and long-lived emission in aqueous buffer under ambient conditions. The DNA-binding and polyplex-formation properties of conjugate 3-PEG-PEI have been studied and compared with those of unmodified PEI. Furthermore, the in vivo toxicity of complex 3-PEG-NH(2) and its PEG-free counterpart 3-Et-NH(2) has been investigated using zebrafish embryos as an animal model. Embryos treated with the PEG complex at high concentrations revealed delayed hatching, which has been ascribed to hypoxia as a result of adhering of the complex to the external surface of the chorion.

Cyclometalated iridium(III)-polyamine complexes with intense and long-lived multicolor phosphorescence: synthesis, crystal structure, photophysical behavior, cellular uptake, and transfection properties.

A new class of phosphorescent cyclometalated iridium(III)-polyamine complexes [{Ir(N^C)(2)}(n)(bPEI)](PF(6))(n)(bPEI=branched poly(ethyleneimine), average M(w =25 kDa, n=15.6-27.4; HN^C=2-phenylpyridine Hppy (1a), 2-((1,1'-biphenyl)-4-yl)pyridine Hpppy (2a), 2-phenylquinoline Hpq (3a), 2-phenylbenzothiazole Hbt (4a), 2-(1-naphthyl)benzothiazole Hbsn (5a)) and [Ir(N^C)(2)(en)](PF(6)) (en=ethylenediamine; HN^C=Hppy (1b), Hpppy (2b), Hpq (3b), Hbt (4b), Hbsn (5b)) have been synthesized and characterized. The X-ray crystal structure of complex 5b was also determined. All of these complexes showed a reversible iridium(IV/III) oxidation couple at +1.01 to +1.26 V and a quasi-reversible ligand-based reduction couple at -1.54 to -2.08 V (versus SCE). Upon photoexcitation, the complexes displayed intense and long-lived green to orange-red emission in fluid solutions at room temperature and in low-temperature glass. Lipophilicity measurements indicated that bPEI played a dominant role in the polar nature of complexes 1a-5a, thus rendering them very soluble in aqueous solutions. Inductively coupled plasma-mass spectrometry (ICP-MS) and confocal laser scanning microscopy (CLSM) data indicated that an energy-requiring process, such as endocytosis, was involved in the cellular uptake of all of the complexes. In addition, the cytotoxicity of the complexes toward human cervix epithelioid carcinoma (HeLa) and human embryonic kidney 293T (HEK293T) cell-lines has been evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay. The DNA-binding properties of complex 5a have been investigated by gel-retardation assays and the polyplexes that were formed from this complex with plasmid DNA (pDNA) were studied by zeta-potential measurements and particle-size estimation. Furthermore, complex 5a was grafted with poly(ethylene glycol) (PEG, average M(w)=2 kDa) to different extents, thereby yielding the phosphorescent copolymers PEG(12.3)-g-5a, PEG(25.4)-g-5a, and PEG(62.1)-g-5a. Interestingly, these copolymers showed enhanced transfection activity, as revealed by in vitro transfection experiments with tissue-culture-based luciferase assays.

Design of a water-soluble hybrid nanocomposite of CdTe quantum dots and an iridium complex for photoinduced charge transfer.

We report the use of an organo-iridium dye conjugated with a water-soluble copolyethylenimine polymer, allowing the hybrid material to be used in combination with thioacid-coated CdTe quantum dots in an aqueous medium. When they are combined, hot carrier cooling observed in the pure quantum-dot case is heavily suppressed indicating fast (ps) electron transfer on a timescale that competes with non-radiative (Auger) relaxation.

Evaluation of patient effective dose from sentinel lymph node lymphoscintigraphy in breast cancer: a phantom study with SPECT/CT and ICRP-103 recommendations.

OBJECTIVE: To evaluate the effective dose delivered to patients undergoing sentinel lymph node (SLN) lymphoscintigraphy by taking into account both the transmission dose using the CT component of a SPECT/CT system and the (99m)Tc internal emission dose. MATERIALS AND METHODS: An adult female humanoid phantom and a set of thermoluminescent dosimeters were used in dose measurement from the CT transmission irradiation. The choice of measurement organs in the humanoid was guided by the recommendations described in the International Commission on Radiological Protection report number 103 (ICRP-103). The effective doses due to (99m)Tc internal emission source were re-calculated from measurement data reported in our previous study on the same subject with the use of tissue weighting factors of ICRP-103. RESULTS: CT transmission dose is the main contribution to the patient total effective dose for both 1-day and 2-day lymphoscintigraphy protocols and for different surgical procedures. Patients undergoing SLN lymphoscintigraphy receive about the same amount of total effective dose of about 3mSv for both 1-day and 2-day protocol, regardless of whether the tissues containing radioactivity would be excised at surgery or not. CONCLUSION: Although the total effective dose from using SPECT/CT is equivalent to the annual natural background radiation of about 3mSv, nuclear medicine physicians should be aware of the increase in effective dose for SLN lymphoscintigraphy using hybrid imaging technique of SPECT/CT when compared to conventional planar (57)Co flood source for transmission scan. Results from the current study provide update information in radiation exposure to patients undergoing SLN lymphoscintigraphy with the use of SPECT/CT.

Modification of luminescent iridium(III) polypyridine complexes with discrete poly(ethylene glycol) (PEG) pendants: synthesis, emissive behavior, intracellular uptake, and PEGylation properties.

We report the synthesis, characterization, and photophysical properties of a new class of luminescent cyclometalated iridium(III) polypyridine poly(ethylene glycol) (PEG) complexes [Ir(N--C)(2)(N--N)](PF(6)) (HN--C=Hppy (2-phenylpyridine), N--N=bpy-CONH-PEG1 (bpy=2,2'-bipyridine; 1a), bpy-CONH-PEG3 (1b); HN--C=Hpq (2-phenylquinoline), N--N=bpy-CONH-PEG1 (2a), bpy-CONH-PEG3 (2b); HN--C=Hpba (4-(2-pyridyl)benzaldehyde), N--N=bpy-CONH-PEG1 (3)) and their PEG-free counterparts (N--N=bpy-CONH-Et, HN--C=Hppy (1c); HN--C=Hpq (2c)). The cytotoxicity and cellular uptake of these complexes have been investigated by the MTT assay, ICPMS, laser-scanning confocal microscopy, and flow cytometry. The results showed that the complexes supported by the water-soluble PEG can act as biological probes and labels with considerably reduced cytotoxicity. Because the aldehyde groups of complex 3 are reactive toward primary amines, the complex has been utilized as the first luminescent PEGylation reagent. Bovine serum albumin (BSA) and poly(ethyleneimine) (PEI) have been PEGylated with this complex, and the resulting conjugates have been isolated, purified, and their photophysical properties studied. The DNA-binding and gene-delivery properties of the luminescent PEI conjugate 3-PEI have also been investigated.