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BACKGROUND: Colorectal cancer (CRC) is globally the third most prevalent cancer and a leading cause of cancer-related deaths. In Alberta, Canada, a significant portion of CRC diagnoses occur following emergency department (ED) presentations. Gaps remain in understanding patient's perspectives on CRC diagnosis after an ED visit. The aim of this study was to examine the experiences and perspectives of a group of patients diagnosed with CRC subsequent to an ED visit in Alberta and their close contacts. METHODS: We conducted a qualitative study using in-depth, semi-structured interviews with patients diagnosed with CRC after an ED visit at the Rockyview General Hospital, Calgary, and their close contacts, from November 2022 to June 2023. Interviews focused on symptom recognition, healthcare interactions, and the decision-making process leading to an ED visit. They were conducted in-person or over the phone, and analysed using thematic analysis. RESULTS: Eighteen participants (12 patients and 6 close contacts) were interviewed, revealing four main themes: (1) variability in symptom recognition and interpretation; (2) inconsistencies in primary care consultations; (3) factors influencing decision-making leading to an ED visit; and (4) recommendations for expedited diagnosis outside of EDs. CONCLUSION: The findings highlight the complexity of the diagnostic journey for CRC patients in Alberta, pointing to significant gaps in symptom recognition and response by patients and healthcare providers. Improved diagnostic protocols and targeted support for healthcare providers, as well as approaches to address systemic delays may help streamline the diagnostic journey. Future research should focus on exploring innovative interventions to address the identified barriers to timely CRC diagnosis.

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Phase variation is defined as the rapid and reversible switching of gene expression, and typically occurs in genes encoding surface features in small genome bacterial pathogens. Phase variation has evolved to provide an extra survival mechanism in bacteria that lack multiple 'sense-and-respond' gene regulation systems. Many bacterial pathogens also encode DNA methyltransferases that are phase-variable, controlling systems called 'phasevarions' (phase-variable regulons). This primer will summarize the current understanding of phase variation, describing the role of major phase-variable factors, and phasevarions, in bacterial pathobiology.

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OBJECTIVE: This study characterized caregivers' beliefs related to early intervention services for children with sickle cell disease (SCD) to gain an indepth understanding of caregivers' experiences and desires for early intervention services. METHODS: Both qualitative and quantitative data were collected from caregivers of children aged 0-4 years with SCD across two sites in the United States. Caregivers completed the Knowledge of Infant Development Inventory, a custom survey about their experiences with early intervention, and a qualitative interview. RESULTS: A total of 127 caregivers were approached, 47 participated in surveys, and 20 completed interviews. Caregivers expressed varying levels of confidence and understanding of developmental milestones across sites. Interviews highlighted three main themes: fear of SCD-related complications, variable buy-in to early intervention, and the importance of provider-caregiver relationships. While some caregivers appreciated early intervention, others questioned its necessity. Caregivers communicated interest in connecting with other families facing similar challenges, emphasizing the need for increased awareness of available resources. CONCLUSIONS: Fear about their child's well-being was expressed by many caregivers, emphasizing the need for a supportive healthcare team that can help families connect with preventive interventions. While about a quarter of children had been referred to rehabilitation services, caregivers were unaware of the elevated risk for developmental delay, which diminished caregiver interest in participating in programs like early intervention. This study underscores the importance of addressing knowledge gaps and overcoming barriers to enhance care for families affected by SCD.

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The delineation of the complex biosynthesis of the potent antibiotic mupirocin, which consists of a mixture of pseudomonic acids (PAs) isolated from Pseudomonas fluorescens NCIMB 10586, presents significant challenges and the timing and mechanisms of several key transformations remain elusive.   Particularly intriguing are the steps that process the linear backbone from the initial polyketide assembly phase to generate the first cyclic intermediate PA-B. These include epoxidation as well as incorporation of the tetrahydropyran (THP) ring and fatty acid sidechain required for biological activity. Here, we show that the mini-module MmpE performs a rare online (ACP-substrate) epoxidation and is integrated ('in-cis') into the polyketide synthase via a docking domain. A linear polyketide fragment with 6 asymmetric centres was synthesised using a convergent approach and used to demonstrate substrate flux via an atypical KS0 and a previously unannotated ACP (MmpE_ACP). MmpE_ACP-bound synthetic substrates were critical in demonstrating successful epoxidation in vitro by the purified MmpE oxidoreductase domain. Alongside feeding studies, these results confirm the timing as well as chain length dependence of this selective epoxidation. These mechanistic studies pinpoint the location and nature of the polyketide substrate prior to the key formation of the THP ring and esterification that generate PA-B.

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IMPORTANCE: There are no definitive guidelines for use of postoperative antibiotics after sacral neuromodulation (SNM) leading to practice pattern variation among health care professionals. OBJECTIVES: The objectives of this study were to determine if additional antibiotics beyond preoperative intravenous antibiotics and surgical preparation decrease postoperative infections and to determine if additional antibiotics are associated with other postoperative complications. STUDY DESIGN: This was a single-center, retrospective cohort study of all SNM procedures from 2014 to 2023 performed by 12 surgeons. Cohorts were stratified between patients who received preoperative antibiotics only (OnlyPreAbx) and patients who received both preoperative antibiotics and postoperative antibiotics (PrePostAbx) after either insertion of tined lead and/or after insertion of a neurostimulator. RESULTS: There were 212 patients included in this study: 70 (33.0%) in the OnlyPreAbx group and 142 (67.0%) in the PrePostAbx group. Of patients receiving postoperative antibiotics, 76 (53.5%) received cephalexin, 49 (34.5%) received sulfamethoxazole-trimethoprim, and 17 (12.0%) received alternative antibiotics. Six patients overall (2.8%) experienced infections after SNM. There was no difference in the rates of infection between groups (4 [1.9%] PrePostAbx vs 2 [0.9%] OnlyPreAbx, P = 0.99). Of the 4 patients with postoperative infections in the PrePostAbx group, 2 had cellulitis requiring antibiotics and 2 required full explantation. Of the 2 patients with postoperative infections in the OnlyPreAbx group, both patients required explantation. In a subanalysis comparing infected and noninfected patients, infected patients (n = 6) had higher rates of hypertension (n = 6, 100%; P = 0.02) and diabetes mellitus (n = 3, 50%; P = 0.05). CONCLUSIONS: Additional postoperative antibiotics did not decrease infection rates in patients undergoing SNM. Similar comparative analyses should be performed with larger sample sizes.

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The energetic disorder induced by fluctuating liquid environments acts in opposition to the precise control required for coherence-based sensing. Overcoming fluctuations requires a protected quantum subspace that only weakly interacts with the local environment. We report a ytterbium complex that exhibited an ultranarrow absorption linewidth in solution at room temperature with a full width at half maximum of 0.625 milli-electron volts. Using spectral hole burning, we measured an even narrower linewidth of 410 pico-electron volts at 77 kelvin. Narrow linewidths allowed low-field magnetic circular dichroism at room temperature, used to sense Earth-scale magnetic fields. These results demonstrated that ligand protection in lanthanide complexes could substantially diminish electronic state fluctuations. We have termed this system an "atomlike molecular sensor" (ALMS) and proposed approaches to improve its performance.

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Atypical diabetes with overlapping clinical features of type 1 (T1D) and type 2 (T2D) is common and challenging diagnostically and for implementing effective treatment. Here, we validate a recently reported genetic probability of type 1 diabetes (GenProb-T1D) from the UK Biobank (UKB) for differentiating type 1 diabetes and type 2 diabetes in a diabetes patient cohort from a healthcare system-based biobank in the USA. Among 3,363 diabetes patients, we confirmed the performance of GenProb-T1D in differentiating typical type 1 diabetes vs type 2 diabetes. Furthermore, for 359 atypical diabetes patients, those with GenProb-T1D higher than the pre-defined cutoff derived from the UKB had clinical presentations more consistent with that of typical type 1 diabetes. Similar findings were found in participants of European and non-European ancestries. This study provides necessary validation to translate GenProb-T1D into genetic testing in a multi-ancestry cohort. Measuring underlying genetic susceptibility of type 1 diabetes and type 2 diabetes can supplement current clinical tools for earlier and more accurate diagnoses of diabetes.

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Objectives: Early removal of chest tubes reduces pain and morbidity. This study aimed to remove chest tubes immediately after robotic pulmonary resection with complete thoracic lymphadenectomy by administering ice cream to rule out chylothorax. Methods: This quality improvement study utilized prospectively gathered data from one thoracic surgeon. Patients were given 3.6 fl oz of ice cream in the recovery room within 1 h after their operation. Chest tubes were removed within 4 h if there was no chylous drainage and air leak on the digital drainage system. Results: From January 2022 to August 2023, 343 patients underwent robotic pulmonary resection with complete thoracic lymphadenectomy. The median time to ingest the ice cream was 1.5 h after skin closure. The incidence of chylothorax was 0.87% (3/343). Two patients were diagnosed with chylothorax after consuming ice cream within 4 h of surgery. One patient, whose chest tube remained in place due to an air leak, had a chylothorax diagnosed on postoperative day 1 (POD1). All three patients were discharged home on POD1 with their chest tubes in place, adhering to a no-fat, medium-chain triglyceride diet. All chylothoraces resolved within 6 days. None of the remaining patients developed chylothorax postoperatively with a minimum follow-up period of 90 days. Conclusions: Providing ice cream to patients after pulmonary resection and complete thoracic lymphadenectomy is an effective and reliable technique to rule out chylothorax early in the postoperative period and facilitates early chest tube removal. Further studies are needed to ensure that this simple, inexpensive test is reproducible.

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CONTEXT: Instrument-assisted soft tissue mobilization (IASTM) continues to increase in popularity and utilization among manual therapists. Despite its popularity, little is known about the consistency in peak or average forces that clinicians apply when performing IASTM treatments with a 2-handed grip. The purpose of this study was to examine intraclinician consistency in peak and average forces when applying a 2-handed IASTM grip. DESIGN: Randomized crossover study conducted in a university biomechanics laboratory. METHODS: Five (5) licensed athletic trainers with prior IASTM training used 5 different IASTM instruments to apply simulated treatment. Average peak forces (Fpeak) and average mean forces (Fmean) were collected via force plate for all 5 IASTM instruments with a skin simulant attached. Descriptive statistics, coefficients of variation (CVs), box and density plots, and Bland-Altman plots were assessed. RESULTS: The clinicians' average Fpeak ranged from 3.0 N to 11.6 N and average Fmean from 1.9 N to 8.1 N. Fpeak CVs for all instruments ranged from 14% to 31%, and Fmean CVs ranged from 15% to 35%. Bland-Altman plots indicated that for both Fpeak and Fmean, 97% of the data points fell within the limits of agreement across instruments and clinicians. Mean differences across instruments ranged from 0.9 N (91.8 g) to 4.1 N (418.1 g) for Fpeak and from 1.0 N (102.0 g) to 2.8 N (285.5 g) for Fmean. Thus, CVs, box and density plots, and Bland-Altman plots supported general force application consistency. CONCLUSION: Trained IASTM clinicians produced consistent treatment application forces (ie, Fpeak and Fmean) within treatment sessions during 2-handed simulated application.

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Coronaviruses have been responsible for numerous viral outbreaks in the past two decades due to the high transmission rate of this family of viruses. The deadliest outbreak is the recent Covid-19 pandemic, which resulted in over 7 million deaths worldwide. SARS-CoV-2 papain-like protease (PLPro) plays a key role in both viral replication and host immune suppression and is highly conserved across the coronavirus family, making it an ideal drug target. Herein we describe a fragment-based screen against PLPro using protein-observed NMR experiments, identifying 77 hit fragments. Analyses of NMR perturbation patterns and X-ray cocrystallized structures reveal fragments bind to two distinct regions of the protein. Importantly none of the fragments identified belong to the same chemical class as the few reported inhibitors, allowing for the discovery of a novel class of PLPro inhibitors.

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Achieving ultranarrow absorption linewidths in the condensed phase enables optical state preparation of specific non-thermal states, a prerequisite for quantum-enabled technologies. The 4f orbitals of lanthanide(iii) complexes are often referred to as "atom-like," reflecting their isolated nature, and are promising substrates for the optical preparation of specific quantum states. To better understand the photophysical properties of 4f states and assess their potential for quantum applications, theoretical building blocks are required for rapid screening. In this study, an atomic-level perturbative calculation (i.e., spin-orbit crystal field, SOCF) is applied to various Yb(iii) complexes to investigate their linear absorption and emission through a fitting mechanism of their experimentally determined transition energies and oscillator strengths. In particular, the optical properties of (thiolfan)YbCl(THF) (thiolfan = 1,1'-bis(2,4-di-tert-butyl-6-thiomethylenephenoxy)ferrocene), a recently reported complex with an ultranarrow optical linewidth, are computed and compared to those of other Yb(iii) compounds. Through a transition energy sampling study, major contributors to the optical linewidth are identified. We observe particularly isolated f-f transitions and narrow linewidths, which we attribute to two distinct factors. Firstly, the ultra-high atomic similarity of the orbitals involved in the optical transition, along with the presence of an anisotropic crystal field, collectively contribute to the observed narrow transitions. Secondly, we note highly correlated excited-ground energy fluctuations that serve to greatly suppress inhomogeneous line-broadening. This article illustrates how SOCF can be used as a low-cost method to probe the influence of crystal field environment on the optical properties of Yb(iii) complexes to assist the development of novel lanthanide series quantum materials.

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Plant-based milk alternatives (PBMAs) are increasingly consumed as a dairy alternative [Olson, S. Milk and Non-Dairy Milk - US - 2021, 2021.]. Plant foods are rich sources of (poly)phenols, but concentrations of these bioactive phytochemicals in processed PBMAs are not well documented. We procured twenty-seven PBMA products of 6 types (almond, coconut, oat, pea, rice, and soy) for (poly)phenol analysis. Samples were analyzed via ultra high-performance liquid chromatography-diode array with mass spectrometry. The (poly)phenol content of PBMAs varies and is dependent on plant source, brand, and added flavorings. Soy milk had the highest concentration and rice milk had the lowest (91.9 ± 2.7 and 0.9 ± 0.2 mean mg ± SD/cup serving, respectively). Almond milk, the most widely consumed PBMA, averaged 12.1 ± 8.2 mg/cup serving, but the majority of (poly)phenols are derived from added flavorings. PBMAs contain a wide range of potentially bioactive (poly)phenols and may contribute significantly to overall dietary (poly)phenol intake with the potential to impact health outcomes.

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LAY ABSTRACT: The Autism Stigma and Knowledge Questionnaire (ASK-Q) was developed to assess autism knowledge across cultural contexts. The current study aimed to examine cultural equivalence of the measure using a large, international database. These analyses identified 18 items in need of examination for removal or revision. A team of autism experts recommended several additional changes to reduce stigma and increase cross-cultural sensitivity and accuracy of the items on the measure. These changes resulted in a briefer measure with maintained statistical support.

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It is imperative for individuals to exhibit flexible behaviour according to ecological context, such as available resources or predation threat. Manipulative studies on responses to threat often focus on behaviour in the presence of a single indicator for the potential of predation, whereas in the wild perception of threat will probably be more nuanced. Here, we examine the collective behaviour of eastern mosquitofish (Gambusia holbrooki) subject to five differing threat scenarios relating to the presence and hunger state of a jade perch (Scortum barcoo). Across threat scenarios, groups exhibit unique behavioural profiles that differ in the durations that particular collective states are maintained, the probability of transitions between states, the size and duration of persistence of spatially defined subgroups, and the patterns of collective order of these subgroups. Under the greatest level of threat, subgroups of consistent membership persist for longer durations. Group-level behaviours, and their differences, are interconnected with differences in estimates of the underlying rules of interaction thought to govern collective motion. The responses of the group are shown to be specific to the details of a potential threat, rather than a binary response to the presence or absence of some form of threat.

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INTRODUCTION: Fragmentation of care (FC, the receipt of care at > 1 institution) has been shown to negatively impact cancer outcomes. Given the multimodal nature of breast cancer treatment, we sought to identify factors associated with FC and its effects on survival of breast cancer patients. METHODS: A retrospective analysis was performed of surgically treated, stage I-III breast cancer patients in the 2004-2020 National Cancer Database, excluding neoadjuvant therapy recipients. Patients were stratified into two groups: FC or non-FC care. Treatment delay was defined as definitive surgery > 60 days after diagnosis. Multivariable logistic regression was performed to identify factors predictive of FC, and survival was compared using Kaplan-Meier and multivariable Cox proportional hazards methods. RESULTS: Of the 531,644 patients identified, 340,297 (64.0%) received FC. After adjustment, FC (OR 1.27, 95% CI 1.25-1.29) was independently associated with treatment delay. Factors predictive of FC included Hispanic ethnicity (OR 1.04, 95% CI: 1.01-1.07), treatment at comprehensive community cancer programs (OR 1.06, 95% CI: 1.03-1.08) and integrated network cancer programs (OR 1.55, 95% CI: 1.51-1.59), AJCC stage II (OR 1.06, 95% CI 1.05-1.07) and stage III tumors (OR 1.06, 95% CI: 1.02-1.10), and HR + /HER2 + tumors (OR 1.05, 95% CI: 1.02-1.07). Treatment delay was independently associated with increased risk of mortality (HR 1.23, 95% CI 1.20-1.26), whereas FC (HR 0.87, 95% CI 0.86-0.88) showed survival benefit. CONCLUSIONS: While treatment delay negatively impacts survival in breast cancer patients, our findings suggest FC could be a marker for multispecialty care that may mitigate some of these effects.

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This study evaluates the R3THA™ assessment protocol (R3THA-AP™), a technology-supported testing module for personalized rehabilitation in children with cerebral palsy (CP). It focuses on the reliability and validity of the R3THA-AP in assessing hand and arm function, by comparing kinematic assessments with standard clinical assessments. Conducted during a 4-week summer camp, the study assessed the functional and impairment levels of children with CP aged 3-18. The findings suggest that R3THA is more reliable for children aged 8 and older, indicating that age significantly influences the protocol's effectiveness. The results also showed that the R3THA-AP's kinematic measurements of hand and wrist movements are positively correlated with the Box and Blocks Test Index (BBTI), reflecting hand function and dexterity. Additionally, the R3THA-AP's accuracy metrics for hand and wrist activities align with the Melbourne Assessment 2's Range of Motion (MA2-ROM) scores, suggesting a meaningful relationship between R3THA-AP data and clinical assessments of motor skills. However, no significant correlations were observed between the R3THA-AP and MA2's accuracy and dexterity measurements, indicating areas for further research. These findings validate the R3THA-AP's utility in assessing motor abilities in CP patients, supporting its integration into clinical practice.

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The phenomenon of cell invasion is an essential step in angiogenesis, embryonic development, immune responses, and cancer metastasis. In the course of cancer progression, the ability of neoplastic cells to degrade the basement membrane and penetrate neighboring tissue (or blood vessels and lymph nodes) is an early event of the metastatic cascade. The Boyden chamber assay is one of the most prevalent methods implemented to measure the pro- or anti-invasive effects of drugs, investigate signaling pathways that modulate cell invasion, and characterize the role of extracellular matrix proteins in metastasis. However, the traditional protocol of the Boyden chamber assay has some technical challenges and limitations. One such challenge is that the endpoint of the assay involves photographing and counting stained cells (in multiple fields) on porous filters. This process is very arduous, requires multiple observers, and is very time-consuming. Our improved protocol for the Boyden chamber assay involves lysis of the dye-stained cells and reading the absorbance using an ELISA reader to mitigate this challenge. We believe that our improved Boyden chamber methodology offers a standardized, high-throughput format to evaluate the efficacy of various drugs and test compounds in influencing cellular invasion in normal and diseased states. We believe that our protocol will be useful for researchers working in the fields of immunology, vascular biology, drug discovery, cancer biology, and developmental biology. Key features • Measurement of tumor invasion using human cancer cells. • Ability to measure the pro-invasive/anti-invasive activity of small molecules and biological modifiers. • Measurement of chemotaxis, chemokines, trafficking of immune cells, and proteolytic activity of matrix metalloproteinases, lysosomal hydrolysates, collagenases, and plasminogen activators in physiological and pathological conditions. • Investigation of the role of extracellular matrix proteins in the crosstalk between endothelial, epithelial, muscle, or neuronal cells and their adjacent stroma.

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The evaluation of the effects of architecture and design in psychiatric hospitals primarily focuses on final outcomes, such as disease progression, and is made from the perspective of evidence-based medicine. Meanwhile, the evidence-informed, realist approach addresses how the intervention works. Understanding the underlying action mechanisms of the intervention is needed to facilitate its scaling-up and adaptation in new environments. This umbrella review reports in which ways architecture and design have an effect on patients' and staff experience in inpatient psychiatric hospital. The search was constructed around three key concepts (psychiatric hospital, design, and staff and patient outcomes) and was conducted across three reference databases (Embase, Medline, and PsychINFO). Academic and gray literature was analyzed. Information on design and architectural features in psychiatric hospitals, their effects on patients and staff experience, and the acting mechanisms enabling these effects were extracted. From 951 original references, 14 full texts were included in the analysis. Design and architectural features (e.g., aesthetic appeal of places, home-like environment) in psychiatric hospitals address patients' stress, boost social interaction, foster patients' autonomy and feelings of control, ensure respect for patient's privacy and dignity, and prevent under-and overstimulation. Using theory-driven evaluation may facilitate future hospital renovation and the evaluation of its effect.

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