To investigate the utility of acupuncture with electrical stimulation (AES) on Lian Quan-S (CV23-S) and Shang Lian Quan-S (Ex-HN21-S), each located bilaterally 1.27 cm (0.5 inches) from their respective acupoints Lian Quan (CV23) and Shang Lian Quan (Ex-HN21), in the treatment of obstructive sleep apnea syndrome (OSAS). Case 1. A 55-year-old male sought acupuncture treatments as an alternative for complications from using a continuous positive airway pressure (CPAP) machine for OSAS. Case 2. A 26-year-old male sought acupuncture treatments to relieve complaints of excessive daytime sleepiness, hunger, and snoring. Case 1. 20 min AES treatments of CV23-S and Ex-HN21-S with various other supplemental acupoints were performed every other day for 1 week, totaling four treatment sessions. Case 2. AES of CV23-S and Ex-HN21-S with another supplemental acupoint. The patient received four trials of care, totaling 24 treatments in 10 months. For the first trial of care, daily 30 min treatments were performed for 8 days. For subsequent trials of care, the treatment frequencies were decreased, but the treatment duration was gradually increased. Case 1. After AES treatments, the patient stopped using the CPAP machine and noticed reduced facial swelling. The patient subjectively described his sleep quality improving from poor to good. His uninterrupted sleep time increased from 3 to 8 h per night. Case 2. After AES treatments, the patient found relief of symptoms and noted more energy during the day. AES on new acupuncture points, CV23-S and Ex-HN21-S, bilaterally has shown reduction of symptoms in OSAS.
Phage display is a widely used approach for the rapid isolation of monoclonal antibodies against a wide range of target antigens. The availability of a diverse antibody library is the essential component of any phage display campaign. The generation of an antibody library is coupled with an iterative process termed as biopanning that allows the identification of monoclonal antibodies. The antibody library consists of the antibody repertoire obtained either from human peripheral blood mononuclear cell (PBMC) or directly from sorted B-cell populations. Depending on the classification of the antibody library sought after, the antibody isotype used would differ. Naïve libraries make use of IgM repertoires, whereas immune libraries would apply IgG repertoires as the antibody gene components. The antibody genes are amplified by polymerase chain reaction (PCR) and cloned in a combinatorial fashion to generate a diverse library repertoire. The protocol describes a two-step cloning approach that can be adapted for the construction of either a naïve or immune human antibody library in Fab format. The protocol would also include a standard biopanning protocol using the Fab library.
We have recently documented significant compressible behaviors in hydrogels implemented in 3D traction force microscopy (TFM). Therefore, here we have developed a new computational pipeline that accounts for this observation. Additionally, the new method accurately recovers large ranges and spatial heterogeneity of hydrogel moduli induced by cellular remodeling associated with enhanced extracellular matrix secretion and MMP-degradation. The algorithm sought best fit of the 3D displacement field with a multi-stage approach, wherein the Tikhonov regularization parameter in L-BFGS was progressively lowered. Forward simulations were performed in FEniCS, with gradients computed with FEniCS-adjoint and MOOLA to weight degrees of freedom according to hydrogel volume affected. Once developed, we conducted a series of synthetic test cases applying actual cell geometries, experimentally matched compressibility, and realistic displacements with experimental noise levels. Employing an incompressible material model resulted in predicted moduli with over 415% mean relative error and predicted strain energies 5-fold greater than the prescribed values. Moreover, errors in predicted traction forces were amplified by a factor of 10. Thus, accounting for hydrogel compressibility was critical for accurate hydrogel moduli and strain energy recovery. To demonstrate the utility of our approach, we applied it to TFM data of human mitral valve interstitial cells embedded in PEG hydrogels with pre-altered moduli of 54 Pa. We determined that J∈[0.45,1.66] and local hydrogel moduli exhibited large variations, 3.6 Pa to 2.4 MPa. This study underscores the need for correct handling of hydrogel compressibility for accurate estimation of local hydrogel moduli and traction forces.
Acute kidney injury (AKI) poses a risk of permanent kidney damage and failure. Conventional management stresses preventing further damage, while integrative approaches also aim to enhance renal function. This case explores the use of acupuncture, ayurveda, and Chinese herbal medicine for a 71-year-old male with fatigue, diagnosed with AKI. Following medical evaluation, the patient sought integrative care outside the nephrologist recommendation. Following 12 months of acupuncture, ayurveda and Chinese herbal renal function demonstrated sustained improvement in blood urea nitrogen (63%), estimated glomerular filtration rate (67%), and creatinine (49%), along with decreased fatigue. An integrative approach may help enhance renal function in AKI. Interprofessional collaboration is recommended.
Evidence remains inconclusive regarding the ability of the inferior vena cava (IVC) distensibility index and common carotid Doppler flow velocity parameters to predict fluid responsiveness before off-pump cardiac surgery. Therefore, we sought to evaluate the relationship between the IVC distensibility index, common carotid Doppler flow velocity parameters, and fluid responsiveness during off-pump coronary artery bypass surgery. In this prospective observational study conducted at Ain Shams University Hospitals (Cardiothoracic Academy), 30 adult patients (ejection fraction > 45%) scheduled for off-pump coronary artery bypass surgery after an 8-h fasting period were enrolled. Following induction of anesthesia, a fluid challenge of 5 ml/kg crystalloid was administered. Hemodynamic variables (mean arterial pressure, heart rate, central venous pressure, IVC distensibility index, common carotid Doppler peak velocity, and transthoracic cardiac output [CO]) were recorded before and after fluid loading. An increase in CO of > 15% after the fluid challenge indicates fluid responsiveness. Sonographic measurements demonstrated statistically significant changes in CO following fluid loading. However, neither the change in the IVC distensibility index (ΔIVC) nor the change in carotid Doppler peak systolic velocity (ΔVpeakCCA) demonstrated adequate discriminatory ability to differentiate fluid responders from non-responders in this cohort. Point-of-care ultrasound parameters, including the IVC distensibility index and carotid Doppler velocity, showed limited value for predicting fluid responsiveness in off-pump cardiac surgery and, therefore, should not be used in isolation to guide perioperative fluid administration.
People experiencing severe and multiple disadvantage (SMD)- including intersecting experiences of homelessness, substance misuse, poor mental health, and domestic violence and abuse- face high levels of unmet health need but encounter significant barriers to accessing general practice. We aimed to explore how interventions or aspects of routine general practice care can improve access for people with SMD, examining what works, for whom, and under what circumstances. We used a realist review approach as both general practice and access to services for people with SMD are complex; bringing them together required a nuanced understanding of underlying mechanisms. We developed an initial programme theory by consulting experts by experience, professional stakeholders, relevant literature and substantive theory. We searched databases and sought literature from relevant networks, including qualitative, quantitative, mixed-methods, and grey literature. We included full texts with relevant data that could inform programme theory development, and organised these into intervention components. We used a realist analytical approach to synthesise evidence and make conclusions. We collaborated with experts by experience and professionals supporting them throughout, to ensure findings and recommendations were relevant and applicable. Themes of belonging, trust and power are key in improving access to primary care for and with people with SMD. Interventions to improve Inclusion Health in primary care include outreach, partnership working, peer involvement and advocacy, flexible access, specialist clinics, staff training, appointment systems, case management, co-design and challenging unjust systems. Using actionable strategies, general practices can better include people with SMD.
Purpose: Core professional values (CPVs) guide both physiotherapist behaviours and the Association's activities. The purpose of this study was to confirm or modify a list of 10 CPVs and their associated behaviours (ABs) through a series of online surveys and member consultation. Method: Members of the Canadian Physiotherapy Association (CPA) rated whether or not 10 CPVs and their ABs were "relevant and essential" through three rounds of electronic Delphi (e-Delphi) surveys. Consensus was defined a priori as 80% agreement. Demographic data and respondents' feedback were collected. Revisions to the CPVs and ABs in subsequent rounds were guided by member ratings and feedback. Additional input was sought through meetings with members, professional leaders and content experts. Results: Over 1,000 members participated. There were 548, 446, and 295 surveys completed for rounds 1, 2, and 3, respectively. Ten CPVs (accountability, advocacy, altruism, client centredness, compassion, equity, excellence, integrity, respect, social responsibility) were confirmed. The number of ABs increased from 29 in the first round to 35 in the final version. Conclusions: Ten CPVs with ABs have been confirmed by members of the CPA. These values can inform the professional activities of clinicians, the CPA, and others. Future work includes the identification of ABs that relate to non-clinical activities and exploring the relationship between demographic factors and the integration of CPVs into practice. Objectif: les valeurs professionnelles fondamentales (VPF) orientent à la fois les comportements des physiothérapeutes et les activités de l'Association. La présente étude visait à confirmer ou à modifier une liste de dix VPF et les comportements associés (CA) au moyen d'une série de sondages en ligne et d'une consultation auprès des membres. Méthodologie: les membres de l'Association canadienne de physiothérapie (ACP) ont déterminé si les dix VPF et les CA étaient « pertinents et essentiels » dans le cadre de trois cycles de sondages Delphi en ligne. Le consensus a été défini a priori comme 80 % d'entente. Les chercheurs ont recueilli les données démographiques et les commentaires des répondants. Lors des cycles suivants, ils ont apporté les révisions aux VPF et aux CA en fonction des notes et des commentaires des membres. Ils ont demandé des points de vue supplémentaires lors de rencontres avec les membres, les dirigeants professionnels et les experts du contenu. Résultats: plus de 1 000 membres ont participé. Au total, 548, 446 et 295 sondages ont été remplis lors des cycles 1, 2 et 3, respectivement. Les dix VPC (responsabilité, représentation, altruisme, être centré sur le client, compassion/sollicitude, équité, excellence, intégrité, respect, responsabilité sociale) ont été confirmées. Le nombre de CA est passé de 29 au premier cycle à 35 au dernier cycle. Conclusions: les membres de l'ACP ont confirmé les dix VPC et les CA. Ces valeurs peuvent éclairer les activités professionnelles des cliniciens, de l'ACP et d'autres intervenants. Les futurs travaux incluent la détermination des CA qui sont liées à des activités non cliniques et exploreront la relation entre les facteurs démographiques et l'intégration des VPC à la pratique.
Background Although many women experience recurrent urinary tract infections (rUTI), their significance for affected women is poorly described and understood. Aim We aimed to explore women's experiences of rUTI and its impact on their lives. Design and Setting A qualitative study embedded in a UK randomised controlled trial (RCT) of D-mannose with women with clinically defined rUTI. Method We conducted semi-structured telephone interviews with 32 women who participated in the RCT. Interviews were audio-recorded and transcribed verbatim. Data were analysed thematically. Results Women reported how the experience of rUTI was burdensome with distressing and debilitating physical symptoms and wider disruptive effects. Women expressed how rUTI had impacted different stages of their lives and we identified two types of impact. Internalised impact included the women's emotional response to rUTI, dread of a recurrence and maintaining readiness to manage it. Externalised impact encompassed actions in response to rUTI, including remaining extremely vigilant about recurrences and seeking help as soon as a recurrence was suspected, and the challenges they faced. The women explained how the responses of Health Care Professionals (HCPs) when they sought care affected their help-seeking and their self-esteem, and could leave them feeling a sense of helplessness. Conclusion Experience of rUTI has taught women to be vigilant and proactive about the condition but this was not always matched with understanding and validation on the part of HCPs. When women experiencing rUTI seek care, clinicians could usefully consider their broader experience of rUTI, including internalised and externalised impacts.
Existing self-administered, pre-participation screening questionnaires for physical exercise have not demonstrated high take-up rates in many populations. There is evidence that part of the reason for this may be the language of these questionnaires and difficulty in understanding these questions by lay persons, especially those with existing medical conditions that may be of concern if engaging in physical exercise. The medical referral rates for existing questionnaires appears excessive. There has also not been a demonstrable decrease in sports emergencies following current use of these questionnaires. Based on the lessons learnt from previous surveys and the evidence behind existing questionnaires, an eight-question International Physical Exercise Screening Questionnaire (IPESQ) is proposed. This paper discusses the roles played by pre-participation screening questionnaires in preventing or minimizing the occurrence of sports emergencies, desired characteristics of pre-participation exercise screening questionnaires and describes the justification for each of the IPESQ questions and how the Questionnaire may be implemented. It proposes a tool that is based on studies that have actively sought public feedback, and used the level of evidence currently available in the scientific literature as proof of relevance and usefulness. The proposed IPESQ will need to be actively implemented and its impact determined with monitoring of sports-related emergency rates. It is relevant to an international audience, since sports emergencies such as cardiovascular collapse, injuries and heat illnesses are universal phenomena. The IPESQ can be regarded as a promising but not yet proven instrument to minimize the occurrence of sports emergencies.
In total hip arthroplasty (THA), accurate reconstruction of physiological joint biomechanics is determined by the individual patient's proximal femoral anatomy and stem design. Previous studies demonstrated a wide variation of femoral canal shapes and an association with extramedullary geometrical features. The purpose of this study was to propose a comprehensive classification for the coronal plane alignment of the hip (CPAH) that incorporates intramedullary and extramedullary parameters. We sought to determine the distribution of femoral morphotypes in an osteoarthritic cohort and to assess the reconstructive potential of four common femoral stem designs in each CPAH type. The preoperative radiographs of 2,345 patients undergoing primary uncemented THA were retrospectively analyzed, including Dorr classification, neck-shaft angle (NSA), femoral offset (FO), and femoral offset ratio (FOR). The CPAH classification defines nine morphotypes based on the combination of Dorr type and NSA. Each morphotype is categorized into a normal- and a high-offset subgroup. Digital templating was conducted to assess the reconstruction of FO, leg length (LL), and the agreement between anatomy and stem geometry. The CPAH types 2N, 5N, 5H, 6N, and 8N accounted for a combined percentage of 82% (n = 1,928), whereas the remaining morphotypes represented less common anatomical constitutions. Canal shape, FO, and NSA were associated with demographic characteristics (age, P < 0.001; sex, P < 0.001). Subgroup analyses stratified by CPAH types revealed that the reconstructive potential of each stem design depends on the patient's femoral morphotype. Across all CPAH types, the short stem was the best-fit implant, whereas a mismatch between anatomy and stem design was evident in up to 80% of the cases using the anatomic stem design. The CPAH classification provides a comprehensive classification system for femoral morphotypes. It enables a phenotyping approach in THA planning and provides practical guidance for individualized implant selection.
We sought to identify racial/ethnic and neighborhood disparities in acute kidney injury (AKI) in children with acute lymphoblastic or myeloid leukemia (ALL, AML). Electronic health record data were retrospectively collected from patients treated for de novo pediatric ALL or AML in the multicenter Leukemia Electronic Abstraction of Records Network. AKI was defined by modified Kidney Disease Improving Global Outcomes criteria. Neighborhood-level resources were defined by the Child Opportunity Level (COL). Prevalence ratios (PRs) for AKI at diagnosis by race/ethnicity and COL were calculated using modified Poisson regression. Cox regression was used to calculate hazard ratios (HRs) of first AKI after initiation of chemotherapy (i.e., "during therapy"). Of 952 ALL patients, Non-Hispanic Black (NHB) ALL patients had significantly increased prevalence of AKI at leukemia diagnosis compared to Non-Hispanic White (NHW) patients in the adjusted model (PR 1.50); there were no significant differences by COL. During ALL therapy overall, NHB patients did not have any significant differences in hazard of AKI by race/ethnicity or COL in adjusted models. Among 168 AML patients, there were no significant differences in AKI at diagnosis by race/ethnicity or COL in AML. During AML therapy overall, NHB patients had significantly higher risk of AKI in both unadjusted (HR 1.95) and adjusted (HR 2.68) models, but no differences by COL. NHB patients with ALL had increased risk of AKI at the time of leukemia diagnosis, and NHB patients with AML had significantly increased risk of AKI during therapy. Further studies to identify drivers and interventions that mitigate AKI risk are warranted.
Disruptive behaviors (non-compliance, aggression) are common in autistic children. Parent-Child Interaction Therapy (PCIT) is a caregiver-mediated intervention utilizing in vivo caregiver coaching that reduces disruptive behaviors and has been shown to be effective for young autistic children. This study sought to identify child and caregiver factors that relate to session-level progress among autistic children and their caregivers. Participants included 98 autistic children aged 2-8 years (91% male) who received PCIT in a university-affiliated clinic. Session-level change was examined using iterative multilevel modeling to examine change in child disruptive behaviors, as measured on the Eyberg Child Behavior Inventory (ECBI), caregiver positive attending skills (Do-skills), and caregiver negative statements (Avoid-skills). Optimal fitting trajectories revealed quadratic change in ECBI scores, Do-skills, and Avoid-skills. The effectiveness of PCIT did not differ based on participants' level of autistic traits or caregiver demographics. Improvements in child disruptive behavior were associated with child adaptability and parenting stress pre-treatment; higher adaptability and lower stress were related to faster declines in child disruptive behavior. Caregivers exhibited slower rates of change in Do-skills when they had lower rates of homework completion, and when their child had lower social responsiveness, and challenges with adaptability and externalizing problems. These findings may help clinicians tailor what factors to emphasize and monitor over the course of PCIT. Parent–Child Interaction Therapy (PCIT) is a therapy that helps caregivers manage challenging behaviors in young children by teaching and coaching them in real time. PCIT works well for autistic children who also show a lot of disruptive behavior, like meltdowns and aggression. However, it is still unclear which factors might influence how well the therapy works for each child. In our study, we found that PCIT was helpful in reducing disruptive behaviors for autistic children across a wide range of cognitive abilities and support needs. However, caregivers who reported higher levels of stress and whose children initially showed more behavior problems and greater difficulty adjusting to change generally made slower progress in learning new skills. These findings could help therapists better support families by focusing more on certain areas during treatment.
The current literature remains inconclusive about whether kinematic alignment (KA) is superior to mechanical alignment (MA) in total knee arthroplasty (TKA). Therefore, this randomized controlled trial sought to provide further clarification. 39 MA patients, 33 KA patients, and 9 healthy controls were included. All participants underwent three-dimensional gait analysis on a treadmill one day before surgery and one year postoperatively. A preoperative range of motion (ROM) score was calculated and correlated with the postoperative Forgotten Joint Score (FJS). One year after surgery, no significant kinematic differences were observed between MA and KA. However, in Coronal Plane Alignment of the Knee (CPAK) type 1 patients, KA knees more closely reproduced the gait of healthy controls and showed higher walking speed. Correlation analysis revealed that patients with a higher preoperative ROM achieved better outcomes with KA, whereas female patients with lower ROM benefit more from MA. Although no kinematic differences were detected, the strong trend toward reduced joint space in MA compared to KA in CPAK type 1 patients may result from subtle deviations in joint-line restoration or postoperative soft-tissue tension. Both factors can affect load distribution and joint perception. The present findings support a patient-specific approach to alignment selection in TKA.
Soil salinization and alkalization severely constrain crop production worldwide, yet the combined effects of mixed saline-alkaline stress on minor cereal germination have received limited investigation. This study sought to elucidate the effects of mixed saline-alkaline stress on seed germination and seedling growth of proso millet (Panicum miliaceum L.) under controlled laboratory conditions, and to comparatively assess the relative contributions of osmotic stress, ionic toxicity, and high-pH damage through analysis of different neutral-to-alkaline salt ratios at equivalent Na⁺ concentrations. Seeds were subjected to nine treatment combinations comprising three salinity levels (80, 160, and 240 mM Na⁺) and three neutral-to-alkaline salt ratios (3:1, 1:1, and 1:3), employing NaCl, Na₂SO₄, NaHCO₃, and Na₂CO₃. Germination characteristics, seedling morphology, and key physiological parameters were assessed over seven days. Mixed saline-alkaline stress markedly suppressed germination in a concentration-dependent manner, with germination percentage decreasing from 94.5% (control) to 23.8% at 240 mM Na⁺ under high-alkali conditions (P < 0.05). At equivalent Na⁺ concentrations, high-alkali treatments (pH > 9.5) diminished germination index by 35.6-52.3% relative to low-alkali treatments. The IC₅₀ values were 187.3 mM Na⁺ (95% CI: 171.2-205.8 mM; R² = 0.982), 142.6 mM Na⁺ (95% CI: 131.4-155.1 mM; R² = 0.976), and 98.4 mM Na⁺ (95% CI: 89.7-108.3 mM; R² = 0.991) for low-, medium-, and high-alkali ratios, respectively. High-alkali stress was associated with 67.4% greater electrolyte leakage and 2.3-fold higher MDA accumulation than neutral salt treatments at equivalent Na⁺ concentrations, indicating greater membrane disruption under high-pH conditions. Two-way ANOVA revealed significant main effects of both Na⁺ concentration and alkaline proportion, as well as a significant salinity × alkalinity interaction (P < 0.001; Supplementary Table S1). These results demonstrate that alkaline stress exerts stronger inhibitory effects on proso millet germination compared to neutral salt stress, with the magnitude of salinity effects being dependent on the pH level. While complete mechanistic separation of osmotic, ionic, and pH components was not achieved due to experimental design limitations (absence of iso-osmotic non-ionic controls and direct ion measurements), comparative analysis across salt ratio treatments suggests that high pH is associated with additional inhibitory effects beyond those observed in neutral salt treatments. These controlled-condition findings establish preliminary germination -stage thresholds that may inform screening protocols for saline-alkaline tolerance breeding in proso millet, pending validation under field conditions.
This study aimed to understand how a routine HPV vaccine recommendation at age 9-10 rather than 11-12 may influence parents' vaccine intentions, including parents with varied experience/prior choices related to HPV vaccine decision-making. Additionally, we sought to identify factors (older child vaccination status, items informed by the Theory of Planned Behavior, and socio-demographic/health characteristics) associated with vaccine intention for ages 9-10. A national online survey of parents of children ages 9-10 who had not yet received the HPV vaccine was conducted in October 2024. Participants were recruited though a US research panel and assigned to one of three groups: (Group 1) parents without an older child; (Group 2) parents with an HPV-vaccinated older child; or (Group 3) parents with a non-HPV-vaccinated older child. Multivariable linear regression models identified factors associated with HPV vaccine intention at ages 9-10 for each group. The final sample included 2272 parents (Group 1: 41%, Group 2: 35%, Group 3: 24%). Overall mean score for intention to vaccinate at ages 9-10 was 3.21. Group 2 parents reported the highest perceived benefits and lowest perceived barriers for vaccinating at ages 9-10. Across all groups, those who indicated they follow health care provider recommendations for age of vaccination and those who perceive a benefit to vaccinating as early as possible had greater intentions to vaccinate at ages 9-10. These findings may help to inform health policy related to HPV vaccination and provider communication strategies. Moving the age of routine vaccination to ages 9-10 may not increase overall vaccination rates, but expansion of the age range (9-12) may create opportunities for repetitive provider recommendation and communication strategies that are personalized based on the parents' prior vaccine decision making.
Patient-reported experience measures (PREM) capture critical aspects of stroke care quality that are not typically reflected in conventional clinical outcomes, particularly during care transition. This quality improvement initiative sought to incorporate PREM into standard acute stroke care and assess the impact of a Patient-Oriented Discharge Summary (PODS) on patient experience and discharge readiness. Employing a two-cycle Plan-Do-Study-Act methodology, a stroke-specific patient experience survey was developed and administered at discharge to patients admitted with stroke or transient ischemic attack (TIA) at Health Sciences North, Sudbury, Ontario. Baseline findings identified experience-related deficiencies despite high overall satisfaction, notably in discharge preparedness, shared decision-making, and information clarity. A PODS-based discharge intervention was implemented and evaluated using defect and top-box analyses. Post-implementation, overall defect rates significantly decreased, and top-box performance improved across all experience domains, most notably in the understanding of the condition and readiness for discharge. These findings indicate that systematic measurement of patient experience, coupled with structured discharge communication, can substantially enhance care transitions and bolster the quality and safety of acute stroke services.
Research payments constitute the largest payment category in the Centers for Medicare and Medicaid Services (CMS) Open Payments program (OPP). We sought to characterize the distributions of and trends in industry-sponsored research payments (ISRPs) to otolaryngologists. OPP data was used to identify ISRPs to otolaryngologists between January 1, 2015 and December 31, 2023. ISRPs were stratified by recipient entity as covered teaching hospitals, covered physicians, and non-covered entities (NCEs) and evaluated using descriptive analysis and multivariable linear regression. ISRPs increased 132% from $15.6 million in 2015 to $36.2 million in 2023 (p < 0.001). Payments to NCEs with an otolaryngologist principal investigator (PI) constituted most payments (80%). Male otolaryngologist PIs decreased by -0.2%, while female otolaryngologist PIs increased by 86% (p < 0.01). Annual median payment values per otolaryngologist PI within NCEs increased 111% from $15,239 in 2015 to $32,097 in 2023 (p < 0.001). Among male otolaryngologist PIs within NCEs, total ISRPs increased 109% from $12.9 million in 2015 to $27.0 million in 2023, and median payment value per PI increased 93% from $17,144 in 2015 to $33,155 in 2023 (p < 0.01). Among female otolaryngologist PIs within NCEs, total ISRPs increased 125% from $0.5 million in 2015 to $1.1 million in 2023, but median payment value per PI only increased 14% from $11,973 in 2015 to $13,614 in 2023 (p = 0.1). ISRPs to otolaryngologists more than doubled from 2015 to 2023, with most payments directed to PIs within NCEs. Median payments to female otolaryngology PIs did not increase, despite an increase in female otolaryngologist PIs. N/A.
Federally qualified health centers (FQHCs) in the United States began the widespread use of telemedicine for HIV care during the COVID-19 pandemic. During a mature phase of the pandemic, we sought to increase the uptake of telemedicine, characterize uptake by modality (telephone versus video), and explore the association of telemedicine use with viral suppression. We implemented a multi-pronged intervention to increase telemedicine (particularly with video) and performed a prospective cohort study to evaluate this intervention. The intervention included: (1) provision of an easy-to-use video visit platform; (2) training on telemedicine best practices; (3) computer-based and support staff reminders to offer a choice of telephone or video telemedicine; (4) a telemedicine navigator; and (5) quarterly quality improvement meetings. We conducted baseline and endline surveys and chart reviews with a cohort of people living with HIV (PLHIV) to measure telemedicine use (including offer, uptake, and visit completion by modality) and changes in viral load. We used mixed effects regression models to evaluate the intervention's association with viral suppression over time (< 40 copies/mL). We enrolled 271 PLHIV between March and November 2022 and implemented the intervention from August 2022-October 2023. Telemedicine visits (telephone and video) in this cohort increased during the intervention period from 13% to 17% of all visits, with this increase predominantly driven by telephone visits. Clinicians' offer of telemedicine visits (based on participant report) varied, with 36% of clients offered both telephone and video visits during the intervention period, 36% offered telephone visits only, and 28% not offered any telemedicine. Visit completion was highest for telephone visits (82%) and lower for video (58%) and in-person (57%) visits. Viral suppression rates were not significantly different from baseline to endline, regardless of telemedicine use: 71.0% to 77.5% in non-users (p = 0.26) and 83.8% to 81.0% (p = 0.19) in users. Our intervention increased the use of telemedicine, predominantly delivered as telephone visits. Additional research is needed on the impact of telemedicine on care engagement over time, on viral suppression over longer follow-up, and on strategies to increase utilization of video visits for PLHIV cared for in FQHC settings.
We sought to determine the pro-apoptotic effects of bevacizumab in glioblastoma (GBM) and to elucidate the contribution of the miR-4695-5p/PKMYT1 pathway to this process. Following treatment of U87MG and U251 GBM cells with dose-gradient bevacizumab, cellular responses were evaluated by measuring apoptosis (flow cytometry) and proliferation (CCK-8), while RT-qPCR quantified changes in miR-4695-5p, Bax, and Bcl-2 expression. PKMYT1, bioinformatically predicted as a downstream target of miR-4695-5p, was verified via luciferase reporter assays. The functional link between miR-4695-5p and PKMYT1 was established using miRNA mimics and PKMYT1 overexpression rescue experiments. The critical role of this pathway in bevacizumab-induced apoptosis was ultimately confirmed by co-treating cells with bevacizumab and either a miR-4695-5p inhibitor or a PKMYT1 overexpression vector. Bevacizumab induced apoptosis in GBM cells U87MG and U251 in a dose-dependent manner. After bevacizumab treatment, the expression level of miR-4695-5p increased, and inhibiting miR-4695-5p expression reduced the pro-apoptotic effect of bevacizumab on U87MG and U251 cells. miR-4695-5p could target and inhibit PKMYT1 expression. Overexpression of PKMYT1 suppressed the pro-apoptotic effect of bevacizumab on U87MG and U251 cells, indicating that bevacizumab induces apoptosis in GBM cells by upregulating miR-4695-5p to target and inhibit PKMYT1. This study reveals the role and mechanism of bevacizumab in inducing apoptosis in GBM cells, namely by upregulating miR-4695-5p expression to target and inhibit the expression of the anti-apoptotic protein PKMYT1, thereby inducing apoptosis in GBM cells. This provides new directions and targets for research and treatment of gliomas.
Mounting evidence points to a potential link between statin therapy and erectile dysfunction (ED). However, the underlying mechanisms remain elusive, particularly concerning potential statin disruption of the inflammatory and immunofibrotic microenvironment within erectile tissue. This study sought to elucidate statin-associated ED and identify key molecular and cellular mediators driving this process. An integrative strategy merging real-world pharmacovigilance, network pharmacology, and toxicological analyses was deployed to explore drug-associated ED. Drug-related and disease-associated targets were intersected and scrutinized using protein-protein interaction (PPI) networks to pinpoint key regulatory genes. Gene expression patterns were evaluated through bioinformatics analyses and validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Molecular docking and molecular dynamics (MD) simulations assessed drug-target interaction stability. Furthermore, single-cell RNA sequencing (scRNA-seq) analysis characterized cell-type-specific alterations and intercellular communication dynamics within erectile tissue. Disproportionality analysis identified atorvastatin (ROR = 3.36, 95% CI = 3.04-3.70) and rosuvastatin (ROR = 3.22, 95% CI = 2.81-3.69) as statins significantly linked to ED, exhibiting moderate predicted toxicity. Four key genes-FGFR1, SERPINE1, TGFB2, and TGFBR2-emerged as potential mediators connecting statin exposure to ED. FGFR1 expression plunged significantly, while SERPINE1 expression surged markedly in ED samples, findings consistently observed in both transcriptomic analyses and RT-qPCR validation. Molecular docking and MD simulations demonstrated stable binding between atorvastatin and FGFR1. Notably, scRNA-seq analysis revealed fibroblasts as central immunomodulatory cells in ED, with their intercellular communication dysregulation closely related to the abnormal activation of the FGFR1 axis, which further mediates the local immunofibrotic disorder of the corpus cavernosum. This study delivers convergent evidence that atorvastatin and rosuvastatin associate with ED and implicates dysregulated inflammatory and immunofibrotic remodeling of erectile tissue as a potential underlying mechanism. The identified key genes and fibroblast-centered cellular interactions yield fresh insights into statin-associated ED and highlight promising molecular targets for future translational and immunomodulatory therapeutic strategies.