Profiles, exposure assessment and expanded screening of PAHs and their derivatives in one petroleum refinery facility of China.

This study investigated environmental distribution and human exposure of polycyclic aromatic hydrocarbons (PAHs) and their derivatives in one Chinese petroleum refinery facility. It was found that, following with high concentrations of 16 EPA PAHs (∑Parent-PAHs) in smelting subarea of studied petroleum refinery facility, total derivatives of PAHs [named as XPAHs, including nitro PAHs (NPAHs), chlorinated PAHs (Cl-PAHs), and brominated PAHs (Br-PAHs)] in gas (mean= 1.57 × 104 ng/m3), total suspended particulate (TSP) (mean= 4.33 × 103 ng/m3) and soil (mean= 4.37 × 103 ng/g) in this subarea had 1.76-6.19 times higher levels than those from other subareas of this facility, surrounding residential areas and reference areas, indicating that petroleum refining processes would lead apparent derivation of PAHs. Especially, compared with those in residential and reference areas, gas samples in the petrochemical areas had higher ∑NPAH/∑PAHs (mean=2.18), but lower ∑Cl-PAH/∑PAHs (mean=1.43 × 10-1) and ∑Br-PAH/∑PAHs ratios (mean=7.49 × 10-2), indicating the richer nitrification of PAHs than chlorination during petrochemical process. The occupational exposure to PAHs and XPAHs in this petroleum refinery facility were 24-343 times higher than non-occupational exposure, and the ILCR (1.04 × 10-4) for petrochemical workers was considered to be potential high risk. Furthermore, one expanded high-resolution screening through GC Orbitrap/MS was performed for soils from petrochemical area, and another 35 PAHs were found, including alkyl-PAHs, phenyl-PAHs and other species, indicating that profiles and risks of PAHs analogs in petrochemical areas deserve further expanded investigation.

Is annual screening by fecal immunochemical test necessary after a recent colonoscopy?

Objective: The population-based colorectal cancer screening guidelines in Japan recommend an annual fecal immunochemical test (FIT). However, there is no consensus on the need for annual FIT screening for patients who recently performed a total colonoscopy (TCS). Therefore, we evaluated the repeated TCS results for patients with positive FIT after a recent TCS to assess the necessity of an annual FIT. Methods: We reviewed patients with positive FIT in opportunistic screening from April 2017 to March 2022. The patients were divided into two groups: those who had undergone TCS within the previous 5 years (previous TCS group) and those who had not (non-previous TCS group). We compared the detection rates of advanced neoplasia and colorectal cancer between the two groups. Results: Of 671 patients, 151 had received TCS within 5 years and 520 had not. The detection rates of advanced neoplasia in the previous TCS and non-previous TCS groups were 4.6% and 12.1%, respectively (p < 0.01), and the colorectal cancer detection rates were 0.7% and 1.5%, respectively (no significant difference). The adenoma detection rates were 33.8% in the previous TCS group and 40.0% in the non-previous TCS group (no significant difference). Conclusions: Only a few patients were diagnosed with advanced neoplasia among the patients with FIT positive after a recent TCS. For patients with adenomatous lesions on previous TCS, repeated TCS should be performed according to the surveillance program without an annual FIT. The need for an annual FIT for patients without adenomatous lesions on previous TCS should be prospectively assessed in the future.

Pilot-Scale Screening of Clinically Approved Drugs to Identify Uridine Insertion/Deletion RNA Editing Inhibitors in Trypanosoma brucei.

RNA editing pathway is a validated target in kinetoplastid parasites (Trypanosoma brucei, Trypanosoma cruzi, and Leishmania spp.) that cause severe diseases in humans and livestock. An essential large protein complex, the editosome, mediates uridine insertion and deletion in RNA editing through a stepwise process. This study details the discovery of editosome inhibitors by screening a library of widely used human drugs using our previously developed in vitro biochemical Ribozyme Insertion Deletion Editing (RIDE) assay. Subsequent studies on the mode of action of the identified hits and hit expansion efforts unveiled compounds that interfere with RNA-editosome interactions and novel ligase inhibitors with IC50 values in the low micromolar range. Docking studies on the ligase demonstrated similar binding characteristics for ATP and our novel epigallocatechin gallate inhibitor. The inhibitors demonstrated potent trypanocidal activity and are promising candidates for drug repurposing due to their lack of cytotoxic effects. Further studies are necessary to validate these targets using more definitive gene-editing techniques and to enhance the safety profile.

In Silico Design, Chemical Synthesis, Biophysical and In Vitro Evaluation for the Identification of 1-ethyl-1H-pyrazolo[3,4-b]pyridine-based BRD9 Binders.

In this work, we report the identification of novel bromodomain-containing protein 9 (BRD9) binders through a virtual screening based on our developed 3D structure-based pharmacophore model. The in silico workflow here described led to the identification of a promising initial hit (1) featuring the 1-ethyl-1H-pyrazolo[3,4-b]pyridine motif which represented an unexplored chemotype for the development of a new class of BRD9 ligands. The encouraging biophysical results achieved for compound 1 prompted us to explore further tailored structural modification around the C-4 and C-6 positions of the central core. Hence, the design and synthesis of a set of 19 derivatives (2-20) were performed to extensively investigate the chemical space of BRD9 binding site. Among them, four compounds (5, 11, 12, and 19) stood out in biophysical assays as new valuable BRD9 ligands featuring IC50 values in the low-micromolar range. Noteworthy, a promising antiproliferative activity was detected in vitro for compound 5 on HeLa and A375 cancer cell line. The successful combination and application of in silico tools, chemical synthesis, and biological assays allowed to identify novel BRD9 binders and to expand the arsenal of promising chemical entities amenable to the recognition of this important epigenetic target.

Association between racial residential segregation and screening uptake for colorectal and cervical cancer among Black and White patients in five US health care systems.

BACKGROUND: Despite increased recognition that structural racism contributes to poorer health outcomes for racial and ethnic minorities, there are knowledge gaps about how current patterns of racial residential segregation are associated with cancer screening uptake. The authors examined associations between Black residential segregation and screening for colorectal cancer (CRC) and cervical cancer among non-Hispanic Black and non-Hispanic White adults. METHODS: This was a retrospective study of CRC and cervical cancer screening-eligible adults from five health care systems within the Population-Based Research to Optimize the Screening Process (PROSPR II) Consortium (cohort entry, 2010-2012). Residential segregation was measured using site-specific quartiles of the Black local isolation score (LIS). The outcome was receipt of CRC or cervical cancer screening within 3 years of cohort entry (2010-2015). Logistic regression was used to calculate associations between the LIS and screening completion, adjusting for patient-level covariates. RESULTS: Among CRC (n = 642,661) and cervical cancer (n = 163,340) screening-eligible patients, 456,526 (71.0%) and 106,124 (65.0%), respectively, received screening. Across PROSPR sites, living in neighborhoods with higher LIS tended to be associated with lower odds of CRC screening (Kaiser Permanente Northern California: adjusted odds ratio [aOR] LIS trend in Black patients, 0.95 [p < .001]; aOR LIS trend in White patients, 0.98 [p < .001]; Kaiser Permanente Southern California: aOR LIS trend in Black patients, 0.98 [p = .026]; aOR LIS trend in White patients, 1.01 [p = .023]; Kaiser Permanente Washington: aOR LIS trend in White patients, 0.97 [p = .002]. However, for cervical cancer screening, associations with the LIS varied by site and race (Kaiser Permanente Washington: aOR LIS trend in White patients, 0.95 [p < .001]; Mass General Brigham: aOR LIS trend in Black patients, 1.12 [p < .001]; aOR LIS trend in White patients, 1.03 [p < .001]). CONCLUSIONS: Across five diverse health care systems, the direction of the association between Black residential segregation and screening varied by PROSPR site, race, and screening type. Additional research, including studies that examine multiple dimensions of segregation and structural racism using intersectional approaches, are needed to further disentangle these relationships.

Feasibility and Acceptability of a Mobile Health Exercise Intervention for Inactive Adults: 3-Arm Randomized Controlled Pilot Trial.

BACKGROUND: Objective monitoring of self-directed physical activity (PA) is a common approach used in both fitness and health settings to promote exercise behavior, but adherence has been poor. Newer mobile health (mHealth) technologies could be a cost-effective approach to broadening accessibility and providing support for PA behavior change; yet, the optimal method of delivery of such interventions is still unclear. OBJECTIVE: This study aimed to determine the feasibility and acceptability of an mHealth exercise intervention delivered in combination with objective monitoring in 3 ways: health education emails, asynchronous exercise videos, or synchronous videoconference exercise classes. METHODS: Physically inactive (<30 min/wk) adults (cisgender women aged 31.5, SD 11.3 years, cisgender men aged 34.1, SD 28.9 years, and nonbinary individuals aged 22.0, SD 0 years) were randomized (1:1:1) to 8 weeks of increasing PA behavioral support: level 1 (health education+objective monitoring, n=26), level 2 (asynchronous contact, level 1+prerecorded exercise videos, n=30), or level 3 (synchronous contact, level 1+videoconference group exercise, n=28). Participants used a heart rate monitor during exercise and a mobile app for interaction. Primary outcomes were feasibility (accrual, retention, and adherence) and acceptability (user experience survey). Secondary outcomes assessed at baseline and 8 weeks included resting heart rate, self-reported PA, and quality of life. The exercise dose was evaluated throughout the intervention. RESULTS: Between August 2020 and August 2021, 204 adults were screened for eligibility. Out of 135 eligible participants, 84 (62%) enrolled in the study. Retention was 50% (13/26) in level 1, 60% (18/30) in level 2 and 82% (23/28) in level 3, while adherence was 31% (8/26) in level 1, 40% (12/30) in level 2 and 75% (21/28) in level 3. A total of 83% (70/84) of the study sample completed the intervention, but low response rates (64%, 54/84) were observed postintervention at week-8 assessments. Program satisfaction was highest in participants receiving exercise videos (level 2, 80%, 8/10) or exercise classes (level 3, 80%, 12/15), while only 63% (5/8) of level 1 reported the program as enjoyable. Level 3 was most likely to recommend the program (87%, 13/15), compared to 80% (8/10) in level 2 and 46% (5/8) in level 1. Self-reported PA significantly increased from baseline to intervention in level 3 (P<.001) and level 2 (P=.003), with no change in level 1. Level 3 appeared to exercise at higher doses throughout the intervention. CONCLUSIONS: Only the videoconference exercise class intervention met feasibility criteria, although postintervention response rates were low across all groups. Both videoconference and prerecorded videos had good acceptability, while objective monitoring and health education alone were not feasible or acceptable. Future studies are needed to examine the effectiveness of videoconference exercise interventions on health-related outcomes during nonpandemic times and how asynchronous interventions might maximize adherence. TRIAL REGISTRATION: ClinicalTrials.gov NCT05192421; https://clinicaltrials.gov/study/NCT05192421.

Characteristics associated with early vs. late adoption of lung cancer screening.

Background: Although lung cancer screening (LCS) reduces lung cancer mortality among high-risk individuals, uptake overall remains low. With all cancer screening modalities, a period of diffusion among medical providers and the public is expected, with screening uptake exhibiting a distribution among early vs. late adoption. We aimed to characterize individuals undergoing LCS based upon the timeframe of screening adoption. Methods: This retrospective study examined patients who underwent LCS between January 2015 - December 2022 in a centralized LCS program. Based on United States Preventive Services Task Force (USPSTF) criteria for LCS, early and late adopters of LCS - defined by time from eligibility to screening completion - were compared. A multivariable regression model was constructed to identify factors associated with early adoption of LCS. Results: Among patients screened during the study period, 90.4% were eligible based on USPSTF 2013 criteria, and 9.6% were eligible based on USPSTF 2021 criteria. Of the USPSTF 2013 eligible persons, multivariable analysis demonstrated Black/African-American individuals and current smokers had significantly greater odds of early adoption (aOR 1.428 and 1.514, respectively). Those without a family history of lung cancer or without a personal history of cancer had significantly lower odds of early adoption of LCS. Conclusions: Early adopters were more likely to report Black/African-American race or current smoking status after adjustment for covariates. Future research should examine how screening diffuses across the overall LCS-eligible population, as well as identify factors that drive and inhibit diffusion to create programs and policies with the ultimate goal of increasing timely LCS uptake.

Postoperative Surprises: A Carcinoid Tumor Within a Perforated Meckel's Diverticulum.

Meckel's diverticulum, a true diverticulum originating from the incomplete closure of the vitelline duct during embryologic development, rarely presents with carcinoid tumors. The coexistence of a Meckel's diverticulum and carcinoid tumor following laparoscopic sigmoid colectomy for diverticulitis is an uncommon phenomenon, with limited documented cases in the literature. We present a case of a 74-year-old male with a past medical history of hypertension and diverticulitis who underwent a laparoscopic sigmoid colectomy for dysplastic and cancerous changes of a polyp revealed during a screening colonoscopy. Initially, the patient's postoperative journey was uneventful with the resumption of regular bowel movements and favorable diet progression. However, he later presented to the emergency department for worsening abdominal pain and distension. Imaging prompted surgical intervention due to perforation and obstruction, resulting in the identification of a carcinoid tumor within a perforated Meckel's diverticulum. This case highlights the intricate challenges of postoperative complications, particularly the unexpected emergence of Meckel's diverticulum pathology following a colectomy. The atypical presentation, featuring a carcinoid tumor within a perforated Meckel's diverticulum, underscores the importance of evaluating abdominal symptoms postoperatively.

Understanding determinants of lung cancer preventive care in at-risk urban American Indians and Alaska Natives: A mixed-methods study.

Introduction: Lung cancer is the leading cause of cancer death among American Indian and Alaska Native (AI/AN) people, and AI/AN people have the highest rate of smoking of any racial or ethnic group in the US. There is limited research to inform culturally-relevant strategies for lung cancer prevention inclusive of lung cancer screening (LCS). The objective of this study was to understand determinants of LCS and tobacco cessation care in at-risk urban-dwelling AI/ANs. Materials and Methods: This was a mixed-methods community-based participatory research study including complimentary qualitative discussions and surveys conducted in Seattle, Washington, USA from 2022 to 2023. The study measures and analytic approach integrated the Consolidated Framework for Implementation Research and Tribal Critical Race Theory and qualitative transcripts were analyzed using thematic analysis. Participants were self-identified AI/AN people who were age ≥ 40 and had ≥ 10-year history of commercial cigarette smoking. Results: Forty-five participants completed surveys and participated in discussions, 48% were female, the median age was 58 and median smoking history was 24 pack-years of commercial cigarette use. Themes revealed prominent barriers to LCS care including access, costs, awareness, and fear. Many reported previous negative and discriminatory encounters within and outside the health system which may also serve as barriers. Most participants endorsed cancer screening and increased education, recommending Indigenous-centered, delivered, and tailored programs, as well barrier-directed support. Conclusions: In a broad sample of at-risk urban-dwelling AI/AN people, our findings suggest enthusiasm for preventive care but several complex barriers. Participants endorsed culturally-tailored programs which could provide relevant education and address barriers.

Awareness of Breast Cancer Risk Factors in Women with vs. Without High Breast Density.

Purpose: Women with high breast density (HBD) carry an increased risk for breast cancer (BC). The aim of the study was to provide data on awareness and knowledge gaps among women with vs w/o HBD about BC risk factors (BCRFs), which is the basis for effective communication about screening. Patients and Methods: This was a web-based survey of 3000 women aged ≥30 and ≤70 from six countries. It comprised of 45 questions. T-tests and chi-square tests with False Discovery Rate adjustments were conducted as applicable, with significant differences reported at α=0.05. Results: Three-thousand women were included in the analysis, 733 (24.4%) had HBD. Overall, 39% of women were familiar with the concept of HBD in the context of BC. Thirty-one percent of women were aware of HBD as BCRF and for 24% of women HBD was personally applicable. A significantly higher proportion of women with HBD were aware of almost all BCRFs compared to women w/o HBD (p ≤ 0.05). Similarly, a significantly higher proportion of women with HBD have undergone screening procedures compared to women w/o HBD (p ≤ 0.05). Women with HBD were significantly better aware of basic facts about BC (p ≤ 0.05). A total of 1617 women underwent mammography, 904 ultrasound and 150 MRI during their last screening. The most relevant source of information about BC was the health care professional, as reported by 63% of women. Conclusion: Overall 39% of women were familiar with HBD as BCRF. Lack of BCRF awareness may contribute to delayed screenings, missed opportunities for early detection, and potentially poorer outcomes for individuals with dense breast tissue. Thus, this information should be communicated more widely.

Socioeconomic differences in discrepancies between expected and experienced discomfort from colonoscopy and colon capsule endoscopy.

Background: Social inequalities in colorectal cancer screening participation are evident. Barriers to screening participation include discomfort from diagnostic modalities. We aimed to describe the discomfort experienced from colonoscopy and colon capsule endoscopy (CCE) and investigate the discrepancy between expected and experienced discomfort stratified by socioeconomic status. Methods: A randomised controlled trial was conducted offering half of the colorectal cancer screening invitees the choice between CCE and colonoscopy after a positive faecal immunochemical test. This paper includes those who elected to undergo CCE. A positive CCE elicited referral for a therapeutic colonoscopy. Participants reported their discomfort from CCE and from any following colonoscopies in electronically distributed questionnaires. Discomfort was measured using visual analogue scales and compared between socioeconomic subgroups determined by educational level and income. Results: The experienced discomfort from CCE and colonoscopy differed significantly between educational levels but not income levels. The bowel preparation contributed the most to the experienced discomfort in both CCE and colonoscopy. The discrepancy between expected and experienced discomfort from colonoscopy increased with increasing educational and income levels. A similar trend was seen in CCE between educational levels but not income levels. Conclusions: None of the results indicated a higher discomfort in lower socioeconomic subgroups. Regardless of the investigation modality, the bowel preparation was the main contributor to experienced discomfort. The discrepancy between expected and experienced discomfort did not seem to be larger in lower socioeconomic subgroups, indicating that this is not a major barrier causing inequalities in screening uptake. This is the first study investigating individual discomfort discrepancy in both CCE and colonoscopy, while being able to stratify by socioeconomic status.

PSA Levels and Mortality in Prostate Cancer Patients.

INTRODUCTION: Prostate cancer (PC) is the second most common cancer among men around the world. Several smaller studies have explored the relationship between elevated PSA and mortality, but results have been conflicting. Additionally, studies have shown that Black men are more likely to be diagnosed with PC at late-stages and may have a twofold increase in mortality risk. This study aims to evaluate the relationship between PSA levels and mortality in patients with PC and differences between Black versus White patients. METHODS: In this retrospective study, the TriNetX database, was used to extract de-identified EMRs of 198,083 patients. Patients were included if they were diagnosed with PC and had obtained a PSA level (measured in ng/mL) within 6 months prior to diagnosis. Cohorts were separated into 7 groups based on intervals of PSA, ranging from < 2 to ≥ 500 and compared to a control cohort with a PSA of 4 to 20 for differing 2-year mortality rates. A subgroup analysis was performed to compare mortality differences between Black and White patients. A posthoc analysis evaluated 5- and 10-year mortality amongst all patients with PC. RESULTS: After propensity matching, mortality risk was significantly lower for patients with PSA < 2 (5.9% vs. 7.5%; RR 0.784; P < .001) when compared to the control cohort. Mortality was significantly higher for all other subsequent PSA intervals > 20, with the lowest risk ratios at PSA 20-100 (24.1% vs. 10.0%; RR 2.419; P < .001) and highest at PSA 200 to 500 (50.4% vs. 10.8%; RR 4.673; P < .001). The sub-group analysis showed that when compared to White patients, Black patients with PSA < 20 had similar mortalities, but had significantly lower 2-year mortality rates at PSA levels ≥ 20. The posthoc analysis of PSA levels and 5- and 10-year mortality of all patients with PC showed similar trends to the 2-year outcomes. CONCLUSION: This study found that prostate cancer patients with significantly elevated PSA levels have a greater mortality, and Black patients have lower 2-year mortality rates than their White counterparts when matched for PSA levels greater than 20.

Nanobody-based strategy for rapid and accurate pathogen detection: A case of COVID-19 testing.

Antibody pairs-based immunoassay platforms served as essential and effective tools in the field of pathogen detection. However, the cumbersome preparation and limited detection sensitivity of antibody pairs challenge in establishment of a highly sensitive detection platform. In this study, using COVID-19 testing as a case, we utilized readily accessible nanobodies as detection antibodies and further proposed an accurate design concept with a more scientific and efficient screening strategy to obtain ultrasensitive antibody pairs. We employed nanobodies capable of binding different antigenic epitopes of the nucleocapsid (NP) or receptor-binding domain (RBD) antigens sandwich as substitutes for monoclonal antibodies (mAbs) sandwich in fast detection formats and utilized time-resolved fluorescence (TRF) microspheres as the signal probe. Consequently, we developed a multi-epitope nanobody sandwich-based fluorescence lateral flow immunoassay (FLFA) strip. Our results suggest that the NP antigen had a detection limit of 12.01pg/mL, while the RBD antigen had a limit of 6.51 pg/mL using our FLFA strip. Based on double mAb sandwiches, the values presented herein demonstrated 4 to 32-fold enhancements in sensitivity, and 32 to 256-fold enhancements compared to commercially available antigen lateral flow assay kits. Furthermore, we demonstrated the excellent characteristics of the proposed test strip, including its specificity, stability, accuracy, and repeatability, which underscores its the prospective utility. Indeed, these findings indicate that our established screening strategy along with the multi-epitope nanobody sandwich mode provides an optimized strategy in the field of pathogen detection.

A stepwise implementation of the Slovenian National Diabetic Retinopathy Screening Program - evaluation of the first 4.5 years.

BACKGROUND: This retrospective cohort study aimed to assess the characteristics of patients enrolled in the national diabetic retinopathy (DR) screening program and evaluate the selected program's quality elements in the first five years after implementation. METHODS: Patients who underwent DR screening between February 2018 and June 2022 at the University Medical Centre Ljubljana were included. General patient characteristics (age, sex, type and therapy of diabetes mellitus (DM), duration of DM, blood HbA1c levels), best corrected visual acuity, stage of DR, presence of sight-threatening diabetic retinopathy (STDR), and selected quality indicators (quality of photographs, re-screening interval, time to treatment) were recorded and evaluated. RESULTS: A total of 34 654 screening examinations were performed on 13 513 patients with diabetes. The majority (77.3%) had Type 2 diabetes, with a mean DM duration of 9.74 ± 9.87 years. In 55.9% of patients, DM duration was less than ten years, and the mean HbA1c was 7.33% ± 1.49. DR signs were noted in 29.1% of patients and 0.89% of patients exhibited STDR. After establishing the diagnosis of STDR, treatment was initiated in 3.43 ± 1.98 months. CONCLUSION: Implementing the DR screening program provides valuable insights into managing diabetic retinopathy nationwide. It allows for the early detection of sight-threatening DR and facilitates timely and effective treatment, which could help prevent severe visual impairment.

Factors affecting global adherence for the uptake of diabetic retinopathy screening: A systematic review and meta-analysis.

PURPOSE: To evaluate diabetic retinopathy (DR) screening global adherence rate and the association between sociodemographic and clinical variables and adherence rates to DR screening in individuals with diabetes. DESIGN: Systematic Review and Meta-Analysis METHODS: : This systematic review was registered with International Prospective Register of Systematic Reviews (ID: CRD42024507035). We conducted a systematic review of relevant literature from inception of databases to February 24, 2024 using electronic databases searches including PubMed, MEDLINE (Ovid), EMBASE, Web of Science, Cochrane CENTRAL, and CDSR and national level DR screening databases through Google searches following PRISMA guidelines. The articles were screened for title and abstract and then for the full-text reports by two independent reviewers and study quality was appraised. Meta-analysis was performed using random effects model to calculate the pooled effects size and 95% confidence interval (CI) of each finding. RESULTS: Data from a total of 11,383,715 participants from 77 studies and two national websites from 28 countries over five continents were included. Global DR screening adherence rate was 66.9% in high-income countries and 39.3% in low-and-middle-income countries. DR screening adherence rate was lowest in Africa (36.1%) and was highest in Europe (81.3%). Older age (odds ratio [OR] 1.45, 95% CI 1.30-1.62), higher education level (OR1.65, 95% CI 1.45-1.78), marriage (OR 1.42, 95% CI 1.14-1.77), living in an urban area (OR 1.57, 95% CI 1.08-2.29), higher family income (OR 1.29, 95% CI 1.24-1.35), having any health insurance (OR 1.90, 95% CI 1.56-2.31), longer duration of diabetes (OR 1.57, 95% CI 1.27-1.94), type 2 diabetes (OR 1.68, 95% CI 1.34-2.10), family history of diabetes (OR 2.25, 95% CI 1.56-3.25), vision impairment (OR 2.07, 95% CI 1.43-2.98), history of eye diseases (OR 1.99, 95% CI 1.36-2.90), insulin treatment (OR 1.38, 95% CI 1.37-1.39), and good mental health (OR 1.14, 95% CI 1.04-1.24) were associated with DR screening adherence. CONCLUSION: This meta-analysis provides key information about which population subgroups may require more targeted intervention and highlights the urgent need to identify ways to improve adherence to DR screening.

Unveiling a Hidden Pocket in HIV-1 Protease: New Insights Into Retroviral Protease Cantilever-Tip Region Characteristics.

The HIV-1 protease is critical for the process of viral maturation and as such, it is one of the most well characterized proteins in the Protein Data Bank. There is some evidence to suggest that the HIV-1 protease is capable of accommodating small molecule fragments at several locations on its surface outside of the active site. However, some pockets on the surface of proteins remain unformed in the apo structure and are termed "cryptic sites." To date, no cryptic sites have been identified in the structure of HIV-1 protease. Here, we characterize a novel cryptic cantilever pocket on the surface of the HIV-1 protease through mixed-solvent molecular dynamics simulations using several probes. Interestingly, we noted that several homologous retroviral proteases exhibit evolutionarily conserved dynamics in the cantilever region and possess a conserved pocket in the cantilever region. Immobilization of the cantilever region of the HIV-1 protease via disulfide cross-linking resulted in curling-in of the flap tips and the propensity for the protease to adopt a semi-open flap conformation. Structure-based analysis and fragment-based screening of the cryptic cantilever pocket suggested that the pocket may be capable of accommodating ligand structures. Furthermore, molecular dynamics simulations of a top scoring fragment bound to the cryptic pocket illustrated altered flap dynamics of the fragment-bound enzyme. Together, these results suggest that the mobility of the cantilever region plays a key role in the global dynamics of retroviral proteases. Therefore, the cryptic cantilever pocket of the HIV-1 protease may represent an interesting target for future in vitro studies.

Examining breast cancer screening recommendations in Canada: The projected resource impact of screening among women aged 40-49.

OBJECTIVE: To quantify the resource use of revising breast cancer screening guidelines to include average-risk women aged 40-49 years across Canada from 2024 to 2043 using a validated microsimulation model. SETTING: OncoSim-Breast microsimulation platform was used to simulate the entire Canadian population in 2015-2051. METHODS: We compared resource use between current screening guidelines (biennial screening ages 50-74) and alternate screening scenarios, which included annual and biennial screening for ages 40-49 and ages 45-49, followed by biennial screening ages 50-74. We estimated absolute and relative differences in number of screens, abnormal screening recalls without cancer, total and negative biopsies, screen-detected cancers, stage of diagnosis, and breast cancer deaths averted. RESULTS: Compared with current guidelines in Canada, the most intensive screening scenario (annual screening ages 40-49) would result in 13.3% increases in the number of screens and abnormal screening recalls without cancer whereas the least intensive scenario (biennial screening ages 45-49) would result in a 3.4% increase in number of screens and 3.8% increase in number of abnormal screening recalls without cancer. More intensive screening would be associated with fewer stage II, III, and IV diagnoses, and more breast cancer deaths averted. CONCLUSIONS: Revising breast cancer screening in Canada to include average-risk women aged 40-49 would detect cancers earlier leading to fewer breast cancer deaths. To realize this potential clinical benefit, a considerable increase in screening resources would be required in terms of number of screens and screen follow-ups. Further economic analyses are required to fully understand cost and budget implications.

Comparing reach distance between the Y-Balance Test-Lower Quarter and Star Excursion Balance Test: Are practitioners using the correct protocol?

OBJECTIVES: To compare reach distances between the YBT-LQ and SEBT using the correct protocols as outlined by the developers. This will provide an accurate insight on the actual magnitude differences in reach distance between the movement screen tests and will safeguard practitioners on the subsequent use of these outcomes to inform clinical decision making. DESIGN: Observational. SETTING: Laboratory. PARTICIPANTS: Participants included sixteen healthy female subjects from the university and amateur sports teams. MAIN OUTCOME: Reach distances in the anterior direction (ANT), posterior medial (PM) and posterior lateral (PL) between participants on the YBT-LQ and SEBT. RESULTS: The principal findings highlighted that a statistically significantly greater reach distance on the left and right side for the YBT-LQ compared to the SEBT in the ANT, PM, and PL directions (p < 0.0005). CONCLUSION: The results of this study suggest that the YBT-LQ and SEBT are not comparable tests due to the differences in reach distance and methodological differences. Therefore, previous, and future research using the YBT-LQ and SEBT cannot be used interchangeably. Not following developed guidelines questions the applicability of the findings of reach distance scores to infer on performance and assessment of injury risk.

Screening the release of chemicals and microplastic particles from diverse plastic consumer products into water under accelerated UV weathering conditions.

Photodegradation of plastic consumer products is known to accelerate weathering and facilitate the release of chemicals and plastic particles into the aquatic environment. However, these processes are complex. In our presented pilot study, eight plastic consumer products were leached in distilled water under strong ultraviolet (UV) light simulating eight months of Central European climate and compared to their respective dark controls (DCs). The leachates and formed plastic particles were exploratorily characterized using a range of chemical analytical tools to describe degradation and leaching processes. These techniques covered (a) microplastic analysis, showing substantial liberation of plastic particles further increased under UV exposure, (b) non-targeted mass spectrometric characterization of the leachates, revealing several hundreds of chemical features with typically only minor agreement between the UV exposure and the corresponding DCs, (c) target analysis of 71 organic analytes, of which 15 could be detected in at least one sample, and (d) metal(loid) analysis, which revealed substantial release of toxic metal(loid)s further enhanced under UV exposure. A data comparison with the US-EPA's ToxVal and ToxCast databases showed that the detected metals and organic additives might pose substantial health and environmental concerns, requiring further study and comprehensive impact assessments.

Non-contrast Abbreviated MRI for the Detection of Hepatocellular Carcinoma in Patients with LI-RADS LR-3 and LR-4 Observations in MRI.

BACKGROUND AND AIMS: With ultrasound sensitivity limited in hepatocellular carcinoma (HCC) surveillance and few prospective studies on non-contrast abbreviated MRI (NC-AMRI), this study aimed to assess its diagnostic performance in detecting HCC. METHODS: This prospective study involved cirrhotic patients with contrast-enhanced MRI (CE-MRI) Liver Imaging Reporting and Data System (LI-RADS) LR-3 and LR-4 observations detected during HCC surveillance. Patients underwent average three complete CE-MRI rounds at 3-6 months interval, with approximately 12-month follow-up. NC-AMRI included diffusion-weighted(DWI), T2-weighted imaging(T2WI), and T1-weighted imaging(T1WI). NC-AMRI protocol images were analyzed for diagnostic performance, with subgroup analyses. CE-MRI and NC-AMRI images were independently reviewed by two experienced radiologists, with inter-reader agreement assessed with Kappa coefficient. The reference standard was the AASLD-defined presence of arterial hypervascularity and washout during the portal-venous or delayed phases on CE-MRI. RESULTS: In 166 CE-MRI follow-ups of 63 patients (median age: 63 years; 60.3% male, 39.7% female), 12 patients developed HCC, with average size of 19.6 mm. The NC-AMRI (DWI+T2WI+T1WI) showed 91.7% sensitivity (95%CI : 61.5-99.8) and 91.6% specificity (95%CI : 86.0-95.4), area under receiver operating characteristic 0.92 (95%CI : 0.83-1.00). Across different Body Mass Index categories, lesion size, Child-Turcotte-Pugh classes, Albumin-Bilirubin (ALBI) grades, and Model for End-Stage Liver Disease classes, sensitivity remained consistent. However, specificity differed significantly between ALBI grade 1 and 2 (86.7% vs. 98.4%,p = 0.010), and between viral and non-viral cirrhosis (93.8% vs. 80.8%,p = 0.010). CONCLUSIONS: NC-AMRI proved clinically feasible, and exhibits high diagnostic performance in HCC detection. ADVANCES IN KNOWLEDGE: This study highlights efficacy of NC-AMRI in detecting HCC among cirrhotic patients with LR-3 and LR-4 observations, representing significant progress in HCC surveillance.