ALK signaling primes the DNA damage response sensitizing ALK-driven neuroblastoma to therapeutic ATR inhibition.

High-risk neuroblastoma (NB) is a significant clinical challenge. MYCN and Anaplastic Lymphoma Kinase (ALK), which are often involved in high-risk NB, lead to increased replication stress in cancer cells, suggesting therapeutic strategies. We previously identified an ATR (ataxia telangiectasia and Rad3-related)/ALK inhibitor (ATRi/ALKi) combination as such a strategy in two independent genetically modified mouse NB models. Here, we identify an underlying molecular mechanism, in which ALK signaling leads to phosphorylation of ATR and CHK1, supporting an effective DNA damage response. The importance of ALK inhibition is supported by mouse data, in which ATRi monotreatment resulted in a robust initial response, but subsequent relapse, in contrast to a 14-d ALKi/ATRi combination treatment that resulted in a robust and sustained response. Finally, we show that the remarkable response to the 14-d combined ATR/ALK inhibition protocol reflects a robust differentiation response, reprogramming tumor cells to a neuronal/Schwann cell lineage identity. Our results identify an ability of ATR inhibition to promote NB differentiation and underscore the importance of further exploring combined ALK/ATR inhibition in NB, particularly in high-risk patient groups with oncogene-induced replication stress.

ALK fusion NSCLC oncogenes promote survival and inhibit NK cell responses via SERPINB4 expression.

Anaplastic lymphoma kinase (ALK) fusion variants in Non-Small Cell Lung Cancer (NSCLC) consist of numerous dimerizing fusion partners. Retrospective investigations suggest that treatment benefit in response to ALK tyrosine kinase inhibitors (TKIs) differs dependent on the fusion variant present in the patient tumor. Therefore, understanding the oncogenic signaling networks driven by different ALK fusion variants is important. To do this, we developed controlled inducible cell models expressing either Echinoderm Microtubule Associated Protein Like 4 (EML4)-ALK-V1, EML4-ALK-V3, Kinesin Family Member 5B (KIF5B)-ALK, or TRK-fused gene (TFG)-ALK and investigated their transcriptomic and proteomic responses to ALK activity modulation together with patient-derived ALK-positive NSCLC cell lines. This allowed identification of both common and isoform-specific responses downstream of these four ALK fusions. An inflammatory signature that included upregulation of the Serpin B4 serine protease inhibitor was observed in both ALK fusion inducible and patient-derived cells. We show that Signal transducer and activator of transcription 3 (STAT3), Nuclear Factor Kappa B (NF-κB) and Activator protein 1 (AP1) are major transcriptional regulators of SERPINB4 downstream of ALK fusions. Upregulation of SERPINB4 promotes survival and inhibits natural killer cell-mediated cytotoxicity, which has potential for therapeutic impact targeting the immune response together with ALK TKIs in NSCLC.

ALK ligand ALKAL2 potentiates MYCN-driven neuroblastoma in the absence of ALK mutation.

High-risk neuroblastoma (NB) is responsible for a disproportionate number of childhood deaths due to cancer. One indicator of high-risk NB is amplification of the neural MYC (MYCN) oncogene, which is currently therapeutically intractable. Identification of anaplastic lymphoma kinase (ALK) as an NB oncogene raised the possibility of using ALK tyrosine kinase inhibitors (TKIs) in treatment of patients with activating ALK mutations. 8-10% of primary NB patients are ALK-positive, a figure that increases in the relapsed population. ALK is activated by the ALKAL2 ligand located on chromosome 2p, along with ALK and MYCN, in the "2p-gain" region associated with NB. Dysregulation of ALK ligand in NB has not been addressed, although one of the first oncogenes described was v-sis that shares > 90% homology with PDGF. Therefore, we tested whether ALKAL2 ligand could potentiate NB progression in the absence of ALK mutation. We show that ALKAL2 overexpression in mice drives ALK TKI-sensitive NB in the absence of ALK mutation, suggesting that additional NB patients, such as those exhibiting 2p-gain, may benefit from ALK TKI-based therapeutic intervention.

Electrochemical coupling in subnanometer pores/channels for rechargeable batteries.

Subnanometer pores/channels (SNPCs) play crucial roles in regulating electrochemical redox reactions for rechargeable batteries. The delicately designed and tailored porous structure of SNPCs not only provides ample space for ion storage but also facilitates efficient ion diffusion within the electrodes in batteries, which can greatly improve the electrochemical performance. However, due to current technological limitations, it is challenging to synthesize and control the quality, storage, and transport of nanopores at the subnanometer scale, as well as to understand the relationship between SNPCs and performances. In this review, we systematically classify and summarize materials with SNPCs from a structural perspective, dividing them into one-dimensional (1D) SNPCs, two-dimensional (2D) SNPCs, and three-dimensional (3D) SNPCs. We also unveil the unique physicochemical properties of SNPCs and analyse electrochemical couplings in SNPCs for rechargeable batteries, including cathodes, anodes, electrolytes, and functional materials. Finally, we discuss the challenges that SNPCs may face in electrochemical reactions in batteries and propose future research directions.

Ultralow Auger-Assisted Interlayer Exciton Annihilation in WS2/WSe2 Moiré Heterobilayers.

Transition metal dichalcogenide (TMD) heterobilayers have emerged as a promising platform for exploring solid-state quantum simulators and many-body quantum phenomena. Their type II band alignment, combined with the moiré superlattice, inevitably leads to nontrivial exciton interactions and dynamics. Here, we unveil the distinct Auger annihilation processes for delocalized interlayer excitons in WS2/WSe2 moiré heterobilayers. By fitting the characteristic efficiency droop and bimolecular recombination rate, we quantitatively determine an ultralow Auger coefficient of 1.3 × 10-5 cm2 s-1, which is >100-fold smaller than that of excitons in TMD monolayers. In addition, we reveal selective exciton upconversion into the WSe2 layer, which highlights the significance of intralayer electron Coulomb interactions in dictating the microscopic scattering pathways. The distinct Auger processes arising from spatial electron-hole separation have important implications for TMD heterobilayers while endowing interlayer excitons and their strongly correlated states with unique layer degrees of freedom.

Increased Apolipoprotein A1 Expression Correlates with Tumor-Associated Neutrophils and T Lymphocytes in Upper Tract Urothelial Carcinoma.

An increased neutrophil-to-lymphocyte ratio (NLR) is a poor prognostic biomarker in various types of cancer, because it reflects the inhibition of lymphocytes in the circulation and tumors. In urologic cancers, upper tract urothelial carcinoma (UTUC) is known for its aggressive features and lack of T cell infiltration; however, the association between neutrophils and suppressed T lymphocytes in UTUC is largely unknown. In this study, we examined the relationship between UTUC-derived factors and tumor-associated neutrophils or T lymphocytes. The culture supernatant from UTUC tumor tissue modulated neutrophils to inhibit T cell proliferation. Among the dominant factors secreted by UTUC tumor tissue, apolipoprotein A1 (Apo-A1) exhibited a positive correlation with NLR. Moreover, tumor-infiltrating neutrophils were inversely correlated with tumor-infiltrating T cells. Elevated Apo-A1 levels in UTUC were also inversely associated with the population of tumor-infiltrating T cells. Our findings indicate that elevated Apo-A1 expression in UTUC correlates with tumor-associated neutrophils and T cells. This suggests a potential immunomodulatory effect on neutrophils and T cells within the tumor microenvironment, which may represent therapeutic targets for UTUC treatment.

Immune infiltration and clinical significance analyses of the cancer-associated fibroblast-related signature in skin cutaneous melanoma.

BACKGROUND: Skin cutaneous melanoma (SKCM) is one of the most aggressive cancers with high mortality rates. Cancer-associated fibroblasts (CAFs) play essential roles in tumor growth, metastasis and the establishment of a pro-tumor microenvironment. This study aimed to establish a CAF-related signature for providing a new perspective for indicating prognosis and guiding therapeutic regimens of SKCM patients. METHODS: In this study, the CAF-related genes were screened out based on melanoma-associated fibroblast markers identified from single-cell transcriptome analysis in the Gene Expression Omnibus (GEO) database and a CAF-related module identified from weighted gene co-expression analysis using The Cancer Genome Atlas (TCGA) dataset. We extracted these gene expression data of SKCM samples from TCGA and constructed a prognostic CAF-related signature. The prediction abilities of the signature for survival prognosis, tumor immune landscape and responses to chemo-/immunotherapies were evaluated in the TCGA-SKCM cohort. RESULTS: We suggested that CAFs were significantly involved in the clinical outcomes of SKCM. A 10-gene CAF-related model was constructed, and the high-CAF risk group exhibited immunosuppressive features and worse prognosis. Patients with high CAF score were more likely to not respond to immune checkpoint inhibitors but were more sensitive to some chemotherapeutic agents, suggesting a potential approach of chemotherapy/anti-CAF combination treatment to improve the SKCM patient response rate of current immunotherapies. CONCLUSIONS: The CAF-related risk score could serve as a robust prognostic indicator and personal assessment of this score could uncover the degree of immunosuppression and provide treatment strategies to improve outcomes in clinical decision-making in SKCM patients.

Nuclear m(6)A Reader YTHDC1 Regulates mRNA Splicing.

The regulatory role of N(6)-methyladenosine (m(6)A) and its nuclear binding protein YTHDC1 in pre-mRNA splicing remains an enigma. Here we show that YTHDC1 promotes exon inclusion in targeted mRNAs through recruiting pre-mRNA splicing factor SRSF3 (SRp20) while blocking SRSF10 (SRp38) mRNA binding. Transcriptome assay with PAR-CLIP-seq analysis revealed that YTHDC1-regulated exon-inclusion patterns were similar to those of SRSF3 but opposite of SRSF10. In vitro pull-down assay illustrated a competitive binding of SRSF3 and SRSF10 to YTHDC1. Moreover, YTHDC1 facilitates SRSF3 but represses SRSF10 in their nuclear speckle localization, RNA-binding affinity, and associated splicing events, dysregulation of which, as the result of YTHDC1 depletion, can be restored by reconstitution with wild-type, but not m(6)A-binding-defective, YTHDC1. Our findings provide the direct evidence that m(6)A reader YTHDC1 regulates mRNA splicing through recruiting and modulating pre-mRNA splicing factors for their access to the binding regions of targeted mRNAs.

Supramolecular salicylic acid combined with niacinamide in chloasma: A randomized controlled trial.

BACKGROUND: No trial of supramolecular salicylic acid (SSA) for chloasma is available yet. OBJECTIVE: The purpose of this study was to assess the efficacy and safety of Bole DA 30% supramolecular salicylic acid (SSA) combined with 10% niacinamide in treating chloasma. METHODS: This multicenter (n=15), randomized, double-blind, parallel placebo-controlled trial randomized the subjects (1:1) to Bole DA 30% SSA or placebo. The primary endpoint was the effective rate after 16 weeks using the modified melasma area severity index (mMASI) [(pretreatment-posttreatment)/pretreatment×100%]. RESULTS: This study randomized 300 subjects (150/group in the full analysis set, 144 and 147 in the per-protocol set). The total mMASI score, overall Griffiths 10 score, left Griffiths 10 score, and right Griffiths 10 score were significantly lower in the Bole DA 30% SSA group than in the placebo group (all P<0.001). One study drug-related AE and one study drug-unrelated adverse events (AE) were reported in the Bole DA 30% SSA group. No AE was reported in the placebo group. CONCLUSION: Bole DA 30% SSA combined with 10% niacinamide is effective and safe for treating chloasma. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR2200065346.

Characteristics of the White Matter Structural Network in Individuals with Subjective Cognitive Decline with and without APOEε4 Based on Graph Theory Study.

PURPOSE: To determine whether individuals with subjective cognitive decline (SCD) have changes in whole-brain network characteristics and intracerebral node characteristics in the structural network, and whether there is a difference between SCD with and without Apolipoprotein E4 (APOEε4). METHODS: This cross-sectional study included 36 individuals without SCD without APOEε4 (healthy control, HC group), 21 individuals with SCD with APOEε4 (APOEε4+ group), and 33 individuals with SCD without APOEε4 (APOEε4- group). The white matter structural network was constructed using the fractional anisotropy (FA) based deterministic fiber tracking method. Graph theory was used to analyze the whole-brain network characteristics and intracerebral node characteristics of the three groups. RESULTS: Regarding the whole-brain network characteristics, all three groups exhibited small-worldness in their structural networks. The clustering coefficient (Cp) and local efficiency (Eloc) in the APOEε4+ and APOEε4- groups were significantly lower than in the HC group (p < 0.05), but no significant difference in Cp or Eloc was observed between the APOEε4+ and APOEε4- groups. Regarding intracerebral node characteristics, there were significant differences in some brain regions, mainly the default mode network (DMN), the occipital lobe, the temporal lobe, and subcortical regions. The change in intracerebral node characteristics was different between the APOEε4+ group and the APOEε4- group. CONCLUSIONS: Individuals with SCD demonstrate changes in whole-brain network characteristics and intracerebral node characteristics in the structural network. Moreover, differences exist between APOEε4+ and APOEε4- individuals.

Acceptability and tolerability of alcohol-based hand rubs among health workers and concessionaires in Malaysia during the COVID pandemic: a hospital-wide cross-sectional study using a modified WHO protocol.

This study evaluated the acceptability and tolerability of three alcohol-based hand rubs (ABHRs) at Sarawak General Hospital, Malaysia. Conducted from 12-26 November 2021 using a modified WHO Protocol, it involved a survey among health workers and concessionaires, with a 35% response rate (1,598 of 4,628 participants). The majority were nurses (60.8%), with the medical division most represented (28.4%). Most respondents (93.2%) used ABHRs at least five days a week and found them easily accessible (72.3%). Product B was the preferred ABHR (65%), primarily for its color and fragrance, surpassing WHO's 50% approval rate in these aspects. However, no other product features met WHO criteria. There were no significant differences in self-reported skin tolerability across the products, and none achieved overall WHO approval. These results offer important insights for ABHR selection in developing countries and highlight the value of the WHO Protocol in assessing product acceptability and tolerability.

Next-Generation Sequencing in Lung Cancers-A Single-Center Experience in Taiwan.

Background and Objectives: Lung cancer is a leading cause of cancer mortality in Taiwan. With rapid advancement of targeted therapeutics in non-small cell lung cancers, next-generation sequencing (NGS) is becoming an important tool for biomarker testing. In this study, we describe institutional experience of NGS analysis in non-small cell carcinoma (NSCLC). Materials and Methods: A cohort of 73 cases was identified from the institutional pathology archive in the period between November 2020 and December 2022. Results: Adenocarcinoma was the most common histologic type (91.8%). Most patients presented with stage IIIB and beyond (87.7%). Twenty-nine patients (39.7%) were evaluated at the time of initial diagnosis, while the others had received prior chemotherapy or targeted therapy. The most frequently mutated gene was EGFR (63%), and this was followed by TP53 (50.7%), KRAS (13.7%), RB1 (13.7%), and CDKN2A (13.7%). Clinically actionable mutations associated with a guideline-suggested targeted therapy were identified in 55 cases (75.3%) overall, and in 47.1% of cases excluding EGFR TKI-sensitizing mutation. Biomarkers other than EGFR TKI-sensitizing mutations were compared. Cases without TKI-sensitizing EGFR mutation had more level 1 or 2 biomarkers (excluding EGFR TKI-sensitizing mutations) than cases with TKI-sensitizing EGFR mutations (47.1% versus 20.1%, p = 0.016). Progressive disease was associated with co-occurrence of clinically actionable mutations (20.5% versus 0%, p < 0.05). Eight of the nine cases with co-occurring actionable genetic alternations had an EGFR mutation. After an NGS test, 46.1% of actionable or potentially actionable genetic alternations led to patients receiving a matched therapy. Conclusions: Our study demonstrated that NGS analysis identifies therapeutic targets and may guide treatment strategies in NSCLC. NGS tests may be advantageous over multiple single-gene tests for optimization of treatment plans, especially for those with non-EGFR mutations or those with progressive disease.

Insight into the Role of Fluoroethylene Carbonate on the Stability of Sb||Graphite Dual-Ion Batteries in Propylene Carbonate-Based Electrolyte.

Sodium dual-ion batteries (Na-DIBs) have attracted increasing attention due to their high operative voltages and low-cost raw materials. However, the practical applications of Na-DIBs are still hindered by the issues, such as low capacity and poor Coulombic efficiency, which is highly correlated with the compatibility between electrode and electrolyte but rarely investigated. Herein, fluoroethylene carbonate (FEC) is introduced into the electrolyte to regulate cation/anion solvation structure and the stability of cathode/anode-electrolyte interphase of Na-DIBs. The FEC modulates the environment of PF6 - solvation sheath and facilitates the interaction of PF6 - on graphite. In addition, the NaF-rich interphase caused by the preferential decomposition of FEC effectively inhibits side reactions and pulverization of anodes with the electrolyte. Consequently, Sb||graphite full cells in FEC-containing electrolyte achieve an improved capacity, cycling stability and Coulombic efficiency. This work elucidates the underlying mechanism of bifunctional FEC and provides an alternative strategy of building high-performance dual ion batteries.

Dry Chemistry-Based Bipolar Electrochemiluminescence Immunoassay Device for Point-of-Care Testing of Alzheimer-Associated Neuronal Thread Protein.

In this study, we developed, for the first time, a novel dry chemistry-based bipolar electrochemiluminescence (ECL) immunoassay device for point-of-care testing (POCT) of Alzheimer-associated neuronal thread protein (AD7c-NTP), where the ECL signals were automatically collected and analyzed after the sample and buffer solutions were manually added onto the immunosensor. The proposed immunoassay device contains an automatic ECL analyzer and a dry chemistry-based ECL immunosensor fabricated with a screen-printed fiber material-based chip and a three-dimensional (3D)-printed shell. Each pad of the fiber material-based chip was premodified with certain reagents for immunoreaction and then assembled to form the ECL immunosensor. The self-enhanced ECL of the Ru(II)-poly-l-lysine complex and the lateral flow fiber material-based chip make the addition of coreactants and repeated flushing unnecessary. Only the sample and buffer solutions are added to the ECL immunosensor, and the process of ECL detection can be completed in about 6 min using the proposed automatic ECL analyzer. Under optimized conditions, the linear detection range for AD7c-NTP was 1 to 104 pg/mL, and the detection limit was 0.15 pg/mL. The proposed ECL immunoassay device had acceptable selectivity, stability, and reproducibility and had been successfully applied to detect AD7c-NTP levels in human urine. In addition, the accurate detection of AD7c-NTP and duplex detection of AD7c-NTP and apolipoprotein E ε4 gene were also validated. It is believed that the proposed ECL immunoassay device may be a candidate for future POCT applications.

Densifying Crystalline-Amorphous Ni3S2/NiOOH Interfacial Sites To Boost Electrocatalytic O2 Production.

The development of an efficient and low-cost electrocatalyst for oxygen evolution reaction (OER) is the key to improving the overall efficiency of water electrolysis. Here, we report the design of a three-dimensional (3-D) heterostructured Ni9S8/Ni3S2 precatalyst composed of unstable Ni9S8 and inert Ni3S2 components, which undergoes in situ electrochemical activation to generate an amorphous-NiOOH/Ni3S2 heterostructured catalyst. In situ Raman spectroscopy combined with ex situ characterizations, such as X-ray diffraction, X-ray photoelectron spectroscopy, and transmission electron microscopy, reveals that during the activation, Ni9S8 loses the sulfur element to form nickel oxides and eventually transforms to amorphous NiOOH at O2-evolving potentials, while the Ni3S2 component is rather inert that its majority in the bulk remains, thus forming a 3-D congee-like NiOOH/Ni3S2 heterostructure with the Ni3S2 crystalline particles randomly dispersed among amorphous NiOOH species. Unlike the sparse heterostructure that consists of a layer of NiOOH on top of Ni3S2, our unique congee-like NiOOH/Ni3S2 heterostructure provides plentiful reactive amorphous-crystalline interfacial sites. Moreover, the partial electron transfer between the NiOOH and remaining Ni3S2, benefiting from their dense interfacial sites, contributes to a higher valence state of the Ni3+ active centers in NiOOH, hence optimizing the adsorption of OER intermediates. Density functional theory calculations further disclose that the electronic structure regulation not only optimizes the Gibbs free energy of intermediate adsorption but also tunes the OH* absorption behavior to be exothermic, elucidating the spontaneous occurrence of OH* absorption and hence improves the OER. Therefore, a low overpotential of only 197 mV at an O2-evolving current density of 10 mA/cm2, a small Tafel slope of 38.8 mV/dec, and good stability are achieved on the amorphous-NiOOH/crystalline-Ni3S2 heterostructured catalyst.

Synthesis of Two-Dimensional (Cu-S)n Metal-Organic Framework Nanosheets Applied as Peroxidase Mimics for Detection of Glutathione.

Facilely synthesized peroxidase-like nanozymes with high catalytic activity and stability may serve as effective biocatalysts. The present study synthesizes peroxidase-like nanozymes with multinuclear active sites using two-dimensional (2D) metal-organic framework (MOF) nanosheets and evaluates them for their practical applications. A simple method involving a one-pot bottom-up reflux reaction is developed for the mass synthesis of (Cu-S)n MOF 2D nanosheets, significantly increasing production quantity and reducing reaction time compared to traditional autoclave methods. The (Cu-S)n MOF 2D nanosheets with the unique coordination of Cu(I) stabilized in Cu-based MOFs demonstrate impressive activity in mimicking natural peroxidase. The active sites of the peroxidase-like activity of (Cu-S)n MOF 2D nanosheets were predominantly verified as Cu(I) rather than Cu(II) of other Cu-based MOFs. The cost-effective and long-term stability of (Cu-S)n MOF 2D nanosheets make them suitable for practical applications. Furthermore, the inhibition of the peroxidase-like activity of (Cu-S)n MOF nanosheets by glutathione (GSH) could provide a simple strategy for colorimetric detection of GSH against other amino acids. This work remarkably extends the utilization of (Cu-S)n MOF 2D nanosheets in biosensing, revealing the potential for 2D (Cu-S)n MOFs.

Enhancement of bicycle exercise capacity in patients with chronotropic incompetence through closed-loop stimulation: a randomized crossover trial.

AIMS: This study aimed to investigate the effectiveness of closed-loop stimulation (CLS) pacing compared with the traditional DDD mode in patients with chronotropic incompetence (CI) using bicycle-based cardiopulmonary exercise testing (CPET). METHODS AND RESULTS: This single-centre, randomized crossover trial involved 40 patients with CI. Patients were randomized to receive either DDD-CLS or DDD mode pacing for 2 months, followed by a crossover to the alternative mode for an additional 2 months. Bicycling-based CPET was conducted at the 3- and 5-month follow-up visits to assess exercise capacity. Other cardiopulmonary exercise outcome measures and health-related quality of life (QoL) were also assessed. DDD-CLS mode pacing significantly improved exercise capacity, resulting in a peak oxygen uptake (14.8 ± 4.0 vs. 12.0 ± 3.6 mL/kg/min, P < 0.001) and oxygen uptake at the ventilatory threshold (10.0 ± 2.2 vs. 8.7 ± 1.8 mL/kg/min, P < 0.001) higher than those of the DDD mode. However, there were no significant differences in other cardiopulmonary exercise outcome measures such as ventilatory efficiency of carbon dioxide production slope, oxygen uptake efficiency slope, and end-tidal carbon dioxide between the two modes. Patients in the DDD-CLS group reported a better QoL, and 97.5% expressed a preference for the DDD-CLS mode. CONCLUSION: DDD-CLS mode pacing demonstrated improved exercise capacity and QoL in patients with CI, highlighting its potential as an effective pacing strategy for this patient population.

The dose response of erythemal area and intensity on the unprotected skin fits well to a logistic 3P model in SPF tests of a Chinese population, which has the potential to improve the precision and consistency of minimal erythema dose determination.

BACKGROUND: The current ISO guidelines for minimal erythema dose (MED) determination require assessment of erythema area of UV-irradiated skin sites. However, this parameter has not been adequately quantified in daily practice. The aims of this study were to investigate the dose response on the unprotected skin sites by quantifying the erythema area and intensity and to show the potential for improving the precision and consistency of MEDu determination by developing predictive models. METHODS: Standard radiation tests were conducted on the back of 31 healthy Chinese volunteers and the MEDu site of each subject was clinically determined by dermatologists. Images of test sites were captured 24 h after radiation, and the erythema area (%EA) and intensity (∆a*) were measured by image analysis. The data were fitted to a logistic 3P function to obtain dose-response curves, and a set of logit (inverse-logistic) models were then derived. An erythema area threshold of %EA = 52% was established to predict MEDu based on the clinical endpoints defined by ISO 24444:2019. RESULTS: Analysis of the clinically determined MEDu sites revealed wide ranges of %EA (62.3 ± 15% SD) and ∆a* (2.96 ± 0.92 SD). The dose response fitted well to a logistic 3P model (mean R2 = 0.965 and 0.975 for %EA and ∆a*, respectively). Applying the area threshold, values of MEDu were determined by the logit model for the test population, which significantly improved the consistency of MEDu determination (52 ± 0% SD and 2.73 ± 0.61 SD for %EA and ∆a*, respectively). CONCLUSION: This study demonstrated that the dose response of UV-induced erythema can be quantified and modeled once the erythema area and intensity are measured. The results of this study show the potential to improve the precision and consistency of MEDu determination in an SPF test. The similar potential in photodermatological, therapeutic, and diagnostic applications was also implied.

Effect of acute normovolemic hemodilution on anesthetic effect, plasma concentration, and recovery quality in elderly patients undergoing spinal surgery.

OBJECTIVE: To explore the effect of acute normovolemic hemodilution (ANH) on the anesthetic effect, plasma concentration, and postoperative recovery quality in elderly patients undergoing spinal surgery. METHODS: A total of 60 cases of elderly patients aged 65 to 75 years who underwent elective multilevel spinal surgery were assigned randomly into the ANH group (n = 30) and control group (n = 30). Hemodynamic and blood gas analysis indexes were observed and recorded before ANH (T1), after ANH (T2), immediately after postoperative autologous blood transfusion (T3), 10 min (T4), 20 min (T5), 30 min (T6), 40 min (T7), and 50 min (T8) after the transfusion, and at the end of the transfusion (i.e., 60 min; T9). At T3 ~ 9, bispectral index (BIS) and train-of-four (TOF) stimulation were recorded and the plasma propofol/cisatracurium concentration was determined. The extubation time and recovery quality were recorded. RESULTS: The ANH group presented a lower MAP value and a higher SVV value at T2, and shorter extubation and orientation recovery time (P < 0.05) compared with the control group. BIS values at T8 and T9 were lower in the ANH group than those in the control group (P < 0.05). TOF values at T7 ~ 9 were lower in the ANH group than those in the control group (P < 0.05). There were no statistically significant differences in the postoperative plasma concentrations of propofol and cisatracurium between the groups (P > 0.05). CONCLUSION: During orthopedic surgery, the plasma concentration of elderly patients is increased after autologous blood transfusion of ANH, and the depth of anesthesia and muscle relaxant effect are strengthened, thus leading to delayed recovery of respiratory function and extubation.

Group Model Building on causes and interventions for falls in Singapore: insights from a systems thinking approach.

BACKGROUND: Falls in older adults are the result of a complex web of interacting causes, that further results in other physical, emotional, and psychological sequelae. A conceptual framework that represents the reciprocal dynamics of these causal factors can enable clinicians, researchers, and policymakers to clarify goals in falls intervention in older adults. METHODS: A Group Model Building (GMB) exercise was conducted with researchers and clinicians from academic units and public healthcare institutes in Singapore. The aim of the exercise was to produce a shared visual representation of the causal structure for falls and engage in discussions on how current and future falls intervention programmes can address falls in the older adults, especially in the Asian context. It was conducted in four steps: 1) Outlining and prioritising desirable patient outcomes, 2) Conceptual model building, 3) Identifying key intervention elements of effective falls intervention programmes, 4) Mapping of interventions to outcomes. This causal loop diagram (CLD) was then used to generate insights into the current understanding of falls causal relationships, current efforts in falls intervention in Singapore, and used to identify gaps in falls research that could be further advanced in future intervention studies. RESULTS: Four patient outcomes were identified by the group as key in falls intervention: 1) Falls, 2) Injurious falls, 3) Fear of falling, and 4) Restricted mobility and life space. A CLD of the reciprocal relationships between risk factors and these outcomes are represented in four sub-models: 1) Fear of falling, 2) Injuries associated with falls, 3) Caregiver overprotectiveness, 4) Post-traumatic stress disorder and psychological resilience. Through this GMB exercise, the group gained the following insights: (1) Psychological sequelae of falls is an important falls intervention outcome. (2) The effects of family overprotectiveness, psychological resilience, and PTSD in exacerbating the consequences of falls are not well understood. (3) There is a need to develop multi-component falls interventions to address the multitude of falls and falls related sequelae. CONCLUSION: This work illustrates the potential of GMB to promote shared understanding of complex healthcare problems and to provide a roadmap for the development of more effective preventive actions.