Three deinoxanthin analogs were found to bind the SDBC, suggesting a non-selective binding site of deinoxanthin in SDBC.2,4-Diamino-2,4,6-trideoxyglucose (bacillosamine) is a monosaccharide found in many pathogenic bacteria, variation in the functionalities appended to the amino groups occurs depending on the species the sugar is derived from. We here report the first synthesis of bacillosamine synthons that allow for the incorporation of two different functionalities at the C-2-N-acetyl and C-4-amines. We have developed chemistry to assemble a set of conjugation ready Neisseria meningitidis C-2-N-acetyl bacillosamine saccharides, carrying either an acetyl or (R)- or (S)-glyceroyl at the C-4 amine. The glyceroyl bacillosamines have been further extended at the C-3-OH with an α-d-galactopyranose to provide structures that occur as post-translational modifications of N. meningitidis PilE proteins, which make up the bacterial pili.The nutraceutical Nicotinamide Riboside (NR), an efficacious biosynthetic precursor to NAD, is readily metabolized by the purine nucleoside phosphorylase (PNP). https://www.selleckchem.com/products/pirtobrutinib-loxo-305.html Access to the PNP-stable versions of NR is difficult because the glycosidic bond of NR is easily cleaved. Unlike NR, NRH, the reduced form of NR, offers sufficient chemical stability to allow the successful functionalisation of the ribosyl-moiety. Here, we report on a series of NRH and NR derived amino acid conjugates, generated in good to excellent yields and show that O5'-esterification prevents the PNP-catalyzed phosphorolysis of these NR prodrugs.Terminal α-2,6-sialylation of N-glycans is a humanized glycosylation that affects the properties and efficacy of therapeutic glycoproteins. Fc di-sialylation (a biantennary N-glycan with two α-2,6-linked sialic acids) of IgG antibodies imparts them with enhanced anti-inflammatory activity and other roles. However, the microheterogeneity of N-glycoforms presents a challenge for therapeutic development. Therefore, controlled sialylation has drawn considerable attention, but direct access to well-defined di-sialylated antibodies remains limited. Herein, a one-pot three-enzyme protocol was developed by engineering a bacterial sialyltransferase to facilitate the modification of therapeutic antibodies with N-acetylneuraminic acid or its derivatives towards optimized glycosylation. To overcome the low proficiency of bacterial sialyltransferase in antibody remodeling, the Photobacterium sp. JT-ISH-224 α-2,6-sialyltransferase (Psp2,6ST) was genetically engineered by terminal truncation and site-directed mutagenesis based on its protein crystal structure. With the optimized reaction conditions and using activity-based screening of various Psp2,6ST variants, a truncated mutant Psp2,6ST (111-511)-His6 A235M/A366G was shown to effectively improve the catalytic efficiency of antibody di-sialylation. Herceptin and the donor substrate promiscuity allow the introduction of bioorthogonal modifications of N-acetylneuraminic acid into antibodies for site-specific conjugation. 2-AB hydrophilic interaction chromatography analysis of the released N-glycans and intact mass characterization confirmed the high di-sialylation of Herceptin via the optimized one-pot three-enzyme reaction. This study established a versatile enzymatic approach for producing highly di-sialylated IgG antibodies. It provides new insights into engineering bacterial sialyltransferase for adaptation to the enzymatic glycoengineering of therapeutic antibodies and the glycosite-specific conjugation of antibodies.Recent studies have suggested that the anticancer activity of disulfiram (DSF, an FDA-approved alcohol-abuse drug) is Cu-dependent. Low system toxicity and explicit pharmacokinetic characteristics of DSF necessitate safe and effective Cu supplementation in local lesion for further applications. Herein, we presented a new conceptual 'nanosized coordination transport' strategy of Cu(ii) that was realized in porphyrin-based metal-organic frameworks, Sm-TCPP, with strong binding ability to Cu(ii) due to their coordination interactions. Sm-TCPP(Cu) was coated by hyaluronic acid (HA) that termed by Sm-TCPP(Cu)@HA, acting as 'beneficial horse' to target the tumor-localized HA receptor (CD44), thus liberating Cu(ii) ions in cellular overexpressed reductants. The CD44-mediated Cu(ii) accumulation efficiency of Sm-TCPP(Cu)@HA was benchmarked in vitro and vivo against the free TCPP (Cu) via ICP-MS analysis. More importantly, the sensitization effects of Sm-TCPP(Cu)@HA on the anticancer activity of DSF were demonstrated in vivo and in vitro. This study offered a new class of targeted Cu supplements to sensitize DSF for the effective treatment of cancer and established a versatile methodology for constructing a safe and specific delivery of metal ions within living organisms.We report a study where Car-Parrinello molecular dynamics simulations and variable-temperature (30-300 K) 1H spin-lattice relaxation time experiments nicely complement each other to characterize the dynamics within a set of four crystalline 1,4-diethynylbicyclo[2.2.2]octane (BCO) rotors assembled in the metal-organic rotor, Li+4(-CO2-Ph-BCO-py)4(H2O)8·2DMF. The remarkable finding of this work is that, despite the individual rotational barriers of four rotors being indiscernible and superimposed in a broad relaxation process, we were able to unravel a strongly interrelated series of rotational motions involving disrotatory and conrotatory motions in pairs as well as rotational steps of single rotators, all three processes with similar, sizeable rotational barriers of 6 kcal mol-1. It is noteworthy that DFT molecular dynamics simulations and variable-temperature (30-300 K) proton spin-lattice relaxation time experiments deliver the same high value for the rotational barriers stressing the potential of the combined use of the two techniques in understanding rotational motion at the nanoscale.A novel and mild Rh(iii)-catalyzed C-H activation/intramolecular condensation of 1-aryl-1H-pyrazol-5-amines with cyclic 2-diazo-1,3-diketones was developed, giving access to various important benzo[f]pyrazolo[1,5-a][1,3]diazepine scaffolds through sequential C-C/C-N bond formation in a one-pot procedure under additive- and oxidant-free conditions. Furthermore, 3-([1,1'-biphenyl]-2-ylamino)-2-ethoxycyclohex-2-enones can be obtained in good yields by constructing C-O and C-N bonds through 1,1'-insertion, dehydration, and isomerization processes.

The use of portable X-ray fluorescence (PXRF) spectrometry to detect external markers on processed or unprocessed cattle and sheep fecal specimens to estimate apparent total tract digestibility (ATTD) was evaluated. Exp. 1 ruminally cannulated Angus-crossbred steers (n = 7; BW = 520 ± 30 kg) were individually fed ad libitum for 21 d in a completely randomized design (CRD). Markers (Cr2O3 and TiO2) were placed inside the rumen twice daily (7.5 g of each marker). Fecal samples were collected twice daily from day 14 to 21. Exp. 2 crossbred wethers (n = 8; BW = 68 ± 3 kg) were individually fed ad libitum for 21 d in a CRD. During this period, 2 g of Cr2O3 and TiO2 were top-dressed onto the feed twice daily. Sheep were housed in metabolism crates for 5 d for total fecal collection. Concentration of markers was determined on diets, refusals, and fecal specimens (fresh, dry-only, and dried/ground) using atomic absorption to detect Cr and spectrophotometry for Ti. Concentration of both markers was also determined viaetection method. The Cr fecal recovery tended (P = 0.10) to be the lowest for dry-only, the greatest for wet chemistry, intermediate for fresh and dry/ground sheep-fecal specimens; while not affected (P = 0.40) for Ti. The PXRF is an accurate technology to detect Cr and Ti in fresh cattle fecal samples to estimate ATTD. For fresh and dry/ground, the technology was effective for determining the concentration of Cr, or dry-only fecal specimens when detecting Ti in sheep specimens. © The Author(s) 2020. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.The recent Collaborative Group on Hormonal Factors in Breast Cancer (CGHFBC) publication calculated the attributable risk of breast cancer from use of estrogen alone and estrogen plus a synthetic progestogen for less then 5 to ≥15 years of use. This CGHFB report calculated attributable risk based on their findings of relative risk from pooled data from 58 studies. Notably, neither the CGHFBC nor other previous studies have examined the effect of underlying risk of breast cancer on attributable risk. This omission prompted us to determine the magnitude of the effect of underlying risk on attributable risk in this Perspective. Meaningful communication of the potential risk of menopausal hormonal therapy requires providing women with the estimated risk above their existing underlying risk (i.e. attributable risk). Therefore we have estimated attributable risks from the data published by the CGHFBC, taking into account varying degrees of underlying risk. Based on the Endocrine Society Guideline on Menopausal Hormone Therapy (MHT), we divided groups into three categories of risk low (1.5%), intermediate (3.0%), and high (6.0%) underlying risk of breast cancer over 5 years. In women taking estrogen plus a synthetic progestogen (E+SP) for 5-9 years, the attributable risks of MHT increased from 12, to 42, to 85 additional women per 1000 in the low, intermediate, and high risk groups respectively. The attributable risks for estrogen alone were lower but also increased based on underlying risk. Notably, the attributable risks were amplified with duration of MHT use which increased both relative risk and breast cancer incidence. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.Clustered regularly interspaced short palindromic repeats (CRISPR) is described as RNA mediated adaptive immune system defense, which is naturally found in bacteria and archaea. CRISPR-Cas9 has shown great promise for cancer treatment in cancer immunotherapy, manipulation of cancer genome and epigenome and elimination or inactivation of carcinogenic viral infections. However, many challenges remain to be addressed to increase its efficacy, including off-target effects, editing efficiency, fitness of edited cells, immune response and delivery methods. Here, we explain CRISPR-Cas classification and its general function mechanism for gene editing. Then, we summarize these preclinical CRISPR-Cas9-based therapeutic strategies against cancer. https://www.selleckchem.com/products/740-y-p-pdgfr-740y-p.html Moreover, the challenges and improvements of CRISPR-Cas9 clinical applications will be discussed. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email journals.permissions@oup.com.OBJECTIVES Patients with congenital adrenal hyperplasia (CAH) require lifelong replacement therapy with glucocorticoids. Optimizing hydrocortisone therapy is challenging, since there are no established cortisol concentration targets other than the cortisol circadian rhythm profile. 17-hydroxyprogesterone (17-OHP) concentrations are elevated in these patients and commonly used to monitor therapy. This study aimed to characterize the pharmacokinetics/pharmacodynamics (PK/PD) of cortisol using 17-OHP as a biomarker in pediatric patients with CAH and to assess different hydrocortisone dosing regimens. METHODS Cortisol and 17-OHP concentrations from 30 CAH patients (7-17 years of age) receiving standard hydrocortisone replacement therapy (5-20 mg) twice (n = 17) or 3 times (n = 13) daily were used to develop a PK/PD model. Sequentially, simulated cortisol concentrations for clinically relevant 3- and 4-times daily dosing regimens were compared with cortisol and 17-OHP target ranges and to concentrations in healthy children. RESULTS Cortisol concentration-time profiles were accurately described by a 2-compartment model with first-order absorption and expected high bioavailability (82.6%). A time-delayed model with cortisol-mediated inhibition of 17-OHP synthesis accurately described 17-OHP concentrations. The cortisol concentration inhibiting 50% of 17-OHP synthesis was 48.6 nmol/L. A 4-times-daily dosing better attained the target ranges and mimicked the cortisol concentrations throughout the 24-hour period than 3-times-daily. CONCLUSIONS A PK/PD model following hydrocortisone administration has been established. An improved dosing regimen of 38% at 0600, 22% at 1200, 17% at 1800, and 22% at 2400 of the daily hydrocortisone dose was suggested. The 4-times-daily dosing regimen was superior, avoiding subtherapeutic cortisol concentrations and better resembling the circadian rhythm of cortisol. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Pollen tube tip growth depends on balancing secretion of cell wall material with endocytic recycling of excess material incorporated into the plasma membrane (PM). The classical model of tip growth, which predicts bulk secretion occurs apically and is compensated by subapical endocytosis, has been challenged in recent years. Many signaling proteins and lipids with important functions in the regulation of membrane traffic underlying tip growth associate with distinct regions of the pollen tube PM, and understanding the mechanisms responsible for the targeting of these regulatory factors to specific PM domains requires quantitative information concerning the sites of bulk secretion and endocytosis. Here, we quantitatively characterized the spatial organization of membrane traffic during tip growth by analyzing steady-state distributions and dynamics of FM4-64-labeled lipids and YFP-tagged transmembrane (TM) proteins in tobacco (Nicotiana tabacum) pollen tubes growing normally or treated with Brefeldin A to block secretion. We established that 1) secretion delivers TM proteins and recycled membrane lipids to the same apical PM domain, and 2) FM4-64-labeled lipids, but not the analyzed TM proteins, undergo endocytic recycling within a clearly defined subapical region. We mathematically modelled the steady-state PM distributions of all analyzed markers to better understand differences between them and to support the experimental data. Finally, we mapped subapical F-actin fringe and trans-Golgi network positioning relative to sites of bulk secretion and endocytosis to further characterize functions of these structures in apical membrane traffic. https://www.selleckchem.com/products/mek162.html Our results support and further define the classical model of apical membrane traffic at the tip of elongating pollen tubes.A study was presented in which sarcomas were microinjected simultaneously with several drugs to study the pharmacodynamic response after resection. This platform may represent a future way of probing efficacy of anticancer agents in the relevant model system human tumors.See related article by Gundle et al., p. XXX.Immunoblotting allows detection of a protein antigen immobilized on the protein-retaining membrane support such as nitrocellulose or polyvinylidene fluoride (PVDF). The detection of the protein of interest relies on the binding of an antibody that specifically recognizes the protein of interest exposed on the membrane. The protein of interest can be purified or mixed with other proteins as in cell or tissue extracts. Usually immunoblotting combines the resolution of proteins by gel electrophoresis with immunochemical detection and is referred to as "western blotting." Immunoblotting can be used to determine the presence and the steady-state level of the protein of interest in the sample, its relative molecular weight, and the distribution of the protein between cellular fractions. Immunoblotting can be performed using the antibodies raised against synthetic peptide antigens modified to mimic posttranslational modifications of proteins, such as phosphorylation and acetylation, to study these modifications in the protein of interest in vivo. When antibodies against the protein of interest are not available, immunoblotting can be performed using antibodies that specifically recognize the recombinant epitope tags (hemagglutinin [HA]-, Flag-, cMyc-, or glutathione-S-transferase [GST]) fused to the protein of interest using recombinant DNA techniques. Immunoblotting has a variety of research, clinical, and forensic medicine applications. It is also one of the standard techniques for characterization of antibodies from different samples of polyclonal sera or hybridoma supernatants.Fusion proteins that contain a glutathione S-transferase (GST) moiety can be purified to near homogeneity by affinity chromatography on glutathione-linked resins. Glutathione immobilized on a chromatography matrix, such as agarose or Sepharose, acts as a substrate for the GST moiety of fusion proteins. Contaminating proteins are washed away, and the bound GST fusion proteins are then readily displaced from the resin by elution with buffers containing free glutathione.Immobilized metal affinity chromatography (IMAC) is based on the affinity of polyhistidine tracts for divalent metal cations (usually Ni2+) immobilized as transition metal chelate complexes on a chromatography resin. The main protocol here is optimized for use of Ni2+-NTA resin to purify soluble 6xHis-tagged proteins by a straightforward batch method during the binding step, followed by gravity flow for washes and elution. This protocol does not require any specialized equipment other than a simple glass or plastic column. IMAC resins can be used in multiple formats, including batch, gravity flow, centrifuge columns, and fast performance liquid chromatography (FPLC) systems. FPLC systems are designed specifically for the chromatographic separations of proteins and other biomolecules. These systems typically contain multiple pumps, an in-line UV absorption monitor, conductivity meter, pH meter, fraction collector, and other options that allow for the simultaneous purification, analysis, and fractionation of the sample. When linked with the appropriate instruments, an FPLC can become a high-precision, automated instrument that separates proteins at a high resolution. An alternative protocol is included here that describes 6xHis-tagged protein purification using FPLC. Procedures for the cleaning and regeneration of the IMAC resin for reuse are also described, and, finally, considerations for storing purified proteins are discussed.Preparing electrocompetent bacteria is considerably easier than preparing cells for transformation by chemical methods. Bacteria are simply grown to mid-log phase, chilled, centrifuged, washed extensively with ice-cold buffer or H2O to reduce the ionic strength of the cell suspension, and then suspended in an ice-cold buffer containing 10% glycerol. DNA may be introduced immediately into the bacteria by exposing them to a short high-voltage electrical discharge. Alternatively, the cell suspension may be snap-frozen and stored at -70°C for up to 6 mo before electroporation, without loss of transforming efficiency.

Hollow mesoporous particles for drug delivery and cancer therapy have attracted significant attention over recent decades. Here, we develop a simple and highly efficient strategy for preparing fluorescent hollow mesoporous carbon spheres (HMCSs). Compared with typical carbon materials such as fullerene C60, carbon nanotubes, reduced graphene oxide, and carbon nanohorns; HMCSs showed fewer effects on cell cycle distribution and lower toxicity to cells. Ten different drugs were incorporated into the HMCSs, and the maximum loading efficiency reached 42.79 ± 2.7%. Importantly, microwaves were found to improve the photothermal effect generated by HMCSs when combined with 980-nm laser irradiation. The cell killing and tumor growth inhibition efficiencies of HMCSs and drug-loaded HMCSs under co-irradiation with laser and microwaves were significantly improved compared with those under laser irradiation alone. After local administration HMCSs were only distributed in tissue at the injection site. HMCSs showed almost no toxicity in mice after local injection and could be completely removed from the injection site. Aspirin-exacerbated respiratory disease (AERD) classically presents with severe asthma, nasal polyposis, and respiratory exacerbations in response to cyclooxygenase (COX)-1 inhibition. Recent advances in our understanding of AERD have revealed multiple facets of immune dysregulation, including diminished prostaglandin E2 (PGE2) function and elevated levels of both cysteinyl leukotrienes (CysLTs) and innate cytokines such as interleukin 33 (IL-33). Inflammatory mediators in AERD heighten the recruitment and activation of innate lymphoid cells type 2 (ILC2), mast cells, eosinophils, and platelet-adherent leukocytes. This contributes to a cyclical pattern of type 2 inflammation. Here, we highlight current understanding of the immunopathogenesis of AERD. The prevalence and disease burden of atopic dermatitis (AD) is substantial. AD causes significant impairment in quality of life. It is also associated with mental disorders as well as cardiovascular diseases. Many factors including race, environment, skin barrier dysfunction, immune regulatory abnormalities, and microbiome have been reported to affect the pathophysiology of AD. A variety of cell types including Th2, Th17, Th22, and type 2 innate lymphoid cells contribute to AD. Cytokines from these immune cells cause abnormal epidermal differentiation and skin barrier dysfunction. Moreover, microbial dysbiosis and deficiency of antimicrobial peptides result in Staphylococcus aureus infection. Recently, new drugs have been successfully launched to target polarized immune pathways that lead to moderate-to-severe AD. BACKGROUND Boron (B) is an abundant element on earth and presents at physiological pH in the form of boric acid (BA). It has both positive and negative effects on biological systems. BA and sodium borates have been considered as being toxic to the reproduction system in animal experiments. Unfortunately, the molecular mechanism underlying the toxic effects of BA is not fully understood. METHODS Here, we demonstrate the influence of BA on mouse TM3 Leydig cells which are male reproductive system cells targeted by BA exposure. The cytotoxicity was evaluated by MTT and NRU assays. Annexin V-FITC/PI double staining kit, mitochondria membrane potential (ΔΨm) assay kit with JC-1 and caspase-3 colorimetric assay kit were used to indicate the cell death pathway. To estimate the role of oxidative stress in BA induced toxicity, glutathione (GSH) level, catalase (CAT) and superoxide dismutase (SOD) activities were measured manually. RESULTS The cell viability assays showed that BA was not cytotoxic within the tested concentrations up to 1000 μM. Sub-toxic concentrations were used for detecting oxidative stress status. BA exposure was significantly reduced GSH level at 1000 μM and CAT activity in a concentration-dependent manner. However, SOD activity was increased at the tested concentrations (100-1000 μM). Moreover, ΔΨm was significantly decreased at 500 and 1000 μM of BA, while caspase-3 activity was not changed apparently. CONCLUSION These findings demonstrated that BA is not cytotoxic and apoptotic but may slightly induces oxidative stress in TM3 Leydig cells at higher concentrations. BACKGROUND Heavy metals that pass through the plasmalemma are expected to influence on lichen metabolic processes; however, lichens may tolerate high concentrations of metals by sequestrating them extracellularly. Heavy metal accumulation level fundamentally determine the success of lichens in the colonisation of polluted sites; however, the proportions between extra- and intracellular metal concentrations in lichen thalli are still poorly recognized. In this study metal accumulation patterns of selected toxic trace elements, i.e. Pb, Cd, and micronutrients, i.e. Zn, Cu and Ni, in Cladonia cariosa thalli were recognised in relation to extra- and intracellular fractions. METHODS The intracellular and total concentrations of Zn, Pb, Cd, Cu and Ni in lichen thalli collected from eleven variously polluted sites were determined by means of atomic absorption spectrometry. Additionally, organic carbon and total nitrogen contents as well as pH of soil substrate were measured. RESULTS The accumulation patterns differear accumulation when a given element is in excess. Such capability may facilitate the colonization of extremely polluted sites by certain pioneer lichens. BACKGROUND Standard treatment for diffuse peritonitis due to colorectal perforation may be insufficient to suppress inflammatory reaction in sepsis. Thus, developing new treatments is important. This study aimed to examine whether intraperitoneal irradiation by artificial sunlight suppresses inflammatory reaction in a lipopolysaccharide (LPS)-induced peritonitis model after surgical treatments. MATERIALS AND METHODS Mice were divided into naive, nontreatment (NT), and phototherapy (PT) groups. In the latter two groups, LPS was intraperitoneally administered to induce peritonitis and removed by intraperitoneal lavage after laparotomy. The PT group was irradiated with artificial sunlight intraperitoneally. We evaluated the local and systemic inflammatory reactions. Murine macrophages were irradiated with artificial sunlight after stimulation by LPS, and cell viability and expression of tumor necrotizing factor-α (TNF-α) were evaluated. https://www.selleckchem.com/products/2-hydroxybenzylamine.html RESULTS As a local inflammatory reaction, the whole cell count, the expression of interleukin-6 and TNF-α in the intra-abdominal fluid, and the peritoneal thickness were significantly lower in the PT group than in the NT group.

The aim of this study was to (i) gain an overview of the protocols of food preference tests in cats through a systematic review, (ii) assess the effects of test duration, time of day, and sex, and (iii) propose a statistical approach based on power analysis to determine sample size and analyze the results. The manuscripts included in this review had marked variations in the number of days (2-56), sample size (9-60 cats), feeding times (2.5-1440 min), and number of meals per day (1-2) during the test. Additionally to the literature review, three palatability tests (lasting 10 days each) were conducted with 40 cats (22 males and 18 females, 1.8 ± 0.16 years, 3.73 ± 0.90 kg) to assess the effects of test duration, time of day, and gender on the results. From the second day of the test, the sensitivity of the results was higher, because on the first day the results in one of the tests differed from the others (p = .0058). There was no difference (p > .05) between times of day (morning vs afternoon) or gender (males vs females) on the results of the feed intake ratio. For a SD of 0.20, p  less then  .05, and delta of 0.10, the minimum number of cats for two-bowl assays is 23 (test power higher than 0.75).The sample size and test duration are critical factors in the decision making by the investigators about the design of food preference tests in cats. The use of a power test is recommended upon planning a food preference test protocol in cats. Previous studies show that the amplitude of pupillary light response (PLR) depends on the corneal flux density (CFD), which is the product of stimulus area by luminance. However, the contribution of CFD has been investigated only when the stimulus was centered on the fovea, whereas perceived luminance to pupillary response would reduce with stimulus eccentricity. Additionally, it has been shown recently that attentional state modulates pupillary response. In this study, we aimed to clarify the complete mechanisms of PLR by manipulating the stimulus size, eccentricity, luminance, and the participants' attentional states. We focused on four indices to examine PLR, that is, pupillary latency (PL), maximum constriction velocity (MCV), maximum constriction (MC), and mean pupil change (MPC). Results showed that PL was a function of CFD, whereas MCV, MC, and MPC were functions of both CFD and stimulus eccentricity. Furthermore, the magnitude of effect due to stimulus eccentricity for MCV and MC was different from that for MPC. These results provided new evidence that the different processing systems in PLR existed. Glucocorticoids reduce phobic fear in anxiety disorders and enhance psychotherapy, possibly by reducing the retrieval of fear memories and enhancing the consolidation of new corrective memories. Glucocorticoid signaling in the basolateral amygdala can influence connected fear and memory-related cortical regions, but this is not fully understood. Previous studies investigated specific pathways moderated by glucocorticoids, for example, visual-temporal pathways; however, these analyses were limited to a-priori selected regions. Here, we performed whole-brain pattern analysis to localize phobic stimulus decoding related to the fear-reducing effect of glucocorticoids. We reanalyzed functional magnetic resonance imaging (fMRI) data from a previously published study with spider-phobic patients and healthy controls. The patients received glucocorticoids or a placebo before the exposure to spider images. There was moderate evidence that patients with phobia had higher decoding of phobic content in the anterior cingulate cortex (ACC) and the left and right anterior insula compared to controls. Decoding in the ACC and the right insula showed strong evidence for correlation with experienced fear. Patients with cortisol reported a reduction of fear by 10-13%; however, there was only weak evidence for changes in neural decoding compared to placebo which was found in the precuneus, the opercular cortex, and the left cerebellum. In pigs, luteolytic sensitivity to PGF-2α (=LS) is delayed until d 13 of the estrous cycle. While the control of LS is unknown, it is temporally associated with macrophage (MAC; which secretes tumor necrosis factor [TNF]-α) infiltration into the corpora lutea (CL), and previous studies have shown that TNF-α induces LS in porcine luteal cells (LCs) in culture. This study was designed to explore the control of LS by CL macrophage (CL MAC)/TNF-α by progesterone (P4), and to examine the hypothesis that P4 acting via the genomic P4 receptor (PGR) inhibits CL MAC TNF-α and thus plays a key role in regulating LS during the pig estrous cycle. In experiment 1, the effects of LCs on CL MAC cytokine/TNF-α mRNA expression in co-culture were examined (MID cycle; ~d 7-12; no LS); results showed that LC was inhibitory to cytokine/TNF-α. In experiment 2, the effects of P4 or R5020 (PGR-agonist) on CL MAC cytokine/TNF-α mRNA expression were examined (MID cycle; ~d 7-12; no LS); results showed that both P4 and R5020 dose-dependently inhibited TNF-α. https://www.selleckchem.com/products/trastuzumab-deruxtecan.html In experiment 3, CL MACs were isolated from CL at MID (~d 7-12; no LS) and LATE (~d 13-18; + LS) cycle, and TNF-α/PGR mRNA measured. Results indicated that while TNF-α mRNA was 4.2-fold greater in CL MACs from LATE vs MID cycle, PGR mRNA was 4.5-fold greater in CL MACs from MID vs LATE cycle. These data support our hypothesis and suggest that progesterone, acting via PGR, plays a critical physiological role in the control of TNF-α production by CL MACs and LS during the pig estrous cycle. Chile as a major international Cu producer faces serious soil contamination issues in mining areas. Currently Chile does not have any specific law governing the maximum permissible concentrations of metals in soils to protect ecosystems and human health. Chile heavily relies on the use of environmental laws of 14 foreign countries; the choice of the country depends on the similarity of its environmental conditions with those in Chile. In this study, we used an online database to compare the similarity of Chilean rocks to those in foreign countries. Likewise, we performed soil sampling and determined the background concentrations of Cu, As, Pb, and Zn in soils of the Aconcagua basin, the largest river basin in the Valparaiso Region of central Chile. The results showed that geochemical patterns in Chile have the greatest resemblance to New Zealand, Mexico, and Italy. The background Cu concentration in the Aconcagua basin (134 mg kg-1) exceeded the legislated limits of New Zealand (100 mg kg-1) and Italy (120 mg kg-1), whereas the background Zn concentration (200 mg kg-1) exceeded the legislated limit of Italy (150 mg kg-1).

BACKGROUND Rheumatoid arthritis (RA) is associated with joint damage. Effectiveness of embelin has been established in a wide variety of inflammatory disorders, but its utility as a therapeutic agent is limited by its poor absorption, rapid metabolism, and fast systemic elimination. To apprehend these limitations, we propose to use highly bioavailable embelin-loaded chitosan nanoparticles (CS-embelin NPs) for the treatment of RA. METHODS The rats were made arthritic using a subcutaneous injection with 0.1 ml complete Freund's adjuvant (CFA) into the footpad of the left hind paw. CS-embelin NPs (25 and 50 mg/kg) was administered from day 15 to day 28 after adjuvant injection. After the experimental period, the animals were sacrificed and various biochemical markers were assessed. RESULTS Arthritic score and paw swelling were significantly reduced after treatment with CS-embelin NPs. Arthritis-induced rats showed a significant increase in malondialdehyde (MDA) and nitric oxide (NO) with a concomitant reduction of antioxidants in the paw tissue. CS-embelin NPs (25 and 50 mg/kg) reduced MDA and NO levels and restored antioxidant levels to normalcy by mitigating oxidative stress. The arthritic rats exhibited elevated tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1beta (IL-1β) serum concentrations, upregulated TNF- α and IL-6 protein levels and upregulated nuclear factor-kB (NF-kB) mRNA expression in paw tissues. Treatment with CS-embelin NPs (25 and 50 mg/kg) significantly reduced serum levels and down-regulated inflammatory markers to normalcy, dose-dependently. CONCLUSION The results suggest that CS-embelin NPs displayed a protective effect against adjuvant-induced arthritis in rats mediated through antioxidant and anti-inflammatory effects. © 2020 International Union of Biochemistry and Molecular Biology.It is uncontroversial to claim that cognitive science studies many complex phenomena. What is less acknowledged are the contradictions among many traditional commitments of its investigative approaches and the nature of cognitive systems. Consider, for example, methodological tensions that arise due to the fact that like most natural systems, cognitive systems are nonlinear; and yet, traditionally cognitive science has relied on linear statistical data analyses. Cognitive science as complexity science is offered as an interdisciplinary framework for the investigation of cognition that can dissolve such contradictions and tensions. Here, cognition is treated as exhibiting the following four key features emergence, nonlinearity, self-organization, and universality. This framework integrates concepts, methods, and theories from such disciplines as systems theory, nonlinear dynamical systems theory, and synergetics. By adopting this approach, the cognitive sciences benefit from a common set of practices to investigate, explain, and understand cognition in its varied and complex forms. This article is categorized under Computer Science > Neural Networks Psychology > Theory and Methods Philosophy > Foundations of Cognitive Science Neuroscience > Cognition. © 2020 Wiley Periodicals, Inc.BACKGROUND Current guidelines recommend methotrexate (MTX) as a glucocorticoid-sparing agent in patients with polymyalgia rheumatica (PMR) who relapse or suffer glucocorticoid adverse effects; although there is no Level 1 evidence to support this recommendation. AIM To review the effect of MTX in PMR on inflammation and glucocorticoid dose. METHODS Patients with PMR from rheumatology outpatient clinics at two tertiary centres were identified. A structured case note review was conducted for patient characteristics at diagnosis and medications including glucocorticoid and MTX use. RESULTS There were 70 patients, 61% female; mean (range) age of 70 (51-87) years. At time of diagnosis, median (±IQR) ESR was 38.5 (26-74) mm/h and CRP 34.5 (6-74 mg/L) with median initiating prednisolone dose of 15 mg (range 5-60 mg). MTX was prescribed in 22 patients (31%). Mean disease duration at MTX initiation was 2.5 years (1-7 years), with median (range) MTX dose of 10 mg (5-20 mg). At MTX initiation, median (IQR) (±SD) ESR was 33 (13-60 mm/h) and CRP 19 (8-42 mg/L). Reasons for commencing MTX were disease relapse (34%) or inability to wean prednisolone dose (66%). Six months after MTX initiation, there was significant reduction in ESR (p = 0.012), CRP (p = 0.0003) and prednisolone dose (p less then  0.0001). Eleven (50%) patients stopped MTX, 5 due to controlled PMR, and 6 to adverse effects. CONCLUSIONS In this study of PMR patients in tertiary care, 31% were co-prescribed MTX, after prolonged disease duration. MTX was associated with improved inflammatory activity and reduced prednisolone dose, with a relatively high risk of adverse events. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Presented here is a concise synthesis of secu'amamine A, and fluvirosaones A and B from readily available allosecurinine and viroallosecurinine. The key C2-enamine derivative of (viro)allosecurinine, the presumed biosynthetic precursors of these natural products, was accessed, for the first time, by a VO(acac)2 -mediated regioselective Polonovski reaction. Formal hydration and 1,2-amine shift of this pluripotent enamine compound afforded secu'amamine A. Formal oxidative [3+2] cycloaddition reaction between this enamine and TMS-substituted methallyl iodide reagent paved the way to the precursors of fluvirosaones A and B. https://www.selleckchem.com/products/JNJ-26481585.html The relative stereochemistry at the C2 position of these advanced intermediates governs the fate of 1,2-amine shift leading to fluvirosaones A and B. The syntheses of potential biosynthetic precursors and investigations of their chemical reactivities have provided insights regarding the biogenesis of these natural products. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.Sulfonamides in environmental water, food, and feed are a major concern for both aquatic ecosystems and public health, because they may lead to the health risk of drug resistance. Thus, numerous sensitive detection and rapid removal methodologies have been established. This review summarizes the sample preparation techniques and instrumental methods used for sensitive detection of sulfonamides. Additionally, adsorption and photocatalysis for the rapid removal of sulfonamides are also discussed. This review provides a comprehensive perspective on future sulfonamide analyses that have good performance, and on the basic methods for the rapid removal of sulfonamides. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

IL-1-stimulated T/C-28a2 cells treated with an A2AR agonist had reduced ROS burden with increased mitochondrial dynamic stability and function, findings which were recapitulated in primary human chondrocytes. In an obesity-induced OA mouse model, there was a marked increase in mitochondrial oxidized material which was markedly improved after intraarticular injections of liposomal A2AR agonist. These results are consistent with the hypothesis that A2AR ligation is mitoprotective in OA. © 2020 Federation of American Societies for Experimental Biology.Muscarinic acetylcholine receptor 1 subtype (M1 ) and muscarinic acetylcholine receptor 2 subtype (M2 ) presynaptic muscarinic receptor subtypes increase and decrease, respectively, neurotransmitter release at neuromuscular junctions. M2 involves protein kinase A (PKA), although the muscarinic regulation to form and inactivate the PKA holoenzyme is unknown. Here, we show that M2 signaling inhibits PKA by downregulating Cβ subunit, upregulating RIIα/β and liberating RIβ and RIIα to the cytosol. This promotes PKA holoenzyme formation and reduces the phosphorylation of the transmitter release target synaptosome-associated protein 25 and the gene regulator cAMP response element binding. Instead, M1 signaling, which is downregulated by M2 , opposes to M2 by recruiting R subunits to the membrane. The M1 and M2 reciprocal actions are performed through the anchoring protein A kinase anchor protein 150 as a common node. Interestingly, M2 modulation on protein expression needs M1 signaling. Altogether, these results describe the dynamics of PKA subunits upon M2 muscarinic signaling in basal and under presynaptic nerve activity, uncover a specific involvement of the M1 receptor and reveal the M1 /M2 balance to activate PKA to regulate neurotransmission. This provides a molecular mechanism to the PKA holoenzyme formation and inactivation which could be general to other synapses and cellular models. © 2020 Federation of American Societies for Experimental Biology.Long non-coding RNAs (lncRNAs) play key roles in various biological processes. However, the roles of lncRNAs in macrophage polarization remain largely unexplored. In this study, thousands of lncRNAs were identified that are differentially expressed in distinct polarized bone marrow-derived macrophages. Among them, Dnmt3aos (DNA methyltransferase 3A, opposite strand), as a known lncRNA, locates on the antisense strand of Dnmt3a. Functional experiments further confirmed that Dnmt3aos were highly expressed in M(IL-4) macrophages and participated in the regulation of Dnmt3a expression, and played a key role in macrophage polarization. The DNA methylation profiles between the Dnmt3aos knockdown group and the control group in M(IL-4) macrophages were determined by MeDIP-seq technique for the first time, and the Dnmt3aos-Dnmt3a axis-mediated DNA methylation modification-regulated macrophage polarization- related gene IFN-γ was identified. Our study will help to enrich our knowledge of the mechanism of macrophage polarization. © 2020 The Authors. The FASEB Journal published by Wiley Periodicals, Inc. on behalf of Federation of American Societies for Experimental Biology.Development of the songbird brain provides an excellent experimental model for understanding the regulation of sex differences in ontogeny. Considering the regulatory role of the hypothalamus in endocrine, in particular reproductive, physiology, we measured the structural (volume) and molecular correlates of hypothalamic development during ontogeny of male and female zebra finches. We quantified by relative quantitative polymerase chain reaction (rqPCR) the expression of 14 genes related to thyroid and steroid hormones actions as well as 12 genes related to brain plasticity at four specific time points during ontogeny and compared these expression patterns with the expression of the same genes as detected by transcriptomics in the telencephalon. These two different methodological approaches detected specific changes with age and demonstrated that in a substantial number of cases changes observed in both brain regions are nearly identical. Other genes however had a tissue-specific developmental pattern. Sex differences or interactions of sex by age were detected in the expression of a subset of genes, more in hypothalamus than telencephalon. These results correlate with multiple known aspects of the developmental and reproductive physiology but also raise a number of new functional questions. © 2020 Federation of American Societies for Experimental Biology.OBJECTIVES Unlike many investigations that focus on suicide ideation rather than suicidal behavior, the present research evaluates the merit and relative efficacy of psychache (i.e., unbearable mental pain) for predicting self-reported suicide attempts among university students who are starting university. METHOD A sample of 516 elevated-risk undergraduates was assessed during the first three weeks of starting university and, again, 10 weeks later. RESULTS Psychache and depression, but not hopelessness, could predict change in suicide attempter status. When measures of psychache, depression, and hopelessness were considered simultaneously, only psychache provided significant, unique predictive power. https://www.selleckchem.com/products/avelestat-azd9668.html CONCLUSIONS Findings are interpreted as supporting Shneidman's model whereby psychache is seen as the cause of suicide. © 2020 The American Association of Suicidology.BACKGROUND AND AIM The purpose of this study was to investigate the long-term oncologic outcomes after stereotactic body radiation therapy (SBRT) for small hepatocellular carcinoma (HCC). METHODS A total of 290 patients with HCC were registered between March 2007 and July 2013. A dose of 10-15 Gy per fraction was given over three to four consecutive days, resulting in a total dose of 30-60 Gy. Overall and recurrence-free survivals were estimated from the date of the start of SBRT to the date of death, the last follow-up examination, or to the date of tumor recurrence. RESULTS The median follow-up period of all patients was 38.2 months, and the median tumor size was 1.7 cm. Overall survival (OS) rate at 5 years was 44.9%. Multivariate analyses revealed that age, Child-Pugh class, tumor size, and albumin levels were significant factors for OS. The 5-year local control rate was 91.3%. In multivariate analysis, tumor size and albumin were significantly associated with local tumor control. However, there was a negative correlation between total dose and tumor size in Pearson's correlation analysis (r = -0.

This paper reviews maladaptive trait development (DSM-5 Section III Criterion B), the development of DSM-5 Section II borderline personality disorder, and research on the development of identity, self-direction, empathy/mentalizing, and intimacy (DSM-5 Section III Criterion A). Combined, these previously disparate literatures begin to point to an integrated developmental theory of personality pathology, which suggests that Criterion A concepts (identity, self-direction, empathy, and intimacy) coalesce around the development of self, marking a discontinuous (qualitative) developmental shift. This developmental shift is a function of the demands placed on individuals to take on independent adult role function, combined with biologically-based maturational cognitive and emotional advances during adolescence. Section II personality disorder ensues when an integrated and coherent sense of self fails to develop, resulting in nonfulfilment of adult role function. In this sense, Criterion A self function can account for the onset of Section II personality disorder in adolescence, while Criterion B provides a useful descriptive account of continuous aspects of personality function over time.No funding supported the writing of this article. The author has nothing to disclose.Objective To propose a set of guidelines for use by health care organizations in the United States that seek useful, comparative clinical information and economic analysis on pharmaceutical products to make sound drug purchasing decisions. Practice innovation Based on a therapy intervention approach, the guidelines provide a structured framework to help managed care purchasers become more consistent in how they evaluate drug products for inclusion in the formulary. The guidelines factor in the need to examine the impact of new drug products on overall costs within the entire health system. Practice setting Intended for use by managed care organizations in the U.S. that purchase prescription drugs. Intervention Not applicable. Main outcome measure Not applicable. Results The guidelines provide MCOs with a new systematic approach for identifying the overall cost and clinical outcomes impact of drug therapies. The guidelines are designed to take into account the characteristics of the patient population being treated and the fact that patients generally are redistributed among different treatment categories once a new drug product is introduced, thus offering MCOs an analysis model that extends beyond the traditional partial cost-outcomes approach. Emphasis is placed on looking at the cost-outomes impact of a new drug or therapy within a systems or disease area framework in which the redistribution of patients between therapy options is explicitly modelled. The guidelines specify that the following information elements be used in pharmacoeonomic analysis product description, place in therapy, comparator products, therapy intervention framework, supporting clinical data, supporting pharmacoeconomic data, system impact assessments-costs-outcomes, overall assessment, and bibliography and supporting materials.Owing to the less volatile and less biodegradable nature of weathered fuel-contaminated soil, it cannot be easily remediated using conventional bioremediation approaches. Therefore, this study was aimed to enhance the landfarming bioremediation process by introducing post-oxidation for the degradation of the residual total petroleum hydrocarbons (TPH) in fuel-contaminated field soil. A laboratory-scale landfarming bioaugmentation process was performed by using oil-degrading microbes, nutrients, and surfactants, followed by chemical oxidation as a post treatment. The results demonstrated that the addition of microbes and nutrients gradually decreased the TPH concentration of the soil (initial TPH = 5932 ± 267 mg/kg) with a removal efficiency of 70-72% (TPH > 800 mg/kg; Korean limit for non-residential sites). However, the use of post-oxidation treatments with 5% KMnO4 decreased the TPH to approximately 401-453 mg/kg (TPH below 500 mg/kg; residential site limit) with an overall efficiency of 92-93% compared to the corresponding value of 13% for the control (water treatment). Performing landfarming through biodegradation followed by chemical oxidation as a post treatment could successfully remove the weathered TPH in soil below the regulatory limits. Furthermore, the post-oxidation treatment may oxidize the less biodegradable portions only after biodegradation, thereby minimizing the oxidant demand and enhancing the soil properties such as the pH, amount of natural substrates and microbial population.To foster teamwork, improve clinical excellence, and promote a culture of safety, perioperative leaders should have a clear understanding of the dynamics that affect clinician communication in the OR. We used social network analysis to characterize the typical OR clinician communication patterns at a military surgery center and determine how clinician relationships influenced individual behavior. We surveyed 50 surgical teams and used the data to develop six relational networks and a clinician communication effectiveness index. The study results showed that communication effectiveness increased in networks in which clinicians reported interacting frequently, having close working relationships, socializing, and seeking advice and providing advice to others. Increases in individual clinician centrality were associated with increased communication effectiveness. Participants rated anesthesia professionals as the most effective communicators, followed by perioperative nurses, surgeons, and surgical technologists. Perioperative leaders should consider surgical team familiarity as a potential option to optimize surgical care and improve communication effectiveness.Procedural anesthesia is administered by family physicians for a variety of conditions, including neuropathies, fracture reduction, foreign body removals, and complex wound management. https://www.selleckchem.com/products/VX-770.html A nerve block may be preferred because it provides effective regional anesthesia with less anesthetic. Nerve blocks require a thorough understanding of relevant anatomy, aiding the physician in optimizing the anesthesia effect while minimizing complications. Nerve blocks can be guided by bony landmarks, peripheral nerve stimulation, or ultrasonography. Ultrasound-guided nerve blocks are superior in decreasing procedural complications and procedure time. Physicians should be aware of these techniques to appropriately counsel their patients on procedural options. Nerve blocks of the ulnar, median, and radial nerves at the wrist and elbow provide effective anesthesia for a wide range of medical procedures in the upper extremity.

RESULTS Ten articles were included. Results were synthesized into six categories; support of physiologic labor and birth, the nurse's own personal view of labor, birth environment, techniques and tools, decision-making, and importance of latent labor discussion during the prenatal period. CLINICAL IMPLICATIONS Support for physiologic labor and birth is an important consideration for use of nonpharmacological methods during latent labor. The nurse's own personal view on labor support can influence the support that laboring women receive. Nurses may need additional education on labor support methods.BACKGROUND Nurses providing home visits were concerned that some mothers were not routinely using safe sleep practices for their newborns and infants. PURPOSE The purpose of this study was to listen to how home visit nurses offer education to their African American clients about the safe to sleep guidelines during the prenatal and postpartum periods and discuss ways nurses could support mothers to be more successful in using safe sleep practices. STUDY DESIGN AND METHODS A focus group was conducted with home visit nurses who partner with pregnant mothers and follow them through the first 2 years of their child's life. We asked the nurses to discuss how they offer information and education to their African American clients about safe sleep practices and what could be done to support adoption of the guidelines. A qualitative narrative approach was used for data analysis. RESULTS Seventeen home visit nurses participated in the focus group. We identified two overall themes with eight subthemes. The first theme focused on nurses' perceptions about challenges some mothers have in following the recommendations. The second theme included nurses' perspectives on how to better promote the safe sleep message and educating mothers within their cultural context. CLINICAL IMPLICATIONS Expectant and new mothers need advice and knowledge about the Safe to Sleep® guidelines that provide ways to decrease risk of infant death. Nurses must be aware of their clients' culture and beliefs so they can offer support and information on infant safety within that context.OBJECTIVES Women with opioid use disorder (OUD) in the USA are at risk for poor reproductive and sexual health (RSH) outcomes. The qualitative research presented here is part of a larger mixed methods study. The qualitative component used an implementation science framework to investigate provider and staff perspectives regarding the integration of RSH education and services for reproductive-age women in opioid treatment programs (OTPs) in North Carolina. METHODS Thirty-one semistructured interviews were conducted with providers and staff at 9 OTPs between November and December, 2017. The Consolidated Framework for Implementation Research (CFIR) was used to assess multilevel implementation contexts (eg, patient, provider, organizational) to identify barriers and facilitators that might influence effective intervention implementation. Interviews were audio-recorded, transcribed, coded, and analyzed to identify key themes. Deductive and inductive approaches were used. RESULTS Barriers included transportation, childcare, and time constraints (patient-level), lack of communication between providers (provider-level), lack of political will, competing priorities, and shortages of available resources (organizational-level). Facilitators included a group education approach (patient-level), strong communication (provider-level), and a culture of collaboration (organizational-level). CONCLUSIONS Assessing determinants of implementation is important to the development of RSH interventions. CFIR constructs were found to be important influences that could facilitate or hinder effective implementation. Integration of RSH education and services is a process, and, when addressed in stages, might be feasible. A broad range of RSH education and services has the potential to have a profound impact on the health of women with OUD and their children, their families, and their communities.BACKGROUND Health care professionals' work motivation is assumed to be crucial for the quality of hospital care, but it is unclear which type of motivation ought to be stimulated to improve quality. Motivation and similar concepts are aligned along a motivational continuum that ranges from (intrinsic) autonomous motivation to (extrinsic) controlled motivation to provide a framework for this mixed-methods systematic review. PURPOSE This mixed-methods systematic review aims to link various types of health care professionals' motivation directly and through their work-related behaviors to quality of care. METHODS Six databases were searched from January 1990 to August 2016. https://www.selleckchem.com/products/avelestat-azd9668.html Qualitative and quantitative studies were included if they reported on work motivation in relationship to work behavior and/or quality, and study participants were health care professionals working in hospitals in high-income countries. Study bias was evaluated using the Standard Quality Assessment Criteria for Evaluating Primary Research Papers from a Variety of Fields. The review protocol was registered in the PROSPERO database (CRD42016043284). RESULTS A total of 84 out of 6,525 unique records met the inclusion criteria. Results show that health care professionals' autonomous motivation improves their quality perceptions and work-related behaviors. Controlled motivation inhibits voicing behavior, but when balanced with autonomous motivation, it stimulates core task and proactive behavior. Proactivity is associated with increased quality of care perceptions. PRACTICE IMPLICATIONS To improve quality of care, policy makers and managers need to support health care professionals' autonomous motivation and recognize and facilitate proactivity as an essential part of health care professionals' jobs. Incentive-based quality improvements need to be complemented with aspects that stimulate autonomous motivation.BACKGROUND Nurses' workload has become increasingly recognized as an important determinant of nurse turnover and shortage and has been also associated with poorer quality of care. Despite strong evidence that heavy workloads have negative consequences, we still lack a comprehensive understanding of the workplace characteristics that contribute most to improving nurses' workload, the relative importance of each in doing so, or indeed the workplace characteristics and other factors that drive nurses' perceptions of their workload. PURPOSE The aim of this study was to examine workplace resources as antecedents of nurses' perceptions of their workload and to investigate their relative importance in explaining workload perceptions. We considered workplace resources related to staffing, professional relationships, and technology. METHODOLOGY The study sample comprised nurse-reported and administrative data from U.S. Veterans Health Administration hospitals between 2014 and 2017. Our multilevel analyses are based on data from 20,330 nurses working in 273 work groups at 123 hospitals.