The Effects of Near-Infrared Phototherapy Preirradiation on Lower-Limb Muscle Strength and Injury After Exercise: A Systematic Review and Meta-analysis.

OBJECTIVE: To assess near-infrared preirradiation effects on postexercise lower-limb muscle damage and function and determine optimal dosage. DATA SOURCES: PubMed, Embase, Cochrane Library, EBSCO, Web of Science, China National Knowledge Infrastructure, and Wanfang Data were systematically searched (2009-2023). STUDY SELECTION: Randomized controlled trials of near-infrared preirradiation on lower-limb muscles after fatigue exercise were incorporated into the meta-analysis. Out of 4550 articles screened, 21 met inclusion criteria. DATA EXTRACTION: The included studies' characteristics were independently extracted by 2 authors, with discrepancies resolved through discussion or by a third author. Quality assessment was performed using the Cochrane risk of bias tool and the Grading of Recommendations, Assessment, Development, and Evaluation System. DATA SYNTHESIS: In 21 studies, near-infrared preirradiation on lower-limb muscles inhibited the decline in peak torque (standardized mean difference [SMD], 1.33; 95% confidence interval [CI], 1.08-1.59; p<.001; increasing 27.97±4.87N·m), reduced blood lactate (SMD, -0.2; 95% CI, -0.37 to -0.03; p=.272; decreasing 0.54±0.42mmol/L), decreased creatine kinase (SMD, -2.11; 95% CI, -2.57 to -1.65; p<.001; decreasing 160.07±27.96U/L), and reduced delayed-onset muscle soreness (SMD, -0.53; 95% CI, -0.81 to 0.24; p<.001). Using a 24-hour cutoff revealed 2 trends: treatment effectiveness depended on power and energy density, with optimal effects at 24.16 J/cm2 and 275 J/cm2 for energy, and 36.81 mW/cm2 and 5495 mW/cm2 for power. Noting that out of 21 studies, 19 are from Brazil, 1 from the United States, and 1 from Australia, and the results exhibit high heterogeneity. CONCLUSIONS: Although we would have preferred a more geographic dispersion of laboratories, our findings indicate that near-infrared preirradiation mitigates peak torque decline in lower-limb muscles. Influenced by energy and power density with a 24-hour threshold, optimal energy and power densities are observed at 24.16 J/cm2, 275 J/cm2, 36.81 mW/cm2, and 5495 mW/cm2, respectively. Laser preirradiation also reduces blood lactate, creatine kinase, and delayed-onset muscle soreness.

Effect of Low-Intensity Bloodflow Restriction Training on Nontraumatic Knee Joint Conditions: A Systematic Review and Meta-analysis.

CONTEXT: Nontraumatic knee conditions are common in clinical practice. Existing pharmaceutical and immobilization approaches provide limited pain relief and functional enhancement. Low-intensity bloodflow restriction training (LI-BFRT) is being investigated as a nonpharmacological alternative; however, its efficacy is uncertain. OBJECTIVE: To assess the effectiveness of LI-BFRT for nontraumatic knee conditions and compare it with high-intensity resistance training (HI-RT) and low-intensity resistance training (LI-RT). DATA SOURCES: PubMed, EBSCO, Science Direct, Cochrane Library, China Knowledge Infrastructure, Wanfang Data, and VIP databases were searched until May 30, 2023. STUDY SELECTION: Original randomized controlled trials involving nontraumatic knee joint conditions with interventions consisting mainly of LI-BFRT, HI-RT, or LI-RT. The results assessed mainly pain and muscle performance. STUDY DESIGN: Systematic review and meta-analysis. LEVEL OF EVIDENCE: Level 1. DATA EXTRACTION: Sample characteristics, study design, country, disease, groups, evaluation time, duration, and outcomes were extracted. RESULTS: A total of 13 randomized controlled trials were included in the systematic review. Compared with pretreatment, LI-BFRT significantly alleviated pain (weighted standardized mean difference [SMD], -1.33; 95% CI, -1.62 to -1.05), with better additional effects on hip muscle training (SMD, -3.14; 95% CI, -4.07 to -2.75). Compared with LI-RT, LI-BFRT significantly relieved pain in male patients (SMD, -1.47; 95% CI, -1.92 to -1.01). LI-BFRT significantly increased quadriceps cross-sectional area (SMD, 0.53; 95% CI, 0.27-0.78), knee extension strength (SMD, 0.84; 95% CI, 0.48-1.2), and leg press strength (SMD, 0.64; 95% CI, 0.34-0.94) compared with pretreatment. Its effects were superior to those of LI-RT and similar to those of HI-RT. However, sex differences in muscle strength improvement were observed. CONCLUSION: In patients with nontraumatic knee joint conditions, LI-BFRT effectively alleviated pain, increased muscle cross-sectional area, and enhanced muscle strength. LI-BFRT showed pain relief comparable with that of LI-RT while surpassing LI-RT in muscle growth and strength improvement.

Developing an adult stem cell derived microphysiological intestinal system for predicting oral prodrug bioconversion and permeability in humans.

Microphysiological systems (MPS) incorporating human intestinal organoids have shown the potential to faithfully model intestinal biology with the promise to accelerate development of oral prodrugs. We hypothesized that an MPS model incorporating flow, shear stress, and vasculature could provide more reliable measures of prodrug bioconversion and permeability. Following construction of jejunal and duodenal organoid MPS derived from 3 donors, we determined the area under the concentration-time (AUC) curve for the active drug in the vascular channel and characterized the enzymology of prodrug bioconversion. Fosamprenavir underwent phosphatase mediated hydrolysis to amprenavir while dabigatran etexilate (DABE) exhibited proper CES2- and, as anticipated, not CES1-mediated de-esterification, followed by permeation of amprenavir to the vascular channel. When experiments were conducted in the presence of bio-converting enzyme inhibitors (orthovanadate for alkaline phosphatase; bis(p-nitrophenyl)phosphate for carboxylesterase), the AUC of the active drug decreased accordingly in the vascular channel. In addition to functional analysis, the MPS was characterized through imaging and proteomic analysis. Imaging revealed proper expression and localization of epithelial, endothelial, tight junction and catalytic enzyme markers. Global proteomic analysis was used to analyze the MPS model and 3 comparator sources: an organoid-based transwell model (which was also evaluated for function), Matrigel embedded organoids and finally jejunal and duodenal cadaver tissues collected from 3 donors. Hierarchical clustering analysis (HCA) and principal component analysis (PCA) of global proteomic data demonstrated that all organoid-based models exhibited strong similarity and were distinct from tissues. Intestinal organoids in the MPS model exhibited strong similarity to human tissue for key epithelial markers via HCA. Quantitative proteomic analysis showed higher expression of key prodrug converting and drug metabolizing enzymes in MPS-derived organoids compared to tissues, organoids in Matrigel, and organoids on transwells. When comparing organoids from MPS and transwells, expression of intestinal alkaline phosphatase (ALPI), carboxylesterase (CES)2, cytochrome P450 3A4 (CYP3A4) and sucrase isomaltase (SI) was 2.97-, 1.2-, 11.3-, and 27.7-fold higher for duodenum and 7.7-, 4.6-, 18.1-, and 112.2-fold higher for jejunum organoids in MPS, respectively. The MPS approach can provide a more physiological system than enzymes, organoids, and organoids on transwells for pharmacokinetic analysis of prodrugs that account for 10% of all commercial medicines.

The effect of myofascial therapy on postpartum rectus abdominis separation, low back and leg pain, pelvic floor dysfunction: A systematic review and meta-analysis.

BACKGROUND: During pregnancy and postpartum, changes in biomechanics can cause dysfunctions in the myofascial system, such as rectus abdominis diastasis, various types of pain, and pelvic floor dysfunction. These common postpartum problems seriously threaten women's health. Myofascial therapy, as an effective means of improving biomechanics, has no unified understanding of its therapeutic effects on postpartum functional disorders. This study aims to systematically evaluate the rehabilitative effects of myofascial therapy on postpartum rectus abdominis diastasis, low back and leg pain, and pelvic floor dysfunction through a meta-analysis of published randomized controlled trials. METHODS: A systematic literature search of databases in Chinese and English was performed through May 2023. The treatment methods were randomized controlled studies using myofascial therapy in the treatment of rectus abdominis separation, lumbo-leg pain, and pelvic floor dysfunction. The main outcome indicators were abdominal circumference, rectus abdominis separation distance, visual analogue pain score, pelvic floor muscle potential, ability to live daily activities, number of events, and treatment effectiveness. RESULTS: There were 22 studies, including 2235 patients. The result showed that compared with control group, myofascial therapy demonstrated to reduce abdominal circumference and rectus abdominis separation index, improve lumbar function significantly, and decrease urinary incontinence and pelvic organ prolapse. In the myofascial therapy group, pelvic floor muscle strength was significantly enhanced, anterior/posterior resting potential of pelvic floor muscle was significantly decreased, and pelvic floor muscle potential was enhanced. Compared with the control group, the number of patients with various types of pain and pain scores were significantly reduced after myofascial therapy. When myofascial therapy lasted <4 weeks, pain relief was greater. In the myofascial therapy group, the ability to perform daily activities was significantly improved. An analysis of the effectiveness of the treatment showed that after myofascial therapy, the patient's symptoms improved significantly. There also saw low heterogeneity among all outcomes. CONCLUSION: The results suggested that myofascial therapy could effectively reduce rectus abdominis separation, relieve pelvic floor muscle dysfunction, enhance lumbar function, relieve pain, and improve the ability of daily living activities. All the data demonstrated that myofascial therapy had a good therapeutic effect on postpartum dysfunction.

Improved estimation of aboveground biomass of regional coniferous forests integrating UAV-LiDAR strip data, Sentinel-1 and Sentinel-2 imageries.

BACKGROUND: Forest aboveground biomass (AGB) is not only the basis for estimating forest carbon storage, but also an important parameter for evaluating forest carbon cycle contribution and forest ecological function. Data saturation and fewer field plots limit the accuracy of AGB estimation. In response to these questions, we constructed a point-line-polygon framework for regional coniferous forests AGB mapping using field survey data, UAV-LiDAR strip data, Sentinel-1 and Sentinel-2 imageries in this study. Under this framework, we explored the feasibility of acquiring the LiDAR sampling plots using the LiDAR sampling strategy consistent with the field survey, and analyzed the potentials of multi-scale wavelet transform (WT) textures and tree species stratification for improving AGB estimation accuracy of coniferous forests in North China. RESULTS: The results showed that UAV-LiDAR strip data of high density point clouds could be used as a sampling tool to achieve sample amplification. Experimental comparison results showed that the Sentinel-based AGB estimation models incorporating the multi-scale WT textures and SAR data performed better, and the model based on coniferous forests tree species significantly improved the performance of AGB estimation. Additionally, the accuracy comparison using different validation sets indicated that the proposed LiDAR sampling strategy under the point-line-polygon framework was suitable for estimating coniferous forests AGB on a large area. The highest accuracy of AGB estimation of larch, Chinese pine and all coniferous forests was 74.55%, 78.96%, and 73.42%, respectively. CONCLUSIONS: The proposed approach can successfully alleviate the data signal saturation issue and accurately produce a large-scale wall-to-wall high-resolution AGB map by integrating optical and SAR data with a relative small number of field plots.

Inhibition of ACAT as a Therapeutic Target for Alzheimer's Disease Is Independent of ApoE4 Lipidation.

APOE4, encoding apolipoprotein E4 (apoE4), is the greatest genetic risk factor for Alzheimer's disease (AD), compared to the common APOE3. While the mechanism(s) underlying APOE4-induced AD risk remains unclear, increasing the lipidation of apoE4 is an important therapeutic target as apoE4-lipoproteins are poorly lipidated compared to apoE3-lipoproteins. ACAT (acyl-CoA: cholesterol-acyltransferase) catalyzes the formation of intracellular cholesteryl-ester droplets, reducing the intracellular free cholesterol (FC) pool. Thus, inhibiting ACAT increases the FC pool and facilitates lipid secretion to extracellular apoE-containing lipoproteins. Previous studies using commercial ACAT inhibitors, including avasimibe (AVAS), as well as ACAT-knock out (KO) mice, exhibit reduced AD-like pathology and amyloid precursor protein (APP) processing in familial AD (FAD)-transgenic (Tg) mice. However, the effects of AVAS with human apoE4 remain unknown. In vitro, AVAS induced apoE efflux at concentrations of AVAS measured in the brains of treated mice. AVAS treatment of male E4FAD-Tg mice (5xFAD+/-APOE4+/+) at 6-8 months had no effect on plasma cholesterol levels or distribution, the original mechanism for AVAS treatment of CVD. In the CNS, AVAS reduced intracellular lipid droplets, indirectly demonstrating target engagement. Surrogate efficacy was demonstrated by an increase in Morris water maze measures of memory and postsynaptic protein levels. Amyloid-beta peptide (Aß) solubility/deposition and neuroinflammation were reduced, critical components of APOE4-modulated pathology. However, there was no increase in apoE4 levels or apoE4 lipidation, while amyloidogenic and non-amyloidogenic processing of APP were significantly reduced. This suggests that the AVAS-induced reduction in Aß via reduced APP processing was sufficient to reduce AD pathology, as apoE4-lipoproteins remained poorly lipidated.

It goes both ways: The relationship between anxiety and mild cognitive impairment.

OBJECTIVE: To investigate the relationship between anxiety and mild cognitive impairment (MCI), and whether it is mediated by perceived stress, at the population level. METHOD AND DESIGN: In a longitudinal study of 368 adults aged 65+ from a population-based cohort, we annually assessed anxiety symptoms (GAD-7), perceived stress (PSS-4), and ratings on the Clinical Dementia Rating (CDR®), where CDR = 0.5 was operationalized as MCI. Examining data from three consecutive assessment waves, we first determined the associations between anxiety at the first wave with MCI at the third wave, and vice versa. We then used mediation analyses to determine whether the pathways in both directions were mediated by perceived stress at the second wave, adjusting for demographics and other relevant covariates. RESULTS: We confirmed significant bidirectional longitudinal associations between anxiety and MCI. Perceived stress was detected as a significant mediator for both pathways between anxiety and MCI, explaining 37.1% of the total effect (TE) of anxiety on incident MCI while conversely explaining 27.1% of the TE of MCI on anxiety. CONCLUSIONS: A bidirectional relationship with a 2-year lag between anxiety and MCI was mediated through perceived stress. Clinicians should be sensitive both to potential consequent anxiety when patients present with cognitive impairment, and to potential incipient MCI when the presenting complaint is anxiety. Managing stress may help mitigate adverse outcomes.

Integrity and efficiency: AbbVie's journey of building an integrated nonregulated bioanalytical laboratory.

While bioanalytical outsourcing is widely adopted in the pharmaceutical industry, AbbVie is one of the few large biopharmaceutical companies having an internal bioanalytical unit to support nearly all its drug metabolism and pharmacokinetic studies. This article highlights our experience and perspective in building an integrated and centralized laboratory to provide early discovery and preclinical-stage bioanalytical support with high operational efficiency, cost-effectiveness and data integrity. The advantages of in-house nonregulated bioanalytical support include better control of data quality, faster turnaround times, real-time knowledge sharing and troubleshooting, and lower near- and long-term costs. The success of an in-house model depends upon a comprehensively optimized and streamlined workflow, fueled by continuous improvements and implementation of innovative technologies.

Insights into the role of prechlorination in algae-laden raw water distribution process: Algal organic matter and microcystin-LR release, extracellular polymeric substances (EPS) aggregation, and pipeline biofilm communities.

Prechlorination routinely applied for the treatment of algae-laden raw water has received extensive attention due to its influence on water quality and aquatic microbes. In this study, prechlorination experiments with different doses were conducted in sets of model raw water distribution systems. With the elevated dose of chlorine and prolonged hydraulic retention time (HRT), the ratio of intact algal cells decreased, and the stability of water enhanced. Dissolved organic carbon (DOC) and nitrogen (DON) increased when chlorine dose elevated from 0 to 0.5 mg/L but decreased with elevations from 0.5 to 2.0 mg/L, while UV254 showed a monotonically increasing tendency. DOC, DON and extracellular microcystin-LR increase initially and decrease thereafter with the prolonged HRT. Notably, the effects of prechlorination on extracellular polymeric substances aggregation behavior on pipe walls and microbial community composition was revealed, providing more profound understanding of the community dynamics in this engineered system. This study helped optimize strategies to improve the stability and efficiency of pretreatment of algae-laden water.

Open Reduction and Internal Fixation by Volar Locking Plates and the "Poking Reduction" Technique in Distal Radius Fractures with Displaced Dorsal Ulnar Fragments: A Retrospective Study.

OBJECTIVE: To investigate the clinical and radiological outcomes of distal radius fractures (DRFs) with displaced dorsal ulnar fragments treated with volar locking plate (VLP) and the "poking reduction" technique. METHODS: Between January 2014 and January 2019, 78 unilateral DRFs with displaced dorsal ulnar fragment (AO type C3) treated with VLP were conducted. According to the reduction technique of the dorsal ulnar fragment, the patients were divided into the conventional reduction (CRG) group (33 patients, 14 males and 19 females, mean age 57.2 ± 12.1 years old) and the "poking reduction" (PRG) group (45 patients, 11 males and 34 females, mean age 60.1 ± 12.4 years old). According to the AO classification, there were 21 cases of C3.1 and 12 of C3.2 in the CPG group, 27 cases of C3.1 and 18 of C3.2 in the PRG group. Clinical and radiographic data were extracted from the electronic medical record system. These data were reviewed for clinical outcomes (range of motion, grip strength), radiological outcomes (volar tilt, radial inclination, radial height, step of articular surface), and postoperative complications. The final functional recovery was evaluated by the disabilities of the arm, shoulder, and hand (DASH) score. RESULTS: The mean duration of follow-up was 27 months (range from 12 to 56). The average operation time and intraoperative blood loss did not significantly differ between groups (p > 0.05). Postoperative CT examination showed that the step of articular surface in CPG group (0.8 ± 0.3 mm) was larger than that in PRG group (0.5 ± 0.2 mm) (p < 0.001). The DASH score did not significantly differ between groups (26.1 ± 4.6 in CRG and 24.7 ± 4.0 in PRG, p > 0.05) at 3 months postoperatively. At 6 months and 12 months postoperatively, the DASH score was better in PRG group (11.8 ± 2.5 and 10.4 ± 2.0) than in CRG group (13.6 ± 2.7 and 12.2 ± 2.5) (p = 0.004, p = 0.001, respectively). At 12 months postoperatively, wrist range of motion did not significantly differ between groups (p > 0.05). There was no significant difference in radiological parameters between the two groups (p > 0.05). The incidence of complications was higher in the CRG group (7/33) than in the PRG group (2/45) (p = 0.009). CONCLUSION: The "poking reduction" technique is a wise option for reduction of dorsal ulnar fragment in DRFs. This innovative technique could restore smoothness of the radiocarpal joint effectively, and the dorsal ulnar fragment could be fixed effectively combined with the volar plate.

HIP1R and vimentin immunohistochemistry predict 1p/19q status in IDH-mutant glioma.

BACKGROUND: IDH-mutant gliomas are separate based on the codeletion of the chromosomal arms 1p and 19q into oligodendrogliomas IDH-mutant 1p/19q-codeleted and astrocytomas IDH-mutant. While nuclear loss of ATRX expression excludes 1p/19q codeletion, its limited sensitivity prohibits to conclude on 1p/19q status in tumors with retained nuclear ATRX expression. METHODS: Employing mass spectrometry based proteomic analysis in a discovery series containing 35 fresh frozen and 72 formalin fixed and paraffin embedded tumors with established IDH and 1p/19q status, potential biomarkers were discovered. Subsequent validation immunohistochemistry was conducted on two independent series (together 77 oligodendrogliomas IDH-mutant 1p/19q-codeleted and 92 astrocytomas IDH-mutant). RESULTS: We detected highly specific protein patterns distinguishing oligodendroglioma and astrocytoma. In these patterns, high HIP1R and low vimentin levels were observed in oligodendroglioma while low HIP1R and high vimentin levels occurred in astrocytoma. Immunohistochemistry for HIP1R and vimentin expression in 35 cases from the FFPE discovery series confirmed these findings. Blinded evaluation of the validation cohorts predicted the 1p/19q status with a positive and negative predictive value as well as an accuracy of 100% in the first cohort and with a positive predictive value of 83%; negative predictive value of 100% and an accuracy of 92% in the second cohort. Nuclear ATRX loss as marker for astrocytoma increased the sensitivity to 96% and the specificity to 100%. CONCLUSIONS: We demonstrate that immunohistochemistry for HIP1R, vimentin, and ATRX predict 1p/19q status with 100% specificity and 95% sensitivity and therefore, constitutes a simple and inexpensive approach to the classification of IDH-mutant glioma.

Fabrication of novel Cu2WS4/NiTiO3 heterostructures for efficient visible-light photocatalytichydrogen evolution and pollutant degradation.

The design and development of efficient and durable catalysts with visible-light response for photocatalytic hydrogen production and pollutants degradation is considered as one of the most challenging tasks. In present work, a novel Cu2WS4/NiTiO3 (abbreviated as × CWS/NTO; x  = 0.25, 0.50, 0.75 and 1.00) composite was prepared via a facile electrospinning/calcination technique along with a convenient hydrothermal method. The as-prepared CWS/NTOcomposite was composed of 2D CWS nanosheets and 1D NTO nanofibers manifested by SEM and TEM images. The results of XPS verified the interfacial interaction between CWS and NTO, confirming the heterojunction formation in CWS/NTOcomposite. Photocatalytic tests demonstrated as-prepared CWS/NTO catalysts exhibited outstanding and stable photocatalytic performances for H2 production and pollutants degradation under visible light (λ > 420 nm) irradiation. Specially, 0.50 CWS/NTO sample displayed the highest H2-evolution activity of 810 µmol·g-1·h-1 with the apparent quantum efficiency (AQE) value of 1.65 % at 420 nm. Additionally, it also exhibited the optimal photodegradation properties with the rate constants of 0.030, 0.413 and 0.028 min-1 for TC, RhB and Cr(VI), respectively. The excellent catalytic activities could be attributed to the enhanced visible-light adsorption, high specific surface area and efficient separation of photogenerated charge carriers. The ESR tests and free radicals capturing experiments confirmed that ·O2- and h+ were primary active species for TC/RhB degradation. Eventually, the probable catalytic mechanism was put forward and detailly analysed. The present work provides perspectives of rational design on NiTiO3-based catalysts with superior photocatalytic performance for energy regeneration and environmental remediation.

Single-Atomic Ruthenium Active Sites on Ti3 C2 MXene with Oxygen-Terminated Surface Synchronize Enhanced Activity and Selectivity for Electrocatalytic Nitrogen Reduction to Ammonia.

Downsizing the catalyst to atom scale offers an effective way to maximize the atom utilization efficiency for electrocatalytic nitrogen reduction reaction (NRR). Herein, single-atomic ruthenium (Ru) anchored on a chemically activated Ti3 C2 with O-terminated groups (Ti3 C2 O) was designed to catalyze the NRR process. The catalyst achieved a superior activity and selectivity with ammonia yield rate of 27.56 µg h-1 mg-1 and faradaic efficiency of 23.3 % at a low potential of -0.20 V versus the reversible hydrogen electrode. According to the atomic resolution images from aberration-corrected scanning transmission electron microscopy, Ru sites on Ti3 C2 O achieved good dispersion on atomic scale. X-ray photoelectron spectroscopy analysis further demonstrated that the O-termination groups were successfully activated. Density functional theory calculations combined with experiments revealed that single Ru sites binding to four oxygen were the main reaction centers that permitted the hydrogenation of *NNH2 to *NHNH2 in a novel distal/alternating hybrid path while reducing the energy barrier of the potential-limiting step to 0.78 eV from 0.96 eV in the distal path alone or 1.18 eV in the alternating path alone, thereby significantly promoting the NRR dynamics.

Variation of carbonaceous disinfectants by-products precursors and their correlation with molecular characteristics of dissolved organic matter and microbial communities in a raw water distribution system.

The raw water distribution systems (RWDSs) play key roles in urban water supply systems. The changes of disinfection byproducts (DBPs) precursors of trihalomethanes (THMs), haloacetic acids (HAAs) and halogenated acetaldehydes (HALs) in the RWDS in Taihu Basin were investigated by formation potentials. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) method and 454-pyrosequencing were employed to study the variation of molecular characteristics of low molecular weight-dissolved organic matter (LMW-DOM) and microbial communities of pipeline biofilms respectively, which played crucial roles in the variation of DBPs precursors. The results showed that both DBPs precursors and the molecular characteristics of LMW-DOM in the RWDS had changed. Moreover, the LMW-DOM could be an indicator due to the good positive correlation with precursors of HAAs and HALs. Specifically, the LMW-DOM showed continuous accumulation in the RWDS. The LMW-DOM tended to possess higher m/z and more CH2 or long alkyl chains while pre-chlorination controlled this trend. The LMW-DOM in the pre-chlorinated pipe section also possessed higher saturation. Additionally, lignins served as an important part of DBPs precursors and dominated the LMW-DOM. The microbial diversity decreased in the RWDS, and the abundance and diversity of the microbial community in the pre-chlorinated section were significantly lower than those in the no-chlorinated section. Finally, most DBPs precursors had positive correlation with dominant phylum and genus in RWDS. This study reveals variation of DBPs precursors, LMW-DOM and microbial pipeline biofilms as well, and provide important data for further research on raw water safety and stability in RWDSs.

The effect of enhanced bone marrow in conjunction with 3D-printed PLA-HA in the repair of critical-sized bone defects in a rabbit model.

BACKGROUND: Traditionally, the iliac crest has been the most common harvesting site for autologous bone grafts; however, it has some limitations, including poor bone availability and donor-site morbidity. This study sought to explore the effect of enhanced bone marrow (eBM) in conjunction with three-dimensional (3D)-printed polylactide-hydroxyapatite (PLA-HA) scaffolds in the repair of critical-sized bone defects in a rabbit model. METHODS: First, 3D-printed PLA-HA scaffolds were fabricated and evaluated using micro-computed tomography (µCT) and scanning electron microscopy (SEM). Twenty-seven New Zealand white rabbits were randomly divided into 3 groups (n=9 per group), and the defects were treated using 3D-printed PLA-HA scaffolds (the PLA-HA group) or eBM in conjunction with 3D-printed PLA-HA scaffolds (the PLA-HA/eBM group), or were left untreated (the control group). Radiographic, µCT, and histological analyses were performed to evaluate bone regeneration in the different groups. RESULTS: The 3D-printed PLA-HA scaffolds were cylindrical, and had a mean pore size of 500±47.1 µm and 60%±3.5% porosity. At 4 and 8 weeks, the lane-sandhu X-ray score in the PLA-HA/eBM group was significantly higher than that in the PLA-HA group and the control group (P<0.01). At 8 weeks, the µCT analysis showed that the bone volume (BV) and bone volume/tissue volume (BV/TV) in the PLA-HA/eBM group were significantly higher than those in the PLA-HA group and the control group (P<0.01). Hematoxylin and eosin staining indicated that the new bone area in the PLA-HA/eBM group was significantly higher than that in the PLA-HA group and the control group (P<0.01). CONCLUSIONS: The group that was treated with eBM in conjunction with 3D-printed PLA-HA showed enhanced bone repair compared to the other 2 groups. PLA-HA/eBM scaffolds represent a promising way to treat critical-sized bone defects.

A Validated Functional Analysis of Partner and Localizer of BRCA2 Missense Variants for Use in Clinical Variant Interpretation.

Clinical genetic testing readily detects germline genetic variants. Yet, the rarity of individual variants limits the evidence available for variant classification, leading to many variants of uncertain significance (VUS). VUS cannot guide clinical decisions, complicating counseling and management. In hereditary breast cancer gene PALB2, approximately 50% of clinically identified germline variants are VUS and approximately 90% of VUS are missense. Truncating PALB2 variants have homologous recombination (HR) defects and rely on error-prone nonhomologous end-joining for DNA damage repair (DDR). Recent reports show that some missense PALB2 variants may also be damaging, but most functional studies have lacked benchmarking controls required for sufficient predictive power for clinical use. Here, variant-level DDR capacity in hereditary breast cancer genes was assessed using the Traffic Light Reporter (TLR) to quantify cellular HR/nonhomologous end-joining with fluorescent markers. First, using BRCA2 missense variants of known significance as benchmarks, the TLR distinguished between normal/abnormal HR function. The TLR was then validated for PALB2 and used to test 37 PALB2 variants. Based on the TLR's ability to correctly classify PALB2 validation controls, these functional data where applied in subsequent germline variant interpretations at a moderate level of evidence toward a pathogenic interpretation (PS3_moderate) for 8 variants with abnormal DDR, or a supporting level of evidence toward a benign interpretation (BS3_supporting) for 13 variants with normal DDR.

Objective postoperative pain assessment using incentive spirometry values: a prospective observational study.

Aim: Determine if incentive spirometry (IS) values correlate with postoperative pain control. Design: Prospective observational study. Setting & participants: A total of 100 patients undergoing major abdominal procedures at the University of North Carolina Medical Center. Interventions: Patients studied as a single cohort. All patients received thoracic epidural analgesia preoperatively. Outcome: Preoperative and daily postoperative numeric pain scores, subjective pain description and IS values were collected for all patients. Results: There was a strong correlation with IS values relative to baseline for both the numeric pain scores (p < 0.0001), postoperative day (p < 0.0001) and the subjective pain score (p < 0.0007). Conclusion: IS values are an objective surrogate data point for pain control after surgery, particularly when followed over time and compared with a preoperative baseline value.

The study of chiral recognition on ibuprofen enantiomers by a fluorescent probe based on ß-cyclodextrin modified ZnS:Mn quantum dots.

In this paper, a fluorescence method for chiral detection of ibuprofen and its enantiomer was developed. The L-cystenine-capped ZnS:Mn quantum dots were synthesized and functionalized with ß-cyclodextrin (ß-CD-QDs). The ß-CD-QDs exhibited different quenching effect to the S-(+)-ibuprofen and the R-(-)-ibuprofen based on the advantage of the inclusion complex of cyclodextrin. It was found that the quenching of ß-CD-QDs by S-(+)-ibuprofen was due to the formation of inclusion complex through both static quenching and photoinduced electron transfer, but only slight quenching with the R-(-)-ibuprofen. The stability constants derived from Hildebrand-Benesi method and absorption titration experiments were applied to determine the stability constants of the formed complexes, the double reciprocal plots suggest that a conclusion complex with a ratio of 1:1 was formed between ß-CD-QDs and S-(+)-ibuprofen, but did not with the R-(-)-ibuprofen. The fluorescence intensity of the ß-CD-QDs was linearly dependent on the concentration of the S-(+)-IBP in the range of 0-0.5 nmol/L with an limit of detection of 0.29 nmol/L.

Effect of ultrafiltration profiling on outcomes among maintenance hemodialysis patients: a pilot randomized crossover trial.

BACKGROUND: More rapid fluid removal during hemodialysis is associated with adverse cardiovascular outcomes and longer dialysis recovery times. The effect of ultrafiltration (UF) profiling, independent of concomitant sodium profiling, on markers of intradialytic hemodynamics and other outcomes has been inadequately studied. METHODS: Four-phase, blinded crossover trial. Participants (UF rates > 10 mL/h/kg) were assigned in random order to receive hemodialysis with UF profiling (constantly declining UF rate, intervention) vs. hemodialysis with conventional UF (control). Each 3-week 9-treatment period was followed by a 1-week 3-treatment washout period. Participants crossed into each study arm twice (2 phases/arm); 18 treatments per treatment type. The primary outcomes were intradialytic hypotension, pre- to post-dialysis troponin T change, and change from baseline in left ventricular global longitudinal strain. Other outcomes included intradialytic symptoms and blood volume measured-plasma refill (post-dialysis volume status measure), among others. Each participant served as their own control. RESULTS: On average, the 34 randomized patients (mean age 56 years, 24% female, mean dialysis vintage 6.3 years) had UF rates > 10 mL/h/kg in 56% of treatments during the screening period. All but 2 patients completed the 15-week study (prolonged hospitalization, kidney transplant). There was no significant difference in intradialytic hypotension, troponin T change, or left ventricular strain between hemodialysis with UF profiling and conventional UF. With UF profiling, participants had significantly lower odds of light-headedness and plasma refill compared to hemodialysis with conventional UF. CONCLUSIONS: Ultrafiltration (UF) profiling did not reduce the odds of treatment-related cardiac stress but did reduce the odds of light-headedness and post-dialysis hypervolemia. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03301740 (registered October 4, 2017).