A tale of two studies: is peripheral eosinophilia associated with Dientamoeba fragilis detection in adult stool samples?

The protozoan parasite Dientamoeba fragilis is a frequently isolated stool organism and postulated cause of gastrointestinal symptoms. Peripheral blood eosinophilia has been described. This is the first study amongst the Australasian adult population to assess the relationship between organism detection and eosinophilia. A case-control study took place over 7 years at a single Sydney laboratory site, evaluating patients with D. fragilis identified on stool using real-time PCR with a recent full blood count, to control groups with Giardia spp. and sequential negatives with neither organism. A nested study compared those with microscopic evidence of D. fragilis as a marker of disease burden, to molecular diagnosis alone. Sixty-four D. fragilis, 30 Giardia spp., and 94 sequential controls were enrolled. Only 60.1% of samples were preserved in sodium acetate-acetic acid formalin (SAF) fixative, indication mostly not documented. The major co-organism detected amongst all participants was Blastocystis sp., particularly in the D. fragilis cohort (37.2%). The most common pathogen amongst sequential controls was Campylobacter spp. (7.4%). Patients with D. fragilis were more likely (12.5%) to have a clinically significant eosinophilia (>0.5×109/L) compared to those with Giardia spp. (3.3%) or sequential controls (4.3%) (p=0.03). A significant difference was also noted in the overall median eosinophil count of those with D. fragilis versus all controls (0.2 vs 0.1×109/L, p=0.01); however, this was within the reference interval (where up to >0.5×109/L is accepted in healthy individuals within a typical population). No eosinophil difference was found between those with molecular versus additional microscopic detection of D. fragilis (0.1 vs 0.1×109/L). These results support an association between the identification of clinically significant peripheral blood eosinophilia and D. fragilis presence, which may impact the diagnostic approach to the patient with unexplained eosinophilia. Further prospective trials may help assess any significance further and the implication of co-carriage with other enteric organisms. The importance of clinical indication and need for appropriate fixative media in diagnostic parasitology are also highlighted.

Extraction and Emulsification of Carotenoids from Carrot Pomaces Using Oleic Acid.

This study aimed to use oleic acid-based ultrasonic-assisted extraction (UAE) to recover carotenoids from carrot pomace and emulsify the enriched-carotenoid oleic acid using spontaneous and ultrasonic-assisted emulsification. The extraction performance of oleic acid was compared with traditional organic solvents, including hexane, acetone, and ethyl acetate. The one-factor experiments were employed to examine the impact of UAE conditions, including liquid-to-solid ratios, temperature, ultrasonic power, and time, on the extraction yield of carotenoids and to find the conditional ranges for the optimization process. The response surface methodology was employed to optimize the UAE process. The second-order extraction kinetic model was used to find the mechanism of oleic acid-based UAE. After that, the enriched-carotenoid oleic acid obtained at the optimal conditions of UAE was used to fabricate nanoemulsions using spontaneous emulsification (SE), ultrasonic-assisted emulsification (UE), and SE-UE. The effect of SE and UE conditions on the turbidity of nanoemulsion was determined. Then, the physiochemical attributes of the nanoemulsion from SE, UE, and spontaneous ultrasonic-assisted emulsification (SE-UE) were determined using the dynamic light scattering method. The extraction yield of carotenoids from carrot pomace by using sonication was the highest. The adjusted optimal conditions were 39 mL/g of LSR, 50 °C, 12.5 min, and 350 W of ultrasonic power. Under optimal conditions, the carotenoid content attained was approximately 163.43 ± 1.83 µg/g, with the anticipated value (166 µg/g). The particle sizes of nanoemulsion fabricated at the proper conditions of SE, UE, and SE-UE were 31.2 ± 0.83, 33.8 ± 0.52, and 109.7 ± 8.24 nm, respectively. The results showed that SE and UE are suitable methods for fabricating nanoemulsions. The research provided a green approach for extracting and emulsifying carotenoids from carrot pomace.

Green extraction of phenolics and flavonoids from black mulberry fruit using natural deep eutectic solvents: optimization and surface morphology.

This study deployed ultrasonic-assisted extraction (UAE), combined with natural deep eutectic solvents (NADES), to extract phenolics and flavonoids from the black mulberry fruit, and the antioxidant activity was examined. The extraction yields of NADES-based UAE were assessed based on the yields of phenolics and flavonoids extracted from the black mulberry fruit. This study selected the molar ratios of hydrogen bond acceptors (HBA) and hydrogen bond donors HBD at 1:2 from previous studies. Choline chloride-lactic acid showed the highest solubility with phenolics and flavonoids among NADES systems. One-factor experiments evaluated the effect of UAE conditions (liquid-to-solid ratio (LSR), water content in NADES, temperature, and time) on TPC, TFC, and antioxidant activity. The suitable NADES-based UAE conditions for extracting phenolics and flavonoids from the black mulberry fruit were 60 ml/g of LSR, 40% water content, 70 °C, and 15 min. Response surface methodology with the Box-Behnken design model optimized the NADES-based UAE process based on response (TPC, TFC, ABTS, OH, and DPPH). The optimal conditions for the NADES-based UAE process were 70 ml/g of LSR, 38.9% water content in NADES, 67.9 °C, and 24.2 min of extraction time. The predicted values of the Box-Behnken design were compatible with the experimental results. Moreover, scanning electron microscopy (SEM) was used to survey the surface of black mulberry fruit with and without sonication. SEM can assist in demonstrating the destructive effect of NADES and ultrasonic waves on material surfaces. SEM findings indicated the high surface destruction capacity of NADES, which partially contributed to a superior extraction yield of NADES than conventional organic solvents. The study proposes an efficient and green method for extracting bioactive compounds from black mulberry fruits. The black mulberry fruit extracts can be applied to meat preservation and beverages with high antioxidants.

Optimizing Ultrasonic-Assisted and Microwave-Assisted Extraction Processes to Recover Phenolics and Flavonoids from Passion Fruit Peels.

This study optimized the ultrasonic-assisted extraction (UAE) and microwave-assisted extraction (MAE) processes to acquire phenolics and flavonoids from passion fruit peels using a mixture of ethanol, acetone, and water. An augmented simplex-centroid design was employed to find the suitable volume ratio among solvent ingredients to attain the highest extraction yield of phenolics and flavonoids. One-factor experiments were conducted to investigate the influence of UAE and MAE parameters on the recovery yield of phenolics and flavonoids before the two processes were optimized using Box-Behnken Design (BBD) models. The optimal UAE conditions for recovering phenolics and flavonoids from passion fruit peel powder (PFP) were 28 mL/g of liquid-to-solid ratio (LSR), 608 W of ultrasonic power, and 63 °C for 20 min to acquire total phenolic content (TPC) and total flavonoid content (TFC) at 39.38 mg of gallic acid equivalents per gram of dried basis (mg GAE/g db) and 25.79 mg of rutin equivalents per gram of dried basis (mg RE/g db), respectively. MAE conditions for attaining phenolics and flavonoids from PFP were 26 mL/g of LSR and 606 W of microwave power for 2 min to recover TPC and TFC at 17.74 mg GAE/g db and 8.11 mg RE/g db, respectively. The second-order kinetic model was employed to determine the UAE and MAE mechanism of TPC and TFC and the thermodynamic parameters of the extraction processes. The antioxidant activities of passion fruit peel extracts at optimal conditions were examined to compare the efficiency of UAE and MAE. This study establishes an effective approach for obtaining phenolics and flavonoids from passion fruit peels.

Evaporation-driven assembly of colloidal nanoparticles into clusters: A dissipative particle dynamics study.

In this work we consider a simulation strategy for assembling Janus nanoparticles in oil-in-water emulsion droplets by evaporation based on the dissipative particle dynamics method. Our simple method reproduces all the observed cluster configurations that have been explored experimentally. In addition, the kinetic process of cluster formation is systematically investigated. We observe a structural transition from spherical packings to minimal second-moment configurations via visual inspection and a simple angle parameter. We reveal that the critical volume at which the transition occurs is a cubic function of the number of particles, N. Our approach also allows us to anticipate higher-order clusters, overcoming the limitations of the standard methods in the literature. Similarly to small N values, we find that for each N in the range of 16-39, all final clusters have a unique configuration.

Producing bacterial cellulose from industrial recycling paper waste sludge.

This study aimed to produce bacterial cellulose from paper waste sludge (PWS) as a method of utilizing the cellulose source from the remaining pulp in the material. Initially, PWS was hydrolyzed by sulfuric acid to create an enriched-reducing sugar hydrolysate. One-factor experiments were conducted with a fixed amount of PWS (5 g) to investigate the influence of hydrolysis conditions, including water, sulfuric acid addition, temperature, and retention time, on the production yield of reducing sugars. Based on these results, the Box-Behnken model was designed to optimize the hydrolysis reaction. The optimal hydrolysis conditions were 10 ml/g of the sulfuric acid solution (30.9%) at 105.5 °C for 90 min of retention time 0.81 (gGE/g PWS), corresponding to a conversion yield of 40.5%). Subsequently, 100 ml of the filtered and neutralized PWS hydrolysate was used as the culture to produce the bacterial cellulose (BC) using Acetobacter xylinum, which produced 12 g/L of bacterial cellulose. The conversion yield of bacterial cellulose calculated as the ratio of the weight of produced bacterial cellulose to that of cellulose in PWS reached 33.3%. The structure of the obtained BC was analyzed using scanning electron microscopy (SEM) and X-ray diffraction (XRD) to indicate the formation of nano-cellulose fiber networks. This research proposed a combined method to convert paper waste sludge into bacterial cellulose, demonstrating the potential for waste utilization and sustainable production of paper industries for added-value products.

P38 kinase in gastrointestinal cancers.

Gastrointestinal cancers are a leading cause of cancer morbidity and mortality worldwide with 4.2 million new cases and 3.2 million deaths estimated in 2020. Despite the advances in primary and adjuvant therapies, patients still develop distant metastases and require novel therapies. Mitogen­activated protein kinase (MAPK) cascades are crucial signaling pathways that regulate many cellular processes, including proliferation, differentiation, apoptosis, stress responses and cancer development. p38 Mitogen Activated Protein Kinases (p38 MAPKs) includes four isoforms: p38α (MAPK14), p38ß (MAPK11), p38γ (MAPK12), and p38δ (MAPK13). p38 MAPK was first identified as a stress response protein kinase that phosphorylates different transcriptional factors. Dysregulation of p38 pathways, in particular p38γ, are associated with cancer development, metastasis, autophagy and tumor microenvironment. In this article, we provide an overview of p38 and p38γ with respect to gastrointestinal cancers. Furthermore, targeting p38γ is also discussed as a potential therapy for gastrointestinal cancers.

Targeting fat mass and obesity-associated protein mitigates human colorectal cancer growth in vitro and in a murine model.

Introduction: Colorectal cancer (CRC) remains a significant cause of cancer related mortality. Fat mass and obesity-associated protein (FTO) is a m6A mRNA demethylase that plays an oncogenic role in various malignancies. In this study we evaluated the role of FTO in CRC tumorigenesis. Methods: Cell proliferation assays were conducted in 6 CRC cell lines with the FTO inhibitor CS1 (50-3200 nM) (± 5-FU 5-80 mM) and after lentivirus mediated FTO knockdown. Cell cycle and apoptosis assays were conducted in HCT116 cells (24 h and 48 h, 290 nM CS1). Western blot and m6A dot plot assays were performed to assess CS1 inhibition of cell cycle proteins and FTO demethylase activity. Migration and invasion assays of shFTO cells and CS1 treated cells were performed. An in vivo heterotopic model of HCT116 cells treated with CS1 or with FTO knockdown cells was performed. RNA-seq was performed on shFTO cells to assess which molecular and metabolic pathways were impacted. RT-PCR was conducted on select genes down-regulated by FTO knockdown. Results: We found that the FTO inhibitor, CS1 suppressed CRC cell proliferation in 6 colorectal cancer cell lines and in the 5-Fluorouracil resistant cell line (HCT116-5FUR). CS1 induced cell cycle arrest in the G2/M phase by down regulation of CDC25C and promoted apoptosis of HCT116 cells. CS1 suppressed in vivo tumor growth in the HCT116 heterotopic model (p< 0.05). Lentivirus knockdown of FTO in HCT116 cells (shFTO) mitigated in vivo tumor proliferation and in vitro demethylase activity, cell growth, migration and invasion compared to shScr controls (p< 0.01). RNA-seq of shFTO cells compared to shScr demonstrated down-regulation of pathways related to oxidative phosphorylation, MYC and Akt/ mTOR signaling pathways. Discussion: Further work exploring the targeted pathways will elucidate precise downstream mechanisms that can potentially translate these findings to clinical trials.

Cellulose Nanocrystals-Incorporated Thermosensitive Hydrogel for Controlled Release, 3D Printing, and Breast Cancer Treatment Applications.

In situ-gel-forming thermoresponsive copolymers have been widely exploited in controlled delivery applications because their critical gel temperature is similar to human body temperature. However, there are limitations to controlling the delivery of biologics from a hydrogel network because of the poor networking and reinforcement between the copolymer networks. This study developed an in situ-forming robust injectable and 3D printable hydrogel network based on cellulose nanocrystals (CNCs) incorporated amphiphilic copolymers, poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-lactide (PCLA). In addition, the physicochemical and mechanical properties of injectable hydrogels were controlled by physically incorporating CNCs with amphiphilic PCLA copolymers. CNCs played an unprecedented role in physically reinforcing the PCLA copolymers' micelle network via intermicellar bridges. Apart from that, the free-flowing closely packed rod-like CNCs incorporated PCLA micelle networks at low temperature transformed to a stable viscoelastic hydrogel network at physiological temperature. CNC incorporated PCLA copolymer sols effectively coordinated with hydrophobic doxorubicin and water-soluble lysozyme by a combination of hydrophobic and hydrogen bonding interaction and controlled the release of biologics. As shown by the 3D printing results, the biocompatible PCLA hydrogels continuously extruded during printing had good injectability and maintained high shape fidelity after printing without any secondary cross-linking steps. The interlayer bonding between the printed layers was high and formed stable 3D structures up to 10 layers. Subcutaneous injection of free-flowing CNC incorporated PCLA copolymer sols to BALB/c mice formed a hydrogel instantly and showed controlled biodegradation of the hydrogel depot without induction of toxicity at the implantation sites or surrounding tissues. At the same time, the in vivo antitumor effect on the MDA-MB-231 tumor xenograft model demonstrated that DOX-loaded hydrogel formulation significantly inhibited the tumor growth. In summary, the CNC incorporated biodegradable hydrogels developed in this study exhibit a prolonged release with special release kinetics for hydrophobic and hydrophilic biologics.

Optimized Cellulase-Hydrolyzed Deoiled Coconut Cake Powder as Wheat Flour Substitute in Cookies.

Deoiled coconut cake powder (DCCP) was hydrolyzed to reduce the ratio of insoluble/soluble dietary fiber (RIS) by partially converting insoluble dietary fiber to soluble using Celluclast 1.5 L, a commercial cellulase preparation in citrate buffer medium. Firstly, the influence of citrate buffer amount, enzyme concentration, pH, and retention time on the enzymatic hydrolysis efficiency was investigated. Then, response surface methodology (RSM) was employed to optimize the process in which the insoluble and soluble dietary fiber contents were the responses. The results revealed that 10.3 g buffer/g of materials, 3.7 U/g of the materials, and 60 min of retention time were the optimal conditions for the enzymatic hydrolysis to obtain the insoluble and soluble contents of 68.21%db and 8.18%db, respectively. Finally, DCCP or hydrolyzed DCCP (HDCCP) was partially substituted for wheat flour at different replacement ratios in a cookie recipe at 0, 10, 20, 30, and 40%. The cookies with a 10% replacement ratio of hydrolyzed deoiled coconut cake powders had a lower RIS by more than two folds those of DCCP and had the same sensorial score as the control sample. This study proposed that Celluclast 1.5 L effectively reduced RIS by partially converting insoluble to soluble dietary fiber, improving the soluble dietary fiber content in fiber-enriched cookies.

A comparison of SARS-CoV-2 RNA extraction with the QuickGene-810 Nucleic Acid Isolation System compared to the EZ1 Advanced DSP Virus Kit.

The QuickGene-810 Nucleic Acid Isolation System is a semi-automated extraction platform which may be used for RNA extraction. New methods were required to support the rapid increase in respiratory virus testing during the SARS-CoV-2 pandemic. The aim of this study was to assess SARS-CoV-2 RNA extraction using the QuickGene-810 kit compared to the EZ1 Advanced Extraction Platform for use on the AusDiagnostics SARS-CoV-2, Influenza and RSV 8-well RT-PCR assay. Qualitative results from all clinical samples were concordant between the QuickGene-810 and the EZ1 extraction methods, demonstrating that the QuickGene-810 kit is suitable for use in pathogen diagnostics. However, there was an average difference of approximately two cycles between the cycle threshold (Ct) values for both SARS-CoV-2 targets, suggesting that the EZ1 kit yields a higher concentration of nucleic acid extract, possibly related to its use of carrier RNA and/or smaller elution volume, which infers the possibility of false negative results for samples with very low viral loads.

Clinical Performance of Real-Time Polymerase Chain Reaction for Strongyloides stercoralis Compared with Serology in a Nonendemic Setting.

Strongyloides stercoralis is a nematode endemic to subtropical and tropical regions that may cause asymptomatic carriage, peripheral eosinophilia, cutaneous, gastrointestinal, and pulmonary disease, or hyperinfection syndrome. Conventional diagnostic methods for strongyloidiasis include feces microscopy and culture, with low sensitivity in chronic infection due to the low helminth burden, and serology, which may be prone to false-negative results with immunocompromise and false-positive results with other infections and immunological disorders. We evaluated a laboratory-developed real-time polymerase chain reaction (RT-PCR), detecting the 18S SSU ribosomal RNA gene, compared with conventional diagnostic methods, using serology via ELISA as the gold-standard. The population studied included tertiary hospital inpatients and outpatients residing in a nonendemic area. Seven hundred fifty unfixed stool specimens submitted sequentially between 2014 and 2018 were tested for S. stercoralis via microscopy and RT-PCR. Agar plate culture (APC), Harada-Mori culture (HMC), and ELISA were performed in conjunction with 141, 135, and 177 of the specimens, respectively. RT-PCR yielded 13 positive and 730 negative results, with inhibition in seven specimens. ELISA yielded 53 positive, 18 equivocal, and 106 negative results. Results for direct diagnostic methods obtained after treatment with ivermectin were excluded from the performance analysis. Compared with ELISA, RT-PCR, microscopy, APC, and HMC exhibited sensitivities of 38%, 6%, 3%, and 0%, respectively, and specificities of 100%. Given the low sensitivities commensurate with testing a population with remote infection and thus low parasite burden, we recommend a combination of serological and molecular diagnostic testing to achieve the best balance of sensitivity and specificity.

High current density electroreduction of CO2 into formate with tin oxide nanospheres.

In this study, we demonstrate three-dimensional (3D) hollow nanosphere electrocatalysts for CO2 conversion into formate with excellent H-Cell performance and industrially-relevant current density in a 25 cm2 membrane electrode assembly electrolyzer device. Varying calcination temperature maximized formate production via optimizing the crystallinity and particle size of the constituent SnO2 nanoparticles. The best performing SnO2 nanosphere catalysts contained ~ 7.5 nm nanocrystals and produced 71-81% formate Faradaic efficiency (FE) between -0.9 V and -1.3 V vs. the reversible hydrogen electrode (RHE) at a maximum formate partial current density of 73 ± 2 mA cmgeo-2 at -1.3 V vs. RHE. The higher performance of nanosphere catalysts over SnO2 nanoparticles and commercially-available catalyst could be ascribed to their initial structure providing higher electrochemical surface area and preventing extensive nanocrystal growth during CO2 reduction. Our results are among the highest performance reported for SnO2 electrocatalysts in aqueous H-cells. We observed an average 68 ± 8% FE over 35 h of operation with multiple on/off cycles. In situ Raman and time-dependent X-ray diffraction measurements identified metallic Sn as electrocatalytic active sites during long-term operation. Further evaluation in a 25 cm2 electrolyzer cell demonstrated impressive performance with a sustained current density of 500 mA cmgeo-2 and an average 75 ± 6% formate FE over 24 h of operation. Our results provide additional design concepts for boosting the performance of formate-producing catalysts.

Evaluation of the influenza and respiratory syncytial virus (RSV) targets in the AusDiagnostics SARS-CoV-2, Influenza and RSV 8-well assay: sample pooling increases testing throughput.

During the COVID-19 pandemic, sample pooling has proven an effective strategy to overcome the limitations of reagent shortages and expand laboratory testing capacity. The inclusion of influenza and respiratory syncytial virus (RSV) in a multiplex tandem PCR platform with SARS-CoV-2 provides useful diagnostic and infection control information. This study aimed to evaluate the performance of the influenza and RSV targets in the AusDiagnostics SARS-CoV-2, Influenza and RSV 8-well assay, including the effect of pooling samples on target detection. RSV target detection in clinical samples was compared to the Cepheid Xpert Xpress Flu/RSV assay as a reference standard. Samples were then tested in pools of four and detection rates were compared. Owing to the unavailability of clinical samples for influenza, only the effect of sample pooling on simulated samples was evaluated for these targets. RSV was detected in neat clinical samples with a positive percent agreement (PPA) of 100% and negative percent agreement (NPA) of 99.5% compared to the reference standard, demonstrating 99.7% agreement. This study demonstrates that sample pooling by four increases the average Ct value by 2.24, 2.29, 2.20 and 1.91 cycles for the target's influenza A, influenza A typing, influenza B and RSV, respectively. The commercial AusDiagnostics SARS-CoV-2, Influenza and RSV 8-well assay was able to detect influenza and RSV at an intermediate concentration within the limit of detection of the assay. Further studies to explore the applicability of sample pooling at the lower limit of detection of the assay is needed. Nevertheless, sample pooling has shown to be a viable strategy to increase testing throughput and reduce reagent usage. In addition, the multiplexed platform targeting various respiratory viruses assists with public health and infection control responses, clinical care, and patient management.

Injectable Hydrogel Based on Protein-Polyester Microporous Network as an Implantable Niche for Active Cell Recruitment.

Despite the potential of hydrogel-based localized cancer therapies, their efficacy can be limited by cancer recurrence. Therefore, it is of great significance to develop a hydrogel system that can provoke robust and durable immune response in the human body. This study has developed an injectable protein-polymer-based porous hydrogel network composed of lysozyme and poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-lactide (PCLA) (Lys-PCLA) bioconjugate for the active recruitment dendritic cells (DCs). The Lys-PCLA bioconjugates are prepared using thiol-ene reaction between thiolated lysozyme (Lys-SH) and acrylated PCLA (PCLA-Ac). The free-flowing Lys-PCLA bioconjugate sols at low temperature transformed to immovable gel at the physiological condition and exhibited stability upon dilution with buffers. According to the in vitro toxicity test, the Lys-PCLA bioconjugate and PCLA copolymer were non-toxic to RAW 263.7 cells at higher concentrations (1000 µg/mL). In addition, subcutaneous administration of Lys-PCLA bioconjugate sols formed stable hydrogel depot instantly, which suggested the in situ gel forming ability of the bioconjugate. Moreover, the Lys-PCLA bioconjugate hydrogel depot formed at the interface between subcutaneous tissue and dermis layers allowed the active migration and recruitment of DCs. As suggested by these results, the in-situ forming injectable Lys-PCLA bioconjugate hydrogel depot may serve as an implantable immune niche for the recruitment and modification of DCs.

A new triterpenoid saponin from Glinus oppositifolius.

From the ethanol extract of Glinus oppositifolius, collected at Phu Yen province, Viet Nam, one new triterpenoid saponin (1) and four known compounds (2-5) were isolated. By means of NMR and HR-ESI-MS analyses, their structure was elucidated as 3-O-(ß-D-xylopyranosyl-(1→3)-ß-D-xylopyranosyl)spergulagenin A or glinusopposide V (1), glinusopposide L (2), spergulin B (3), vitexin (4) and astralagin (5). Two compounds (1-2) showed weak inhibitory activity against α-glucosidase.

Mechanistic insights into the dehydrogenation of formaldehyde, formic acid and methanol using the Pt4 cluster as a promising catalyst.

Reaction mechanisms of the dehydrogenation of formaldehyde, formic acid and methanol on the Pt4 cluster were computationally investigated using density functional theory (DFT) with the B3LYP functional in the conjunction with the aug-cc-pVTZ basis sets for H, C and O atoms, and the cc-pVDZ-PP basis set for Pt. Herein, the key mechanistic aspects of three possible pathways of the dehydrogenation of these compounds are summarized. The results indicate that the formation of H2 and CO or CO2 molecules is more energetically favorable than the generation of H and H2O, HCHO products. Generally, the formation of H2 molecule in the presence of catalysts is more favorable than the direct decomposition of either HCHO, HCOOH or CH3OH molecule. The use of Pt4 catalyst significantly reduces the energy barriers for C-H and O-H bond cleavage of all three compounds to 14, 9 and 12 kcal/mol, respectively. The decomposition of HCOOH is found to be the most energetically favorable. In addition, the mechanistic insights of the reactions confirm the reduction of the energy barriers of the gas-phase dehydrogenation by 67-82 kcal/mol and bring it to the values smaller than 14 kcal/mol in the presence of the Pt4 catalysts.

Undocumented immigrants and mental health: A systematic review of recent methodology and findings in the United States.

This study reviewed the methodology and findings of 44 peer-reviewed studies on psychosocial risk factors associated with mental health outcomes among undocumented immigrants (UIs) in the United States. Findings showed a considerable advancement over the past seven years in the methods and measures used in the included studies. Nonetheless, there is a need for continued methodological rigor, innovative study designs, greater diversity of samples, and in-depth exploration of constructs that facilitate resilience. Identifying avenues to reduce risk in this population is essential to inform intervention and advocacy efforts aimed at overcoming distress from the current U.S. anti-immigrant and socio-political climate.

Inhibition of de novo pyrimidine synthesis augments Gemcitabine induced growth inhibition in an immunocompetent model of pancreatic cancer.

Leflunomide (Lef) is an agent used in autoimmune disorders that interferes with DNA synthesis. De Novo pyrimidine synthesis is a mechanism of Gemcitabine (Gem) resistance in pancreatic cancer. This study aims to assess the efficacy and changes in the tumor microenvironment of Lef monotherapy and in combination with Gem, in a syngeneic mouse model of pancreatic cancer. Methods: MTS proliferation assays were conducted to assess growth inhibition by Gem (0-20 nM), Lef (0-40 uM) and Gem+Lef in KPC (KrasLSL.G12D/+;p53R172H/+; PdxCretg/+) cells in vitro. An in vivo heterotopic KPC model was used and cohorts were treated with: PBS (control), Gem (75 mg/kg/q3d), Lef (40 mg/kg/d), or Gem+Lef. At d28 post-treatment, tumor burden, proliferation index (Ki67), and vascularity (CD31) were measured. Changes in the frequency of peripheral and intratumoral immune cell subsets were evaluated via FACS. Liquid chromatography-mass spectrometry was used for metabolomics profiling. Results: Lef inhibits KPC cell growth and synergizes with Gem in vitro (P<0.05; Combination Index 0.44 (<1 indicates synergy). In vivo, Lef alone and in combination with Gem delays KPC tumor progression (P<0.001). CTLA-4+T cells are also significantly decreased in tumors treated with Lef, Gem or in combination (Gem+Lef) compared to controls (P<0.05). Combination therapy also decreased the Ki67 and vascularity (P<0.01). Leflunomide inhibits de novo pyrimidine synthesis both in vitro (p<0.0001) and in vivo (p<0.05). Conclusions: In this study, we demonstrated that Gem+Lef inhibits pancreatic cancer growth, decrease T cell exhaustion, vascularity and as proof of principle inhibits de novo pyrimidine synthesis. Further characterization of changes in adaptive immunity are necessary to characterize the mechanism of tumor growth inhibition and facilitate translation to a clinical trial.

Aminoglycosides in Critically Ill Septic Patients With Acute Kidney Injury Receiving Intermittent Hemodialysis: A Multicenter, Observational Study.

PURPOSE: Data on aminoglycoside stewardship in critically ill septic patients with acute kidney injury (AKI) needing intermittent hemodialysis (IH) are scarce. The first objective of the study was to evaluate whether aminoglycoside administration occurs before vs after IH in the real-life management of critically ill septic patients with AKI needing IH. The second objective was to assess the delay in achieving a potential reinjection window for a second dose of aminoglycoside, which should be obtained with a postdialysis vs predialysis regimen. METHODS: A post hoc observational analysis of a multicenter randomized trial of critically ill patients with AKI needing renal replacement therapy was conducted. Inclusion criteria consisted of any patients receiving IH for AKI during an antimicrobial therapy for a septic episode. FINDINGS: Among 206 of 341 septic patients (60%) receiving aminoglycosides, 90 underwent IH (46 with previous continuous renal replacement therapy and 44 without). Amikacin and gentamicin were administered for a mean (SD) of 2.2 (1.5) and 2.5 (2.1) days with mean (SD) doses of 20.6 (6.6) and 5.4 (2.5) mg/kg, respectively. In the 44 patients undergoing exclusive IH, aminoglycosides were administered in a predialysis in 53% of episodes versus 35% in a postdialysis schedule. The first Cmin target was obtained earlier with a predialysis vs postdialysis schedule (33.9 [14.2] hours vs 50.9 [12.2] hours, P = 0.009). IMPLICATIONS: Despite being less frequently used than a predialysis schedule, the postdialysis administration of aminoglycosides remains a regular practice in the intensive care unit. A predialysis schedule of administration in IH reduces the interval time to tolerable aminoglycoside redosing.