bluuebunny/crossref_metadata_2025 huggingface dataset:
Progressive Multicomponent Intervention for Older Adults in Home Health Settings Following Hospitalization: Randomized Clinical Trial
Authors: Garbin Alexander J , Falvey Jason R , Cumbler Ethan , Derlein Danielle , Currier Deborah , Nordon-Craft Amy , Will Robert , Olivos Maegan , Forster Jeri E , Mangione Kathleen K , Stevens-Lapsley Jennifer E
Published: December 2024

Objectives

Reduced physical function following hospitalization places older adults at risk of adverse health events. Many older adults receive home health physical therapy to reverse their deconditioning; however, optimal approaches to improve physical function are currently not known. This study aimed to evaluate the effectiveness of a home health care approach comprised of high-intensity exercise, enhanced care transition, and protein supplementation.

Methods

Eligible participants included adults aged 65 years or older referred to home health care following hospitalization. Two hundred older adults who are medically complex were enrolled and were randomized 1:1 to (1) a high-intensity progressive, multi-component (PMC) intervention or (2) enhanced usual care (UC) comparison group. All participants received 12 visits over 60 days. The primary study outcome was change in the Short Physical Performance Battery (SPPB) from baseline to 60 days. Secondary outcomes included gait speed (usual, fast), modified Physical Performance Test, grip strength, Fatigue Severity Scale, Falls Efficacy Scale-International, physical activity (step count), and adverse events (falls, emergency department visits, hospitalizations). All outcomes were collected at baseline, then 30, 60, 90, and 180 days post baseline.

Results

There was no difference in 60-day SPPB change between groups with both groups experiencing significant improvements (PMC = 1.53 [95% CI: 1.00–2.05]; enhanced UC = 1.39 [95% CI = 0.89–1.88]). Differences were also not observed in secondary measures or adverse events at any time point.

Conclusion

An intervention consisting of high-intensity exercise, enhanced care transition, and protein supplementation was not associated with greater functional improvement at 60 days compared to enhanced UC in older adults receiving home health physical therapy.

Impact

The findings of this study demonstrate that a high-intensity progressive, multi-component intervention results in similar physical functional changes as an enhanced UC intervention in older adults who are medically complex and receiving home health care following hospital-associated deconditioning.
Comparison of melanocortin-4 reptor and α-melanoside stimulated hormone levels in healthy female volunteers and female patients with and without sexual functional disorders related to the use of selective serotonin reaptake inhibitors
Authors: Kurt Kaya Simge N , Safak Yasir , Ozdemir Seyda
Published: December 2024

Background

Sexual dysfunction (SD) due to Selective Serotonin Reuptake Inhibitors (SSRI) use is a common condition encountered by psychiatrists and its etiology has not been fully elucidated.

Aim

To determine the relationship between alpha Melanocyte Stimulating Hormone (α-MSH) and Melanocortin-4 receptor (MCR4) levels and sexual function levels of patients with and without SSRI related SD and control group and to examine whether α-MSH and MCR4 play a role in the etiology of SSRI related SD.

Methods

A total of 92 patients and 49 healthy volunteers who applied to psychiatry outpatient clinic were included in the study. Sociodemographic form, sexual history form, Structured Clinical Interview for DSM 5, Psychotropic Related Sexual Dysfunction-Turkish version (PreSexDQ-T), Arizona Sexual Experiences Scale, Beck Depression and Anxiety Inventory were used in the evaluation interview with the referred patients. Patient groups were formed according to whether there was SSRI related SD according to the sexual history and PreSexDQ-T scale.

Outcomes

The α-MSH and MCR4 levels were significantly lower in patients with SD due to SSRI use.

Results

α-MSH and MCR4 levels were lower in the SSRI related SD (SSRI-SD (+)) group than in the not experiencing SD with SSRIs (SSRI-SD (–)) and control groups. The mean α-MSH and MCR4 value of the control group was found to be significantly higher than the SSRI-SD (+) patient group, the mean MCR4 value of the control group was found to be significantly higher than the mean MCR4 value of the SSRI-SD (–) patient group. The mean MCR4 and a-MSH values of the SSRI-SD(+) group using SSRI with fluoxetine were significantly lower than the SSRI-SD (–) group using SSRI with fluoxetine.

Clinical implications

There is a role for α-MSH and MCR4 in SSRI related SD.

Strengths and limitations

Its strength is that it is the first human study in this field. Limitations include small sample size and unknown baseline levels of α-MSH and MCR4.

Conclusion

The fact that α-MSH and MCR4 play a role in the etiology of SD due to SSRI use in woman and that there was a significant difference between SSRI-SD (+) and SSRI-SD (–) groups when α-MSH and MCR4 levels were compared in fluoxetine users supports the hypothesis that serotonin may mediate SD via α-MSH and MCR4 through 5-hydroxytryptamine-2C (5-HT2C) antagonism.
Unveiling the Diversity and Virulence of Seedborne Fusarium Species in Lentil Production: Insights from a Two-Year Study in the Northern Great Plains
Authors: Bugingo Collins , Brelsford Monica , Burrows Mary , Fonseka Dimitri L. , Pasche Julie
Published: December 2024

Fusarium root rot/wilt caused by various Fusarium spp. significantly threatens lentil (Lens culinaris Medikus) production in the Northern Great Plains (NGP) region. However, the specific composition of seedborne Fusarium spp. causing this disease is not well understood. To address this gap, we conducted a comprehensive study spanning 2019 and 2020, collecting lentil seeds from 75 commercial fields across Montana, North Dakota, Washington, Idaho, and Ontario. Our analysis focused on both externalized and internalized pathogens, with particular attention to Fusarium spp., employing morphological and molecular techniques for identification. In total, 486 and 228 Fusarium isolates were recovered in 2019 and 2020, respectively. Predominant species included F. equiseti, F. acuminatum, F. oxysporum, F. tricinctum, F. graminearum, F. proliferatum, F. redolens, F. avenaceum, and F. sporotrichioides. Virulence studies conducted in the greenhouse revealed varying levels of aggressiveness among Fusarium spp., with F. sporotrichioides, F. oxysporum, and F. graminearum demonstrating the highest virulence. Further investigation into pathogen internalization within seed lots revealed that incidence was highest in the seed coat, followed by the cotyledon, with the lowest occurrence in the embryo. F. avenaceum was prevalently isolated from the seed coat, cotyledon and embryo. Additionally, Fusarium spp. isolated from the seed coat and cotyledon exhibited higher virulence and greater diversity compared to those from the embryo. This study reports the first comprehensive assessment of both externalized and internalized seedborne Fusarium spp. in the NGP region. The insights gained from our findings will inform the development of targeted management strategies for Fusarium root rot/wilt, ultimately aiding in the preservation of lentil crop health and productivity in the NGP and beyond.
Outcomes of a Novel Autografting Procedure Combining Two Synergistic Techniques in One Stage for Improved Wound Healing: Two Case Reports
Authors: Davenport Thomas , Stavrides Steve , Agrawal Aniket , Borrelli Mimi R.
Published: December 2024

Hard-to-heal wounds represent a global and growing medical and economic burden. Skin autografting is a useful treatment option but is often limited by donor site morbidity, logistical considerations, and grafting success in compromised wound beds. Combining autologous skin cell suspension (ASCS) technology with minced dermal grafts can allow for dermal elements and epithelial healing as well as closed donor sites. This study explores the combination of minced autografting with ASCS in healing recalcitrant wounds. Two patients with diabetic foot ulcers (DFUs) whose previous skin grafting had failed were included. Under local anesthesia, donor skin was harvested as a full-thickness ellipse and divided into a superficial split-thickness graft (STSG) and a dermal autograft. ASCS was prepared from the STSG, and the dermal component was finely minced using a scalpel. Prepared wound beds were directly dressed with Telfa clear and compression dressings. Patients included a 62-year-old man with a DFU (15 cm2) on the left plantar heel present for 2 years, and a 53-year-old man with a DFU (10 cm2) on the plantar surface of the first metatarsal head present for 2 years. After combination treatment, complete closure was achieved by days 27 and 24, respectively. There was evidence of continued remodeling and skin thickening for the following 4 months. Combining dermal mincing with ASCS promotes healing of both dermal and epidermal layers while enabling primary closure of donor sites. These initial cases are encouraging, and ongoing studies are validating outcomes in more patients with various hard-to heal wounds.
Randomized Controlled Trial: Acquisition of Basic Microsurgical Skills Through Smartphone Training Model
Authors: De Fré Maxime , Verstreken Andreas , Vermeersch Nicolas , Vissers Gino , Verhoeven Veronique , Sener Süleyman , Verstreken Frederik , Menovsky Tomas , Tondu Thierry , Thiessen Filip E.F.
Published: December 2024

Background:

Microsurgery is essential in various surgical specialties, but learning these skills is challenging due to work hour limitations, patient safety concerns, documentation time, and ethical objections to practicing on live animals. This randomized controlled trial compares 2 microsurgical training models: the smartphone model and the microscope model.

Methods:

Thirty students without prior microsurgery experience were randomized into 3 groups: control (CG), smartphone (SG), and microscope (MG). Participants performed microsurgical skill tests and a chicken femoral artery anastomosis before and after 10 hours of standardized training according to their assigned models. The CG performed the test twice without training. Performance was assessed by time to complete the anastomosis, University of Western Ontario Microsurgery Skills Assessment scale, anastomosis patency, and time to complete the round-the-clock test.

Results:

No significant differences were observed among groups at baseline. Significant improvement in anastomosis time was achieved in the MG (27.4 minutes, P = 0.005) and SG (27.0 minutes, P = 0.005), but not in the CG (13.1 minutes, P = 0.161). On the University of Western Ontario scale, the MG improved by 6.0 points (P = 0.002), the SG by 5.1 points (P = 0.006), and the CG by 2.4 points (P = 0.009). Patency rate significantly improved in the MG and SG (P = 0.002) but not the CG (P = 0.264). Round-the-clock time improved in all groups (P < 0.001).

Conclusions:

Basic microsurgical skills can be effectively learned using the smartphone training model, with performance improvements comparable to the microscope model. Its main limitation is the lack of stereoscopy.
Orbital Bone Fracture Repair Evaluation Through 3-Dimensional Computational Reconstruction and Orbital Volumetric Assessment
Authors: Passaglia Igor R. G. , Bastos Endrigo O. , Moura Lucas B. , Secanho Murilo S. , Alonso Nivaldo
Published: December 2024

Background:

Three-dimensional (3D) models generated from computed tomography (CT) images efficiently and accurately complement surgical comprehension. Additionally, computer modeling provides a substrate for comparative analysis of the treated orbit volume. This study aimed to investigate cases of orbital bone fractures with regard to orbital-defect correction, through 3D computational structural modeling and evaluation of orbital volume.

Methods:

A total of 136 cases of orbital fractures with a diagnosis and surgical treatment were identified, of which 15 were selected based on inclusion and exclusion criteria. The construction of the preoperative and postoperative 3D models was based on CT images, supported by a medical imaging design system; this technique enabled the calculation of orbital volumetric measurements with the normal contralateral orbit as a reference.

Results:

Three-dimensional modeling in the preoperative and postoperative periods was performed for each patient. This study revealed that (1) preoperatively, the affected side had greater volume followed by postoperative reduction and (2) after surgical correction, the affected side had smaller volume and was equivalent to the unaffected side. However, there were no statistically significant differences between the periods (preoperative and postoperative) with regard to the mean and distribution of orbital volume or between the mean orbital volumes of the 2 sides.

Conclusions:

Using 3D computer modeling of bone structures, it is possible to evaluate orbital bone fractures after surgical correction. The effectiveness of preoperative and postoperative treatments was confirmed by comparing orbital volumetrics. It was not possible to assess soft tissues due to postoperative edema.
2019-2023 National drug registration analysis and research on drug development trends in Jiangxi Province
Authors: Duan Fangmei , Zhang Zhaoxia , Xiong Zhenqiu , Zha Wenjing , Guan Yongmei , Nie Heyun , Luo Jing
Published: December 2024

Objective:

To summarize and analyze the analysis of drug registration review in China and Jiangxi Province from 2019 to 2023, and to conduct statistical analysis and evaluation based on the data of drug registration applications, which is an important reference for the revision of relevant policies for drug research re-evaluation in Jiangxi Province.

Methods:

Mathematical statistical methods were used to analyze and evaluate the drug acceptance, registration application type and application area published on the website of the Center for Drug Evaluation of the National Medical Products Administration. In doing so, the results of the analysis are presented in an intuitive chart with the help of ChartCool Tool, a professional charting tool.

Results:

In 2023, a total of 13,144 drug registration applications were accepted nationwide. Compared with previous years, the number of drug registration applications accepted in the country and Jiangxi Province has shown an increasing trend. Compared with previous years, the proportion of drug registration applications accepted in Jiangxi Province is increasing, with a large number of applications for traditional Chinese medicine and chemical drugs, and an increase in the number of applications for innovative drugs, mainly involving tumors, cardiovascular and other fields.

Conclusion:

By analyzing the drug registration review situation in the country and Jiangxi Province in 2023, the enthusiasm for drug R&D and registration applications continues to rise, and the number of drug registration applications accepted in the country and Jiangxi Province shows an increasing trend.
Derived Neutrophil-to-Lymphocyte and Neutrophil-to-Platelet Ratios Distinguish Sinusitis-Related Orbital Cellulitis From Periorbital Necrotizing Fasciitis
Authors: Wladis Edward J. , LeSage Colin , Paez Maria , Grube Jordon G. , Pokabla Michael J. , Adam Alejandro P.
Published: December 2024

Purpose:

Periorbital necrotizing fasciitis (NF) and sinusitis-related orbital cellulitis (OC) present with common clinical features, although the management algorithms for these ailments vary considerably. Previous investigations have failed to identify biomarkers that distinguish between these entities. This study was designed to explore the role of the derived neutrophil-to-lymphocyte and neutrophil-to-platelet ratios in discerning NF from OC.

Methods:

The derived neutrophil-to-lymphocyte and neutrophil-to-platelet ratios were calculated in nonimmunocompromised adult patients with NF and OC from the first blood draw upon presentation to the emergency department at a single academic medical center. Mann–Whitney nonparametric analyses and the area under the receiver-operator curve were analyzed via a dedicated computerized software package.

Results:

A total of 16 patients with NF (mean age = 54.5 years) and 12 patients with OC (mean age = 50.8 years) were identified. The mean derived neutrophil-to-lymphocyte ratios were 5.74 (standard deviation = 4.20) and 2.36 (standard deviation = 1.75) for NF and OC, respectively (p = 0.0037), resulting in an area under the receiver-operator curve of 0.82 (95% confidence interval = 0.66–0.98). The mean neutrophil-to-platelet ratios were 0.073 (standard deviation = 0.044) and 0.020 (standard deviation = 0.0084) for NF and OC, respectively (p < 0.001), yielding an area under the receiver-operator curve of 0.92 (95% confidence interval = 0.80–1.00).

Conclusions:

In nonimmunocompromised adult patients, the derived neutrophil-to-lymphocyte ratio and neutrophil-to-platelet ratio both appear to distinguish NF from OC. While further study is required in larger cohorts to ensure the robustness of these findings, these initial results suggest that these biomarkers may be coupled with appropriate examinations to diagnose patients with these conditions and initiate the appropriate steps in the management of patients with orbital infectious disease.
Presentation of Orbital Metastases
Authors: Nghiem Allan Z. , Islam Meriam , Goh Li Yen , Sawhney Amrita , Vahdani Kaveh , Rose Geoffrey E.
Published: December 2024

Purpose:

To compare clinical characteristics of patients with and without a known systemic malignancy at the time of diagnosis of orbital metastases.

Methods:

Retrospective case note and imaging review for patients with orbital metastases presenting between 1980 and 2022. Patients were classified as having known malignancy at orbital presentation (group I) or without known malignancy (group II).

Results:

Of 159 patients with orbital metastases, breast cancer was the commonest (77/159; 48%), followed by neuroendocrine tumors (10%), melanoma (7%), and lung or prostate cancers (5% of each); cancers with unknown primary site comprised 11%. There were 105/159 (66%) group I patients with known primary tumor, their having more females (79% group I vs. 61% group II; p = 0.02), breast cancers (58% vs.30%; p = 0.0004), and melanomas (10% vs. 0%; p = 0.02). Compared with group II, group I had a lower rate of globe dystopia (21% vs. 38%; p = 0.03) and fewer extraconal lesions (33% vs. 50%; p = 0.05), but more involvement of the posterior third of the orbit (21% vs. 6%; p = 0.03). Imaging revealed a distinct orbital mass in 74%, with breast cancer often presenting as ill-defined or infiltrative lesions (29%).

Conclusion:

Most orbital metastases originate from breast, neuroendocrine tumors, or melanoma, with about a third presenting before a primary systemic malignancy is detected. Those from breast and melanoma were more frequent in patients with a known primary tumor. Symptoms and signs were similar in patients with or without known systemic tumor at the time of orbital presentation, and most presented with features due to a mass effect.
Converging inputs compete at the lateral parabrachial nuclei to dictate the affective-motivational responses to cold pain
Authors: Reddy Prannay , Narayan Prajapati Jagat , Chaterji Shrivas , Varughese Austin , Chaudhary Yatika , Sathyamurthy Anupama , Barik Arnab
Published: December 2024

The neural mechanisms of the affective-motivational symptoms of chronic pain are poorly understood. In chronic pain, our innate coping mechanisms fail to provide relief. Hence, these behaviors are manifested at higher frequencies. In laboratory animals, such as mice and rats, licking the affected areas is a behavioral coping mechanism and it is sensitized in chronic pain. Hence, we have focused on delineating the brain circuits mediating licking in mice with chemotherapy-induced peripheral neuropathy (CIPN). Mice with CIPN develop intense cold hypersensitivity and lick their paws upon contact with cold stimuli. We studied how the lateral parabrachial nucleus (LPBN) neurons facilitate licking behavior when mice are exposed to noxious thermal stimuli. Taking advantage of transsynaptic viral, optogenetic, and chemogenetic strategies, we observed that the LPBN neurons become hypersensitive to cold in mice with CIPN and facilitate licks. Furthermore, we found that the expression of licks depends on competing excitatory and inhibitory inputs from the spinal cord and lateral hypothalamus (LHA), respectively. We anatomically traced the postsynaptic targets of the spinal cord and LHA in the LPBN and found that they synapse onto overlapping populations. Activation of this LPBN population was sufficient to promote licking due to cold allodynia. In sum, our data indicate that the nociceptive inputs from the spinal cord and information on brain states from the hypothalamus impinge on overlapping LPBN populations to modulate their activity and, in turn, regulate the elevated affective-motivational responses in CIPN.
Posttraumatic hyperalgesia and associated peripheral sensitization after temporomandibular joint injury in mice
Authors: Alshanqiti Ishraq , Son Hyeonwi , Shannonhouse John , Hu Jiaxin , Kumari Sinu , Parastooei Ghazaal , Raman Swarnalakshmi , Wang Sheng , Ro Jin Y. , Kim Yu Shin , Chung Man-Kyo
Published: December 2024

Temporomandibular disorder (TMD) is the most prevalent painful condition in the craniofacial area. Recent studies have suggested that external or intrinsic trauma to the temporomandibular joint (TMJ) is associated with the onset of painful TMD in patients. Here, we investigated the effects of TMJ trauma through forced-mouth opening (FMO) in mice to determine pain behaviors and peripheral sensitization of trigeminal nociceptors in both sexes. Forced-mouth opening increased mechanical pain as assessed by the von Frey test, with spontaneous pain-like behaviors assessed using the mouse grimace scale and anxiety-like behaviors assessed using the open-field test. Changes in pain-like behaviors were not different between male and female mice. However, in vivo GCaMP Ca2+ imaging of intact trigeminal ganglia (TG) showed modality- and sex-dependent changes. Forced-mouth opening increased spontaneous Ca2+ responses and mechanical hypersensitivity of TG neurons compared to the sham group, which was more pronounced in male mice. Forced-mouth opening also increased Ca2+ responses evoked by cold, heat, and capsaicin stimuli, which was not different between the sexes. In retrogradely labeled trigeminal TMJ afferents, FMO induced an increase in small-sized neuronal proportions with increased colocalization with calcitonin gene–related peptides and transient receptor potential vanilloid subtype 1, which was modestly sex dependent. These results suggest that TMJ injury leads to persistent posttraumatic hyperalgesia associated with peripheral sensitization of trigeminal nociceptors with distinct sex dependency.
Neurotoxic effects of the chemotherapeutic drug “methotrexate”: a literature review
Authors: Mshaymesh Sarah
Published: December 2024

Introduction:

Methotrexate (MTX) is currently considered the go-to drug in chemotherapy, although it possesses neurological dangers. In this review paper, research and records of MTX-induced neurotoxicity in different types of adult and pediatric cancers will be discussed. The general description and function of MTX are still not completely known. How biological ratios in the body fluctuate with low and high methotrexate doses are still unknown as well. Therefore, this is a hot topic for experts, especially those active in neuro-oncology research. Scientists and physicians are now using different protocols to understand, control, manage, and prevent MTX-neurotoxic events.

Aim:

By evaluating various studies, case reports, and clinical trials, this comprehensive review seeks to clarify the mechanisms underlying MTX-induced neurotoxicity, highlight potential strategies for prevention and management, and guide future research in mitigating the adverse neurological effects of MTX treatment.

Methods:

Several databases were employed to gather this information, mainly PubMed.

Results:

The precise mechanisms of MTX-induced neurotoxicity remain unclear. Multiple hypotheses suggest involvement of genes related to neurogenesis, but no definitive cause has been identified. Regular patient monitoring, long-term follow-up, variable therapies, and early MRI detection are recommended.

Conclusion:

Despite advancements, no longitudinal studies have conclusively determined effective strategies to prevent MTX-induced neurotoxicity. Demographic factors and cancer types do not consistently predict neurotoxicity. Future research should focus on genetic counseling prior to chemotherapy, targeted monitoring protocols, and long-term patient follow-up to better understand and mitigate the neurotoxic impacts of MTX. Pharmacokinetics and advanced neuroimaging techniques are also essential for improving patient outcomes.
Nurses as Human Capital, Not Human Resources
Authors: Drenkard Karen
Published: December 2024

Determining the economic value of nursing is a pivotal paradigm shift that needs to take place to transform healthcare. It is essential to recognize that nurses' interventions are fundamental to improving patient outcomes and enhancing the efficiency of the entire healthcare system. Nursing services should be seen as human capital worthy of investment versus human resources that are expendable.
HPV Vaccination and Awareness Programs at Maryland Colleges and Universities
Authors: Soori Mehrnoosh , D’Souza Gypsyamber , Mattingly Brian , Kanarek Norma
Published: December 2024

Context:

About half of adolescents aged 13 to 17 in United States are not fully vaccinated against human papillomavirus (HPV). As they age into young adulthood, colleges may be an excellent target population nexus for implementing interventions to improve HPV vaccination uptake.

Objectives:

Our study goal was to generate knowledge about HPV vaccine offerings and awareness programs at colleges to ascertain the extent of campus-facilitated access to HPV immunization and education in 1 state.

Design:

An electronic survey was designed and emailed to 32 of 47 Maryland colleges for which relevant campus contacts could be identified.

Settings:

The study took place at Johns Hopkins Bloomberg School of Public Health in consultation with the Maryland Cancer Collaborative and the Maryland Department of Health.

Participants:

Maryland colleges and universities

Main Outcome Measures:

HPV vaccine and awareness program offerings on college and university campuses.

Results:

Twenty Maryland colleges responded. Two colleges offer awareness programs only. Ten colleges offer HPV vaccine, covering about 39% of Maryland college students. Of these, 4 colleges schedule “periodic” campus health clinics or provide an immunization prescription, which is filled at nearby pharmacies. In all colleges, which offer HPV vaccine, immunization is offered to everyone (both men and women) at no out-of-pocket cost.

Conclusions:

In cooperation with the Maryland Cancer Collaborative, the implementation arm for the Maryland Cancer Control Plan, we showed that college campuses are an excellent target site for implementation of interventions to improve access of college age students to HPV vaccine and awareness programs. We lay the groundwork for recommendations, programs and policies that can improve HPV vaccine offerings among college students thus raising the HPV vaccination rate in young adults. Simple inexpensive alternatives to offering vaccine at college health centers may be periodic campus health clinics and arrangements with nearby pharmacies.
An Analysis on the Impact of Childhood Adversity, Anxiety, and C-Reactive Protein on Adult Chronic Pain in the Midlife in the United States (MIDUS) Study
Authors: Dalechek Danielle E. , Caes Line , McIntosh Gwenne , Whittaker Anna C.
Published: December 2024

Objective

This study used the Midlife-Development in the United States (MIDUS) dataset to a) examine relationships between reported childhood adversity (CA), anxiety, and pain; b) assess associations between CAs, anxiety, C-reactive protein (CRP) levels, and pain; and c) explore how CAs, anxiety, and CRP are associated with pain medication consumption.

Methods

Data were from Project-4 of MIDUS-II (n = 1225), which utilized Project-1 demographics and supplemental chart review. For objectives 1–2, structural equational modeling (SEM) followed by general linear modeling (GLM) regression was conducted. For objective 3, all variables from the objective 1–2 dataset were used as possible independent variables for the exploratory regression.

Results

For objectives 1–2, CRP was significantly correlated with anxiety, emotional abuse, physical neglect, and chronic pain (n = 1173). The SEM (n = 1173) indicated that CAs, anxiety, and CRP all played a role in predicting chronic pain. Regression results (n = 1173) indicated that gender, total income, and highest education were significant predictors of chronic pain. Significant interactions to explain chronic pain included physical abuse/emotional neglect, emotional abuse/physical abuse, physical abuse/minimization, physical neglect/education, CRP/income, and CRP/education. For objective 3 (n = 600), there were no significant main effects, but a large variety of interactions contributed to predicting pain medication consumption. CAs interacting significantly to explain this included emotional abuse/physical abuse, physical abuse/emotional neglect, physical abuse/minimization, and sexual abuse/minimization. There were also significant interactions between CRP/income and CRP/education.

Conclusions

Based on a large US sample, sociodemographics played a meaningful role in predicting chronic pain in adults, and CRP was significantly correlated with anxiety, emotional abuse, physical neglect, multiple sociodemographic variables, and chronic pain. The influence of CAs on predicting long-term medication use for chronic pain was complex and warrants further study.
Registered Reports in Biopsychosocial Science and Medicine: To Infinity and Beyond
Authors: O’Connor Daryl B.
Published: December 2024

In April 2023, Psychosomatic Medicine, now renamed Biopsychosocial Science and Medicine, introduced registered reports as a new article format. Registered reports are a type of scientific article in which the research methods and proposed analyses are preregistered and peer-reviewed before the data are collected or analyzed. We were excited to be joining a growing number of journals internationally to offer this format and to be aligning with the Behavioral Medicine Research Council’s statement on open science, recognizing the value of publishing registered reports in our field. Recent work has shown that there is a 2-year lag between journals adopting registered reports and publishing their first registered report. Therefore, right in line with this timetable, we are delighted to be publishing our first full registered report article in this first issue that bears the Journal’s new name. This article is noteworthy for several reasons, not least because the findings make an important scientific contribution to the broader early life adversity literature but also because the article applies the registered report format to secondary data analyses. We hope that you, our readership, feel inspired to give the registered report approach a chance, whether it is for primary or secondary data collection approaches, and that you send your first, or next Stage 1 registered report to Biopsychosocial Science and Medicine.
A Framework for the Analysis of Communication Errors in Health Care
Authors: Bender John A. , Thiyagarajan Sreedevi , Morrish Wendy , Mims Maisha , Yackel Edward E.
Published: December 2024

Objectives:

The goal of this study was to develop a systematic method to identify and classify different types of communication failures leading to patient safety events. We aimed to develop a taxonomy code sheet for identifying communication errors and provide a framework tool to classify the communication error types.

Methods:

This observational study used the Delphi method to develop a taxonomy code sheet for identifying communication errors reported in the Veterans Health Administration patient safety databases between April 2018 and March 2021. We also used Natural Language Processing to create a framework tool to classify the 9 types of communication errors using this taxonomy. Finally, analysis was done to identify affected clinical locations.

Results:

We identified 9 types of communication failures that impacted clinical outcomes using the taxonomy code sheet developed. The top 3 errors were related to nonadherence to facility standard operating procedures (993, 37.6%), followed by written errors (e.g., unclear documentation or not using plain language) (587, 22.3%) and no communication (347, 13.2%). The remaining categories of communication types are electronic (253, 9.6%), verbal (205, 7.8%), hand-off (124, 4.7%), visual (76, 2.9%), listening (41, 1.6%), and nonverbal (12, 0.5%). A cognitive aide was developed to demonstrate the step-by-step method for using the framework tool to classify the communication errors.

Conclusions:

The cognitive aide and the framework tool developed in this study can be used in any healthcare setting to identify and classify communication failures and mitigate potential risks contributing to safety events.
Uptake of HIV Preexposure Prophylaxis Among Medicare Beneficiaries — United States, 2014-2021
Authors: Huang Ya-Lin A. , Chang Man-Huei , Zhu Weiming , Hoover Karen W.
Published: December 2024

Background:

Previous studies have estimated preexposure prophylaxis (PrEP) use among persons with commercial health insurance and Medicaid. However, data are lacking regarding PrEP use among those with Medicare.

Methods:

Using a previously developed algorithm, we estimated the number of Medicare beneficiaries (MBs) with fee-for-service (FFS) claims who were prescribed PrEP from 2014 to 2021. The analysis was stratified by age, sex, and race/ethnicity. We also examined trends in PrEP prevalence by U.S. state and demographic characteristics during 2014-2021.

Results:

The number of Medicare PrEP users increased 11-fold, from 388 in 2014 to 4,685 in 2021. MBs prescribed PrEP were predominantly younger men, White persons, residing in the South or West regions, living with a disability, and dually eligible for both Medicare and Medicaid. The prevalence of PrEP prescriptions among MBs increased 12-fold, from 9.7 per million in 2014 to to 120.0 per million in 2021. Black/African American persons had the highest prevalence of PrEP use, followed by Hispanic/Latino and White persons in 2021. The District of Columbia had the highest prevalence of PrEP use compared with other U.S. states in 2021. Significant increasing trends in PrEP use were observed across sex, age groups, and race/ethnicity.

Conclusions:

Disparities in PrEP uptake existed across MB demographic subgroups from 2014 to 2021. Public health interventions are needed to increase PrEP access and utilization, particularly among women, younger MBs, Black persons, and Hispanic persons, including those with Medicare. Strategies and policies to expand PrEP use are essential for optimal HIV prevention in the United States.
Potential role of Gut Bacteria in the development of hepatocellular carcinoma
Authors: Yan bingqing , Wang Yuchao , Wang Ziqi , Huang Ailong , Jin Xiuxiu , Jiang Tiantian , Xue Hong , Shen Zheyu , Wang Shifang , Xu Haiyan , Zhu Renfei
Published: December 2024

Liver cancer is the fourth most deadly cancer and early detection and timely treatment apparently play a crucial role in it. Intestinal bacteria affect the development of liver cancer through various pathways. In this study, the gut bacteria of liver cancer patients is analyzed in detail by using macro-genome sequencing technology, and some of the bacterial species and metabolic pathways that may affect the development of liver cancer have been identified, in addition, the bacterial factors that may affect the tumor size and other important clinical indicators have also been identified, which provides a scientific basis for the research related to the development of liver cancer and new insights for the clinical treatment of liver cancer.
Strategies for robust, accurate, and generalizable benchmarking of drug discovery platforms
Authors: Van Norden Melissa , Mangione William , Falls Zackary , Samudrala Ram
Published: December 2024

Benchmarking is an important step in the improvement, assessment, and comparison of the performance of drug discovery platforms and technologies. We revised the existing benchmarking protocols in our Computational Analysis of Novel Drug Opportunities (CANDO) multiscale therapeutic discovery platform to improve utility and performance. We optimized multiple parameters used in drug candidate prediction and assessment with these updated benchmarking protocols. CANDO ranked 7.4% of known drugs in the top 10 compounds for their respective diseases/indications based on drug-indication associations/mappings obtained from the Comparative Toxicogenomics Database (CTD) using these optimized parameters. This increased to 12.1% when drug-indication mappings were obtained from the Therapeutic Targets Database. Performance on an indication was weakly correlated (Spearman correlation coefficient>0.3) with indication size (number of drugs associated with an indication) and moderately correlated (correlation coefficient>0.5) with compound chemical similarity. There was also moderate correlation between our new and original benchmarking protocols when assessing performance per indication using each protocol. Benchmarking results were also dependent on the source of the drug-indication mapping used: a higher proportion of indication-associated drugs were recalled in the top 100 compounds when using the Therapeutic Targets Database (TTD), which only includes FDA-approved drug-indication associations (in contrast to the CTD, which includes associations drawn from the literature). We also created compbench, a publicly available head-to-head benchmarking protocol that allows consistent assessment and comparison of different drug discovery platforms. Using this protocol, we compared two pipelines for drug repurposing within CANDO; our primary pipeline outperformed another similarity-based pipeline still in development that clusters signatures based on their associated Gene Ontology terms. Our study sets a precedent for the complete, comprehensive, and comparable benchmarking of drug discovery platforms, resulting in more accurate drug candidate predictions.
Knock-inKcnh2Rabbit Model of Long QT Syndrome Type-2, Epilepsy, and Sudden Death
Authors: Singh Veronica , Wagner Kyle T. , Williams Laura G. , Ryan Justin M. , Keller Katherine R. , Mohnkern Jonathan D. , Gardner Robert S. , Dang Louis T. , Ziobro Julie M. , Wojcikiewicz Richard J. H. , Tucker Nathan R. , Auerbach David S.
Published: December 2024

Background

Long QT Syndrome Type-2 (LQT2) is due to loss-of-functionKCNH2variants.KCNH2encodes Kv11.1 that forms a delayed-rectifier potassium channel in the brain and heart. LQT2 is associated with arrhythmias, seizures, sudden cardiac death, and sudden unexpected death in epilepsy (SUDEP). The goal of the study is to develop a translational model that reproduces the neuro-cardiac electrical abnormalities and sudden death seen in people with LQT2.

Methods

We generated the first knock-in rabbit model of LQT2 (Kcnh2(+/7bp-del)), due to a 7 base-pair (7bp) deletion in the pore domain of the endogenous rabbitKcnh2gene.

Results

MutantKcnh2is expressed in the heart and brain and constitutes 11% of totalKcnh2inKcnh2(+/7bp-del)rabbits. TotalKcnh2, WTKcnh2, and WT Kv11.1 expression is lower inKcnh2(+/7bp-del)vs. WT rabbits.Kcnh2(+/7bp-del)rabbits exhibit prolonged cardiac ventricular repolarization (QTc, JTec, JTpc). There is an increased prevalence of spontaneous epileptiform activity and clinical seizures inKcnh2(+/7bp-del)(7 of 37 rabbits) vs. WT rabbits (1:68 rabbits,p<0.003). 18.9% ofKcnh2(+/7bp-del)vs. 1.5% of WT rabbits died suddenly and spontaneously (p<0.003). We recorded 2 spontaneous lethal events inKcnh2(+/7bp-del)rabbits: (1) sudden cardiac death and (2) seizure-mediated sudden death due to generalized tonic-clonic seizures, post-ictal generalized EEG suppression, bradycardia, ECG-T-wave inversion, focal cardiac activity, and asystole/death.

Conclusions

We developed the first genetic rabbit model of LQT2 that reproduces the cardiac and epileptic phenotypes seen in people with LQT2.Kcnh2(+/7bp-del)rabbits provide a valuable tool for future mechanistic studies, development of neurotherapeutics, and cardiac-safety testing.
Collaterals influence oxygen metabolism on admission MRI in acute ischemic stroke
Authors: Patural Paul , Bani-Sadr Alexandre , Riva Roberto , Frindel Carole , de Bourguignon Charles , Hermier Marc , Gamondes Delphine , Jupin-Delevaux Emilien , Derex Laurent , Cho Tae-Hee , Mechtouff Laura , Nighoghossian Norbert , Berthezene Yves
Published: December 2024

Introduction

This study aimed to correlate cerebral collateral status and MRI-derived oxygen metabolism at admission in acute ischemic stroke (AIS) patients treated with mechanical thrombectomy.

Methods

The HIBISCUS-STROKE cohort (CoHort of Patients to Identify Biological an Imaging markerS of CardiovascUlar Outcomes in Stroke; NCT: 03149705), a single-center observational study, enrolled AIS patients for thrombectomy following MRI triage due to anterior circulation large vessel occlusion treated with mechanical thrombectomy. Dynamic-Susceptibility Contrast perfusion (DSC perfusion), Diffusion-Weighted Imaging (DWI) and penumbral volume (Tmax ≥ 6 secs) were post-processed to generate oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) maps within DWI and penumbral anomalies, compared to contralateral areas. Collateral status, assessed via pretreatment digital subtraction angiography, was categorized as poor (0–2) or good (3–4) based on ASITN/SIR collateral grading system score from Higashida.

Results

Between October 2016 and October 2022, 321 participants were enrolled in the cohort. Of these, 184 (57.3%) were excluded due to missing admission DSC perfusion MRI in 61 patients and artifacts precluding collateral status evaluation on DSA. A total of 137 patients were included (mean age 71 years; 56.2% male). The median National Institutes of Health Stroke Scale (NIHSS) score was 15 (interquartile range [IQR]: 8.0–18.0), and the median time from symptom onset to admission was 96.0 minutes ([IQR]: 78.0–137.0). Patients with good collaterals (78) exhibited a smaller baseline infarct core (median 9.83 mL; (P<0.0001) less impairment cerebral blood flow (CBF) within the DWI lesion (median -65.89%; (P<0.0001), and less severe decrease CMRO2 within the ischemic penumbra (median -17.29%; (P=0.03). Good collaterals were independently associated with a smaller baseline infarct core volume and less decrease in CMRO2 within the ischemic penumbra (respectively OR = 0.94; 95% CI: [0.92; 0.96]; (P<0.0001), and (OR = 1.30; 95% CI: [1.06; 1.82]; P=0.001).

Conclusion

Good collaterals are associated with a smaller infarct core and better CMRO2 within the ischemic penumbra.
FAF2 is a bifunctional regulator of peroxisomal homeostasis and saturated lipid responses
Authors: Kim Choah , Gabriel Katlyn R. , Boone Dylan , Brown Matthew R. , Oppenheimer Katherine , Kost-Alimova Maria , Pablo Juan Lorenzo B. , Greka Anna
Published: December 2024

Exposure to saturated fatty acids (SFAs), such as palmitic acid, can lead to cellular metabolic dysfunction known as lipotoxicity. Although canonical adaptive metabolic processes like lipid storage or desaturation are known cellular responses to saturated fat exposure, the link between SFA metabolism and organellar biology remains an area of active inquiry. We performed a genome-wide CRISPR knockout screen in human epithelial cells to identify modulators of SFA toxicity. The screen revealed peroxisomal proteins, especially those that impact ether lipid synthesis, as important regulators of lipotoxicity. We identified Fas-associated factor family member 2 (FAF2) as a critical bifunctional co-regulator of peroxisomal and fatty acid biology. We further uncovered a new biological function for the ubiquitin-regulatory X (UBX) and UAS thioredoxin-like domains of FAF2, demonstrating their requirement for peroxisomal protein abundance and SFA-induced cellular stress. Our work highlights the role of FAF2 in regulating peroxisomal abundance and function, and the peroxisome as a key organelle in the cellular response to SFAs.
Thermal selection shifts genetic diversity and performance in blue mussel juveniles
Authors: Nascimento-Schulze Jennifer C. , Vajedsamiei Jahangir , Bean Tim P , Frankholz Lisa , Brennan Reid S. , Melzner Frank , Ellis Robert P
Published: December 2024

Mussels from the genus Mytilus, key inhabitants of the benthos, are important for the aquaculture industry and one of the most sustainable sources of animal protein available. Species within theMytilus eduliscomplex (M. edulis, M. galloprovincialisandM. trossulus) are commonly found in temperate regions globally and can easily hybridise whenever their geographic distributions overlap. In the Baltic Sea, populations are formed byM. edulisandM. trossulushybrids with low levels ofM. galloprovincialisintrogression. Given the economic and ecological relevance of mussels, this study aimed to investigate mechanisms through which their resilience towards global warming may be fast-tracked. For this, we developed two cohorts of juvenile mussels (i.e. recently settled animals) from the Baltic Sea (Kiel, Germany), one exposed to an extreme heat event early in life and one naïve to this stressor. Both cohorts were then exposed to experimental temperatures at the proposed upper thermal limit for this population, 21°C to 26°C, with animal performance measured after 25 days. We then assessed the impacts of thermal stress on the genetic composition of each cohort by genotyping 50 individuals using the blue mussel 60K SNP-array. We observed a significant increase inM. edulisgenotypes together with a decrease inM. trossulusin the S cohort in comparison with NS juveniles. We also found that exposure to high temperature has an effect on the performance of mussel cohorts, reducing dry tissue weight of the selected individuals. Results from this study provide relevant insights on how selection through thermal stress impacts performance and genetic composition of blue mussel juveniles, with key implications for understanding and managing mussel populations under future warming scenarios.
NRBP1 pseudokinase binds to and activates the WNK pathway in response to osmotic stress
Authors: Amnekar Ramchandra V , Dite Toby , Lis Pawel , Bell Sebastian , Brown Fiona , Johnson Clare , Wilkinson Stuart , Raggett Samantha , Dorward Mark , Wightman Mel , Macartney Thomas , Soares Renata F , Lamoliatte Frederic , Alessi Dario R
Published: December 2024

WNK family kinases are regulated by osmotic stress and control ion homeostasis by activating SPAK and OXSR1 kinases. Using a proximity ligation approach, we found that osmotic stress promotes the association of WNK1 with the NRBP1 pseudokinase and TSC22D2/4 adaptor proteins, results that are confirmed by immunoprecipitation and mass spectrometry and immunoblotting studies. NRBP1 pseudokinase is closely related to WNK isoforms and contains a RΦ-motif binding conserved C-terminal (CCT) domain, similar to the CCT domains in WNKs, SPAK and OXSR1. Knockdown or knock-out of NRBP1 markedly inhibited sorbitol-induced activation of WNK1 and downstream components. We demonstrate recombinant NRBP1 can directly induce the activation of WNK4in vitro. AlphaFold-3 modelling predicts that WNK1, SPAK, NRBP1, and TSC22D4 form a complex, in which two TSC22D4 RΦ-motifs interact with the CCTL1 domain of WNK1 and the CCT domain of NRBP1. Our data indicates NRBP1 functions as an upstream activator of the WNK pathway.

Teaser

NRBP1 functions as a scaffolding component regulating the assembly of a multi-subunit complex, required for the activation of the WNK Lysine Deficient Protein Kinase family in response to osmotic stress.

Graphical Abstract