Patent foramen ovale (PFO) is highly prevalent and associated with more than 150,000 strokes per year. Traditionally, it is thought that PFOs facilitate strokes by allowing venous clots to travel directly to the brain. However, only a small portion of PFO stroke patients have a known tendency to form blood clots, and the optimal treatment for this multiorgan disease is unclear. Therefore, mapping the changes in systemic circulation of PFO-related stroke is crucial in understanding the pathophysiology to individualize the best clinical treatment for each patient. We initiated a study using a novel quantitative, 2-pass discovery workflow using high-resolution liquid chromatography-mass spectrometry/mass spectrometry coupled with label-free analysis to track protein expression in PFO patients before and after endovascular closure of the PFO. Using this approach, we were able to demonstrate quantitative differences in protein expression between both PFO-related and non-PFO-related ischemic stroke groups as well as before and after PFO closure. As an initial step in understanding the molecular landscape of PFO-related physiology, our methods have yielded biologically relevant information on the synergistic and functional redundancy of various cell-signaling molecules with respect to PFO circulatory physiology. The resulting protein expression patterns were related to canonical pathways including prothrombin activation, atherosclerosis signaling, acute-phase response, LXR/RXR activation, and coagulation system. In particular, after PFO closure, numerous proteins demonstrated reduced expression in stroke-related canonical pathways such as acute inflammatory response and coagulation signaling. These findings demonstrate the feasibility and robustness of using a proteomic approach for biomarker discovery to help gauge therapeutic efficacy in stroke.
Pancreatic ductal adenocarcinoma (PDAC) has one of the poorest prognoses of all malignancies, with a 5-year survival rate <8%.1,2 Suspicious lesions are typically diagnosed via endoscopic ultrasound-guided fine-needle aspiration or endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB).3 Fewer needle passes decreases the risk of postprocedure complications, including pancreatitis and hemorrhage, while allowing additional needle passes to be used for adjuvant tissue testing, such as organoid creation and DNA sequencing.
Hispanic people with HIV who smoke cigarettes experience unique stressors (eg, stigma), which contribute to health disparities. Anxiety sensitivity (AS) may worsen mood management problems, which are a leading barrier to smoking cessation. Interventions targeting AS can improve HIV-specific outcomes and smoking cessation. However, no prior research has culturally tailored an AS reduction program to improve quality of life among Hispanic people with HIV who smoke. The research team previously developed a mobile health (mHealth) intervention addressing AS reduction, smoking cessation, and HIV care management for Black people with HIV who smoke. Building on this work, this study represents a formative, exploratory phase to develop culturally tailored mHealth content for Hispanic people with HIV across 3 distinct regions (Mexico, Central America, and South America), which share many similarities but differ in some cultural and linguistic respects. This work will inform the refinement of materials for these groups and the future development of an integrated mHealth app for smoking, AS, and HIV among this population (ie, VITAL). This study aimed to culturally tailor evidence-based smoking cessation content targeting AS reduction and HIV management among Hispanic adults to inform the development of the VITAL mHealth program. Intervention content was culturally adapted using a theory-informed intervention adaptation framework that integrated a cultural considerations document derived from existing literature on smoking cessation and HIV care among the Hispanic population, along with iterative consultation with a Community Research Advisory Board. This resulted in linguistically tailored content in English and Spanish. The pilot study consisted of Hispanic people with HIV who smoke (N=80), divided into 3 subgroups: Mexican/Mexican American, Central American, and South American. Participants completed self-report assessments and a semistructured interview assessing the treatment videos for content relevance, appropriateness, and ease of understanding. Interviews were conducted online in Spanish or English by trained interviewers. Interview transcripts will be coded by a multidisciplinary qualitative team using a 2-pass approach: initial coding of the interview question followed by higher-level concepts. Themes will be reviewed by another member of the team to assess trustworthiness, saturation, and triangulated with quantitative data, then analyzed by geographic subgroup. Three linguistically tailored versions of the intervention materials were developed. Data collection began August 19, 2024, and finished June 26, 2025. Data cleaning is ongoing, and analyses will begin in April 2026. Content refinement and app integration are anticipated to be completed by September 2026. Upon completion of analysis, data will be used to further refine culturally tailored intervention content for Hispanic adult subgroups. This formative pilot study will inform the cultural adaptation and refinement of an mHealth app, VITAL, which will be tested in a subsequent randomized controlled trial to improve health disparities and assist Hispanic people with HIV in quitting smoking.
Interpreting patient-reported outcomes (PROMs) is enhanced by establishing clinical threshold values. This study determined the minimal important change (MIC), patient acceptable symptom state (PASS), treatment failure (TF) thresholds and responsiveness for the Self-reported Foot and Ankle Score (SEFAS) and the EuroQol 5 Dimensions (EQ-5D) in patients from the Swedish National Foot and Ankle Register (Swefoot). A cohort of 139 randomly selected patients (mean age 55, SD:13; 60% women) from Swefoot (2021-2024) was analyzed. MIC, PASS and TF thresholds were estimated using anchor-based adjusted predictive modelling with logistic regression. Responsiveness was evaluated using effect size (ES), calculated as the mean change divided by the preoperative standard deviation. For forefoot disorders, SEFAS thresholds were: MIC 7.2, PASS 36.3 and TF 30.7. For ankle/hindfoot disorders, corresponding thresholds were: MIC 8.8, PASS 33.7 and TF 32.5. EQ-5D thresholds for forefoot disorders were: MIC 0.09, PASS 0.67 and TF 0.70; for ankle/hindfoot disorders: MIC 0.16, PASS 0.77 and TF 0.76. SEFAS responsiveness was 1.31 for forefoot and 1.64 for ankle/hindfoot; EQ-5D responsiveness was 0.69 and 0.97, respectively. The established thresholds enhance the interpretability and clinical utility of SEFAS and EQ-5D in patients undergoing foot and ankle surgery. III.
For single-isocentre multi-target (SIMT) stereotactic radiosurgery (SRS), benchmarking, auditing and inter-institutional standardisation of dose verification remain challenging as they require specialized equipment and expertise. This work aims to develop and validate an electronic portal imaging device (EPID)-based technique to determine 3D dose in a virtual spherical phantom which is applicable across institutions for SIMT SRS dose verification. Small-field output factors from 11 international centres were measured in-water for the TrueBeam linear accelerator, including jaw-defined and high-definition multi-leaf collimator (MLC) fields from 0.5 × 0.5 to 20 × 20 cm2 and depths from 1.5-20 cm. Matching EPID images were collected at each centre. Utilising the average-centre data, jaw-derived and MLC-derived models were created to convert EPID images to three-dimensional dose in a virtual spherical phantom. Models were validated by comparing EPID-derived dose with film in a three-dimensional-printed spherical phantom for 11 non-coplanar SIMT SRS plans. Output factors estimated from EPID-to-dose models were within 1.8% (jaw-derived) and 1.0% (MLC-derived) of measured factors at 10 cm depth. For SIMT SRS plans, target dose differences were -0.3 ± 2.4% (mean ± standard deviation) and gamma pass rates were 99.6 ± 1.7% (5%/1.5 mm) for the jaw-derived model compared to film. For the MLC-derived model, -0.2 ± 2.1% dose differences and 99.7 ± 1.2% pass rates (5%/1.5 mm) were achieved. The EPID-based three-dimensional dose reconstruction method was modelled using multi-institutional data and validated for static and SIMT SRS deliveries. This method requires no specialised equipment and can be applied across institutions for benchmarking, auditing and standardised patient-specific quality assurance for SRS.
Solid phantoms streamline carbon ion therapy quality assurance (QA), but introduce dose deviations as treatment planning system's (TPS) pencil beam algorithms (PBA) calculate dose in water. This study develops a fluence-corrected PBA, enabling accurate patient-specific QA directly in solid phantoms at Heavy Ion Medical Machine (HIMM) centers. Beam modeling was done in TOPAS Monte Carlo simluation platform to match the integrated depth doses (IDD) and phase space parameters to the clinical commissioning data. Depth-dose data in PTW RW3 slab phantom and in water were simulated, from which energy- and depth-dependent fluence correction (FC) factors (FCFs) were derived. The FCFs were validated experimentally and incorporated into the PBA. 4 types of QA workflows were compared for 2 patient plans at varying equivalent depths: 1) phantom CT without FC-PBA 2) phantom CT with FC 3) virtual CT with stopping power ratio overwritten to 1 with FC, and 4) virtual CT overwritten with phantom SPR with FC. A simplified depth-dependent correction table was fitted from measurement. The simulated FCFs increased with energy and depth from about 0.4% at 2 centimeters to 5% at 25 centimeters, which agreed with the measurement within ±0.5%. At depths < 100 mm, the gamma pass rates were similar for all 4 workflows. For depths > 100 mm, the gamma pass rates increased from (81, 77, 69)% for workflow 1 to (99, 99, 97)% on average for workflows 2-4, under 3 mm/3%, 2 mm/3% and 2 mm/2% criteria, respectively. Workflow 2 and 4 gave similar results with mean difference 0.1(±0.6)%. The simplified table gave 0.0231% FC per millimeter of RW3 thickness, which agreed to the simulation within 1%. Carbon ion therapy QA in the RW3 requires FCFs particularly for > 100 mm depths. Under ≥ 2% pass rate criteria, either the fluence-corrected PBA or the simplified table could be adopted on a virtual phantom to support easier QA workflow.
Despite the clinical data showing the importance of ascorbic acid (AA or vitamin C) in managing viral respiratory infections, biosensors for their simultaneous detection are lacking. To address this need, we developed a portable and wireless device for simultaneous detection of AA and SARS-CoV-2 virus by integrating commercial transistors with printed laser-induced graphene (LIG) as the extended gate. We studied the effect of laser printing pass number and showed that with two laser printing passes (2-pass LIG), the sensor sensitivity and limit of detection (LOD) for AA improved by a factor of 1.6 and 12.8, respectively. Using complementary characterization methods, we attribute the improved response to a balanced interplay of crystallinity, defect density, surface area, surface roughness, pore density and diameter, and mechanical integrity/stability. These factors enhance analyte transport, reduce noise/variability, and ensure consistent sensor performance, making 2-pass LIG the most effective material in this work. Our sensors exhibit promising performance for detecting AA with a selective response in the presence of common salivary interfering molecules, with sensitivity and LOD of 73.67 mV/dec and 54.04 nM in 1× phosphate buffered saline and 81.05 mV/dec and 78.34 nM in artificial saliva, respectively. We also showed that functionalization of the 2-pass LIG gate with S-protein antibody enables the detection of SARS-CoV-2 protein antigens with an ultralow LOD of 52 zg/mL─an improvement of more than 10-fold compared to 1-pass LIG─and 4 particles/mL for virion mimics with a selective response against influenza virus and multiple human coronavirus strains. With low signal drift/hysteresis and wireless capabilities, the developed device holds great potential for improving at-home monitoring and clinical decision-making.
Mechanical thrombectomy devices have potential to injure the vessel during treatment of acute ischemic stroke. The goal of the current work was to tailor in vitro endothelialized silicone models for stent retriever assessment and to evaluate endothelial injury following treatment by various stent retriever designs and sizes. Clinically relevant neurovascular geometries were first modeled out of silicone, then sterilized, coated with fibronectin, placed in bioreactors, seeded with human endothelial cells, and cultivated under flow. Several sizes of 2 different commercially available stent retrievers were then deployed in, and retracted through, vessels. Vessels were immediately harvested and stained. Endothelial injury, identified as denudation, was quantified by using ImageJ. Results illustrated that endothelial injury ranged from 16%-18% in wire/microcatheter-only treated vessels, 37%-61% in 1-pass treatments, and 52%-70% in 2-pass treatments. Overall, this work showcases an in vitro approach for early stage assessment of the extent and location of vascular injury following stent retriever retraction.
An on-chip optical delay line with low-loss and compact waveguide configurations is a crucial component for functional photonic integrated circuits, such as optical coherence tomography, optical gyroscopes, and frequency-modulated continuous-wave (FMCW) LiDAR systems. In this paper, we proposed a low-loss and compact on-chip delay line structure integrated with a polarization transformation-enabled 2-pass architecture. A total delay of 10.46 ns is achieved using a 0.8-m-long silicon nitride waveguide spiral. The losses of the delay line operating in the TE and TM modes are 0.083 dB/cm and 0.213 dB/cm, respectively. Further, the nonlinearity calibration of the frequency-swept laser is conducted with the assistance of the designed delay line. It is indicated that the calibration method is validated in an FMCW LiDAR system, and a significant enhancement in the signal-to-noise ratio is achieved. This work offers valuable insights into developing highly integrated on-chip FMCW LiDAR systems with an improved linearity of frequency-swept output light.
Cervical cancer screening is a crucial public health intervention, but screening disparities exist for women with physical disabilities (WWPD). To explore the experiences of WWPD with both traditional speculum examination-based screening and at-home self-sampling for cervical cancer screening. This qualitative study enrolled 56 WWPD to test self-sampling kits, provide feedback via a survey, and participate in a qualitative interview. An interprofessional team conducted semistructured interviews with 16 key informants and 40 pilot participants for 56 WWPD from November 1, 2021, through April 30, 2023. All completed a self-administered quantitative survey. Key informants' experiences with 4 self-sampling devices helped determine which 2 self-sampling kits would be offered to participants in a pilot study. A coding scheme was developed to represent inductive codes generated through preliminary coding and deductive codes representing domains from the Theoretical Domains Framework. This coding scheme was used to conduct a 2-pass thematic analysis. Of the 56 WWPD (mean [SD] age, 45.4 [9.1] years) who participated in the study, 28 (50.0%) were up to date with cervical cancer screening. Participants described accessibility barriers and clinician ableism that made speculum-based in-office examinations difficult, leading some participants to delay or avoid screening. In contrast, participants described self-screening as more comfortable and convenient, regardless of whether they prefer future speculum-based screening. Their responses also allowed for the exploration of how screening preferences may impact future screening behavior. Interviews with WWPD suggested that access to self-sampling screening options would be more comfortable for cervical cancer screening participation. Understanding participants' experiences with self-sampling devices generates insights into improving screening experiences for WWPD.
In late 2020, the National Board of Osteopathic Medical Examiners (NBOME) announced that the Comprehensive Osteopathic Medical Licensing Examination (COMLEX-USA) Level 1 would discontinue reporting numeric scores, only providing a Pass/Fail designation. The National Board of Medical Examiners (NBME) changed the core reports for the United States Medical Licensing Examination (USMLE) Step-1 to Pass/Fail in early 2020. Subsequently, residency program directors were reported to migrate toward increased reliance on COMLEX-USA Level 2CE and USMLE Step 2CK scores, the prestige of medical schools, and the status of the authors of letters of reference during their review of residency applicants. Funded by an American Association of Colleges of Osteopathic Medicine (AACOM) research grant, A.T. Still University - Kirksville College of Osteopathic Medicine (ATSU-KCOM) and the Arkansas College of Osteopathic Medicine (ARCOM) generated a series of five hypotheses to investigate the perceived impact of the transition to Pass/Fail scoring. Both institutional review boards (IRBs) provided exempt status for this study. The hypotheses were examined through surveys distributed to current osteopathic medical students (OMS), recent graduates (classes of 2021 and 2022), academic advisors, and college of osteopathic medicine (COM) curriculum committee members in this cohort study. The investigative process consisted of two surveys: an initial survey to collect data on all five hypotheses and a focused, follow-up survey designed to better understand the impact of the scoring change. The surveys collected respondent feedback based on a Likert Scale. Standard descriptive statistics were assembled and analyzed. Qualitative responses were coded into thematic elements to examine response patterns. The initial survey collected responses from 302 respondents (23.2 % response rate) based on a scale from 1 (strongly disagree) to 4 (strongly agree). The survey results revealed the means for the following items based on a 4-point Likert scale (1=Strongly Disagree; 2=Disagree; 3=Agree; 4=Strongly Agree): (1) Increase chances of matching into residency: 2.35; (2) Pass/Fail is a positive change: 2.71; (3) Pass/Fail will reduce competition in competitive residency programs: 1.94; (4) clinical skills will be more strongly considered: 2.60; and (5) new score reports provide a robust analysis of strengths and weaknesses in basic science: 2.24. Almost half (46 %) of the respondents expressed negative sentiments toward the Pass/Fail change. Reasons included more emphasis on COMLEX-USA Level 2CE, decreased motivation to perform on COMLEX-USA Level 1, and the perceived disadvantages that resulted during the residency match process. Among the survey respondents, many, especially students, do not view the change as favorable. Respondents cited the primary reasons for their unfavorable perception as a lack of motivation to perform on COMLEX-USA Level 1 and the added stress of performing on COMLEX-USA Level 2CE. Additionally, respondents viewed the change as negatively impacting their audition rotations and subsequent residency competitiveness.
Systematic review. This study aims to evaluate the variability of minimum clinically important difference (MCID) and patient acceptable symptom state (PASS) thresholds in current anterior cervical discectomy and fusion (ACDF) literature. Patient-reported outcome measures (PROMs) are increasingly emphasized in recent studies evaluating outcomes of ACDF. To distinguish clinically meaningful improvements in PROMs, thresholds such as MCID and PASS have been delineated. However, the variability of the MCID/PASS threshold values can significantly influence study outcomes, limit the validity of the results, and complicate comparisons between studies. PubMed and Embase were queried for articles from January 1, 2000, to May 1, 2024, reporting MCID or PASS values for PROMs following ACDF. Patient demographics, study characteristics, MCID/PASS thresholds, and threshold calculation methods were extracted for all PROMs. A total of 55 studies were identified, including 16 unique PROMs reported. There were 231 MCID threshold values and 2 PASS threshold values included. Of these, 47 studies referenced previously established values, while six studies calculated new thresholds. Among these six studies, 15 novel MCID thresholds and one novel PASS threshold were reported across eight distinct PROMs. The ranges of MCID thresholds for the most common PROMs were 7.5-20 for NDI, 2.5-3.1 for VAS-neck, 2.5-4.6 for VAS-arm, 4.1-11.1 for SF-12 PCS, 4.7-9.7 for SF-12 MCS, and 4.5-8 for PROMIS-PF. There is a high degree of variability among MCID thresholds in the ACDF literature, especially for NDI, VAS-arm, SF-12 PCS, SF-12 MCS, and PROMIS-PF. Interestingly, threshold values may even vary among papers citing the same studies for their reference MCID thresholds, with previously calculated MCID thresholds being cited incorrectly in some cases. This study emphasizes the need for improved standardization of MCID threshold values in spine literature for more reliable and consistent assessments of surgical outcomes.
The extension of onboard cone-beam CT (CBCT) imaging for real-time treatment planning is constrained by limitations in image quality. Synthetic CT (sCT) generation using deep learning provides a potential solution to these limitations. This study was dedicated to creating a model capable of rapidly generating sCT images from CBCT scans, specifically for the entire spine. This work aims to be a step towards a CT simulation-free workflow by using onboard imaging for real-time palliative radiotherapy treatments for patients with spinal metastases. Using CBCT and planning fan-beam CT images from 220 patients, we developed and validated a two-stage sCT generation model. The initial stage used a conditional generative adversarial network (GAN) to minimize streaking artifacts in CBCT images, using 7400 images for training and 1000 for validation. The second stage used a cycle-consistent GAN to produce sCT images, training on 14,700 images and validating on 500 images. The quality of the sCT images was evaluated quantitatively using a distinct dataset from 33 patients who received same-day palliative radiotherapy for spinal metastases. Our two-stage model generated high-quality sCT images from CBCT scans across the entire spine, significantly improving HU accuracy and dosimetric agreement with planning CT images. Mean Absolute Error was reduced from 225 ± $\,\pm\,$ 62 HU in CBCT to 86 ± $\,\pm\,$ 24 HU in sCT images, and Mean Error was improved from 178 ± $\,\pm\,$ 91 HU to -8 ± $\,\pm\,$ 20 HU. Dosimetric comparison for a subset of 20 patients indicated that the mean dose discrepancy for sCT-based calculations was lower than CBCT-based calculations by 4.5%, with the gamma (2 mm/2%) pass rate increasing by 34% on average. This study demonstrates how a two-stage network facilitates CBCT-based sCT generation across the entire spine without prior CT knowledge, improving HU accuracy and potentially enabling highly-conformal palliative treatment planning for spinal metastases in real time.
Medium vessel occlusions (MeVOs) account for 25-40% of acute ischemic stroke. The Tenzing 5 (Route 92 Medical, San Mateo, California, USA) and FreeClimb 54 (Route 92 Medical, San Mateo, California, USA) catheter is a novel delivery-aspiration catheter combination designed to facilitate aspiration thrombectomy (AT) of MeVOs. We report our clinical experience using the Tenzing assisted delivery of aspiration (TADA) technique with FreeClimb 54 for first-line AT of MeVO. We retrospectively reviewed consecutive patients who underwent MeVO first-line AT using TADA with FreeClimb 54 at nine institutions in the USA and one in New Zealand. 94 MeVOs (65 primary, 29 secondary) were treated in 92 patients: median age 71 (IQR 58-81) years; 49/92 (53%) women. FreeClimb 54 was successfully delivered by Tenzing 5 to all 94/94 MeVOs: 26 proximal M2; 44 distal M2; 5 M3; 6 A2; 4 A3; and 8 P2. Median target vessel diameter on DSA was 1.7 (IQR 1.4-1.8) mm. A leading microwire was used to advance Tenzing in 84% of cases. A stent retriever was used for additional thrombectomy passes in 6/94 (6%) patients. For a primary MeVO, final modified expanded Thrombolysis in Cerebral Infarction (meTICI) 2B-3 reperfusion was achieved in 63/65 (97%) patients, after a median of 1 (IQR 1-2) pass, with a first pass effect (FPE, meTICI 2C-3) in 43/65 (66%). Secondary MeVO FPE (eTICI 2C-3) was achieved in 20/29 (69%) patients. Tenzing 5-FreeClimb 54 related complications occurred in 2/94 (2%) patients: one perforation with asymptomatic subarachnoid hemorrhage and one embolus to new territory. MeVO first-line AT using the TADA technique with Tenzing 5 and FreeClimb 54 had a high FPE with a low complication rate.
Medial meniscus posterior root tear (MMPRT) repair is indicated in patients with preserved articular cartilage to prevent rapidly progressive osteoarthritis. However, there is limited published data on midterm outcomes after MMPRT repair. To report the patient-reported outcome measures (PROMs), complication, and failure rate for patients undergoing MMPRT repair at a minimum of 5-year follow-up. Case series; Level of evidence, 4. A single-institution prospectively collected database was retrospectively queried for patients who underwent isolated MMPRT repair from January 2016 to March 2019. Exclusion criteria included Kellgren-Lawrence grade ≥3 osteoarthritis, concurrent ligamentous or realignment procedures, all-inside suture anchor repair, and concomitant lateral meniscal tears. The clinical outcome measures included conversion to knee arthroplasty, the shortened Knee injury and Osteoarthritis Outcome (KOOS) Jr, International Knee Documentation (IKDC), and Veterans RAND 12-Item Health Survey (VR-12) scores. Clinical failure was defined as failing to achieve the minimal clinically important difference (MCID) for ≥1 PROM. The MCID and Patient Acceptable Symptom State (PASS) thresholds were derived from a peer-reviewed study and were as follows: IKDC (MCID, 10.2; PASS, 67.8), KOOS Jr (MCID, 10.4; PASS, 71.9) and VR-12 Physical (MCID, 6.1; PASS, 47.8). A total of 38 patients who met inclusion criteria and underwent transtibial root repair before March 2019 were retrospectively identified, of which 36 (94.7%) were available for follow-up at mean 65.8 ± 6.7 months (range, 60-81). Of this total, 5 patients (13.9%) converted to arthroplasty (mean ± SD, 41.8 ± 28.0 months). Transtibial pullout repair had an overall survivorship of 97.2%, 94.4%, and 91.6% at the 1-year, 2-year, and 5-year time points, while 2 patients failed after 60 months postoperatively, for an 86.1% arthroplasty-free survivorship at mean 65.8 months. MCID and PASS achievement rates at final follow-up for KOOS Jr were 74.2% and 51.6%, respectively. Three patients (8.3%) failed to achieve MCID for any 1 of the 3 PROMs while 28 patients (77.8%) achieved the MCID for ≥1 PROM. Clinically significant outcomes for KOOS Jr were achieved in 74.2% and 51.6% of patients undergoing transtibial pullout repair for isolated MMPRT at 5-year follow-up. There was an 86.1% survivorship free of arthroplasty at midterm follow-up.
This multi-omic study investigates the bidirectional interactions between gut microbiota and silymarin metabolism, highlighting the differential effects across various age groups. Silymarin, the extract from Silybum marianum (milk thistle), is commonly used for its hepatoprotective effects. An in vitro fermentation colon model was used with microbiota from 20 stool samples obtained from healthy donors divided into two age groups. A combination of three analytical advanced techniques, namely proton nuclear magnetic resonance (1H NMR), next-generation sequencing (NGS), and liquid chromatography-mass spectrometry (LC-MS) was used to determine silymarin microbial metabolites over 24 h, overall metabolome, and microbiota composition. Silymarin at a low diet-relevant dose of 50 µg mL-1 significantly altered gut microbiota metabolism, reducing short-chain fatty acid (acetate, butyrate, propionate) production, glucose utilization, and increasing alpha-diversity. Notably, the study reveals age-related differences in silymarin catabolism. Healthy elderly donors (70-80 years) exhibited a significant increase in a specific catabolite associated with Oscillibacter sp., whereas healthy young donors (12-45 years) showed a faster breakdown of silymarin components, particularly isosilybin B, which is associated with higher abundance of Faecalibacterium and Erysipelotrichaceae UCG-003. This study provides insights into microbiome functionality in metabolizing dietary flavonolignans, highlighting implications for age-specific nutritional strategies, and advancing our understanding of dietary (poly)phenol metabolism.
Although patient-reported outcomes (PROs), such as the Patient-Reported Outcomes Measurement Information System (PROMIS), are a key element of evaluating success after total ankle replacement (TAR), many do not explicitly state a key factor of postoperative success: is the patient satisfied with their outcome after TAR? The patient acceptable symptom state (PASS) represents the symptom threshold beyond which patients consider themselves well. This study aimed to establish the PROMIS thresholds for the PASS in a primary cohort of TAR patients. This single-institution study included 127 primary TAR patients with preoperative and 2-year postoperative PROMIS scores. At 2 years postoperatively, patients answered 2 PASS anchor questions (Satisfaction, Delighted-Terrible scale) with Likert-scale responses. PASS thresholds with 95% confidence intervals (CIs) were calculated from PROMIS scores using an anchor-based method. Using a bootstrapping technique with 1,000 iterations, the Youden index was calculated to determine the best specificity and sensitivity coordinates to maximize their combination. Finally, preoperative variables associated with the likelihood of achieving the PASS were assessed. There was a strong association between PASS thresholds and PROMIS domains, especially Pain Interference (PASS threshold of <56.0, area under the receiver operating characteristic curve [AUC] = 0.940), Pain Intensity (<48.4, AUC = 0.936), and Physical Function (>44.7, AUC = 0.883). The likelihood of achieving the PASS was not affected by age, race, gender, American Society of Anesthesiologists (ASA) class, body mass index, or severity of ankle deformity. Patients with worse preoperative Physical Function and Global Mental Health scores were less likely to meet the PASS threshold for Physical Function postoperatively (p = 0.028 and 0.041). The ability to reach the PASS after TAR was most strongly associated with postoperative PROMIS pain scores. However, PASS thresholds were generally poorer than population means. This demonstrates that patients do not need to reach normal pain or physical function levels to have an acceptable symptom state after TAR. Prognostic Level IV . See Instructions for Authors for a complete description of levels of evidence.
The rapid increase in the number of osteopathic medical schools creates a highly competitive medical school environment as each osteopathic medical school seeks to enroll top-performing students. This results in osteopathic colleges' need to be innovative in the academic support interventions they provide to help increase their student's chances of successfully passing their Comprehensive Osteopathic Medical Licensing Exam (COMLEX) level 1 and 2 board exams on their first attempt. A correlation analysis was performed of the Alabama College of Osteopathic Medicine's (ACOM) class of 2024's (188 students) pre-matriculation metrics, including Grade Point Average(GPA), Science Grade Point Average (SGPA), and Medical College Admissions Test (MCAT), performance in each course, and on two specific exams to determine if causality or correlation existed between these variables and first-time Comprehensive Osteopathic Medical Licensing Exam (COMLEX) level 1 and level 2 pass rates. Using the Spearman correlation (significant at the p<0.01 level) reveals that, if a student was in the lowest quartile in any of the following courses, they were at risk of failing COMLEX level 1: medical biochemistry (00.156), neuroanatomy (00.168), cardiology (00.275), renal (00.176), respiratory (00.235), or gastrointestinal (00.209). The lowest quartile performance in neuroanatomy (00.228) and gastrointestinal (00.154 - significant at the p<0.05 level) correlates to a first-time failure of COMLEX level 2. Specific Interventions have been developed for students in the lowest quartile of the courses identified in the findings of the institutional data analysis to better prepare them to pass the COMLEX level 1 and level 2 board exams.
Parasites are a key driving force behind many ecological and evolutionary processes. Prevalence and diversity of parasites, as well as their effects on hosts, are not uniform across host species. As such, the potential parasite spillover between species can significantly influence outcomes of interspecific interactions. We screened two species of Luscinia nightingales for haemosporidian blood parasites (Plasmodium, Leucocytozoon and Haemoproteus) along an approximately 3000 km transect in Europe, incorporating areas of host distant allopatry, close allopatry and sympatry. We found significant differences in infection rates between the two host species, with common nightingales having much lower parasite prevalence than thrush nightingales (36.7% versus 83.8%). This disparity was mostly driven by Haemoproteus prevalence, which was significantly higher in thrush nightingales while common nightingales had a small, but significantly higher, Plasmodium prevalence. Furthermore, we found no effect of proximity to the contact zone on infection rate in either host species. Despite having lower infection prevalence, common nightingales were infected with a significantly higher diversity of parasite lineages than thrush nightingales, and lineage assemblages differed considerably between the two species, even in sympatry. This pattern was mostly driven by the large diversity of comparatively rare lineages, while the most abundant lineages were shared between the two host species. This suggests that, despite the close evolutionary relationships between the two nightingales, there are significant differences in parasite prevalence and diversity, regardless of the distance from the contact zone. This suggests that spillover of haemosporidian blood parasites is unlikely to contribute towards interspecific interactions in this system.
The aim of this study was to compare the cytological adequacy rates of different needle passes in ultrasound-guided fine-needle aspiration biopsy of thyroid nodules and, thus, to help establish the criterion for selecting the number of needle passes according to the characteristics of thyroid nodules. This single-center and randomized prospective study involved 207 consecutive patients with 240 solid or predominantly solid thyroid nodules. These nodules were randomly divided into a 1-pass group, a 2-pass group, and a 3-pass group. Then the nodules were sent for cytopathological diagnosis, and cytological results were classified according to the Bethesda classification. Bethesda I was defined as inadequate, and Bethesda Ⅱ-Ⅵ were defined as adequate. Then the cytological adequacy rates of different groups were compared. In total, 221 nodule specimens were considered as adequate and 19 nodule specimens inadequate. The overall adequacy rate was 92.1%. However, there were no significant differences among the 1, 2, and 3-pass groups in terms of adequacy rates (91.3%, 92.5%, and 92.5%, respectively). The number of needle passes does not significantly affect the cytological adequacy in ultrasound-guided fine-needle aspiration of solid or predominantly solid thyroid nodules. The cytological adequacy of one-needle pass is comparable to those of two and three-needle passes.