Obesity Inhibits Alveolar Macrophage Responses to Pseudomonas aeruginosa Pneumonia via Upregulation of Prostaglandin E2 in Male, but Not Female, Mice.

Obesity is associated with increased morbidity and mortality during bacterial pneumonia. Cyclooxygenase-2 (COX-2) and PGE2 have been shown to be upregulated in patients who are obese. In this study, we investigated the role of obesity and PGE2 in bacterial pneumonia and how inhibition of PGE2 improves antibacterial functions of macrophages. C57BL/6J male and female mice were fed either a normal diet (ND) or high-fat diet (HFD) for 16 wk. After this time, animals were infected with Pseudomonas aeruginosa in the lung. In uninfected animals, alveolar macrophages were extracted for either RNA analysis or to be cultured ex vivo for functional analysis. HFD resulted in changes in immune cell numbers in both noninfected and infected animals. HFD animals had increased bacterial burden compared with ND animals; however, male HFD animals had higher bacterial burden compared with HFD females. Alveolar macrophages from HFD males had decreased ability to phagocytize and kill bacteria and were shown to have increased cyclooxygenase-2 and PGE2. Treating male, but not female, alveolar macrophages with PGE2 leads to increases in cAMP and decreased bacterial phagocytosis. Treatment with lumiracoxib-conjugated nanocarriers targeting alveolar macrophages improves bacterial phagocytosis and clearance in both ND and HFD male animals. Our study highlights that obesity leads to worse morbidity during bacterial pneumonia in male mice because of elevated PGE2. In addition, we uncover a sex difference in both obesity and infection, because females produce high basal PGE2 but because of a failure to signal via cAMP do not display impaired phagocytosis.

Digital and Absolute Assays for Low Abundance Molecular Biomarkers.

There has been a recent surge of advances in biomolecular assays based on the measurement of discrete molecular targets as opposed to signals averaged across molecular ensembles. Many of these "digital" assay designs derive from now-mature technologies involving single-molecule imaging and microfluidics and provide an assortment of new modalities to quantify nucleic acids and proteins in biospecimens such as blood and tissue homogenates. A primary new benefit is the robust detection of trace analytes at attomolar to femtomolar concentrations for which many ensemble assays cannot distinguish signals above noise levels. In addition, multiple biomolecules can be differentiated within a mixture using optical barcodes, with much faster and simpler readouts compared with sequencing methods. In ideal digital assays, signals should, in theory, further represent absolute molecular counts, rather than relative levels, eliminating the need for calibration standards that are the mainstay of typical assays. Several digital assay platforms have now been commercialized but challenges hinder the adoption and diversification of these new formats, as there are broad needs to balance sensitivity and dynamic range of detection, increase analyte multiplexing, improve sample throughput, and reduce cost. Our lab and others have developed technologies to address these challenges by redesigning molecular probes and labels, improving molecular transport within detection focal volumes, and applying solution-based readout methods in flow.This Account describes the principles, formats, and design constraints of digital biomolecular assays that apply optical labels toward the goal of simple and routine target counting that may ultimately approach absolute readout standards. The primary challenges can be understood from fundamental concepts in thermodynamics and kinetics of association reactions, mass transport, and discrete statistics. Major advances include (1) new inorganic nanocrystal probes for more robust counting compared with dyes, (2) diverse molecular amplification tools that endow attachment of numerous labels to single targets, (3) specialized surfaces with patterned features for electromagnetic coupling to labels for signal amplification, (4) surface capture enhancement methods to concentrate targets through disruption of diffusion depletion zones, and (5) flow counting in which analytes are rapidly counted in solution without pull-down to a surface. Further progress and integration of these tools for biomolecular counting could improve the precision of laboratory measurements in life sciences research and benefit clinical diagnostic assays for low abundance biomarkers in limiting biospecimen volumes that are out of reach of traditional ensemble-level bioassays.

High-resolution 1H-MRSI at 9.4 T by integrating relaxation enhancement and subspace imaging.

Achieving high-resolution and high signal-to-noise ratio (SNR) in vivo metabolic imaging via fast magnetic resonance spectroscopic imaging (MRSI) has been a longstanding challenge. This study combines the methods of relaxation enhancement (RE) and subspace imaging for the first time, enabling high-resolution and high-SNR in vivo MRSI of rodent brains at 9.4 T. Specifically, an RE-based chemical shift imaging sequence, which combines a frequency-selective pulse to excite only the metabolite frequencies with minimum perturbation of the water spins and a pair of adiabatic pulses to spatially localize the slice of interest, is designed and evaluated in vivo. This strategy effectively shortens the apparent T1 of metabolites, thereby increasing the SNR during relatively short repetition time ((TR) compared with acquisitions with only spatially selective wideband excitations, and does not require water suppression. The SNR was further enhanced via a state-of-the-art subspace reconstruction method. A novel subspace learning strategy tailored for 9.4 T and RE acquisitions is developed. In vivo, high-resolution (e.g., voxel size of 0.6 × 0.6 × 1.5 mm3) MRSI of both healthy mouse brains and a glioma-bearing mouse brain in 12.5 min has been demonstrated.

Analysis of the adhesive secreting cells of Arion subfuscus: insights into the role of microgels in a tough, fast-setting hydrogel glue.

The slug Arion subfuscus produces a tough, highly adhesive defensive secretion. This secretion is a flexible hydrogel that is toughened by a double network mechanism. While synthetic double network gels typically require extensive time to prepare, this slug creates a tough gel in seconds. To gain insight into how the glue forms a double-network hydrogel so rapidly, the secretory apparatus of this slug was analyzed. The goal was to determine how the major components of the glue were distributed and mixed. Most of the glue comes from two types of large unicellular glands; one secretes polyanionic polysaccharides in small, membrane-bound packets, the other secretes proteins that appear to form a cross-linked network. The latter gland shows distinct regions where cross-linking appears to be occurring. These regions are darker, more homogeneous and appear more solid than the rest of the secretory material. The enzyme catalase is highly abundant in these regions, as are basic proteins. These results suggest that a rapid oxidation event occurs in this protein-containing gland, triggering cross-linking before the glue is released. The cross-linked microgels would then join together after secretion to form a granular hydrogel. The polysaccharide-filled packets would be mixed and interspersed among these microgels and may contribute to joining them together. This is an unexpected and highly effective way to form a tough gel rapidly.

Five-year recurrence/survival after pancreatoduodenectomy for pancreatic adenocarcinoma: does pre-existing diabetes matter? Results from the Recurrence After Whipple's (RAW) study.

BACKGROUND: Diabetes mellitus (DM) has a complex relationship with pancreatic cancer. This study examines the impact of preoperative DM, both recent-onset and pre-existing, on long-term outcomes following pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). METHODS: Data were extracted from the Recurrence After Whipple's (RAW) study, a multi-centre cohort of PD for pancreatic head malignancy (2012-2015). Recurrence and five-year survival rates of patients with DM were compared to those without, and subgroup analysis performed to compare patients with recent-onset DM (less than one year) to patients with established DM. RESULTS: Out of 758 patients included, 187 (24.7%) had DM, of whom, 47 of the 187 (25.1%) had recent-onset DM. There was no difference in the rate of postoperative pancreatic fistula (DM: 5.9% vs no DM 9.8%; p = 0.11), five-year survival (DM: 24.1% vs no DM: 22.9%; p = 0.77) or five-year recurrence (DM: 71.7% vs no DM: 67.4%; p = 0.32). There was also no difference between patients with recent-onset DM and patients with established DM in postoperative outcomes, recurrence, or survival. CONCLUSION: We found no difference in five-year recurrence and survival between diabetic patients and those without diabetes. Patients with pre-existing DM should be evaluated for PD on a comparable basis to non-diabetic patients.

Design and Synthesis of CdHgSe/HgS/CdZnS Core/Multi-Shell Quantum Dots Exhibiting High-Quantum-Yield Tissue-Penetrating Shortwave Infrared Luminescence.

Cdx Hg1- x Se/HgS/Cdy Zn1- y S core/multi-shell quantum dots (QDs) exhibiting bright tissue-penetrating shortwave infrared (SWIR; 1000-1700 nm) photoluminescence (PL) are engineered. The new structure consists of a quasi-type-II Cdx Hg1- x Se/HgS core/inner shell domain creating luminescent bandgap tunable across SWIR window and a wide-bandgap Cdy Zn1- y S outer shell boosting the PL quantum yield (QY). This compositional sequence also facilitates uniform and coherent shell growth by minimizing interfacial lattice mismatches, resulting in high QYs in both organic (40-80%) and aqueous (20-70%) solvents with maximum QYs of 87 and 73%, respectively, which are comparable to those of brightest visible-to-near infrared QDs. Moreover, they maintain bright PL in a photocurable resin (QY 40%, peak wavelength ≈ 1300 nm), enabling the fabrication of SWIR-luminescent composites of diverse morphology and concentration. These composites are used to localize controlled amounts of SWIR QDs inside artificial (Intralipid) and porcine tissues and quantitatively evaluate the applicability as luminescent probes for deep-tissue imaging.

Minimal geological methane emissions during the Younger Dryas-Preboreal abrupt warming event.

Methane (CH4) is a powerful greenhouse gas and plays a key part in global atmospheric chemistry. Natural geological emissions (fossil methane vented naturally from marine and terrestrial seeps and mud volcanoes) are thought to contribute around 52 teragrams of methane per year to the global methane source, about 10 per cent of the total, but both bottom-up methods (measuring emissions) and top-down approaches (measuring atmospheric mole fractions and isotopes) for constraining these geological emissions have been associated with large uncertainties. Here we use ice core measurements to quantify the absolute amount of radiocarbon-containing methane (14CH4) in the past atmosphere and show that geological methane emissions were no higher than 15.4 teragrams per year (95 per cent confidence), averaged over the abrupt warming event that occurred between the Younger Dryas and Preboreal intervals, approximately 11,600 years ago. Assuming that past geological methane emissions were no lower than today, our results indicate that current estimates of today's natural geological methane emissions (about 52 teragrams per year) are too high and, by extension, that current estimates of anthropogenic fossil methane emissions are too low. Our results also improve on and confirm earlier findings that the rapid increase of about 50 per cent in mole fraction of atmospheric methane at the Younger Dryas-Preboreal event was driven by contemporaneous methane from sources such as wetlands; our findings constrain the contribution from old carbon reservoirs (marine methane hydrates, permafrost and methane trapped under ice) to 19 per cent or less (95 per cent confidence). To the extent that the characteristics of the most recent deglaciation and the Younger Dryas-Preboreal warming are comparable to those of the current anthropogenic warming, our measurements suggest that large future atmospheric releases of methane from old carbon sources are unlikely to occur.

Endoscopic ultrasound guided gastrojejunostomy in the treatment of gastric outlet obstruction: multi-centre experience from the United Kingdom.

BACKGROUND: Endoscopic ultrasound guided gastrojejunostomy (EUS-GJ) with lumen apposing metal stents has recently emerged as a viable option, as an alternative to surgical gastrojejunostomy and endoscopic enteral stenting, for managing gastric outlet obstruction (GOO). We aim to perform a retrospective analysis of the efficacy, safety and outcomes of EUS-GJ performed at three tertiary institutions in the United Kingdom. METHODS: Consecutive patients who underwent EUS-GJ between August 2018 and March 2021 were identified from a prospectively maintained database. Data were obtained from interrogation of electronic health records. RESULTS: Twenty five patients (15 males) with a median age of 63 years old (range 29-80) were included for analysis. 88% (22/25) of patients had GOO due to underlying malignant disease. All patients were deemed surgically inoperable or at high surgical risk. Both technical and clinical success were achieved in 92% (23/25) of patients. There was an improvement in the mean Gastric Outlet Obstruction Scoring System scores following a technically successful EUS-GJ (2.52 vs 0.68, p < 0.01). Adverse events occurred in 2/25 patients (8%), both due to stent maldeployment necessitating endoscopic closure of the gastric defect with clips. Long-term follow-up data were available for 21 of 23 patients and the re-intervention rate was 4.8% (1/21) over a median follow-up period of 162 (range 5-474) days. CONCLUSION: EUS-GJ in carefully selected patients is an effective and safe procedure when performed by experienced endoscopists.

fullROC: An R package for generating and analyzing eyewitness-lineup ROC curves.

A police lineup is a procedure in which a suspect is surrounded by known-innocent persons (fillers) and presented to the witness for an identification attempt. The purpose of a lineup is to test the investigator's hypothesis that the suspect is the culprit, and the investigator uses the witness' identification decision and the associated confidence level to inform this hypothesis. Whereas suspect identifications provide evidence of guilt, filler identifications and rejections provide evidence of innocence. Despite the capacity of lineups to provide exculpatory information, past research has focused, almost exclusively, on inculpatory behaviors. We recently developed a method for incorporating all lineup outcomes in a single receiver operator characteristic (ROC) curve. The area under the full lineup ROC curve reflects the total capacity of a lineup procedure to discriminate guilty suspects from innocent suspects. Here, we introduce a Comprehensive R Archive Network (CRAN) package, fullROC, to support eyewitness researchers in using the full ROC approach to analyze lineup data. The fullROC package provides functions for adjusting identification rates, generating full ROC curves for lineup data, computing the area under the ROC curves (AUC), and statistically comparing the AUCs of different lineups. Using both simulated and empirical data, we illustrate the functionality of the fullROC CRAN package. In brief, the fullROC package provides a useful tool for eyewitness researchers to analyze lineup data using the full ROC method, which incorporates both the inculpatory and exculpatory information of eyewitness behaviors.

Predictors of actual five-year survival and recurrence after pancreatoduodenectomy for ampullary adenocarcinoma: results from an international multicentre retrospective cohort study.

BACKGROUND: Pancreatoduodenectomy (PD) is recommended in fit patients with a resectable ampullary adenocarcinoma (AA). We aimed to identify predictors of five-year recurrence/survival. METHODS: Data were extracted from the Recurrence After Whipple's (RAW) study, a multicentre retrospective study of PD patients with a confirmed head of pancreas or periampullary malignancy (June 1st, 2012-May 31st, 2015). Patients with AA who developed recurrence/died within five-years were compared to those who did not. RESULTS: 394 patients were included and actual five-year survival was 54%. Recurrence affected 45% and the median time-to-recurrence was 14 months. Local only, local and distant, and distant only recurrence affected 34, 41 and 94 patients, respectively (site unknown: 7). Among those with recurrence, the most common sites were the liver (32%), local lymph nodes (14%) and lung/pleura (13%). Following multivariable tests, number of resected nodes, histological T stage > II, lymphatic invasion, perineural invasion (PNI), peripancreatic fat invasion (PPFI) and ≥1 positive resection margin correlated with increased recurrence and reduced survival. Furthermore, ≥1 positive margin, PPFI and PNI were all associated with reduced time-to-recurrence. CONCLUSIONS: This multicentre retrospective study of PD outcomes identified numerous histopathological predictors of AA recurrence. Patients with these high-risk features might benefit from adjuvant therapy.

OPTN recruitment to a Golgi-proximal compartment regulates immune signalling and cytokine secretion.

Optineurin (OPTN) is a multifunctional protein involved in autophagy and secretion, as well as nuclear factor κB (NF-κB) and IRF3 signalling, and OPTN mutations are associated with several human diseases. Here, we show that, in response to viral RNA, OPTN translocates to foci in the perinuclear region, where it negatively regulates NF-κB and IRF3 signalling pathways and downstream pro-inflammatory cytokine secretion. These OPTN foci consist of a tight cluster of small membrane vesicles, which are positive for ATG9A. Disease mutations in OPTN linked to primary open-angle glaucoma (POAG) cause aberrant foci formation in the absence of stimuli, which correlates with the ability of OPTN to inhibit signalling. By using proximity labelling proteomics, we identify the linear ubiquitin assembly complex (LUBAC), CYLD and TBK1 as part of the OPTN interactome and show that these proteins are recruited to this OPTN-positive perinuclear compartment. Our work uncovers a crucial role for OPTN in dampening NF-κB and IRF3 signalling through the sequestration of LUBAC and other positive regulators in this viral RNA-induced compartment, leading to altered pro-inflammatory cytokine secretion.

EUS-guided choledochoduodenostomy with electrocautery-enhanced lumen-apposing metal stents in patients with malignant distal biliary obstruction: multicenter collaboration from the United Kingdom and Ireland.

BACKGROUND AND AIMS: EUS-guided choledochoduodenostomy (EUS-CDD) with an electrocautery-enhanced lumen-apposing metal stent (EC-LAMS) has emerged as a viable method of establishing biliary drainage in patients with malignant distal biliary obstruction (MDBO). Our aim was to assess the efficacy, safety, and outcomes in patients with MDBO who underwent EUS-CDD with an EC-LAMS. METHODS: A retrospective review of consecutive patients with MDBO who underwent EUS-CDD with EC-LAMSs at 8 tertiary institutions across the United Kingdom and Ireland between September 2016 and November 2020 was undertaken. RESULTS: One hundred twenty patients (55% men) with a median age of 73 years (interquartile range, 17; range, 43-94) were included. The median follow-up period in 117 patients was 70 days (interquartile range, 169; range, 3-869), and 23 patients (19.2%) were alive at the end of the follow-up. Three patients were lost to follow-up. Technical success was achieved in 109 patients (90.8%). Clinical success (reduction of serum bilirubin to ≤50% of original value within 14 days) was achieved in 94.8% of patients (92/97). The adverse event rate was 17.5% (n = 21). Biliary reintervention after initial technical success was required in 9 patients (8.3%). CONCLUSIONS: EUS-CDD with EC-LAMSs at tertiary institutions within a regional hepatopancreatobiliary network for treatment of MDBO was effective in those where ERCP was not possible or was unsuccessful. When technical failures or adverse events occur, most patients can be managed with conservative or endoscopic therapy.

Controlling Doxorubicin Release from a Peptide Hydrogel through Fine-Tuning of Drug-Peptide Fiber Interactions.

Hydrogels are versatile materials that have emerged in the last few decades as promising candidates for a range of applications in the biomedical field, from tissue engineering and regenerative medicine to controlled drug delivery. In the drug delivery field, in particular, they have been the subject of significant interest for the spatially and temporally controlled delivery of anticancer drugs and therapeutics. Self-assembling peptide-based hydrogels, in particular, have recently come to the fore as potential candidate vehicles for the delivery of a range of drugs. In order to explore how drug-peptide interactions influence doxorubicin (Dox) release, five ß-sheet-forming self-assembling peptides with different physicochemical properties were used for the purpose of this study, namely: FEFKFEFK (F8), FKFEFKFK (FK), FEFEFKFE (FE), FEFKFEFKK (F8K), and KFEFKFEFKK (KF8K) (F: phenylalanine; E: glutamic acid; K: lysine). First, Dox-loaded hydrogels were characterized to ensure that the incorporation of the drug did not significantly affect the hydrogel properties. Subsequently, Dox diffusion out of the hydrogels was investigated using UV absorbance. The amount of drug retained in F8/FE composite hydrogels was found to be directly proportional to the amount of charge carried by the peptide fibers. When cation-π interactions were used, the position and number of end-lysine were found to play a key role in the retention of Dox. In this case, the amount of Dox retained in F8/KF8K composite hydrogels was linked to the amount of end-lysine introduced, and an end-lysine/Dox interaction stoichiometry of 3/1 was obtained. For pure FE and KF8K hydrogels, the maximum amount of Dox retained was also found to be related to the overall concentration of the hydrogels and, therefore, to the overall fiber surface area available for interaction with the drug. For 14 mM hydrogel, ∼170-200 µM Dox could be retained after 24 h. This set of peptides also showed a broad range of susceptibilities to enzymatic degradation opening the prospect of being able to control also the rate of degradation of these hydrogels. Finally, the Dox released from the hydrogel was shown to be active and affect 3T3 mouse fibroblasts viability in vitro. Our study clearly shows the potential of this peptide design as a platform for the formulation of injectable or sprayable hydrogels for controlled drug delivery.

Rapid quantification of microRNA-375 through one-pot primer-generating rolling circle amplification.

A recent surge of interest in microRNA has been driven by its discovery as a circulating biomarker of disease, with many diagnostic test platforms currently under development. Alternatives to widely used microRNA quantification methods such as quantitative reverse transcriptase PCR (qRT-PCR) are needed for use in portable and point-of-care devices which are incompatible with complex sample processing workflows and thermal cycling. Rolling circle amplification (RCA) is a one-pot assay technique which directly amplifies nucleic acids using sequence-specific microRNA priming to initiate a single-step isothermal reaction that is compatible with simple devices. Sensitivity remains a limitation of RCA methods, however, and detection limits do not typically reach the femtomolar level in which microRNA targets are present in blood. RCA assays have previously been improved by digestion of the amplification products using a nicking endonuclease to exponentially generate new reaction primers. Here we describe how a ligation-free version of this technique performed in a single tube can be used to improve the limit of detection for microRNA-375, an important blood biomarker for prostate cancer. Endonuclease addition changes a linear process into an exponential amplification reaction which results in a 61-fold improvement of the limit of detection (5.9 fM), a dynamic range wider than 5-log(10), and a shorter reaction time. By eliminating the need for microRNA reverse transcription and thermal cycling, this single-step one-pot method provides a more rapid and simplified alternative to qRT-PCR for ultrasensitive microRNA quantification in blood extracts.

A proof of concept pilot trial of probiotics in symptomatic oral lichen planus (CABRIO).

OBJECTIVE: To preliminary evaluate the clinical effects of probiotics in individuals with symptomatic oral lichen planus and the possible mechanisms of action. SUBJECTS AND METHODS: A group of 30 individuals with symptomatic oral lichen planus were recruited in a randomised double-blind parallel group controlled (1:1) proof-of-concept pilot trial of probiotic VSL#3 vs placebo. Efficacy outcomes included changes in pain numeric rating scale, oral disease severity score and the chronic oral mucosal disease questionnaire. Adverse effects, home diary and withdrawals were assessed as feasibility outcomes. Mechanistic outcomes included changes in salivary and serum levels of CXCL10 and IFN-γ and in oral microbial composition. RESULTS: The probiotic VSL#3 was safe and well tolerated. We observed no statistically significant change in pain, disease activity, quality of life, serum/salivary CXCL10 or oral microbial composition with respect to placebo. Salivary IFN-γ levels demonstrate a trend for a reduced level in the active group (p = 0.082) after 30 days of probiotic consumption. CONCLUSIONS: The present proof-of-concept study provides some weak not convincing indication of biological and clinical effects of probiotic VSL#3 in individuals with painful oral lichen planus. Further research in this field is needed, with the current study providing useful information to the design of future clinical trials.

Digital-resolution detection of microRNA with single-base selectivity by photonic resonator absorption microscopy.

Circulating exosomal microRNA (miR) represents a new class of blood-based biomarkers for cancer liquid biopsy. The detection of miR at a very low concentration and with single-base discrimination without the need for sophisticated equipment, large volumes, or elaborate sample processing is a challenge. To address this, we present an approach that is highly specific for a target miR sequence and has the ability to provide "digital" resolution of individual target molecules with high signal-to-noise ratio. Gold nanoparticle tags are prepared with thermodynamically optimized nucleic acid toehold probes that, when binding to a target miR sequence, displace a probe-protecting oligonucleotide and reveal a capture sequence that is used to selectively pull down the target-probe-nanoparticle complex to a photonic crystal (PC) biosensor surface. By matching the surface plasmon-resonant wavelength of the nanoparticle tag to the resonant wavelength of the PC nanostructure, the reflected light intensity from the PC is dramatically and locally quenched by the presence of each individual nanoparticle, enabling a form of biosensor microscopy that we call Photonic Resonator Absorption Microscopy (PRAM). Dynamic PRAM imaging of nanoparticle tag capture enables direct 100-aM limit of detection and single-base mismatch selectivity in a 2-h kinetic discrimination assay. The PRAM assay demonstrates that ultrasensitivity (<1 pM) and high selectivity can be achieved on a direct readout diagnostic.

Hydrogels from the Assembly of SAA/Elastin-Inspired Peptides Reveal Non-Canonical Nanotopologies.

Peptide-based hydrogels are of great interest in the biomedical field according to their biocompatibility, simple structure and tunable properties via sequence modification. In recent years, multicomponent assembly of peptides have expanded the possibilities to produce more versatile hydrogels, by blending gelating peptides with different type of peptides to add new features. In the present study, the assembly of gelating P5 peptide SFFSF blended with P21 peptide, SFFSFGVPGVGVPGVGSFFSF, an elastin-inspired peptides or, alternatively, with FF dipeptide, was investigated by oscillatory rheology and different microscopy techniques in order to shed light on the nanotopologies formed by the self-assembled peptide mixtures. Our data show that, depending on the added peptides, cooperative or disruptive assembly can be observed giving rise to distinct nanotopologies to which correspond different mechanical properties that could be exploited to fabricate materials with desired properties.

Early oral feeding after pancreatoduodenectomy: a systematic review and meta-analysis.

BACKGROUND: The effect of early oral feeding (EOF) after pancreatoduodenectomy (PD) upon perioperative complications and outcomes is unknown, therefore the aim of this systematic review and meta-analysis was to investigate the effect of EOF on clinical outcomes after PD, such as postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE) and length of stay (LOS). METHODS: A systematic review and meta-analysis was performed in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance and assimilated evidence from studies reporting outcomes for patients who received EOF after PD compared to enteral tube feeding (EN) or parenteral nutrition (PN). RESULTS: Four studies reported outcomes after EOF compared to EN/PN after PD and included 553 patients. Meta-analyses showed no difference in rates of CR-POPF (OR 0.74; 95%CI 0.44-1.24; p = 0.25) or DGE (Grade B/C) (OR 0.83; 95%CI 0.31-2.21; p = 0.70). LOS was significantly shorter in the EOF group compared to the EN/PN group (Mean Difference -3.40 days; 95% -6.11-0.70 days; p = 0.01). CONCLUSION: Current available evidence suggests that EOF after PD is not associated with increased risk of DGE, does not exacerbate POPF and appears to reduce length of stay.

Inorganic-Ligand Quantum Dots Meet Inorganic-Ligand Semiconductor Nanoplatelets: A Promising Fusion to Construct All-Inorganic Assembly.

By the reaction of inorganic-ligand CdS/Cd2+ quantum dots (QDs) with inorganic-ligand CdSe/CdS/S2- nanoplatelets (NPLs), semiconductor CdS QDs were fused with CdSe/CdS NPLs to yield all-inorganic assemblies, accompanied by great photoluminescence-enhancement. These all-inorganic assemblies facilitate charge transport between each other and open up interesting prospects with electronic and optoelectronic nanodevices.

Providing witnesses with an option to say "I'm not sure" to a showup neither improves classification performance nor the reliability of suspect identifications.

Objective: Past research with one-person showup identification procedures suggests that providing witnesses with an explicit option to opt-out reduces innocent-suspect identifications without reducing culprit identifications (Weber & Perfect, 2012). This finding suggests that improving performance from identification procedures might be as simple as providing witnesses with the option to opt-out from deciding. We examined whether providing witnesses with an option to say "not sure" improved performance from showup procedures. Hypotheses: We predicted that participants would opt-out more when given a poor view. We also predicted that classification performance would be better for those who had option to opt-out, and this improvement would be more pronounced for those who had a poor view. Finally, we predicted that the opt-out option would reduce more low-confidence than high-confidence decisions. Method: We randomly assigned Amazon Mechanical Turk Workers (Experiment 1A: N = 2,003, average age = 36.90 [SD = 11.67], 57.86% female) and university students (Experiment 1B: N = 721, average age = 19.91 (SD = 3.99), 69.72% female) to a 2 (culprit: present, absent) × 2 (memory strength: strong, weak) × 2 (not sure option: yes, no) between-participants design. We manipulated memory strength by giving witnesses either a clear or degraded view of the encoding video. After watching the encoding video, participants completed a 10-min filler task and were then presented with a showup procedure. Results: Participants who were given a poor view were more likely to opt-out than were participants who were given a clear view. Participants who were given the option to respond not sure reported higher confidence in their decisions. However, the not sure option did not improve classification performance. Conclusion: Contrary to our prediction, we found no evidence that an opt-out option improves performance from a showup procedure, which is consistent with past research examining opt-out options with lineup procedures. (PsycInfo Database Record (c) 2021 APA, all rights reserved).