Multiple Sites Research Articles

Development of antibody-engineered molecularly imprinted polymers for selective capture of aflatoxin B1 from starchy food and medicinal materials

Molecularly imprinted polymers(MIPs) have been widely used as selective recognition materials for analysis and detection of mycotoxins, such as aflatoxin B1(AFB1). However, little attention was given to investigate key factors that affecting selectivity and specificity of MIPs, such as functional monomers and imprinted cavity compatibility. Inspired by the recognition of antibody to antigen, we designed and employed amino acids as functional monomers with multiple interaction sites via hydrogen bonding and aromatic π-π stacking, meanwhile, synthesized structurally matched alternative template, 5,7-dimethoxycyclopentenone [2,3-c]coumarin(DMPC) to prepare MIPs via silica surface grafting. The adsorption of antibody-engineered MIPs was enhanced significantly compared to that of MIPs prepared by conventional functional monomers and dummy templates for selective capture of AFB1. And the specific recognition sites of MIPs left by DMPC conferred the most remarkable selectivity toward AFB1 among aflatoxins. The mechanism and contribution of functional groups and imprinted cavities for selective adsorption of AFB1 were elucidated, providing a different approach to improving functional monomers and templates in MIPs. The solid phase extraction cartridges packed DMPC-ATry-MIPs@SiO2 were used for enrichment of AFB1 in Lotus seeds and Coix seeds. The recoveries were 94.48–112.90 % and 83.32–116.04 % respectively, even after being used five times repeatedly. The cartridges could replace expensive and low-reusability immunoaffinity columns in the analysis and detection of AFB1 in real samples, providing a kind of promising sample pretreatment materials for trace analysis in food and drugs.

Sp1 facilitates continued HSV-1 gene expression in the absence of key viral transactivators.

Productive replication of herpes simplex virus (HSV) relies upon a well-ordered transcriptional cascade flowing from immediate-early (IE) to early (E) to late (L) gene products. While several virus-encoded transcriptional activators are involved in this process, IE and E gene promoters also contain multiple binding sites for the ubiquitously expressed cellular transcription factor Sp1. Sp1 has been previously implicated in activating HSV-1 gene transcription downstream of these sites, but why Sp1-binding sites are maintained in the promoters of genes activated by virus-encoded activators remains unclear. We hypothesized that Sp1 enables continued HSV-1 transcription and replication when viral transactivators are limited. We used a depletion-based approach in human foreskin fibroblasts to investigate the specific contribution of Sp1 to the initiation and progression of the HSV-1 lytic gene cascade. We found that Sp1 increased viral transcript levels, protein expression, and replication following infection with VP16- or ICP0-deficient viruses but had little to no effect on rescued viruses or during wild-type (WT) HSV-1 infection. Moreover, Sp1 promoted WT virus transcription and replication following interferon treatment of fibroblasts and thus may contribute to viral immune evasion. Interestingly, we observed reduced expression of Sp1 and Sp1-family transcription factors in differentiated sensory neurons compared to undifferentiated cells, suggesting that reduced Sp1 levels may also contribute to HSV-1 latent infection. Overall, these findings indicate that Sp1 can promote HSV-1 gene expression in the absence of key viral transactivators; thus, HSV-1 may use Sp1 to maintain its gene expression and replication under adverse conditions.IMPORTANCEHerpes simplex virus (HSV) is a common human pathogen that actively replicates in the epithelia but can persist for the lifetime of the infected host via a stable, latent infection in neurons. A key feature of the HSV replication cycle is a complex transcriptional program in which virus and host-cell factors coordinate to regulate expression of the viral gene products necessary for continued viral replication. Multiple binding sites for the cellular transcription factor Sp1 are located in the promoters of HSV-1 genes, but how Sp1 binding contributes to transcription and replication of wild-type virus is not fully understood. In this study, we identified a specific role for Sp1 in maintaining HSV-1 gene transcription under adverse conditions, as when virus-encoded transcriptional activators were absent or limited. Preservation of Sp1-binding sites in HSV-1 gene promoters may thus benefit the virus as it navigates diverse cell types and host-cell conditions during infection.

Interrogating l-fuconate dehydratase with tartronate and 3-hydroxypyruvate reveals subtle differences within the mandelate racemase-subgroup of the enolase superfamily

Enzymes of the enolase superfamily share a conserved structure and a common partial reaction (i.e., metal-assisted, Brønsted base-catalyzed enol(ate) formation). The architectures of the enolization apparatus at the active sites of the mandelate racemase (MR)-subgroup members MR and l-fuconate dehydratase (FucD) are almost indistinguishable at the structural level. Tartronate and 3-hydroxypyruvate (3-HP) recognize the enolization apparatus and can be used to interrogate the active sites for differences that may not be apparent from structural data. We report a circular dichroism-based assay of FucD activity that monitors the change in ellipticity at 216 nm (Δ[Θ]S–P = 8985 ± 87 deg cm2 mol−1) accompanying the conversion of l-fuconate to 2-keto-3-deoxy-l-fuconate. Tartronate was a linear mixed-type inhibitor of FucD (Ki = 8.4 ± 0.7 mM, αKi = 63 ± 11 mM), binding 18-fold weaker than l-fuconate, compared with 2-fold weaker binding of tartronate by MR relative to mandelate. 3-HP irreversibly inactivated FucD (kinact/KI = 0.018 ± 0.002 M−1s−1) with an efficiency that was ∼4.6 × 103-fold less than that observed with MR. The inactivation arose predominantly from modifications at multiple sites and Tris-HCl, but not l-fuconate, afforded protection against inactivation. Similar to the reaction of 3-HP with MR, 3-HP modified the Brønsted base catalyst (Lys 220) at the active site of FucD, which was facilitated by the Brønsted acid catalyst His 351. Thus, the interactions of tartronate and 3-HP with MR and FucD revealed differences in binding affinity and reactivity that differentiated between the enzymes’ enolization apparatuses.

One-step synthesis of CoxS/Ni3S2@NF on 3D nickel foam with different sulfur sources as a novel heterogeneous catalyst efficient activation of peroxymonosulfate in lomefloxacin degradation

In this study, we have successfully synthesized Co9S8/CoS/Ni3S2 and Co3S4/Ni3S2 materials in situ on three-dimensional (3D) nickel foam (NF) substrates using a one-step hydrothermal process with different sulfur sources. Under the experimental conditions of catalyst dosage of 0.50 cm × 0.50 cm and peroxymonosulfate (PMS) dosage of 0.30 g/L, the Co3S4/Ni3S2@NF catalyst exhibited superior catalytic performance in activating PMS and degrading 91.0 % of lomefloxacin (LOM) as compared to 76 % of Co9S8/CoS/Ni3S2@NF. Both Co9S8/CoS/Ni3S2@NF and Co3S4/Ni3S2@NF showed excellent stability and performed effectively over a wide pH range. The Co9S8/CoS/Ni3S2@NF and Co3S4/Ni3S2@NF demonstrated significant differences in morphology, crystal plane properties, surface functional groups, chemical composition, elemental valence states, and coordination environment as revealed by XRD, TEM, SEM, FTIR, and XPS analyses, contributing to their distinct mechanisms and performance in LOM degradation. Additionally, the NF acted as a support carrier, exposing multiple active sites to enhance electron transport and providing a nickel source for the catalytic reaction. The degradation of LOM in the CoxS/Ni3S2@NF&PMS system was thoroughly investigated, revealing the involvement of SO4−, OH, 1O2, and electron transfer in the process. Additionally, the mechanism of PMS activation and the pathway of LOM decomposition in the reaction system were elucidated by theoretical analysis. Furthermore, the ecotoxicity of the by-products generated during LOM degradation was assessed using the ECOSAR software. In summary, the CoxS/Ni3S2@NF catalysts proved to be efficient, stable, easily prepared, environmentally friendly, and recyclable heterogeneous nanocomposites. It is a promising candidate for heterogeneous PMS process.

Kidney-specific methylation patterns correlate with kidney function and are lost upon kidney disease progression

BackgroundChronological and biological age correlate with DNA methylation levels at specific sites in the genome. Linear combinations of multiple methylation sites, termed epigenetic clocks, can inform us the chronological age and predict multiple health-related outcomes. However, why some sites correlating with lifespan, healthspan, or specific medical conditions remain poorly understood. Kidney fibrosis is the common pathway for chronic kidney disease, which affects 10% of European and US populations.ResultsHere we identify epigenetic clocks and methylation sites that correlate with kidney function. Moreover, we identify methylation sites that have a unique methylation signature in the kidney. Methylation levels in majority of these sites correlate with kidney state and function. When kidney function deteriorates, all of these sites regress toward the common methylation pattern observed in other tissues. Interestingly, while the majority of sites are less methylated in the kidney and become more methylated with loss of function, a fraction of the sites are highly methylated in the kidney and become less methylated when kidney function declines. These methylation sites are enriched for specific transcription-factor binding sites. In a large subset of sites, changes in methylation patterns are accompanied by changes in gene expression in kidneys of chronic kidney disease patients.ConclusionsThese results support the information theory of aging, and the hypothesis that the unique tissue identity, as captured by methylation patterns, is lost as tissue function declines. However, this information loss is not random, but guided toward a baseline that is dependent on the genomic loci.Significance statementDNA methylation at specific sites accurately reflects chronological and biological age. We identify sites that have a unique methylation pattern in the kidney. Methylation levels in the majority of these sites correlate with kidney state and function. Moreover, when kidney function deteriorates, all of these sites regress toward the common methylation pattern observed in other tissues. Thus, the unique methylation signature of the kidney is degraded, and epigenetic information is lost, when kidney disease progresses. These methylation sites are enriched for specific and methylation-sensitive transcription-factor binding sites, and associated genes show disease-dependent changes in expression. These results support the information theory of aging, and the hypothesis that the unique tissue identity, as captured by methylation patterns, is lost as tissue function declines.

Comparative life-cycle sustainability assessment of centralized and decentralized remediation strategies at the city level

Remediation of contaminated soil at industrial sites has become a challenge and an opportunity for sustainable urban land use, considering the substantial secondary impacts resulting from remediation activities. The design of soil remediation strategies for multi-site remediation from a regional perspective is of great significance for cities with a large number of brownfields. Centralized and decentralized facilities have been studied in different environmental fields, yet limited research has focused on centralized soil remediation, specifically the treatment of contaminated soil from different sites through the construction of shared soil treatment facilities. This study proposes a framework for comparing centralized and decentralized strategies for contaminated soil remediation based on the integration of life-cycle sustainability assessment and multi-objective optimization. With Zhuzhou, an industrial city in China, serving as an example, results show that after optimization, the centralized scenario can reduce total environmental impacts by 25 %–41 %. In addition, the centralized scenario can reduce economic costs by 27 %–39 %, saving up to 176 million USD. The advantages of the centralized soil remediation strategy include: (1) increased use of soil washing, (2) reduced use of off-site disposal, and (3) reduced construction and efficient utilization of soil treatment facilities. In conclusion, the centralized strategy is relatively suitable for cities or areas with a large number of medium or small-sized contaminated sites. The built framework can quantitatively evaluate multiple sites soil remediation at both the city and individual site level, allowing for a straightforward and objective comparison with the optimal remediation design.

Field-based assessments of the seasonality of Culexpipiens sensu lato in England: an important enzootic vector of Usutu and West Nile viruses

BackgroundUsutu virus (USUV), which is closely related to West Nile virus (WNV), sharing a similar ecology and transmission cycle, was first reported in the UK in the southeast of England in 2020. Both USUV and WNV are emerging zoonotic viruses hosted by wild birds. The 2020 finding of USUV in England raised awareness of this virus and highlighted the importance of understanding the seasonality of Culexpipiens sensu lato (Cx. pipiens s.l.), the main enzootic vector of these viruses. Zoos are prime locations for trapping mosquitoes because of their infrastructure, security, and range of vertebrate hosts and aquatic habitats.MethodsThree independent zoo-based case studies at four locations that cover the seasonality of Cx.pipiens s.l. in England were undertaken: (i) London Zoo (Zoological Society London [ZSL]) and surrounding areas, London; (ii) Chester Zoo (Cheshire); (ii) Twycross Zoo (Leicestershire); and (iv) Flamingo Land (zoo; North Yorkshire). Various adult mosquito traps were used to catch adult Cx.pipiens s.l. across seasons.ResultsHigh yields of Cx.pipiens s.l./Culex torrentium were observed in Biogents-Mosquitaire and Center for Disease Control and Prevention Gravid traps in all studies where these traps were used. Mosquito counts varied between sites and between years. Observations of adult Cx.pipiens s.l./Cx. torrentium abundance and modelling studies demonstrated peak adult abundance between late July and early August, with active adult female Cx.pipiens s.l./Cx. torrentium populations between May and September.ConclusionsThe information collated in this study illustrates the value of multiple mosquito monitoring approaches in zoos to describe the seasonality of this UK vector across multiple sites in England and provides a framework that can be used for ongoing and future surveillance programmes and disease risk management strategies.Graphical

A unified framework for time‐to‐detection occupancy and abundance models

Abstract Time‐to‐detection (TTD) occupancy models are increasingly used to study site occupancy of organisms. Occupancy is a reduced representation of abundance (distinguishing only between and individuals), which is also often a quantity of interest. In this paper, we present a novel framework for TTD occupancy models that address limitations of existing approaches. Our approach incorporates factors that accommodate detection heterogeneity among sites/visits and inter‐visit dependency, allowing for the relaxation of some restrictive assumptions inherent in previous models. As a result, our framework offers a robust and versatile tool for analysing various ecological data sets. We employ a maximum likelihood approach to estimate model parameters and conduct inference for the proposed TTD occupancy models. A key feature of these models is the introduction of a community parameter. This parameter characterizes the similarity of detectabilities, ranging from complete independence to complete identity, across multiple site visits. This framework disentangles the detection rate, abundance and occupancy, similar to the popular N‐mixture model. For situations where abundance estimation is not the primary goal, a family of mixed gamma exponential TTD models is developed, which generally exhibit more stable numerical properties compared to N‐mixture type TTD models. The performance of the proposed models and some reduced models is evaluated through simulation studies. The results indicate that the N‐mixture TTD model tends to considerably overestimate the occupancy probability when the community parameter is less than one, a condition necessary to satisfy the strict closure population assumption. On the other hand, the standard exponential TTD occupancy model underestimates the occupancy probability in the presence of unobserved detection heterogeneity and inter‐visit dependency. An analysis of bird species in the Karoo region of South Africa demonstrates the enhanced flexibility of the proposed TTD occupancy models for data fitting. This paper demonstrates the importance of employing more flexible and general models to accurately capture the complexities of ecological systems or survey data. We provide R‐code to fit all considered models to data. The proposed TTD model framework contributes to enhancing our understanding of species occupancy distributions.

Computational design and engineering of self-assembling multivalent microproteins with therapeutic potential against SARS-CoV-2

Multivalent drugs targeting homo-oligomeric viral surface proteins, such as the SARS-CoV-2 trimeric spike (S) protein, have the potential to elicit more potent and broad-spectrum therapeutic responses than monovalent drugs by synergistically engaging multiple binding sites on viral targets. However, rational design and engineering of nanoscale multivalent protein drugs are still lacking. Here, we developed a computational approach to engineer self-assembling trivalent microproteins that simultaneously bind to the three receptor binding domains (RBDs) of the S protein. This approach involves four steps: structure-guided linker design, molecular simulation evaluation of self-assembly, experimental validation of self-assembly state, and functional testing. Using this approach, we first designed trivalent constructs of the microprotein miniACE2 (MP) with different trimerization scaffolds and linkers, and found that one of the constructs (MP-5ff) showed high trimerization efficiency, good conformational homogeneity, and strong antiviral neutralizing activity. With its trimerization unit (5ff), we then engineered a trivalent nanobody (Tr67) that exhibited potent and broad neutralizing activity against the dominant Omicron variants, including XBB.1 and XBB.1.5. Cryo-EM complex structure confirmed that Tr67 stably binds to all three RBDs of the Omicron S protein in a synergistic form, locking them in the “3-RBD-up” conformation that could block human receptor (ACE2) binding and potentially facilitate immune clearance. Therefore, our approach provides an effective strategy for engineering potent protein drugs against SARS-CoV-2 and other deadly coronaviruses.Graphical

Constructing heterojunctions of CoAl2O4 and Ni3S2 anchored on carbon cloth to acquire multiple active sites for efficient overall water splitting

Constructing heterojunction interface is an efficient strategy to accelerate the catalytic activity for electrochemical reaction. In this work, a novel composite heterojunction electrocatalyst (CAO/NiS400/CC), deriving from the combination of CoAl2O4 (CAO) and Ni3S2 anchored on carbon cloth (CC) was prepared, through hydrothermal process followed by electrodeposition. After successful synthesis, CoAl2O4 particles were intricately embedded in Ni3S2 and formed an active heterostructure, exhibited outstanding catalytic capacity for both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) and improved the efficiencies of overall water splitting. As expected, the composite heterojunction electrocatalyst demonstrated excellent catalytic performances with lower overpotential of 163.2 mV at 100 mA·cm−2 and Tafel slope of 20.4 mV·dec-1for HER and 400 mV at 100 mA·cm−2 and Tafel slope of 51.1 mV·dec-1 for OER, respectively, accompanied by long-term structural stability after 40 h and 3000 Cyclic Voltammetry (CV) cycles. Moreover, Density functional theory (DFT) calculation illustrated that the robust electrocatalytic performance was attributed to the simultaneous presence of multiple catalytic active sites surrounding the heterojunction interface. Furthermore, CAO/NiS400/CC electrocatalyst facilitated the overall water splitting reaction under a cell voltage of only 1.48 V with dual catalytic capabilities for HER and OER. The combined action of active catalytic sites within both CAO and Ni3S2 around the interface contributed the optimal electrocatalytic performance, making the CAO/NiS400/CC as a promising alternative to electrocatalysts for water splitting.

Multisite Thrombosis in a Patient with Paroxysmal Nocturnal Hemoglobinuria

AbstractCase: Paroxysmal nocturnal hemoglobinuria (PNH) is an extremely rare bone marrow disorder caused by acquired mutations in the phosphatidylinositol glycan class A gene, which lead to a partial or total loss of the cellular complement regulators CD55 and CD59.1 In addition to complement-mediated hemolysis and cytopenia, venous and arterial thromboses at multiple and/or unusual sites are a common complication and occur in up to 44% of patients in historic PNH cohorts.1 2

Draft genome of Staphylococcus capitis O112, isolated from the cheek swab of a healthy female.

Staphylococcus capitis is a Gram-positive bacterium that is part of the normal human flora, found in multiple anatomical sites. Here, we present the 2.5-Mbp draft genome of S. capitis O112, isolated from a cheek swab collected from a healthy female.

Simultaneous Electrochemical Detection of Dopamine and Uric Acid via Au@Cu-Metal Organic Framework.

The incorporation of noble metals with metal-organic frameworks (MOFs) are conducive to the simultaneous electrochemical detection of analytes owing to multiple accessible reaction sites. Herein, Au@Cu-metal organic framework (Au@Cu-MOF) is successfully synthesized and modified as a screen-printed carbon electrode (SPCE), which serves as an excellent electrocatalyst for the oxidation of dopamine (DA) and uric acid (UA). The sensor shows a linear range from 10 μM to 1000 μM, with sensitivity and detection limit of 0.231 μA μM-1 cm-2 and 3.40 μM for DA, and 0.275 μA μM-1 cm-2 and 10.36 μM for UA. Au@Cu-MOF could realize the individual and simultaneous electrochemical sensing of DA and UA, with distinguishable oxidation peak potentials. Moreover, it exhibits reproducibility, repeatability, and stability. Ultimately, the sensor provides an avenue for an ultrasensitive label-free electrochemical detection of DA and UA.

Moving beyond traditional therapies: the role of nanomedicines in lung cancer.

Amidst a global rise in lung cancer occurrences, conventional therapies continue to pose substantial side effects and possess notable toxicities while lacking specificity. Counteracting this, the incorporation of nanomedicines can notably enhance drug delivery at tumor sites, extend a drug's half-life and mitigate inadvertent toxic and adverse impacts on healthy tissues, substantially influencing lung cancer's early detection and targeted therapy. Numerous studies signal that while the nano-characteristics of lung cancer nanomedicines play a pivotal role, further interplay with immune, photothermal, and genetic factors exist. This review posits that the progression towards multimodal combination therapies could potentially establish an efficacious platform for multimodal targeted lung cancer treatments. Current nanomedicines split into active and passive targeting. Active therapies focus on a single target, often with unsatisfactory results. Yet, developing combination systems targeting multiple sites could chart new paths in lung cancer therapy. Conversely, low drug delivery rates limit passive therapies. Utilizing the EPR effect to bind specific ligands on nanoparticles to tumor cell receptors might create a new regime combining active-passive targeting, potentially elevating the nanomedicines' concentration at target sites. This review collates recent advancements through the lens of nanomedicine's attributes for lung cancer therapeutics, the novel carrier classifications, targeted therapeutic modalities and their mechanisms, proposing that the emergence of multi-target nanocomposite therapeutics, combined active-passive targeting therapies and multimodal combined treatments will pioneer novel approaches and tools for future lung cancer clinical therapies.

Biodiversity and Structural Analysis of Woody Plant Species of Home Gardens in Basona Worana District, North Shoa Zone of Central Ethiopia.

The purpose of this study was to investigate the biodiversity and structure of woody plants of HGs in the Basona Worana district (BWD). For this, six kebeles and 138 HGs from three agroecologies of BWD were selected using various sampling techniques. The plot size used per HG was 400 m2. Diversity and important value indices (IVIs) were computed. For their structural analysis, the diameter at breast height (DBH) and height were also measured for trees and shrubs fulfilling the standards (diameters at breast height (DBH) ≥2.5 cm and height >2 m). Thus, a total of 42 woody species belonging to 37 genera and 26 families were identified. Fabaceae was the most abundant family, followed by Euphorbiaceae. Trees were the dominant habit. The richness in Kola HGs (33) was higher than Dega (14) and Woinadega (19) HGs, with an overall mean richness of 4.14 per HG of BWD. The Shannon, Simpson, and evenness indices for HGs in the district were 1.05, 0.55, and 0.75, respectively, showing their moderate diversity with even distribution. The Sorenson's similarity of HGs between Dega and Woinadega, Kola and Dega, and Kola and Woinadega were 40%, 28%, and 32%, respectively. The multiple site similarities of woody species among three ecological zones (36%) were still <50%, showing no similarity. The overall DBH and height classes' patterns of the woody species individuals abruptly decreased towards their highest classes. Similar DBH and height classes' patterns of woody species individuals were also observed in Kola and Woinadega agroecologies, indicating their selective tree cutting. The mean values of DBH, height, basal, and crown areas of the woody species in the district were ∼14 cm, ∼6 m, ∼29 m2·ha-1, and 5 m2, respectively. Based on IVI, most of the HGs were dominated by Eucalyptus globules (93.35), followed by Eucalyptus camaldulensis (45.04), Rhamnus prinoides (22.4), and Cupressus lusitanica (22.33). Hence, actions should be taken to promote the diversity and managing of HGs' woody species of BWD.

A feasibility (pilot) mixed methods study of an innovative non-pharmacological breath-based yoga and social-emotional intervention program in an at-risk youth sample in London, Canada

BackgroundVarious service provision models for youth at risk of homelessness have been researched and implemented, including access to housing and physical and mental health resources. However, even with these interventions, we remain unaware of how best to manage symptoms of depression and anxiety and the rate of drug use in these populations primarily because of a lack of feasibility data.MethodsThis paper presents the results of a mixed-methods study in London, Canada, that examined the feasibility of implementing a biopsychosocial intervention, SKY Schools, in at-risk youth aged between 16 and 25 (n = 49). The study also recorded qualitative responses about the program’s usefulness from the perspective of the service users. The SKY Schools intervention consisted of social-emotional learning combined with Sudarshan Kriya Yoga, a standardized yoga-based breathing exercise routine. The intervention program was divided into two phases: an active learning phase and a reinforcement phase. The following feasibility outcome measures were collected: (1) the number of potential participants approached per month, (2) number (proportion) who were successfully screened, (3) the proportion of screened participants who enrolled, (4) the rate of retention in the study, (5) rate of adherence to study protocol, (6) proportion of planned ratings that were completed, (7) intervention cost per case, (8) completeness of final data for analysis, (9) length of time to collect all data, (10) quality of all collected data, (11) determining if partnering community organizations were willing to conduct the study as per study protocol, (12) determining if there were any capacity issues with partners providing intervention and investigators being able to perform the tasks that they were committed to doing, (13) determining if there were any problems of entering the data into a computer, (14) preliminary data about the safety of the intervention, and (15) preliminary estimate of treatment effects.ResultsAll feasibility outcome measures were collectible. In the city of London, Canada it was feasible to conduct a pilot study in this population of youth at risk of homelessness. Foremost among the findings was a high retention rate (61.2%) and overall positive qualitative feedback with a number of potential suggestions to improve the delivery and quality of the intervention. However, we had a significantly low recruitment rate (0.27 participants per week) suggesting that multiple sites will be needed to achieve an adequate sample size for a subsequent definitive trial.ConclusionsFuture researchers may consider the findings of this feasibility study when designing a randomized control trial to further assess the efficacy and tolerability of SKY Schools.Trial registrationTrial registration: Clinicaltrials.gov, identifier NCT02749240. Registered April 22, 2016, https://clinicaltrials.gov/ct2/show/NCT02749240.

Masculinity, Rather Than Biological Sex, Is Associated With Psychological Comorbidities in Patients With Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) generally shows sex differences, and psychiatric comorbidities play an important role in its pathogenesis. We aim to measure the levels of gender roles and investigate their relationship with psychiatric factors in patients with IBS versus healthy controls. Patients diagnosed with IBS by Rome III and whose colonoscopy findings were normal were enrolled at multiple sites in Korea. The participants completed the Korean Sex Role Inventory-Short Form (KSRI-SF) to assess masculinity and femininity, the stress questionnaire, the Hospital Anxiety Depression Scale (HADS), and the 36-item Short Form Health Survey questionnaire to assess the quality of life (QOL). In total, 102 patients with IBS (male:female = 35:67; mean age 42.6 ± 16.7 years) and 55 controls (male:female = 20:35; mean age 42.4 ± 11.1 years) were recruited. IBS patients had higher stress (9.69 ± 8.23 vs 4.56 ± 8.31, P < 0.001) and HADS scores (16.12 ± 7.17 vs 10.22 ± 5.74, P < 0.001) than the control group, but showed no significant difference in KSRI-SF scores. No significant differences in HADS and KSRI-SF scores were found between males and females. However, IBS patients whose symptoms worsened due to stress and patients with anxiety or depression had significantly lower masculinity. QOL was poorer in IBS patients than in controls. In stepwise multivariate analyses, the anxiety score, depression score, and the degree of daily life disturbance, not masculinity, were associated with the QOL of IBS patients. IBS patients had higher stress, more psychiatric comorbidities, and lower QOL than controls. Low masculinity, rather than sex, was associated with stress and psychological comorbidities, which deteriorated the QOL in IBS patients.

Student challenges during third-year perioperative clerkships through the lens of faculty and residents: A qualitative study.

Studies of medical students suggest they often find the transition from the pre-clinical curriculum to clinical rotations particularly challenging during perioperative clerkships. Educators could add a new perspective into students' clerkship experiences and potential interventions to improve them. The purpose of this study was to examine the educator perspective on students' experiences in perioperative clerkships. The findings could inform potential curricular interventions to facilitate student transition from a didactic environment into perioperative clerkships. Semi-structured qualitative interviews were conducted with 16 faculty and residents in the departments of anaesthesia, obstetrics and gynaecology (OBGYN), and general surgery across multiple clinical teaching sites at one institution. Interview questions explored their perceptions of the challenges students face during their transition into perioperative clerkships and probed thoughts on curriculum interventions they believed would be the most beneficial. Interviews were recorded, transcribed and analysed thematically. Three themes were identified. Faculty and residents perceive that student experiences on perioperative clerkships are shaped by (1) students' ability to adapt to the specialty and operating room norms on these clerkships, (2) students' understanding of how they can meaningfully contribute to the clinical team, and (3) dedicated teaching time constraints. Interventions were suggested to address educator expectations and student gaps, such as implementing a pre-clerkship orientation across anaesthesia, general surgery and OBGYN. To facilitate the medical student transition to perioperative clerkships, interventions should aid students in adapting to clerkship norms for these specialties and clarifying their role and expectations within the care team.

Carbohydrate-binding ability of a recombinant protein containing the DM9 motif from Drosophila melanogaster.

Proteins containing DM9 motifs, which were originally identified in the Drosophila melanogaster genome, are widely distributed in various organisms and are assumed to be involved in their innate immune response. In this study, we produced a recombinant protein of CG13321 (rCG13321) from D. melanogaster, which consists of four DM9 motifs, in Escherichia coli cells. In affinity chromatography using a mannose-immobilized column, rCG13321 exhibited mannose-binding ability and was separated into high-affinity and low-affinity fractions, named HA and LA, respectively, based on its binding ability to the column. In addition to having a higher affinity for the column, HA exhibited self-oligomerization ability, suggesting slight differences in tertiary structure. Both LA and HA showed hemagglutinating activity and were able to agglutinate an oligomannose-containing dendrimer, indicating that they have multiple carbohydrate-binding sites. Glycan array analysis suggested that rCG13321 primarily recognizes D-mannose and D-rhamnose through hydrogen bonding with the 2-, 3-, and 4-hydroxy groups. Isothermal titration calorimetry demonstrated that rCG13321 has a comparable affinity to typical lectins. These findings suggest that CG13321 functions as a carbohydrate-binding protein or lectin that recognizes mannose and related carbohydrate-containing molecules on the surface of foreign organisms as a pattern recognition molecule.

A needs assessment for simulation in African surgical education.

There is a critical need for comprehensive surgical training in African countries given the unmet surgical burden of disease in this region. Collaborative and progressive initiatives in global surgical education will have the greatest impact on trainees. Little is known about surgical education needs from the perspective of practicing surgeons and trainees in low-middle-income countries (LMICs). Even less is known about the potential role for simulation to augment training. A modified Delphi methodology with 2 rounds of responses was employed to survey program directors (PD) and associate program directors (APD) of Pan-African Association of Christian Surgeons (PAACS) general surgery residency programs across eight low-middle-income countries in Africa. 3 PD/APDs and 2 surgical residents participated in semi-structured interviews centered around the role of simulation in training. Descriptive analysis was performed to elicit key themes and illustrative examples. The survey of program directors revealed that teaching residents the psychomotor skills need to perform intracorporeal suturing was both high priority and desired in multiple training sites. Other high priority skills were laparoscopic camera driving and medial visceral rotation. The interviews revealed a specific desire to perform laparoscopic surgery and a need for a simulation curriculum to familiarize staff and trainees with laparoscopic techniques. Several barriers to laparoscopic surgery exist, such as lack of staff familiarity with the equipment, lack of public buy in, and lack of generalizable and adaptable educational modules. Trainees saw utility in the use of simulation to optimize time in the operating room and sought opportunities to improve their laparoscopic skills. Faculty and surgical trainees in LMICs have interest in learning advanced surgical techniques, such as laparoscopy. Developing a simulation curriculum tailored to the trainees' local context has the potential to fill this need.