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Rapid passivation and aggregation of nanoscale zero-valent iron (nZVI) seriously limit its performance in the remediation of different contaminants from wastewater. To overcome such issues, in the present study, nano-palladium/iron (nPd/Fe) was simultaneously improved by biochar (BC) prepared from discarded peanut shells and green complexing agent sodium citrate (SC). For this purpose, a composite (SC-nPd/Fe@BC) was successfully synthesized to remove 2,4-dichlorophenol (2,4-DCP) from wastewater. In the SC-nPd/Fe@BC, BC acts as a carrier with dispersed nPd/Fe particles to effectively prevent its agglomeration, and increased the specific surface area of the composite, thereby improving the reactivity and stability of nPd/Fe. Characterization results demonstrated that the SC-nPd/Fe@BC composites were well dispersed, and the agglomeration was weakened. The formation of the passivation layer on the surface of the particles was inhibited, and the mechanism of SC and BC improving the reactivity of nPd/Fe was clarified. Different factors were found to influence the reductive dichlorination of 2,4-DCP, including Pd loading, Fe:C, SC addition, temperature, initial pH, and initial pollutant concentration. The dechlorination results revealed that the synergistic effect of the BC and SC made the removal efficiency and dechlorination rate of 2,4-DCP by SC-nPd/Fe@BC reached to 96.0 and 95.6%, respectively, which was better than that of nPd/Fe (removal: 46.2%, dechlorination: 45.3%). Kinetic studies explained that the dechlorination reaction of 2,4-DCP and the data were better represented by the pseudo-first-order kinetic model. The reaction rate constants followed the order of SC-nPd/Fe@BC (0.0264 min-1) > nPd/Fe@BC (0.0089 min-1) > SC-nPd/Fe (0.0081 min-1) > nPd/Fe (0.0043 min-1). Thus, SC-nPd/Fe@BC was capable of efficiently reducing 2,4-DCP and the dechlorination efficiency of BC and SC synergistically assisted composite on 2,4-DCP was much better than that of SC-nPd/Fe, nPd/Fe@BC and nPd/Fe. Findings suggested that SC-nPd/Fe@BC can be promising for efficient treatment of chlorinated pollutants.

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Adult attention deficit hyperactivity disorder (ADHD) is often associated with personality pathology. However, only few studies have been conducted on the link between ADHD and pathological narcissism (PN), with or without a diagnosis of narcissistic personality disorder (NPD). In order to fill this gap, PN and NPD were assessed in 164 subjects suffering from ADHD, with several other measures including ADHD severity, quality of life, depression, anxiety, impulsivity, and emotion dysregulation (ED). We found that a significant proportion of ADHD patients suffered from NPD, and that both narcissistic grandiosity and vulnerability were associated with ADHD hyperactivity and impulsivity symptoms, but not with inattentive symptoms. These two dimensions seemed to be negatively associated with well-being and positively associated with most of the other studied psychiatric dimensions except ED, the latter being only associated with vulnerability, even after adjustment on borderline symptoms. Overall, despite important limitations that limit the generalizability of our findings to the overall ADHD population (notably linked to selection bias), we believe that this exploratory study sheds light on the potential clinical relevance of narcissistic pathology in adult ADHD patients.

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New product development (NPD) frequently encounters failures, whether during the development phase or in the subsequent commercialization stage. These failures can often be attributed to root causes originating in the early stages of NPD, known as the front end. This study aims to investigate the factors that contribute to NPD success and the challenges faced by firms throughout the development process. To achieve this objective, an in-depth qualitative approach utilizing interviews was employed to explore the internal and external factors influencing NPD success. Additionally, the study aims to identify specific challenges encountered by firms during the NPD process. The identification of these factors and challenges are crucial for companies as it can lead to long-term cost savings. The findings of this study have broad implications for firms regardless of their product plans. By adopting the derived approach, companies can effectively navigate the product development process and gain insights into the potential challenges associated with introducing a new product into an existing market. As customer preferences evolve with technological advancements, the barriers and challenges faced by new products entering established markets also increase. Therefore, firms that incorporate the results of this study into their product development practices across various industries can avoid pitfalls and achieve greater efficiency in terms of time and costs. This research sheds light on critical areas that contribute to successful product development and provides valuable guidance for firms striving to excel in their NPD endeavors.

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The programmed cell death 1 ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) axis is primarily associated with immunosuppression in cytotoxic T lymphocytes (CTLs). However, mounting evidence is supporting the thesis that PD-L1 not only functions as a ligand but mediates additional cellular functions in tumor cells. Moreover, it has been demonstrated that PD-L1 is not exclusively localized at the cellular membrane. Subcellular fractionation revealed the presence of PD-L1 in various cellular compartments of six well-characterized head and neck cancer (HNC) cell lines, including the nucleus. Via Western blotting, we detected PD-L1 in its well-known glycosylated/deglycosylated state at 40-55 kDa. In addition, we detected previously unknown PD-L1 variants with a molecular weight at approximately 70 and > 150 kDa exclusively in nuclear protein fractions. These in vitro findings were confirmed with primary tumor samples from head and neck squamous cell carcinoma (HNSCC) patients. Furthermore, we demonstrated that nuclear PD-L1 variant expression is cell-cycle-dependent. Immunofluorescence staining of PD-L1 in different cell cycle phases of synchronized HNC cells supported these observations. Mechanisms of nuclear PD-L1 trafficking remain less understood; however, proximity ligation assays showed a cell-cycle-dependent interaction of the cytoskeletal protein vimentin with PD-L1, whereas vimentin could serve as a potential shuttle for nuclear PD-L1 transportation. Mass spectrometry after PD-L1 co-immunoprecipitation, followed by gene ontology analysis, indicated interaction of nuclear PD-L1 with proteins involved in DNA remodeling and messenger RNA (mRNA) splicing. Our results in HNC cells suggest a highly complex regulation of PD-L1 and multiple tumor cell-intrinsic functions, independent of immune regulation. These observations bear significant implications for the therapeutic efficacy of immune checkpoint inhibition.

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The rapid growth of biotherapeutic industry, with more and more complex molecules entering the market, forces the need for advanced analytical platforms that can quickly and accurately identify and quantify product quality attributes. Mass spectrometry has the potential to provide more detailed information about the quality attributes of complex products, and MS methods are more sensitive than UV methods for detection of impurities. The multi-attribute method (MAM), a liquid chromatography-mass spectrometry based analytical approach is an emerging platform which supports biotherapeutic characterization and cGMP testing. The main advantage lies in the ability to monitor multiple quality attributes in a single assay, both at the peptide and the intact level, facilitating streamlined biopharmaceutical production, from research and development to the QC environment. This review highlights the current landscape of the MAM approach with special attention given to increased analytical throughput, general requirements for QC in terms of instrumentation and software, regulatory requirements, and industry acceptance of the MAM platform.

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Cyclic AMP signalling in trypanosomes differs from most eukaryotes due to absence of known cAMP effectors and cAMP independence of PKA. We have previously identified four genes from a genome-wide RNAi screen for resistance to the cAMP phosphodiesterase (PDE) inhibitor NPD-001. The genes were named cAMP Response Protein (CARP) 1 through 4. Here, we report an additional six CARP candidate genes from the original sample, after deep sequencing of the RNA interference target pool retrieved after NPD-001 selection (RIT-seq). The resistance phenotypes were confirmed by individual RNAi knockdown. Highest level of resistance to NPD-001, approximately 17-fold, was seen for knockdown of CARP7 (Tb927.7.4510). CARP1 and CARP11 contain predicted cyclic AMP binding domains and bind cAMP as evidenced by capture and competition on immobilised cAMP. CARP orthologues are strongly enriched in kinetoplastid species, and CARP3 and CARP11 are unique to Trypanosoma. Localization data and/or domain architecture of all CARPs predict association with the T. brucei flagellum. This suggests a crucial role of cAMP in flagellar function, in line with the cell division phenotype caused by high cAMP and the known role of the flagellum for cytokinesis. The CARP collection is a resource for discovery of unusual cAMP pathways and flagellar biology.

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This study explores how to enhance the decision-making processes in the phases of idea generation or alternative selection during the new product development (NPD) process. NPD is acknowledged as the central function of businesses in an increasingly competitive marketplace. In the current era, the highly uncertain and rapidly changing market environment makes the NPD extremely vague and complex. To be able to find a suitable solution to this complexity, the proposed research aims to categorize the decision points in the process of NPD regarding software development and identify the fuzziness elements affecting the process. The goal of a decision-making process is to prioritize several alternatives with respect to some required objectives and to select the best among them. Multi-Criteria Decision-Making (MCDM) may support reaching a consensus judgment with the collective assessment of Decision Makers (DMs). We introduce a novel evaluation approach for this problem. The proposed approach employs a MULTIMOORA (Multi-objective Optimization by Ratio Analysis plus the Full Multiplicative Form) MCDM technique under Pythagorean Fuzzy Sets (PFSs) objective world environment to cope with an ambiguous environment using Group Decision Making (GDM) setting to shape the decisions. The PFSs have demonstrated their advantages in dealing with vagueness and uncertainty over crisp, fuzzy, or intuitionistic fuzzy sets. Therefore, PFSs can represent the DMs' judgments and preferences in a better structure, ensuring enhanced decision-making in a group consensus. A case study on gaming software and app development is presented to validate the functionality of the proposed method. The results are compared and assessed with the help of a sensitivity analysis. This research makes a real contribution to the literature by proposing a novel evaluation method to rate and select NPD (gaming software and apps) to deal with the inexactness and vagueness associated with the criteria and alternatives.

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Background: Very few extensive studies have measured the prevalence and usage pattern of drug information leaflet (DIL) for oral non-prescription drugs (ONPDs) or identified the associated risk factors for not reading DIL among university students in the UAE. Objective: The current study aimed to estimate the prevalence of the usage pattern of DIL for ONPDs, and delineate the associated risk factors for not reading the DIL among university students. Methods: A cross-sectional survey-based multistage sampling technique conducted among 2875 students at three major universities in UAE. The self-administered validated questionnaire was constructed and developed based on Andersen's behavioral model. Binomial logistic regression performed to ascertain the effects of 25 potential predictors on the likelihood that participants not reading (discarded) the DIL after reading them. The primary outcome measure was reading (discarding without reading) the DIL, and the associated behaviours. Results: 2875 university students were eligible to participate in the study, but only 2519 students agreed to participate, indicating an 88% of intent participation. However, only 2,355 (81.9%) students completed the questionnaire. 1348 respondents reported using NPD (response rate 46.9%) during the past three months before conducting the study, which comprised the sample analysis (1307 were excluded). More than three-quarters of them read the DIL (always or often) at the first use (1049 of 1348, 77.8%). Approximately a quarter of those who read the DIL reported that they discarded them after reading (24.1%). The survey has identified four risk factors for not reading the DIL: those who get the drug information from physicians or pharmacists had lower odds of discarding the DIL (odds ration [OR] = 0.491, 95% confidence interval [CI]: 0.273-0.884, p value< 0.05). Medical students had lower odds of discarding the DIL (OR = 0.598, 95% CI: 0.412-0.868, p value< 0.05). Those participants who believe that NPDs are as effective as prescription drugs had lower odds of discarding the DIL (OR = 0.342, 95% CI: 0.123-0.948, p value< 0.05). Participants who use more than one NPD to treat a single symptom a day have higher odds of discarding the DIL (OR = 1.625, 95% CI: 1.122 -2.355, p value< 0.05). Conclusion: The prevalence of drug usage pattern in this population was 57.5% as 1348 subjects reported using NPD during the past 90 days before conducting the study. We have identified four risk factors for not reading the DIL, those who get the drug information from physicians or pharmacists, medical students, those respondents who believe that NPDs were as effective as prescription drugs, and respondents self-treating a single symptom with more than one NPD. It was evident from the findings that usage pattern of NPD for DIL varied among the students, with no specific pattern dominating.

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Background: Very few extensive studies have measured the prevalence and usage pattern of drug information leaflet (DIL) for oral non-prescription drugs (ONPDs) or identified the associated risk factors for not reading DIL among university students in the UAE. Objective: The current study aimed to estimate the prevalence of the usage pattern of DIL for ONPDs, and delineate the associated risk factors for not reading the DIL among university students. Methods: A cross-sectional survey-based multistage sampling technique conducted among 2875 students at three major universities in UAE. The self-administered validated questionnaire was constructed and developed based on Andersen’s behavioral model. Binomial logistic regression performed to ascertain the effects of 25 potential predictors on the likelihood that participants not reading (discarded) the DIL after reading them. The primary outcome measure was reading (discarding without reading) the DIL, and the associated behaviours. (AU)

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Objective: To evaluate risk factors for neuropsychiatric disorders (NPD) in recipients of CART therapy. Methods: Patients ≥ 18 years with acute lymphoblastic leukemia (ALL), and aggressive B-cell lymphomas who received CART in 2018 were evaluated. Patients with and without NPD were compared. Results: NPD was diagnosed in 31.2% of patients. Compared to patients without NPD, patients with NPD were likely to be females (P = 0.035) and have ALL (P = 0.039). NPD was significantly associated with female gender (OR = 2.03) and diagnosis of ALL (OR = 2.76). No association between NPD and outcomes. Conclusions: Female gender and ALL were risk factors for NPD.

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Inflammation is known to cause pain, and pain is of one of the cardinal signs of inflammation. Mounting evidence suggests that acute inflammation also resolves pain through specialized pro-resolving mediators (SPMs) and macrophage signaling. GPR37 is expressed by neurons and oligodendrocytes in the brain and has been implicated in multiple disorders, such as demyelination, Parkinson's disease, stroke, and cancer. Recent studies have demonstrated that GPR37 is expressed by macrophages and confers protection against infection by bacteria and parasites. Furthermore, GPR37 promotes the resolution of inflammatory pain and infection-induced pain, as the duration of pain after tissue injury and infection is prolonged in mice lacking Gpr37. Mechanistically, activation of GPR37 enhances macrophage phagocytosis, and Gpr37-deficient macrophages exhibit dysregulations of pro-inflammatory and anti-inflammatory cytokines, switching from M2- to M1-like phenotypes. We also discuss novel ligands of GPR37, including neuroprotectin D1 (NPD1), a SPM derived from docosahexaenoic acid (DHA), and bone-derived hormone osteocalcin (OCN), which can suppress oligodendrocyte differentiation and myelination. NPD1 stimulates macrophage phagocytosis via GPR37 and exhibits potent analgesic actions in various animal models of inflammatory and neuropathic pain. Targeting GPR37 may lead to novel therapeutics for treating inflammation, infection, pain, and neurological diseases.

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The role of non-coding RNAs in neuropsychiatric disorders (NPDs) is an emerging field of study. The long non-coding RNAs (lncRNAs) are shown to sponge the microRNAs (miRNAs) from interacting with their target mRNAs. Investigating the sponge activity of lncRNAs in NPDs will provide further insights into biological mechanisms and help identify disease biomarkers. In this study, a large-scale inference of the lncRNA-related miRNA sponge network of pan-neuropsychiatric disorders, including autism spectrum disorder (ASD), schizophrenia (SCZ), and bipolar disorder (BD), was carried out using brain transcriptomic (RNA-Seq) data. The candidate miRNA sponge modules were identified based on the co-expression pattern of non-coding RNAs, sharing of miRNA binding sites, and sensitivity canonical correlation. miRNA sponge modules are associated with chemical synaptic transmission, nervous system development, metabolism, immune system response, ribosomes, and pathways in cancer. The identified modules showed similar and distinct gene expression patterns depending on the neuropsychiatric condition. The preservation of miRNA sponge modules was shown in the independent brain and blood-transcriptomic datasets of NPDs. We also identified miRNA sponging lncRNAs that may be potential diagnostic biomarkers for NPDs. Our study provides a comprehensive resource on miRNA sponging in NPDs.

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Objective: To identify whether preoperative magnetic resonance imaging findings of the brain can predict postoperative delirium in patients who undergo arch replacement for aneurysms. Methods: Overall, 193 patients who underwent aortic replacement for the first time at a single institution between April 2014 and September 2020 were enrolled in this retrospective study. After we excluded patients with acute aortic dissection, no preoperative magnetic resonance imaging findings of the brain, and postoperative cerebral infarction, 50 patients were included and divided into 2 groups, according to their confusion scale results: postoperative delirium (group D) and nonpostoperative delirium (group ND). Preoperative magnetic resonance imaging findings of the brain were classified into lacunar stroke, periventricular hyperintensity, and deep subcortical white matter hyperintensity groups; the latter 2 groups were further classified based on the Fazekas scale, grade 0 to 3. Results: There were 23 patients (46%) in group D and 27 (54%) in group ND. The mean age was significantly greater in group D than in group ND (75 vs 70 years; P = .007). The mean operative time was significantly longer in group D than in group ND (447 vs 384 minutes; P = .024). As for preoperative magnetic resonance imaging findings of the brain, there were significantly more lacunar stroke cases in group D than in group ND (P = .027). In multivariable logistic regression with stepwise selection, high-grade periventricular hyperintensity was significantly related to postoperative delirium (odds ratio, 9.38; 95% confidence interval, 1.55-56.56; P = .015). Conclusions: Silent cerebral ischemia detected by preoperative magnetic resonance imaging of the brain was a significant risk factor for postoperative delirium.

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Excitatory-inhibitory (E-I) imbalance has been shown to contribute to the pathogenesis of a wide range of neurodevelopmental disorders including autism spectrum disorders, epilepsy, and schizophrenia. GABA neurotransmission, the principal inhibitory signal in the mature brain, is critically coupled to proper regulation of chloride homeostasis. During brain maturation, changes in the transport of chloride ions across neuronal cell membranes act to gradually change the majority of GABA signaling from excitatory to inhibitory for neuronal activation, and dysregulation of this GABA-shift likely contributes to multiple neurodevelopmental abnormalities that are associated with circuit dysfunction. Whilst traditionally viewed as a phenomenon which occurs during brain development, recent evidence suggests that this GABA-shift may also be involved in neuropsychiatric disorders due to the "dematuration" of affected neurons. In this review, we will discuss the cell signaling and regulatory mechanisms underlying the GABA-shift phenomenon in the context of the latest findings in the field, in particular the role of chloride cotransporters NKCC1 and KCC2, and furthermore how these regulatory processes are altered in neurodevelopmental and neuropsychiatric disorders. We will also explore the interactions between GABAergic interneurons and other cell types in the developing brain that may influence the GABA-shift. Finally, with a greater understanding of how the GABA-shift is altered in pathological conditions, we will briefly outline recent progress on targeting NKCC1 and KCC2 as a therapeutic strategy against neurodevelopmental and neuropsychiatric disorders associated with improper chloride homeostasis and GABA-shift abnormalities.

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In recent years, organic food, produced with the use of natural means and production methods, has been gaining more and more popularity among consumers. This is due, inter alia, to their belief that it is more abundant in health-promoting bioactive compounds and safer than conventional food. Consumers are increasingly aware of the harmfulness of plant protection products used in intensive agriculture, which are not allowed in organic production. At the same time, it is reported that a certain share of organic products on the EU market are contaminated with pesticide residues, which may raise consumer concerns and lead to a loss of trust in organic food. The aim of the present study was to investigate the problem of pesticide residues occurrence in random samples of organically produced fruits and vegetables (apples, potatoes, carrots, and beetroots) commonly used in the Polish households, and which are available directly from the organic producers in open markets in Poland. For simultaneous analysis of 375 pesticides, an LC-MS/MS system consisting of an Eksigent expert ultraLC 100-XL coupled to a triple quadrupole mass spectrometer QTRAP 6500 and GC Agilent 6890 N equipped with ECD/NPD system were used. Among the 96 vegetable and fruit samples studied, 89 samples (92.7%) were free from detectable pesticide residues, 7 samples (7.3%) of carrot (5) and potato (2) were contaminated, and in 1 of them (1.0%) the detected residues exceeded the maximum residue limit (MRL). None of the tested apple and beetroot samples were found to contain detectable residues. These findings are important for Polish consumers who look for high-quality organic food. However, the presence of detectable residues in a small proportion of the organic samples indicates a need to strengthen the monitoring of pesticides in organic crops, to educate farmers and to raise their awareness regarding the risks of unauthorized use of pesticides banned in organic farming, which can damage the reputation of the whole organic sector.

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OBJECTIVE: We tested the hypothesis that blocking pro-inflammatory platelet-activating factor receptor (PAFR) with LAU-0901 (LAU) plus administering a selected docosanoid, aspirin-triggered neuroprotectin D1 (AT-NPD1), which activates cell-survival pathways after middle cerebral artery occlusion (MCAo), would lead to neurological recovery. Dose-response and therapeutic window were investigated. MATERIALS AND METHODS: Male SD rats were subjected to 2 hours of MCAo. Behavior testing (days 1-7) and ex vivo MRI on day 7 were conducted. In dose-response, rats were treated with LAU (45 and 60 mg/kg; IP), AT-NPD1 (111, 222, 333 µg/kg; IV), LAU+AT-NPD1 (LAU at 3 hours and AT-NPD1 at 3.15 hours) or vehicle. In the therapeutic window, vehicle, LAU (60 mg/kg), AT-NPD1 (222 µg/kg), and LAU+AT-NPD1 were administered at 3, 4, 5, and 6 hours after onset of MCAo. RESULTS: LAU and AT-NPD1 treatments alone improved behavior by 40-42% and 20-30%, respectively, and LAU+AT-NPD1 by 40% compared to the vehicle group. T2-weighted imaging (T2WI) volumes were reduced with all doses of LAU and AT-NPD1 by 73-90% and 67-83% and LAU+AT-NPD1 by 94% compared to vehicle. In the therapeutic window, LAU+AT-NPD1, when administered at 3, 4, 5, and 6 hours, improved behavior by 50, 56, 33, and 26% and reduced T2WI volumes by 93, 90, 82, and 84% compared to vehicle. CONCLUSIONS: We have shown here for the first time that LAU plus AT-NPD1 treatment affords high-grade neuroprotection in MCAo, equaling or exceeding that afforded by LAU or AT-NPD1 alone at considerably moderate doses. It has a broad therapeutic window extending to 6 hours after stroke onset.

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Background: Repetitive transcranial magnetic stimulation (rTMS) has been proven to be a useful tool for the treatment of several severe neuropsychiatric disorders. Accelerated (a)rTMS protocols may have the potential to result in faster clinical improvements, but the effects of such accelerated paradigms on brain function remain to be elucidated. Objectives: This sham-controlled arTMS study aimed to evaluate the immediate and delayed effects of accelerated high frequency rTMS (aHF-rTMS) on glucose metabolism in healthy beagle dogs when applied over the left frontal cortex. Methods: Twenty-four dogs were randomly divided into four unequal groups: five active (n = 8)/ sham (n = 4) stimulation sessions (five sessions in 1 day), 20 active (n = 8)/ sham (n = 4) stimulation sessions (five sessions/ day for 4 days), respectively. [18F] FDG PET scans were obtained at baseline, 24 h poststimulation, after 1 and 3 months post the last stimulation session. We explicitly focused on four predefined regions of interest (left/right prefrontal cortex and left/right hippocampus). Results: One day of active aHF-rTMS- and not sham- significantly increased glucose metabolism 24 h post-active stimulation in the left frontal cortex only. Four days of active aHF-rTMS only resulted in a nearly significant metabolic decrease in the left hippocampus after 1 month. Conclusions: Like in human psychiatric disorders, active aHF-rTMS in healthy beagles modifies glucose metabolism, although differently immediately or after 1 month post stimulation. aHF-rTMS may be also a valid option to treat mentally disordered dogs.

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Cyanide is a powerful and rapidly acting poison. In Japan, cyanide poisoning is rare, and regular cyanide testing can be costly and time consuming. In contrast, alcohol analysis is routinely performed in most forensic laboratories. In this study, we attempted to develop a method for the simultaneous quantification of cyanide and alcohols in blood using headspace gas chromatography (HS-GC). As nitrogen-phosphorus detection (NPD) is more sensitive to hydrogen cyanide than mass spectrometry (MS), a Deans switch was used to switch the detectors during a single run. The separation provided by three analytical columns, PoraBOND Q, CP-Sil 5 CB, and HP-INNOWax, was investigated, and PoraBOND Q was selected. The use of HS-GC-MS/NPD with a Deans switch enabled the simple and simultaneous quantification of cyanide, ethanol, and 1-propanol. Eighteen other volatile compounds were detected in the SIM/scan mode of the MS.

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OBJECTIVES: In recent clinical studies, saxagliptin exhibited nephroprotective potential by lowering albuminuria. In this study, we aimed to determine whether these kidney effects of saxagliptin were mediated by changes in markers of kidney tubular damage, including urinary neutrophil gelatinase-associated protein (uNGAL) and liver-type fatty acid-binding protein (uL-FABP). METHODS: Our study included 80 patients with type 2 diabetes, hypertension and mild to moderate diabetic kidney disease (DKD) with prevalent albuminuria. Patients were either randomly assigned to saxagliptin as add-on therapy or remained unchanged on their stable antidiabetic therapy as a control arm. RESULTS: Saxagliptin significantly reduced uNGAL with a median change of -25.4% (interquartile range [IQR], -35.6% to -12.2%) compared with the control group (median change, -0.91%; IQR, -12% to 11.88%; p<0.001) after 3 months. Similarly, patients given saxagliptin had a highly significant reduction in uL-FABP (median change, -24.4%; IQR, -30.5% to -15.1%) compared with controls (median change, -3.8%; IQR -10% to 12.5%; p<0.001). Median estimated glomerular filtration rate (eGFR) values after 3 months in the saxagliptin arm were significantly higher (76.5 mL/min per 1.73 m2; IQR, 70 to 92.75 mL/min per 1.73 m2) in the low-risk uNGAL group compared with controls (59.8 mL/min per 1.73 m2; IQR, 51 to 76.2 mL/min per 1.73 m2; p=0.002). Also, higher-although not significantly-posttreatment eGFR levels were observed in patients with low risk of uL-FABP (73 mL/min per 1.73 m2; IQR, 58 to 91.3 mL/min per 1.73 m2) compared with controls (57.3 mL/min per 1.73 m2; IQR, 49.5 to 72.6 mL/min per 1.73 m2; p=0.06). No significant increase was observed in high-risk patients for either marker when compared with controls. CONCLUSIONS: The albuminuria-lowering effect of saxagliptin may be due to inhibition of kidney tubular damage. Use of tubular markers may be a promising approach to identifying kidney responders to gliptins.

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