Reactivity of HLADR antibody manifests expression of surface MHC II molecules on peripheral blood T lymphocytes in new world monkeys.

BACKGROUND: Major histocompatibility complex (MHC) class II molecules expressed on B cells, monocytes and dendritic cells present processed peptides to CD4+ T cells as one of the mechanisms to combat infection and inflammation. AIM: To study MHC II expression in a variety of nonhuman primate species, including New World (NWM) squirrel monkeys (Saimiri boliviensis boliviensis), owl monkeys (Aotus nancymae), common marmosets (Callithrix spp.), and Old World (OWM) rhesus (Macaca mulatta), baboons (Papio anubis). METHODS: Two clones of cross-reactive mouse anti-human HLADR monoclonal antibodies (mAb) binding were analyzed by flow cytometry to evaluate MHC II expression on NHP immune cells, including T lymphocytes in whole blood (WB) and peripheral blood mononuclear cells (PBMC). RESULTS: MHC class II antibody reactivity is seen with CD20+ B cells, CD14+ monocytes and CD3+ T lymphocytes. Specific reactivity with both clones was demonstrated in T lymphocytes: this reactivity was not inhibited by purified CD16 antibody but was completely inhibited when pre-blocked with purified unconjugated MHC II antibody. Freshly prepared PBMC also showed reactivity with T lymphocytes without any stimulation. Interestingly, peripheral blood from rhesus macaques and olive baboons (OWM) showed no such T lymphocyte associated MHCII antibody reactivity. DISCUSSION & CONCLUSION: Our results from antibody (MHC II) reactivity clearly show the potential existence of constitutively expressed (with no stimulation) MHC II molecules on T lymphocytes in new world monkeys. These results suggest that additional study is warranted to evaluate the functional and evolutionary significance of these finding and to better understand MHC II expression on T lymphocytes in new world monkeys.

Neutrophil to lymphocyte ratio in captive olive baboons (Papio anubis): The effects of age, sex, rearing, stress, and pregnancy.

In apes and humans, neutrophil to lymphocyte ratio (NLR) can be used as a predictive indicator of a variety of clinical conditions, longevity, and physiological stress. In chimpanzees specifically, NLR systematically varies with age, rearing, sex, and premature death, indicating that NLR may be a useful diagnostic tool in assessing primate health. To date, just one very recent study has investigated NLR in old world monkeys and found lower NLR in males and nursery-reared individuals, as well as a negative relationship between NLR and disease outcomes. Given that baboons are increasingly used as research models, we aimed to characterize NLR in baboons by providing descriptive data and examinations of baboon NLR heritability, and of the relationships between NLR, age, rearing, and sex in 387 olive baboons (Papio anubis) between 6 months and 19 years of age. We found that (1) mother-reared baboons had higher NLRs than nursery-reared baboons; (2) females had higher NLRs than males; and (3) there was a quadratic relationship between NLR and age, such that middle-aged individuals had the highest NLR values. We also examined NLR as a function of transport to a new facility using a subset of the data. Baboons exhibited significantly higher transport NLRs compared to routine exam NLRs. More specifically, adult baboons had higher transport NLRs than routine NLRs, whereas juveniles showed no such difference, suggesting that younger animals may experience transport stress differently than older animals. We also found that transport NLR was heritable, whereas routine NLR was not, possibly suggesting that stress responses (as indicated in NLR) have a strong genetic component. Consistent with research in humans and chimpanzees, these findings suggest that NLR varies with important biological and life history variables and that NLR may be a useful health biomarker in baboons.

Modulation of Heterotypic and Homotypic Interactions to Visualize the Evolution of Organic Aggregates in a Fluorescence Turn-on Manner.

The abnormal evolution of membrane-less organelles into amyloid fibrils is a causative factor in many neurodegenerative diseases. Fundamental research on evolving organic aggregates is thus instructive for understanding the root causes of these diseases. In-situ monitoring of evolving molecular aggregates with built-in fluorescence properties is a reliable approach to reflect their subtle structural variation. To increase the sensitivity of real-time monitoring, we presented organic aggregates assembled by TPAN-2MeO, which is a triphenyl acrylonitrile derivative. TPAN-2MeO showed a morphological evolution with distinct turn-on emission. Upon rapid nanoaggregation, it formed non-emissive spherical aggregates in the kinetically metastable state. Experimental and simulation results revealed that the weak homotypic interactions between the TPAN-2MeO molecules liberated their molecular motion for efficient non-radiative decay, and the strong heterotypic interactions between TPAN-2MeO and water stabilized the molecular geometry favorable for the non-fluorescent state. After ultrasonication, the decreased heterotypic interactions and increased homotypic interactions acted synergistically to allow access to the emissive thermodynamic equilibrium state with a decent photoluminescence quantum yield (PLQY). The spherical aggregates were eventually transformed into micrometer-sized blocklike particles. Under mechanical stirring, the co-assembly of TPAN-2MeO and Pluronic F-127 formed uniform fluorescent platelets, inducing a significant enhancement in PLQY. These results decipher the stimuli-triggered structural variation of organic aggregates with concurrent sensitive fluorescence response and pave the way for a deep understanding of the evolutionary events of biogenic aggregates.

Recyclable and Environmentally Friendly Magnetic Nanoparticles with Aggregation-Induced Emission Photosensitizer for Sustainable Bacterial Inactivation in Water.

Bacterial photodynamic inactivation based on the combined actions of photosensitizers, light, and oxygen presents a promising alternative for eliminating bacteria compared to conventional water disinfection methods. However, a significant challenge in this approach is the inability to retrieve photosensitizers after phototreatment, posing potential adverse environmental impacts. Additionally, conventional photosensitizers often exhibit limited photostability and photodynamic efficiency. This study addresses these challenges by employing an aggregation-induced emission (AIE) photosensitizer, iron oxide magnetic nanoparticles (Fe3O4 MNPs), and Pluronic F127 to fabricate AIE magnetic nanoparticles (AIE MNPs). AIE MNPs not only exhibit fluorescence imaging capabilities and superior photosensitizing ability but also demonstrate broad-spectrum bactericidal activities against both Gram-positive and Gram-negative bacteria. The controlled release of TPA-Py-PhMe and magnetic characteristics of the AIE MNPs facilitate reuse and recycling for multiple cycles of bacterial inactivation in water. Our findings contribute valuable insights into developing environmentally friendly disinfectants, emphasizing the full potential of AIE photosensitizers in photodynamic inactivation beyond biomedical applications.

The Role of Structural Hydrophobicity on Cationic Amphiphilic Aggregation-Induced Emission Photosensitizer-Bacterial Interaction and Photodynamic Efficiency.

The aggregation-induced emission photosensitizer (AIE PS) has stood out as an alternative and competent candidate in bacterial theranostics, particularly with the use of cationic AIE PS in bacterial discrimination and elimination. Most reported work emphasizes the role of electrostatic interaction between cationic AIE PS and negatively charged bacterial surfaces, enabling broad applications from bacterial discrimination to bacterial killing. However, the underlying targeting mechanism and the design rationale of the cationic AIE PS for effective bacterial labeling remain poorly investigated. In this Article, we designed and synthesized a series of cationic amphiphilic AIE PSs with different calculated log P values. Then, we systemically studied the relationship between the hydrophobicity variation of AIE PS and bacterial targeting outcomes, the dose of AIE PS needed to label various species of bacteria, and their photodynamic antibacterial efficiency. The findings in this work provide a better understanding of the unclear AIE PS-bacterial interaction mechanism and some insights into the structural design strategies of cationic amphiphilic AIE PS for better development in bacterial theranostics.

A global catalog of whole-genome diversity from 233 primate species.

The rich diversity of morphology and behavior displayed across primate species provides an informative context in which to study the impact of genomic diversity on fundamental biological processes. Analysis of that diversity provides insight into long-standing questions in evolutionary and conservation biology and is urgent given severe threats these species are facing. Here, we present high-coverage whole-genome data from 233 primate species representing 86% of genera and all 16 families. This dataset was used, together with fossil calibration, to create a nuclear DNA phylogeny and to reassess evolutionary divergence times among primate clades. We found within-species genetic diversity across families and geographic regions to be associated with climate and sociality, but not with extinction risk. Furthermore, mutation rates differ across species, potentially influenced by effective population sizes. Lastly, we identified extensive recurrence of missense mutations previously thought to be human specific. This study will open a wide range of research avenues for future primate genomic research.

Adipocyte-Targeting Type I AIE Photosensitizer for Obesity Treatment via Photodynamic Lipid Peroxidation.

Obesity is a surging public health risk and is often associated with fatal diseases, including diabetes, stroke, and myocardial infarction. Common methods for obesity treatment include diet control, weight-loss medicine, and bariatric surgery, but these methods are often ineffective or unsafe. Herein, we introduce a minimally invasive and effective approach to reduce excessive fat accumulation by utilizing red/near-infrared emissive and lipid droplet targeting aggregation-induced emissive luminogens (AIEgens), namely, TTMN and MeTTMN, for specific targeting and photoinduced peroxidation of large lipid droplets in adipocytes. The reported AIEgens can trace and monitor the formation process of adipocytes from pre-adipocytes with a high signal-to-noise ratio. In addition, the presented AIEgens act as Type I photosensitizer that generates highly reactive hydroxyl radicals and superoxides under white light to eliminate mature adipocytes through the chain reactions of lipid peroxidation, even under low oxygen supply. We also demonstrate the use of AIEgens for in vivo photodynamic therapy (PDT) for subcutaneous fat reduction treatment. This work demonstrates the use of AIEgen as a dual imaging and Type I photosensitizer for photodynamic therapeutics to induce adipocyte apoptosis, involving a simple fabrication and treatment process. The suggested in vivo photodynamic obesity treatment processes have negligible toxicity toward nontargeted normal tissues, providing an alternative approach for effective and relatively safer obesity treatment in the future.

Dorsal root ganglion stimulation for the treatment of chronic pelvic pain: A systematic review.

BACKGROUND: Chronic pelvic pain (CPP) is a difficult condition to treat. Due to complex pelvic innervation, dorsal column spinal cord stimulation (SCS) has not been shown to produce the same effect as dorsal root ganglion stimulation (DRGS) given emerging evidence suggesting that applying DRGS may result in favorable outcomes for individuals with CPP. The aim of this systematic review is to investigate the clinical use and effectiveness of DRGS for patients with CPP. MATERIALS AND METHODS: A systematic review of clinical studies demonstrating the use of DRGS for CPP. Searches were conducted using four electronic databases (PubMed, EMBASE, CINAHL, and Web of Science) across August and September 2022. RESULTS: A total of nine studies comprising 65 total patients with variable pelvic pain etiologies met the inclusion criteria. The majority of subjects implanted with DRGS reported >50% mean pain reduction at variable times of follow-up. Secondary outcomes reported throughout studies including quality of life (QOL) and pain medication consumption were reported to be significantly improved. CONCLUSIONS: Dorsal root ganglion stimulation for CPP continues to lack supportive evidence from well-designed, high-quality studies and recommendations from consensus committee experts. However, we present consistent evidence from level IV studies showing success with the use of DRGS for CPP in reducing pain symptoms along with reports of improved QOL through periods as short as 2 months to as long as 3 years. Because the available studies at this time are of low quality with a high risk of bias, we strongly recommend the facilitation of high-quality studies with larger sample sizes in order to better ascertain the utility of DRGS for this specific patient population. At the same time, from a clinical perspective, it may be reasonable and appropriate to evaluate patients for DRGS candidacy on a case-by-case basis, especially those patients who report CPP symptoms that are refractory to noninterventional measures and who may not be ideal candidates for other forms of neuromodulation.

An Alkaline Phosphatase-Responsive Aggregation-Induced Emission Photosensitizer for Selective Imaging and Photodynamic Therapy of Cancer Cells.

Fluorescence-guided photodynamic therapy (PDT) has been considered as an emerging strategy for precise cancer treatment by making use of photosensitizers (PSs) with reactive oxygen species (ROS) generation. Some efficient PSs have been reported in recent years, but multifunctional PSs that are responsive to cancer-specific biomarkers are rarely reported. In this study, we introduced a phosphate group as a cancer-specific biomarker of alkaline phosphatase (ALP) on a PS with the features of aggregation-induced emission (AIE) for cancer cell imaging and therapy. In cancer cells with high ALP expression, the phosphate group on the AIE probe is selectively hydrolyzed by ALP. Consequently, the hydrophobic probe residue is aggregated in aqueous media and gives a "turn on" fluorescent response. Moreover, fluorescence-guided PDT was realized by the aggregates of probe residue with strong ROS generation efficiency under white light irradiation. Overall, this work presents a strategy of applying ALP-responsive AIE PS for specific imaging cancer cells and succeeding with specific PDT upon the cancer biomarker stimulated responsive reactions.

Autophagy-Activated Self-reporting Photosensitizer Promoting Cell Mortality in Cancer Starvation Therapy.

Cancer starvation therapy have received continuous attention as an efficient method to fight against wide-spectrum cancer. However, during cancer starvation therapy, the protective autophagy promotes cancer cells survival, compromising the therapeutic effect. Herein, a novel strategy by combination of autophagy-activated fluorescent photosensitizers (PSs) and cancer starvation therapy to realize the controllable and efficient ablation of tumor is conceived. Two dual-emissive self-reporting aggregation-induced emission luminogens (AIEgens), TPAQ and TPAP, with autophagy-activated reactive oxygen species (ROS) generation are prepared to fight against the protective autophagy in cancer starvation therapy. When protective autophagy occurs, a portion of TPAQ and TPAP will translocate from lipid droplets to acidic lysosomes with significant redshift in fluorescence emission and enhanced ROS generation ability. The accumulation of ROS induced by TPAQ-H and TPAP-H causes lysosomal membrane permeabilization (LMP), which further results in cell apoptosis and promotes cell death. In addition, TPAQ and TPAP can enable the real-time self-reporting to cell autophagy and cell death process by observing the change of red-emissive fluorescence signals. Particularly, the efficient ablation of tumor via the combination of cancer starvation therapy and photodynamic therapy (PDT) induced by TPAQ has been successfully confirmed in 3D tumor spheroid chip, suggesting the validation of this strategy.

Chronic low back pain comorbidity count and its impact on exacerbating opioid and non-opioid prescribing behavior.

RESEARCH OBJECTIVES: The objective of the study was to determine the characteristics of chronic low back pain (CLBP) comorbidity and its impact on opioid and non-opioid treatments among Chicagoland patients with CLBP. DESIGN: A retrospective cross-sectional study comparing differences in comorbidity and treatment patterns among Chicagoland patients with CLBP against a matched control arm without chronic low back pain (NCLBP). SETTING: Academic hospital system outpatient services. PARTICIPANTS: Using the International Classification of Diseases, 10th Revision codes (ICD 10) 9589 patients were identified with CLBP with a median age of 57 years old and 62.32% female distribution. The NCLBP group comprised 9589 age-, sex-, race-, and region-matched patients. RESULTS: An increased prevalence across all 17 studied comorbidities was found in CLBP patients as compared to NCLBP patients. CLBP patients carried an average of 3.5 comorbidities compared with 2.4 comorbidities in NCLBP patients. Rheumatoid arthritis (RA), joint arthritis, and obesity had the strongest relationship with CLBP. Additionally, we found that the most prescribed treatment for CLBP were opioids, which ranked above NSAIDs and physical therapy. 56% of CLBP patients were prescribed opioids as compared to 36% of NCLBP patients (Odds Ratio = 2.28, 95% CI: 2.16-2.42). Tramadol was the agent with the strongest relationship to CLBP. CLBP patients were more likely to use two or more opioids concomitantly. The number of total treatments was positively associated with the number of comorbidities in both CLBP and NCLBP patients (Cochran-Armitage trend test p < 0.0001). CONCLUSIONS: Chronic low back pain patients showed a higher number of comorbidities than their NCLBP counterparts. Comorbidity count trended positively with higher treatment burden with opioids being the most prescribed treatment, often with poly-opioid use, over conservative modalities such as NSAIDs and physical therapy.

Acclimation and Compensating Metabolite Responses to UV-B Radiation in Natural and Transgenic Populus spp. Defective in Lignin Biosynthesis.

Plants have evolved to protect leaf mesophyll tissue from damage caused by UV-B radiation by producing an array of UV-absorbing secondary metabolites. Flavonoids (phenolic glycosides) and sinapate esters (hydroxycinnamates) have been implicated as UV-B protective compounds because of the accumulation in the leaf epidermis and the strong absorption in the wavelengths corresponding to UV. Environmental adaptations by plants also generate a suite of responses for protection against damage caused by UV-B radiation, with plants from high elevations or low latitudes generally displaying greater adaptation or tolerance to UV-B radiation. In an effort to explore the relationships between plant lignin levels and composition, the origin of growth elevation, and the hierarchical synthesis of UV-screening compounds, a collection of natural variants as well as transgenic Populus spp. were examined for sensitivity or acclimation to UV-B radiation under greenhouse and laboratory conditions. Noninvasive, ecophysiological measurements using epidermal transmittance and chlorophyll fluorescence as well as metabolite measurements using UPLC-MS generally revealed that the synthesis of anthocyanins, flavonoids, and lignin precursors are increased in Populus upon moderate to high UV-B treatment. However, poplar plants with genetic modifications that affect lignin biosynthesis, or natural variants with altered lignin levels and compositions, displayed complex changes in phenylpropanoid metabolites. A balance between elevated metabolic precursors to protective phenylpropanoids and increased biosynthesis of these anthocyanins, flavonoids, and lignin is proposed to play a role in the acclimation of Populus to UV-B radiation and may provide a useful tool in engineering plants as improved bioenergy feedstocks.

Inspiration from nature: BioAIEgens for biomedical and sensing applications.

Owing to high sensitivity, selectivity, and non-invasiveness, fluorescence has been widely applied in the biomedical and sensing fields. Among the pool of fluorescent probes, luminogens with aggregation-induced emission (AIE) characteristic exhibit unique strengths in biological applications. However, most reported AIE luminogens (AIEgens) require complicated synthetic procedures, which raise the costs and biocompatibility concerns, especially in biomedical imaging and therapy. In contrast, bioproduct-inspired AIEgens (BioAIEgens) can compensate for the weakness of synthetic AIEgens in terms of their high biocompatibility, low costs, and easy preparation. This review highlights the latest development of BioAIEgens discovered from natural herbs, as well as their potential biomedical and sensing applications. As nature is full of potential resources, studying AIEgens from natural herbs can facilitate the strength of AIE properties in diverse applications and offer more inspiration to the future BioAIEgen structural design and development.

Analysis of Outcomes Associated With Outpatient Management of Nonoperatively Treated Patients With Appendicitis.

Importance: In the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial, which found antibiotics to be noninferior, approximately half of participants randomized to receive antibiotics had outpatient management with hospital discharge within 24 hours. If outpatient management is safe, it could increase convenience and decrease health care use and costs. Objective: To assess the use and safety of outpatient management of acute appendicitis. Design, Setting, and Participants: This cohort study, which is a secondary analysis of the CODA trial, included 776 adults with imaging-confirmed appendicitis who received antibiotics at 25 US hospitals from May 1, 2016, to February 28, 2020. Exposures: Participants randomized to antibiotics (intravenous then oral) could be discharged from the emergency department based on clinician judgment and prespecified criteria (hemodynamically stable, afebrile, oral intake tolerated, pain controlled, and follow-up confirmed). Outpatient management and hospitalization were defined as discharge within or after 24 hours, respectively. Main Outcomes and Measures: Outcomes compared among patients receiving outpatient vs inpatient care included serious adverse events (SAEs), appendectomies, health care encounters, satisfaction, missed workdays at 7 days, and EuroQol 5-dimension (EQ-5D) score at 30 days. In addition, appendectomy incidence among outpatients and inpatients, unadjusted and adjusted for illness severity, was compared. Results: Among 776 antibiotic-randomized participants, 42 (5.4%) underwent appendectomy within 24 hours and 8 (1.0%) did not receive their first antibiotic dose within 24 hours, leaving 726 (93.6%) comprising the study population (median age, 36 years; range, 18-86 years; 462 [63.6%] male; 437 [60.2%] White). Of these participants, 335 (46.1%; site range, 0-89.2%) were discharged within 24 hours, and 391 (53.9%) were discharged after 24 hours. Over 7 days, SAEs occurred in 0.9 (95% CI, 0.2-2.6) per 100 outpatients and 1.3 (95% CI, 0.4-2.9) per 100 inpatients; in the appendicolith subgroup, SAEs occurred in 2.3 (95% CI, 0.3-8.2) per 100 outpatients vs 2.8 (95% CI, 0.6-7.9) per 100 inpatients. During this period, appendectomy occurred in 9.9% (95% CI, 6.9%-13.7%) of outpatients and 14.1% (95% CI, 10.8%-18.0%) of inpatients; adjusted analysis demonstrated a similar difference in incidence (-4.0 percentage points; 95% CI, -8.7 to 0.6). At 30 days, appendectomies occurred in 12.6% (95% CI, 9.1%-16.7%) of outpatients and 19.0% (95% CI, 15.1%-23.4%) of inpatients. Outpatients missed fewer workdays (2.6 days; 95% CI, 2.3-2.9 days) than did inpatients (3.8 days; 95% CI, 3.4-4.3 days) and had similar frequency of return health care visits and high satisfaction and EQ-5D scores. Conclusions and Relevance: These findings support that outpatient antibiotic management is safe for selected adults with acute appendicitis, with no greater risk of complications or appendectomy than hospital care, and should be included in shared decision-making discussions of patient preferences for outcomes associated with nonoperative and operative care. Trial Registration: ClinicalTrials.gov Identifier: NCT02800785.

Direct Visualization of Supramolecular Binding and Separation of Light Hydrocarbons in MFM-300(In).

The purification of light olefins is one of the most important chemical separations globally and consumes large amounts of energy. Porous materials have the capability to improve the efficiency of this process by acting as solid, regenerable adsorbents. However, to develop translational systems, the underlying mechanisms of adsorption in porous materials must be fully understood. Herein, we report the adsorption and dynamic separation of C2 and C3 hydrocarbons in the metal-organic framework MFM-300(In), which exhibits excellent performance in the separation of mixtures of ethane/ethylene and propyne/propylene. Unusually selective adsorption of ethane over ethylene at low pressure is observed, resulting in selective retention of ethane from a mixture of ethylene/ethane, thus demonstrating its potential for a one-step purification of ethylene (purity > 99.9%). In situ neutron powder diffraction and inelastic neutron scattering reveal the preferred adsorption domains and host-guest binding dynamics of adsorption of C2 and C3 hydrocarbons in MFM-300(In).

Comparative Analysis of the Chloroplast Genomes of Quercus × morehus and the Presumptive Parents Q. wislizeni and Q. kelloggii (Fagaceae) from California.

Here, we present the complete chloroplast genomes of Quercus × morehus, Q. wislizeni, and Q. kelloggii from California. The genomes are 161,119 to 161,130 bp and encode 132 genes. Quercus × morehus and Q. wislizeni are identical in sequence but differ from Q. kelloggii by three indels and eight SNPs.

Small bowel obstruction due to Roux-en-Y enterolith 13 years following deceased donor liver transplantation: a case report.

Primary sclerosing cholangitis (PSC) is a progressive, cholestatic liver disease, and liver transplantation (LT) is considered the only therapeutic option for patients with end-stage liver disease secondary to PSC. Intestinal obstruction in adults after LT surgery is a rare complication with diverse clinical presentations. The most common etiology is intestinal adhesions, but this can also result from other rare causes such as enterolith. We describe the first case report of small bowel obstruction secondary to biliary stone formation in the common limb of Roux-en-Y hepaticojejunostomy 13 years after the deceased donor LT. The patient failed initial conservative management and developed peritonitis, requiring urgent surgical exploration to remove the enterolith and resect the involved small bowel. In conclusion, small bowel obstructions due to enteroliths are unusual clinical complications following LT, which require a high degree of suspicion in patients who develop a bowel obstruction in the setting of a previous hepaticojejunostomy.

Remifentanil requirement for acceptable intubation conditions with two different doses of ketamine without a neuromuscular blocking agent in pediatric patients.

OBJECTIVE: The optimal remifentanil concentration for improving intubation conditions when intubation is performed without neuromuscular blocking agents (NMBAs) but with ketamine as an induction agent remains unknown. Here, we aimed to identify the effective bolus doses of remifentanil required to achieve acceptable intubation conditions upon anesthesia induction with 1 or 2 mg/kg ketamine without NMBAs. PATIENTS AND METHODS: In this prospective, double-blinded, randomized up-down sequential allocation study, we enrolled pediatric patients aged 3-12 years undergoing general anesthesia for inguinal hernia surgery. The patients were randomly allocated to one of two groups to receive either ketamine 1.0 mg/kg (K1 group) or 2.0 mg/kg (K2 group) intravenously until seven success-failure pairs were achieved. The remifentanil dose for each patient was determined using the modified Dixon's up-and-down method with an initial dose of 2.5 µg/kg and a step size of 0.5 µg/kg. RESULTS: In total, 51 patients (22 in the K1 group and 29 in the K2 group) were enrolled. The effective dose (ED)50s of remifentanil for obtaining clinically acceptable intubation conditions under anesthesia induction with ketamine but without NMBAs was 3.2 µg/kg in the K1 group and 1.6 µg/kg in the K2 group. High-dose remifentanil with 1 mg/kg ketamine was associated with more severe chest wall rigidity and lower mean blood pressure and heart rate than was low-dose remifentanil with 2 mg/kg ketamine. CONCLUSIONS: The ED50 of remifentanil required for clinically acceptable intubation conditions with anesthesia induction using 1 mg/kg ketamine without NMBAs in pediatric patients was twice that when using 2 mg/kg ketamine. The combination of 2 mg/kg ketamine and remifentanil was better at preventing chest wall rigidity.

A ratiometric theranostic system for visualization of ONOO- species and reduction of drug-induced hepatotoxicity.

Peroxynitrite (ONOO-) is a potent reactive nitrogen species that plays a role as a critical mediator in liver injury elicited by drugs such as acetaminophen (APAP). At a therapeutic dosage, most APAP is metabolized by liver cells and then excreted in the urine. However, excessive APAP intake can cause an acute production of ONOO-, which induces mitochondrial oxidative stress and necrosis of the liver cells. Therefore, the ONOO- levels in hepatocytes have been considered as an early sign of hepatotoxicity associated with drug overdosage. Herein, a ratiometric theranostic system based on aggregation-induced emission luminogens (AIEgens) for the visualization of ONOO- and reduction of drug-induced hepatotoxicity is developed. The AIEgen ATV-PPB shows a ratiometric fluorescence response from red to green upon cleavage of arylboronic ester moieties by ONOO- with high sensitivity and selectivity. Meanwhile, experiments reveal that ATV-PPB not only acts as a fluorescent probe for ONOO- but also as an intracellular ONOO- scavenger to reduce the hepatotoxicity under overdose APAP treatment.

System Analysis of Wildfire-Water Supply Risk in Colorado, USA with Monte Carlo Wildfire and Rainfall Simulation.

Water supply impairment from increased contaminant mobilization and transport after wildfire is a major concern for communities that rely on surface water from fire-prone watersheds. In this article we present a Monte Carlo simulation method to quantify the likelihood of wildfire impairing water supplies by combining stochastic representations of annual wildfire and rainfall activity. Water quality impairment was evaluated in terms of turbidity limits for treatment by modeling wildfire burn severity, postfire erosion, sediment transport, and suspended sediment dilution in receiving waterbodies. Water supply disruption was analyzed at the system level based on the impairment status of water supply components and their contributions to system performance. We used this approach to assess wildfire-water supply impairment and disruption risks for a system of water supply reservoirs and diversions in the Front Range Mountains of Colorado, USA. Our results indicate that wildfire may impair water quality in a concerning 15.7-19.4% of years for diversions from large watersheds. Reservoir impairment should be rare for off-network reservoirs-ranging from at most 0.01% of years for large reservoirs to nearly 2% of years for small reservoirs. System redundancy meaningfully reduced disruption risk for alternative conveyance routes (4.3-25.0% reduction) and almost eliminated disruption risk for a pair of substitutable terminal sources (99.9% reduction). In contrast, dependency among reservoirs on a conveyance route nearly doubled risk of disruption. Our results highlight the importance of considering water system characteristics when evaluating wildfire-water supply risks.