Implementation of an integrated primary care prevention and management program for chronic low back pain (LBP): patient-reported outcomes and predictors of pain interference after six months.

BACKGROUND: Integrated primary care programs for patients living with chronic pain which are accessible, interdisciplinary, and patient-centered are needed for preventing chronicity and improving outcomes. Evaluation of the implementation and impact of such programs supports further development of primary care chronic pain management. This study examined patient-reported outcomes among individuals with low back pain (LBP) receiving care in a novel interdisciplinary primary care program. METHODS: Patients were referred by primary care physicians in four regions of Quebec, Canada, and eligible patients received an evidence-based interdisciplinary pain management program over a six-month period. Patients were screened for risk of chronicity. Patient-reported outcome measures of pain interference and intensity, physical function, depression, and anxiety were evaluated at regular intervals over the six-month follow-up. A multilevel regression analysis was performed to evaluate the association between patient characteristics at baseline, including risk of chronicity, and change in pain outcomes. RESULTS: Four hundred and sixty-four individuals (mean age 55.4y, 63% female) completed the program. The majority (≥ 60%) experienced a clinically meaningful improvement in pain intensity and interference at six months. Patients with moderate (71%) or high risk (81%) of chronicity showed greater improvement in pain interference than those with low risk (51%). Significant predictors of improvement in pain interference included a higher risk of chronicity, younger age, female sex, and lower baseline disability. CONCLUSION: The outcomes of this novel LBP program will inform wider implementation considerations by identifying key components for further effectiveness, sustainability, and scale-up of the program.

Impact of Obesity-Related Endoplasmic Reticulum Stress on Cancer and Associated Molecular Targets.

Obesity, characterized by excessive body fat, is closely linked to endoplasmic reticulum (ER) stress, leading to insulin resistance and type 2 diabetes. Inflammatory pathways like c-Jun N-terminal kinase (JNK) worsen insulin resistance, impacting insulin signaling. Moreover, ER stress plays a substantial role in cancer, influencing tumor cell survival and growth by releasing factors like vascular endothelial growth factor (VEGF). The unfolded protein response (UPR) is pivotal in this process, offering both pro-survival and apoptotic pathways. This review offers an extensive exploration of the sophisticated connection between ER stress provoked by obesity and its role in both the onset and advancement of cancer. It delves into the intricate interplay between oncogenic signaling and the pathways associated with ER stress in individuals who are obese. Furthermore, this review sheds light on potential therapeutic strategies aimed at managing ER stress induced by obesity, with a focus on addressing cancer initiation and progression. The potential to alleviate ER stress through therapeutic interventions, which may encompass the use of small molecules, FDA-approved medications, and gene therapy, holds great promise. A more in-depth examination of pathways such as UPR, ER-associated protein degradation (ERAD), autophagy, and epigenetic regulation has the potential to uncover innovative therapeutic approaches and the identification of predictive biomarkers.

Resveratrol-based Delivery Systems as Contemporary Nominees for Combating Pulmonary Diseases: A Comprehensive Review.

Exploiting different formulation approaches, each designed to improve the clinical use of resveratrol (RES) in treating several lung diseases. Accentuating the rationale for using RESbased delivery systems in different clinical applications in pulmonary diseases. Resveratrol (RES), a well-known natural polyphenol stilbenoid, possesses tremendous potential to treat various lung diseases owing to its anti-inflammatory, antioxidant, antiapoptotic, antiviral, and anticancer activities. Its physicochemical properties have restricted the beneficial activities of resveratrol, as it is characterized by low aqueous solubility, bioavailability and stability in addition to high photosensitivity. With the growing understanding of the effectiveness of RES in treating lung diseases, the need for attempts and advances in RES formulations should be evolved to enhance its involvement in pharmaceutical applications. This review discusses the role of RES in treating several pulmonary illnesses. For the first time, different approaches and strategies to evade its limitations and allow its clinical applications via various routes for managing a variety of respiratory ailments are presented rigorously.

Hepatocellular carcinoma patients serum modulates the regenerative capacities of adipose mesenchymal stromal cells.

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers causing the highest mortality rate worldwide. Treatment options of surgery, radiation, cytotoxic drugs and liver transplantation suffer significant side effects and a high frequency of relapse. Stem cell therapy has been proposed as a new effective therapy, however, controversial reports are emerging on the role of mesenchymal stem cells in cancer. In this work, we aimed to assess the regenerative capacities of adipose mesenchymal stem cells when exposed to serum from HCC patients, by assessing the effect of the sera on modulating the regenerative capacities of h-AMSCs and the cancer properties in HCC cells. This will pave the way for maximizing the efficacy of MSCs in cancer therapy. Our data show that HCC serum-treated hA-MSCs suffered oncogene-induced senescence as shown by their altered morphology and ameliorated proliferation and differentiation. The cells were enlarged with small irregular nuclei, swollen rough endoplasmic reticulum cisternae, and aging lysosomes typified by dark residual bodies. HCC serum-treated Huh-7 cancer cells on the other hand displayed higher tumor aggressiveness as depicted by altered morphology, increased cellular proliferation and migration, and decreased percentage of early and late apoptotic cells. Our findings provide evidence that exposure of hA-MSCs to the serum of HCC patients decreases their regenerative capacities and should be considered when employed as a potential therapy in HCC patients.

Susceptible bacteria can survive antibiotic treatment in the mammalian gastrointestinal tract without evolving resistance.

Antibiotic resistance and evasion are incompletely understood and complicated by the fact that murine interval dosing models do not fully recapitulate antibiotic pharmacokinetics in humans. To better understand how gastrointestinal bacteria respond to antibiotics, we colonized germ-free mice with a pan-susceptible genetically barcoded Escherichia coli clinical isolate and administered the antibiotic cefepime via programmable subcutaneous pumps, allowing closer emulation of human parenteral antibiotic dynamics. E. coli was only recovered from intestinal tissue, where cefepime concentrations were still inhibitory. Strikingly, "some" E. coli isolates were not cefepime resistant but acquired mutations in genes involved in polysaccharide capsular synthesis increasing their invasion and survival within human intestinal cells. Deleting wbaP involved in capsular polysaccharide synthesis mimicked this phenotype, allowing increased invasion of colonocytes where cefepime concentrations were reduced. Additionally, "some" mutant strains exhibited a persister phenotype upon further cefepime exposure. This work uncovers a mechanism allowing "select" gastrointestinal bacteria to evade antibiotic treatment.

The cross talk between type II diabetic microenvironment and the regenerative capacities of human adipose tissue-derived pericytes: a promising cell therapy.

BACKGROUND: Pericytes (PCs) are multipotent contractile cells that wrap around the endothelial cells (ECs) to maintain the blood vessel's functionality and integrity. The hyperglycemia associated with Type 2 diabetes mellitus (T2DM) was shown to impair the function of PCs and increase the risk of diabetes complications. In this study, we aimed to investigate the deleterious effect of the diabetic microenvironment on the regenerative capacities of human PCs. METHODS: PCs isolated from human adipose tissue were cultured in the presence or absence of serum collected from diabetic patients. The functionality of PCs was analyzed after 6, 14, and 30 days. RESULTS: Microscopic examination of PCs cultured in DS (DS-PCs) showed increased aggregate formation and altered surface topography with hyperbolic invaginations. Compared to PCs cultured in normal serum (NS-PCs), DS-PCs showed more fragmented mitochondria and thicker nuclear membrane. DS caused impaired angiogenic differentiation of PCs as confirmed by tube formation, decreased VEGF-A and IGF-1 gene expression, upregulated TSP1, PF4, actin-related protein 2/3 complex, and downregulated COL21A1 protein expression. These cells suffered more pronounced apoptosis and showed higher expression of Clic4, apoptosis facilitator BCl-2-like protein, serine/threonine protein phosphatase, and caspase-7 proteins. DS-PCs showed dysregulated DNA repair genes CDKN1A, SIRT1, XRCC5 TERF2, and upregulation of the pro-inflammatory genes ICAM1, IL-6, and TNF-α. Further, DS-treated cells also showed disruption in the expression of the focal adhesion and binding proteins TSP1, TGF-ß, fibronectin, and PCDH7. Interestingly, DS-PCs showed resistance mechanisms upon exposure to diabetic microenvironment by maintaining the intracellular reactive oxygen species (ROS) level and upregulation of extracellular matrix (ECM) organizing proteins as vinculin, IQGAP1, and tubulin beta chain. CONCLUSION: These data showed that the diabetic microenvironment exert a deleterious effect on the regenerative capacities of human adipose tissue-derived PCs, and may thus have possible implications on the vascular complications of T2DM. Nevertheless, PCs have shown remarkable protective mechanisms when initially exposed to DS and thus they could provide a promising cellular therapy for T2DM.

Sustainability of an outcome measure in outpatient stroke rehabilitation: A realist evaluation.

RATIONALE: Only half of newly implemented evidence-based practices are sustained. Though poor sustainment can lead to negative consequences for clinical teams, organizations and patients, the causal explanations of sustainment are largely unknown. AIMS AND OBJECTIVES: We aimed to ascertain how (mechanisms) and in what circumstances (context) a newly implemented outcome measure in rehabilitation was sustained or not (outcome). METHODOLOGY: Informed by an integrated knowledge translation approach, we conducted a realist evaluation using a mixed method, embedded single case study design with data collection up to 18 months following the implementation of the Mayo-Portland Adaptability Inventory - version 4 (MPAI-4), a rehabilitation outcome measure. Quantitative data (survey and patient charts) was analysed using descriptive statistics, then integrated with qualitative data (interviews with 10 key informants) and analysed using inductive and deductive retroduction. We integrated the data to develop a case description and ultimately, to refine the programme theory to better understand the sustainability of the MPAI-4. RESULTS: We linked context, mechanisms and outcomes, and also emphasized sustainability strategies in 18 explanations of how sustainability works. These explanations provide evidence for four overarching patterns: (1) implementation and sustainability phases are interconnected, (2) outcomes build on each other recursively, with patient benefits as the keystone outcome, (3) sustainment is achieved to varying levels across different sustainability outcomes [e.g., high level (e.g., rate of MPAI-4 scoring: 77.7%) to low level (e.g., rate of MPAI-4 application to clinical decision-making: 3.7%)] and (4) the work of sustaining the MPAI-4 is shared amongst different stakeholders. CONCLUSION: Implementation teams can draw from this programme theory to improve the sustainment of outcomes measures while researchers could continue to refine the theory. Continued investigation of sustainability, including diverse and continuous sustainability outcomes, is needed to understand how to maintain improvements in quality of care and patient outcomes.

Collaborative sustainability planning for an outcome measure in outpatient stroke rehabilitation: A qualitative description study.

RATIONALE: Evidence suggests that sustainability planning and the use of a collaborative approach to planning result in better sustainability outcomes and more relevant knowledge. Yet, both approaches appear to be underutilized. A detailed description of collaborative sustainability planning may encourage the use of these two impactful strategies. AIMS AND OBJECTIVES: To explore the collaborative sustainability planning process for a single outcome measure in three rehabilitation sites. METHODOLOGY: Within the Mayo-Portland Adaptability Inventory-version 4 (MPAI-4) implementation project, we conducted a qualitative description study. We used data from 12 core sustainability planning meetings and 108 follow-up meetings that included a total of 31 clinical and research team participants. Sustainability planning was informed by an MPAI-4-specific implementation guide, and by the results from a realist review of the sustainability of rehabilitation practices and the Clinical Sustainability Assessment Tool. We analyzed qualitative data using thematic content analysis. RESULTS: Three themes describe the collaborative sustainability planning process: (1) "collaboration as a driver for sustainability" which captures the active collaboration underpinning sustainability planning; (2) "co-creation of a sustainability plan to achieve shared objectives" which captures the identified barriers and facilitators, and selected sustainability strategies linked to one of six collaboratively identified shared objectives; and (3) "the iterative nature of sustainability planning" which captures the necessity of an agile and responsive sustainability planning process. CONCLUSION: Identified strategies may be useful to support (collaborative) sustainment. Future research could investigate the effect of collaborative sustainability planning on sustainability objectives, and the relationship between these objectives.

Enrollment and dropout rates of individuals with chronic obstructive pulmonary disease approached for telehealth interventions: A systematic review and meta-regression analysis.

Introduction: Telehealth interventions have the potential of improving health outcomes for individuals with chronic obstructive pulmonary disease (COPD). However, the precise impact of telehealth on exacerbation and hospital readmissions remains inconclusive. This lack of knowledge on the effectiveness of telehealth for COPD care might be due to lack of clarity regarding which variables are most strongly associated with enrolment and dropout rates. Objectives: Among individuals with COPD in telehealth studies, we aimed to: (1) estimate the extent to which trial-related variables are associated with enrolment and dropout rates, and identify reasons for dropouts; (2) estimate the extent to which patients-related and intervention-related variables are associated with dropout rates; (3) estimate the effect of enrolment rate and dropout rate on effect size; (4) estimate the effect of trial-related, patient-related, and intervention-related variables on effect size. Methods: A systematic literature search was conducted using four electronic databases. Two independent reviewers screened all retrieved titles, abstracts and full texts according to the inclusion criteria and extracted the data. A random-effect meta-regression analysis was conducted to estimate the overall enrolment and dropout rates, and estimated the different variables' effects on the enrolment rate, dropout rate, and effect sizes in the studies included in the review. Results: A total of 56 studies comprising 7530 participants were identified. The estimated enrolment and dropout rates were 50.3 % and 14.9 %, respectively. Trial-related variables influence enrollment and dropout rates, including RCT designs and the recruitments. The patient-related variables, including age and severity of the disease, and intervention-related variables, including the components of the intervention and mode of delivery, influence dropout rates. Studies with low dropout rates had a bigger effect size by 0.23. The main reported reasons for dropping out of the intervention were related to death (21 %) followed by lost to follow-up (14 %). Conclusion: Trial, patient, and intervention-related variables were found to influence the enrolment and dropout rates. This would help plan and develop a more appealing telehealth intervention that patients can easily accept and incorporate into their everyday lives. Registration information: International Prospective Register of Systematic Reviews (PROSPERO); ID: CRD42017078541.

Bioproduction and optimization of newly characterized melanin pigment from Streptomyces djakartensis NSS-3 with its anticancer, antimicrobial, and radioprotective properties.

BACKGROUND: Melanin is a natural pigment that is considered a promising biomaterial for numerous biotechnological applications across several industries. Melanin has biomedical applications as antimicrobial, anticancer, and antioxidant properties. Additionally, in the pharmaceutical and cosmetic industries, it is used in drug delivery and as a radioprotective agent. Also, melanin has environmental uses in the fields of bioremediation and the food industry. The biosynthesis of melanin pigment is an area of interest for researchers due to its multifunctionality, high compatibility, and biodegradability. Therefore, our present work is the first attempt to characterize and optimize the productivity of melanin pigment from Streptomyces djakartensis NSS-3 concerning its radioprotection and biological properties. RESULTS: Forty isolates of soil actinobacteria were isolated from the Wadi Allaqui Biosphere Reserve, Egypt. Only one isolate, ACT3, produced a dark brown melanin pigment extracellularly. This isolate was identified according to phenotypic properties and molecular phylogenetic analysis as Streptomyces djakartensis NSS-3 with accession number OP912881. Plackett-Burman experimental design (PBD) and response surface methodology (RSM) using a Box-Behnken design (BBD) were performed for optimum medium and culturing conditions for maximum pigment production, resulting in a 4.19-fold improvement in melanin production (118.73 mg/10 mL). The extracted melanin pigment was purified and characterized as belonging to nitrogen-free pyomelanin based on ultraviolet-visible spectrophotometry (UV-VIS), Fourier transform infrared (FT-IR), Raman spectroscopy, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and NMR studies. Purified melanin demonstrated potent scavenging activity with IC50 values of 18.03 µg/mL and revealed high potency as sunscreens (in vitro SPF = 18.5). Moreover, it showed a nontoxic effect on a normal cell line (WI38), while it had a concentration-dependent anticancer effect on HCT116, HEPG, and MCF7 cell lines with IC50 = 108.9, 43.83, and 81.99 µg/mL, respectively. Also, purified melanin had a detrimental effect on the tested MDR bacterial strains, of which PA-09 and SA-04 were clearly more susceptible to melanin compared with other strains with MICs of 6.25 and 25 µg/mL, respectively. CONCLUSION: Our results demonstrated that the newly characterized pyomelanin from Streptomyces djakartensis NSS-3 has valuable biological properties due to its potential photoprotective, antioxidant, anticancer, antimicrobial, and lack of cytotoxic activities, which open up new prospects for using this natural melanin pigment in various biotechnological applications and avoiding chemical-based drugs.

Expert-centered Evaluation of Deep Learning Algorithms for Brain Tumor Segmentation.

Purpose To present results from a literature survey on practices in deep learning segmentation algorithm evaluation and perform a study on expert quality perception of brain tumor segmentation. Materials and Methods A total of 180 articles reporting on brain tumor segmentation algorithms were surveyed for the reported quality evaluation. Additionally, ratings of segmentation quality on a four-point scale were collected from medical professionals for 60 brain tumor segmentation cases. Results Of the surveyed articles, Dice score, sensitivity, and Hausdorff distance were the most popular metrics to report segmentation performance. Notably, only 2.8% of the articles included clinical experts' evaluation of segmentation quality. The experimental results revealed a low interrater agreement (Krippendorff α, 0.34) in experts' segmentation quality perception. Furthermore, the correlations between the ratings and commonly used quantitative quality metrics were low (Kendall tau between Dice score and mean rating, 0.23; Kendall tau between Hausdorff distance and mean rating, 0.51), with large variability among the experts. Conclusion The results demonstrate that quality ratings are prone to variability due to the ambiguity of tumor boundaries and individual perceptual differences, and existing metrics do not capture the clinical perception of segmentation quality. Keywords: Brain Tumor Segmentation, Deep Learning Algorithms, Glioblastoma, Cancer, Machine Learning Clinical trial registration nos. NCT00756106 and NCT00662506 Supplemental material is available for this article. © RSNA, 2023.

Thymoquinone-protoflavone hybrid molecules as potential antitumor agents.

We describe herein the synthesis of eight new ester-coupled hybrid compounds from thymoquinone and protoflavone building blocks, and their bioactivity testing against multiple cancer cell lines. Among the hybrids, compound 14 showed promising activities in all cell lines studied. The highest activities were recorded against breast cancer cell lines with higher selectivity to MDA-MB-231 as compared to MCF-7. Even though the hybrids were found to be completely hydrolysed in 24 h under cell culture conditions, compound 14 demonstrated a ca. three times stronger activity against U-87 glioblastoma cells than a 1:1 mixture of its fragments. Further, compound 14 showed good tumour selectivity: it acted 4.4-times stronger on U-87 cells than on MRC-5 fibroblasts. This selectivity was much lower, only ca. 1.3-times, when the cells were co-treated with a 1:1 mixture of its non-coupled fragments. Protoflavone-thymoquinone hybrids may therefore serve as potential new antitumor leads particularly against glioblastoma.

Magnetic resonance imaging of pilonidal sinus disease: interobserver agreement and practical MRI reporting tips.

OBJECTIVE: To evaluate the interobserver agreement for the features of natal cleft pilonidal sinus disease (PSD) on magnetic resonance imaging (MRI) and propose a standardized checklist for reporting PSD on MRI. MATERIALS AND METHODS: Forty MRI studies of 39 discrete patients with PSD were retrospectively evaluated by five independent radiologists using a standardized checklist. Fleiss' Kappa (k) coefficients of agreement were used to test the agreement between categorical variables. The MRI features of the natal cleft sepsis associated with PSD were classified into four main categories: morphology, branching and extensions, external skin openings, and the relationship of the PSD to the coccyx. A survey was created and disseminated online among general surgeons who treat patients with PSD to assess the relevance of the MRI features proposed in the standardized checklist. RESULTS: The overall agreement regarding the identification of morphology of the natal cleft sepsis was moderate (k = 0.59). Lateral and caudal extensions interobserver agreement was substantial (k = 0.64 and 0.71, respectively). However, the overall agreement regarding the individual parts of anal sphincter involved was moderate (k = 0.47). Substantial interobserver agreement was found in assessing the proximity of the PSD to the coccyx (k = 0.62). CONCLUSION: Preoperative MRI can delineate the extensions and branching of PSD with substantial agreement. MRI is superior in describing the deep extensions of PSD with better reliability than assessing the number and locations of the external openings. Expert consensus agreement is needed to establish the MRI features necessary for optimal reporting of PSD. CLINICAL RELEVANCE STATEMENT: MRI can offer valuable information about the extent of sepsis associated with pilonidal sinus disease, particularly in cases with involvement of critical anatomical structures such as the coccyx and anal triangle. MRI can potentially contribute to more accurate patient stratification and surgical planning. KEY POINTS: • The interobserver agreement for assessing PSD's lateral and caudal extension on MRI is substantial. • MRI can describe deep extensions and branching of PSD with superior reliability than assessing the number and site of external openings. • Reporting the relationship between natal cleft sepsis in PSD and the anal region may influence the surgical approach and postoperative healing.

Reliability and Validity of the Youth and Young-Adult Participation and Environment Measure (Y-PEM): An Initial Evaluation.

AIM: To examine psychometric properties and aspects of utility of the Youth and young-adult Participation and Environment Measure (Y-PEM). METHODS: Young people with and without physical disabilities (n = 113) aged 12 to 31 (x¯ = 23; SD = 4.3) completed an online survey containing the Y-PEM and QQ-10 questionnaire. To examine construct validity, differences in participation levels and environmental barriers/facilitators were examined between those with (n = 56) and without disabilities (n = 57) via t-test. Internal consistency was computed using Cronbach's alpha. To examine test-retest reliability, a sub-sample of 70 participants completed the Y-PEM a second time, 2-4 weeks apart. The Intraclass correlation coefficient (ICC) was calculated. RESULTS: Descriptively, participants with disabilities had lower levels of frequency and involvement across all four settings: home, school/educational, community, workplace. Internal consistency were 0.71 and above (up to 0.82) across all scales with the exception of home (0.52) and workplace frequency (0.61). Test-retest reliability were 0.70 and above (up to 0.85) across all settings except for environmental supports at school (0.66) and workplace frequency (0.43). Y-PEM was perceived as a valuable tool with relatively low burden. CONCLUSIONS: Initial psychometric properties are promising. Findings support Y-PEM's use as a feasible self-reported questionnaire for individuals aged 12-30 years old.

Investigation of autosegmentation techniques on T2-weighted MRI for off-line dose reconstruction in MR-linac workflow for head and neck cancers.

BACKGROUND: In order to accurately accumulate delivered dose for head and neck cancer patients treated with the Adapt to Position workflow on the 1.5T magnetic resonance imaging (MRI)-linear accelerator (MR-linac), the low-resolution T2-weighted MRIs used for daily setup must be segmented to enable reconstruction of the delivered dose at each fraction. PURPOSE: In this pilot study, we evaluate various autosegmentation methods for head and neck organs at risk (OARs) on on-board setup MRIs from the MR-linac for off-line reconstruction of delivered dose. METHODS: Seven OARs (parotid glands, submandibular glands, mandible, spinal cord, and brainstem) were contoured on 43 images by seven observers each. Ground truth contours were generated using a simultaneous truth and performance level estimation (STAPLE) algorithm. Twenty total autosegmentation methods were evaluated in ADMIRE: 1-9) atlas-based autosegmentation using a population atlas library (PAL) of 5/10/15 patients with STAPLE, patch fusion (PF), random forest (RF) for label fusion; 10-19) autosegmentation using images from a patient's 1-4 prior fractions (individualized patient prior [IPP]) using STAPLE/PF/RF; 20) deep learning (DL) (3D ResUNet trained on 43 ground truth structure sets plus 45 contoured by one observer). Execution time was measured for each method. Autosegmented structures were compared to ground truth structures using the Dice similarity coefficient, mean surface distance (MSD), Hausdorff distance (HD), and Jaccard index (JI). For each metric and OAR, performance was compared to the inter-observer variability using Dunn's test with control. Methods were compared pairwise using the Steel-Dwass test for each metric pooled across all OARs. Further dosimetric analysis was performed on three high-performing autosegmentation methods (DL, IPP with RF and 4 fractions [IPP_RF_4], IPP with 1 fraction [IPP_1]), and one low-performing (PAL with STAPLE and 5 atlases [PAL_ST_5]). For five patients, delivered doses from clinical plans were recalculated on setup images with ground truth and autosegmented structure sets. Differences in maximum and mean dose to each structure between the ground truth and autosegmented structures were calculated and correlated with geometric metrics. RESULTS: DL and IPP methods performed best overall, all significantly outperforming inter-observer variability and with no significant difference between methods in pairwise comparison. PAL methods performed worst overall; most were not significantly different from the inter-observer variability or from each other. DL was the fastest method (33 s per case) and PAL methods the slowest (3.7-13.8 min per case). Execution time increased with a number of prior fractions/atlases for IPP and PAL. For DL, IPP_1, and IPP_RF_4, the majority (95%) of dose differences were within ± 250 cGy from ground truth, but outlier differences up to 785 cGy occurred. Dose differences were much higher for PAL_ST_5, with outlier differences up to 1920 cGy. Dose differences showed weak but significant correlations with all geometric metrics (R2 between 0.030 and 0.314). CONCLUSIONS: The autosegmentation methods offering the best combination of performance and execution time are DL and IPP_1. Dose reconstruction on on-board T2-weighted MRIs is feasible with autosegmented structures with minimal dosimetric variation from ground truth, but contours should be visually inspected prior to dose reconstruction in an end-to-end dose accumulation workflow.

Dental Technicians' Perception of the Quality of Dentists' Communication on the Fabrication of Removable Partial Dentures: A Cross-Sectional Study in Saudi Arabia.

BACKGROUND: Effective and clear communication between the dentist and dental technician plays a vital role in rendering quality prostheses for patients. When fabricating a removable dental prosthesis, it is uncertain if the information received by the dental laboratory technician is clear and sufficient. This investigation aimed to assess dental technicians' perceptions of the quality of dentists' communication on the fabrication of removable partial dentures (RPDs) in Saudi Arabia. METHODOLOGY: After obtaining the institutional review board (IRB) approval from Riyadh Elm University, Riyadh, Saudi Arabia, a cross-sectional survey on a convenient sample of 115 dental technicians registered with the Saudi Commission for Health Specialties was conducted in January 2022. The voluntary participation of 94 technicians fabricating RPDs was included. A 19-item online questionnaire was developed, including quality of written instruction, selection of impression trays, and impression materials for RPD fabrication, shared through Google Docs. Descriptive statistics were tabulated, and responses were displayed as a percentage of the total. RESULTS: Of the 94 study subjects, 35% had less than five years of experience, 44% stated that they routinely receive work authorizations with clear instructions, 13% always used digital technology to fabricate prostheses, and 58% reported difficulty with communicated work authorization by dentists having less than five years of experience. Thirty-three respondents (35.1%) reported that 75% or more of the fabricated partial dentures were cast framework partials. Thirty-three respondents (35.1%) indicated that the master casts received for partial framework construction were usually accurate. Tooth alterations, however, were reported as usually adequate by only 28 respondents (29.8%). For creating the artificial gingiva portion of cast partials, 56 respondents (59.6%) preferred heat-cured acrylic resin. Furthermore, 40 respondents (42.6%) said that 75% or more of the requested partials were entirely made out of acrylic resin. Regarding case design discussions, 26 respondents (27.7%) always engaged with dentists, while 39 (41.5%) did so occasionally. CONCLUSION: The obtained assessments pointed to the fact that dental technicians expressed a perception of inadequacy regarding the work authorizations provided by dentists for the fabrication of RPDs, where they seemingly felt that the instructions conveyed by the dentists were not sufficiently comprehensive or clear.

Utility of Tumor Mutational Burden as a Biomarker for Response to Immune Checkpoint Inhibition in the VA Population.

PURPOSE: Immune checkpoint inhibitors (ICIs) are used for an increasing number of indications across various tumor types, as well as several tumor-agnostic indications in patients with advanced cancer. Although many patients benefit from ICI therapy, others do not, highlighting a need for better predictive biomarkers. Tumor mutational burden (TMB) reflects the global number of mutations within a tumor and has been widely explored as a predictive biomarker of ICI response. The current tumor type-agnostic US Food and Drug Administration approval of pembrolizumab for metastatic solid tumors defines high TMB (TMB-H) as ≥10 mut/Mb as measured by FoundationOne CDx. This fixed cutoff may not be the ideal value across all solid tumors. METHODS: We performed a retrospective analysis of the association of survival outcomes with TMB in patients treated with ICI for five major cancer types, using real-world data from the VA. Survival was measured from initiation of ICI, and Kaplan-Meier survival curves were compared by log-rank test. RESULTS: Overall survival (OS) was significantly longer for patients with TMB-H versus TMB low tumors in non-small-cell lung cancer (NSCLC; n = 1,593), head and neck (H&N) cancer (n = 222), and urothelial cancer (n = 332). OS was not significantly different based on TMB status in melanoma (n = 207) or esophageal/gastric cancer (n = 248). CONCLUSION: Consistent with previous studies, a predictive value of TMB ≥10 mut/Mb for ICI response was found in NSCLC and H&N, but not in esophageal/gastric cancer. Although inconclusive in the literature, significant association was found in urothelial cancer. The predictive value of TMB in melanoma was inconclusive. Our analysis does not support the use of a fixed threshold for TMB as a standalone predictive biomarker for ICI across all solid tumors.

Euglycemic diabetic ketoacidosis in a pregnant woman.

Background: Euglycemic diabetic ketoacidosis (EDKA) carries serious risks for mortality and morbidity for both the mother and the baby, and it is essential to recognize it early and start immediate treatment. Case Presentation: We present a case of EDKA in a 28-week pregnant woman known to have type 1 diabetes. She was found to have severe acidosis with a blood sugar level of 10.6 mmol/L (190.8 mg/dL) and normal anion gap. She was found to have EDKA, which was confirmed later with a depressed venous pH and bicarbonate level and an increased serum ketone level. The patient's acidosis was not improving significantly with 0.05 units/kg/h of insulin infusion, so a full dose of 0.1 unit/kg/h of insulin infusion was started following a full diabetic ketoacidosis (DKA) protocol regardless of her blood sugar level. The patient showed gradual improvement and was discharged home after 4 days, with follow-up with endocrinology and obstetrics. Conclusion: In conclusion, EDKA is a critical complication of diabetes, especially in pregnant women. Therefore, it is crucial to treat it early and potentially consider following a full DKA protocol using 0.1 unit/kg/h insulin infusion instead of 0.05 unit/kg/h.

Creating synergies among education/research, practice, and policy environments to build capacity for the scholar role in occupational therapy and physiotherapy in the Canadian context.

Scholarly practice (SP) is considered a key competency of occupational therapy and physiotherapy. To date, the three sectors-education/research, practice, and policy/regulation-that support SP have been working relatively independently. The goals of this project were to (a) understand how representatives of the three sectors conceptualize SP; (b) define each sector's individual and collective roles in supporting SP; (c) identify factors influencing the enactment of SP and the specific needs of how best to support SP; and (d) co-develop goals and strategies to support SP across all sectors. We used interpretive description methodology. Consistent with an integrated knowledge translation approach, partners representing the three sectors across Canada recruited individuals from each sector, developed the content and questions for three focus groups, and collected and analyzed the data. Inspired by the Consolidated Framework for Implementation Research, we developed the questions for the second focus group. We analyzed the data using an inductive thematic analysis method. Thirty-nine participants from the three sectors participated. Themes related to participants' conceptualization of SP included (a) ongoing process, (b) reflective process, (c) broad concept, and (d) collective effort. Themes describing factors influencing and supporting SP were (a) recognition, (b) appropriate conceptualization, (c) social network, (d) accessibility to resources, and (e) forces outside of practitioners' effort. Goals to support SP included (a) further recognizing SP, (b) sustaining SP competency, and (c) ensuring access to information. SP requires collaborative and integrated intersectoral support and further recognition of its importance through the collaboration of multiple stakeholders.

Development and implementation of optimized endogenous contrast sequences for delineation in adaptive radiotherapy on a 1.5T MR-linear-accelerator: a prospective R-IDEAL stage 0-2a quantitative/qualitative evaluation of in vivo site-specific quality-assurance using a 3D T2 fat-suppressed platform for head and neck cancer.

Purpose: To improve segmentation accuracy in head and neck cancer (HNC) radiotherapy treatment planning for the 1.5T hybrid magnetic resonance imaging/linear accelerator (MR-Linac), three-dimensional (3D), T2-weighted, fat-suppressed magnetic resonance imaging sequences were developed and optimized. Approach: After initial testing, spectral attenuated inversion recovery (SPAIR) was chosen as the fat suppression technique. Five candidate SPAIR sequences and a nonsuppressed, T2-weighted sequence were acquired for five HNC patients using a 1.5T MR-Linac. MR physicists identified persistent artifacts in two of the SPAIR sequences, so the remaining three SPAIR sequences were further analyzed. The gross primary tumor volume, metastatic lymph nodes, parotid glands, and pterygoid muscles were delineated using five segmentors. A robust image quality analysis platform was developed to objectively score the SPAIR sequences on the basis of qualitative and quantitative metrics. Results: Sequences were analyzed for the signal-to-noise ratio and the contrast-to-noise ratio and compared with fat and muscle, conspicuity, pairwise distance metrics, and segmentor assessments. In this analysis, the nonsuppressed sequence was inferior to each of the SPAIR sequences for the primary tumor, lymph nodes, and parotid glands, but it was superior for the pterygoid muscles. The SPAIR sequence that received the highest combined score among the analysis categories was recommended to Unity MR-Linac users for HNC radiotherapy treatment planning. Conclusions: Our study led to two developments: an optimized, 3D, T2-weighted, fat-suppressed sequence that can be disseminated to Unity MR-Linac users and a robust image quality analysis pathway that can be used to objectively score SPAIR sequences and can be customized and generalized to any image quality optimization protocol. Improved segmentation accuracy with the proposed SPAIR sequence will potentially lead to improved treatment outcomes and reduced toxicity for patients by maximizing the target coverage and minimizing the radiation exposure of organs at risk.