bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Factors for De Novo Overactive Bladder After Midurethral Sling
Authors: Serna-Gallegos Tasha , Dutta Sonia , Crowder Carly , Wadensweiler Paul , Whitcomb Emily L. , Guaderrama Noelani M.
Published: April 2024

(Abstracted from Urogynecology 2024;30:59–64

The standard surgical treatment for stress urinary incontinence is midurethral sling (MUS) placement, due to its excellent efficacy, minimally invasive approach, and low overall rates of complication. However, development of de novo overactive bladder (OAB) symptoms is a known complication of anti-incontinence procedures and previously described as occurring in 5%–32% after fascial sling or Burch urethropexy.
Diagnosis, management and therapeutic options for eosinophilic esophagitis
Authors: Caminati Marco , Senna Gianenrico , Maule Matteo , Di Sabatino Antonio , Rossi Carlo Maria
Published: April 2024

Purpose of review

Eosinophilic esophagitis is a chronic and commonly evolving condition leading to relevant and potentially irreversible burden in terms of tissue damage and related functional impairment, thus significantly impacting on quality of life. The aim of the present review is to summarize the recent advances in terms of diagnostic work-up and pharmacological and nonpharmacological management of the disease, under the broader perspective of type 2 inflammation.

Recent findings

Two major novelties have prompted an innovative approach to EoE. In terms of diagnosis, it has been proposed to dissect the disease heterogeneity in three endotypes, independent from tissue eosinophil number: EoEe1, characterized by normal appearing oesophagus; EoEe2, associated with type 2 inflammation and steroid-refractoriness; EoEe3, whose features include adult onset, a more fibro-stenotic aspect and loss of epithelial gene expression. Concerning treatment, two recently licensed drugs for EoE, oro-dispersible budesonide and dupilumab represent the first treatment options specifically developed for EoE and addressing EoE-related peculiar pathobiological features.

In the era of precision medicine, managing EoE according to a phenotype-driven approach might be helpful in defining the best treatment options in the different disease forms or stages. In addition, exploring the coexistence or the previous occurrence of other type 2 conditions may suggest the opportunity to specifically target type 2 inflammation through biologic therapy. The complex EoE pathobiology combining inflammatory and functional features, both at organ and systemic level, requires a multidimensional approach relying on the strict integration of gastroenterologists and allergist-immunologists.
Global and Regional Heterogeneity of Lung Aeration in Neonates with Different Respiratory Disorders: A Physiologic Observational Study
Authors: Loi Barbara , Sartorius Victor , Vivalda Laura , Fardi Avand , Regiroli Giulia , Dellacà Raffaele , Ahsani-Nasab Sara , Vedovelli Luca , De Luca Daniele
Published: April 2024

Background

Aeration heterogeneity affects lung stress and influences outcomes in adults with acute respiratory distress syndrome (ARDS). The authors hypothesize that aeration heterogeneity may differ between neonatal respiratory disorders and is associated with oxygenation, so its evaluation may be relevant in managing respiratory support.

Methods

This was an observational prospective study. Neonates with respiratory distress syndrome, transient tachypnea of the neonate, evolving bronchopulmonary dysplasia, and neonatal ARDS were enrolled. Quantitative lung ultrasound and transcutaneous blood gas measurements were simultaneously performed. Global aeration heterogeneity (with its intra- and interpatient components) and regional aeration heterogeneity were primary outcomes; oxygenation metrics were the secondary outcomes.

Results

A total of 230 (50 respiratory distress syndrome, transient tachypnea of the neonate or evolving bronchopulmonary dysplasia, and 80 neonatal ARDS) patients were studied. Intrapatient aeration heterogeneity was higher in transient tachypnea of the neonate (mean ± SD, 61 ± 33%) and evolving bronchopulmonary dysplasia (mean ± SD, 57 ± 20%; P < 0.001), with distinctive aeration distributions. Interpatient aeration heterogeneity was high for all disorders (Gini–Simpson index, between 0.6 and 0.72) except respiratory distress syndrome (Gini–Simpson index, 0.5), whose heterogeneity was significantly lower than all others (P < 0.001). Neonatal ARDS and evolving bronchopulmonary dysplasia had the most diffuse injury and worst gas exchange metrics. Regional aeration heterogeneity was mostly localized in the upper anterior and posterior zones. Aeration heterogeneity and total lung aeration had an exponential relationship (P < 0.001; adj-R
2 = 0.62). Aeration heterogeneity is associated with greater total lung aeration (i.e., higher heterogeneity means a relatively higher proportion of normally aerated lung zones, thus greater aeration; P < 0.001; adj-R
2 = 0.83) and better oxygenation metrics upon multivariable analyses.

Conclusions

Global aeration heterogeneity and regional aeration heterogeneity differ among neonatal respiratory disorders. Transient tachypnea of the neonate and evolving bronchopulmonary dysplasia have the highest intrapatient aeration heterogeneity. Transient tachypnea of the neonate, evolving bronchopulmonary dysplasia, and neonatal ARDS have the highest interpatient aeration heterogeneity, but the latter two have the most diffuse injury and worst gas exchange. Higher aeration heterogeneity is associated with better total lung aeration and oxygenation.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
50 years of spondyloarthritis: a look back and a look ahead
Authors: Helliwell Philip S.
Published: April 2024

Purpose of review

It is now 50 years since the concept of spondyloarthritis was introduced by Moll, Wright and co-authors from Leeds, UK. This review will review the original concept and mark significant milestones over the last 50 years while looking ahead to developments in the future.

Recent findings

While the diseases included under this rubric in the original description may have changed the core conditions remain and are still characterized by axial inflammation as a common feature. Imaging, animal models, genetics and immunology have contributed to our knowledge of the pathogenesis and classification of these diseases and have led to the development of more effective treatments.

Future developments, facilitated by large research consortia, will help build on our current knowledge and will help clarify disease heterogeneity and provide insights into new therapeutic pathways.
Racial and Socioeconomic Disparities in Laminoplasty Versus Laminectomy With Fusion in Patients With Cervical Spondylosis
Authors: Hou Brian Q. , Croft Andrew J. , Vaughan Wilson E. , Davidson Claudia , Pennings Jacquelyn S. , Bowers Mitchell F. , Vickery Justin W. , Abtahi Amir M. , Gardocki Raymond J. , Lugo-Pico Julian G. , Zuckerman Scott L. , Stephens Byron F.
Published: April 2024

Study Design.

A retrospective cohort study using prospectively collected data.

Objective.

The aim of this study was to investigate preoperative differences in racial and socioeconomic factors in patients undergoing laminoplasty (LP) versus laminectomy and fusion (LF) for degenerative cervical myelopathy (DCM).

Summary of Background Data.

DCM is prevalent in the United States, requiring surgical intervention to prevent neurological degeneration. While LF is utilized more frequently, LP is an emerging alternative. Previous studies have demonstrated similar neurological outcomes for both procedures. However, treatment selection is primarily at the discretion of the surgeon and may be influenced by social determinants of health that impact surgical outcomes.

Materials and Methods.

The Quality Outcome Database (QOD), a national spine registry, was queried for adult patients who underwent either LP or LF for the management of DCM. Covariates associated with socioeconomic status, pain and disability, and demographic and medical history were collected. Multivariate logistic regression was performed to assess patient factors associated with undergoing LP versus LF.

Results.

Of 1673 DCM patients, 157 (9.4%) underwent LP and 1516 (90.6%) underwent LF. A significantly greater proportion of LP patients had private insurance (P<0.001), a greater than high school level education (P<0.001), were employed (P<0.001), and underwent primary surgery (P<0.001). LP patients reported significantly lower baseline neck/arm pain and Neck Disability Index (P<0.001). In the multivariate regression model, lower baseline neck pain [odds ratio (OR)=0.915, P=0.001], identifying as non-Caucasian (OR=2.082, P<0.032), being employed (OR=1.592, P=0.023), and having a greater than high school level education (OR=1.845, P<0.001) were associated with undergoing LP rather than LF.

Conclusions.

In DCM patients undergoing surgery, factors associated with patients undergoing LP versus LF included lower baseline neck pain, non-Caucasian race, higher education, and employment. While symptomatology may influence the decision to choose LP over LF, there may also be socioeconomic factors at play. The trend of more educated and employed patients undergoing LP warrants further investigation.
Distal Upper Extremity Arterial Calcification as a Predictor for Subclinical Coronary Artery Disease by Coronary Artery Calcium Scoring
Authors: Iskandarova Aygul , Rao Shiavax J. , Yohe Gabriel J. , Shah Ankit B. , Giladi Aviram M.
Published: April 2024

Several studies have linked calcification of the thoracic and lower extremity arterial trunks to an increased risk of developing coronary artery disease (CAD). Calcifications of the radial and/or ulnar artery are regularly identified in hand/wrist x-rays; however, the clinical relevance of these findings as related to identifying subclinical CAD is not well understood. Associations between CAD and upper extremity calcifications have been reported, but the timeline is unclear. The purpose of this study was to evaluate the association between upper extremity arterial calcifications on hand radiographs with CAD by coronary artery calcification (CAC) scoring in patients with no known history of CAD. This is a pilot single-center, prospective, matched cohort study. We included patients with no known history of CAD, related symptoms, or major risk factors. We recruited five patients with calcifications (cal+) and five patients matched by age, race, sex, and medical history but without calcifications (cal−). CAC scores were determined from computed tomography scanning, and lipid profile was evaluated. In the cal+ group, the mean CAC total score was 244.1; in the control (cal−) group, it was 85.2. The mean total cholesterol levels were 220.8 mg per dL and 167 mg per dL in the cal+ and cal− groups, respectively. Two cal+ patients with CAC scores of 937 and 669 died shortly after being enrolled in our study. Preliminary findings suggest that calcifications in the radial or ulnar artery in otherwise asymptomatic patients with no history of CAD may be an independent sign of CAD.
Modulation of Cellular Stemness for Enhanced Fat Grafting
Authors: Izadpanah Amin , Chaffin Abigail E. , Jansen David A. , Alt Eckhard U. , Izadpanah Reza
Published: April 2024

Low volumetric retention limits the utility of fat grafting. Although inclusion of stem cells and platelet-rich plasma have been proposed to enhance graft retention, accumulating evidence has failed to show a clear benefit. Here, we propose a strategy to pharmacologically enhance stemness of stem and progenitor cell populations in fat grafts to promote increased volume retention and tissue health. We also propose how to integrate stemness-promoting and differentiation-promoting therapies such as platelet-rich plasma, and viability promoting therapies within the common fat grafting workflow to achieve optimal fat grafting results.
Infectious Complications From Body Piercings—A Narrative Review
Authors: Peterson Christopher J. , Lee Benjamin , Lacy Mark
Published: April 2024

Body piercings are common methods of self-expression and cultural identity and have existed for millennia. However, breaching the dermis and insertion of a foreign object entails risk, including infectious complications. Although serious complications are typically rare, especially in environments where proper piercing techniques and sanitation are practiced, the general public and healthcare professionals may be unaware of the risk for these complications. Serious complications may include tissue necrosis, endocarditis, and brain abscesses. Selection of a proper piercing locale and professional, and the use of personal hygiene practices and piercing site care can go a long way toward preventing infections. Avoidance of especially risky piercing sites or techniques may also be advisable.
An Atypical Presentation of Pulmonary Mucormycosis
Authors: Divyashree Krishna , Singh Harpreet , Suri Vikas , Bhalla Ashish , Valliapan M , Sharma Aman , Singh Harkant , Chaluvashetty Sreedhar B. , Bal Amanjit
Published: April 2024

Mucormycosis is a life-threatening invasive fungal infection caused by fungi belonging to mucorales order. Manifestations vary from localized disease to disseminated infection. Various types of mucormycosis are rhino-orbito-cerebral, pulmonary, cutaneous, gastrointestinal, renal, and disseminated. Pulmonary form is more common in patients with solid organ transplant and post hematopoietic stem cell transplantation. Multimodality treatment is used in the form of aggressive antifungals, surgery where possible, and control of underlying disease/factors. Here, we present an unusual presentation of pulmonary mucormycosis successfully managed with liposomal amphotericin B and surgical lobectomy.
Baseline coronary artery stenosis severity is an independent predictor of subsequent poor sleep quality in patients with acute coronary syndrome
Authors: Yakut Idris , Kanal Yücel , Konte Hasan Can , Ozbay Mustafa Bilal , Yüksekkaya Baran , Celebi Ozlem Ozcan , Ozeke Ozcan , Aydoğdu Sinan
Published: April 2024

Aim

To investigate the relationship between coronary artery lesion severity determined using the baseline SYNTAX score and sleep problems that might occur after discharge determined using the Pittsburgh Sleep Quality Index (PSQI).

Methods

This prospective study included patients with first acute coronary syndrome (ACS) who underwent percutaneous coronary angiography between February 2019 and August 2019. The severity of coronary artery stenosis was classified according to coronary angiography and SYNTAX scores. Patients were grouped as those with a SYNTAX score of ≤22 and >22. Sleep quality after discharge was classified according to the PSQI. PSQI ≤5 represented good sleep quality, and PSQI >5 represented poor sleep quality. Univariate and multivariate logistic regression was used to investigate the relationship between sleep quality and coronary artery stenosis severity.

Results

A total of 424 patients were included in the study. Of these, 294 (69.34%) had a SYNTAX score of ≤22 and 130 (30.66%) had a SYNTAX score of >22. The mean age of all patients was 60.37 ± 12.23 years, 59.69 ± 11.85 years in the SYNTAX ≤22 groups and 61.90 ± 12.98 years in the SYNTAX >22 group (P = 0.086). The majority (78.54%) of the patients were male and there was no significant difference between the SYNTAX ≤22 group and the SYNTAX >22 group in terms of sex distribution (P = 0.383). According to the univariate logistic regression analysis, age (P = 0.014), diabetes (P = 0.027), left ventricular ejection fraction (P = 0.001), estimated glomerular filtration rate (P = 0.039), creatine kinase MB (P = 0.040) and SYNTAX scores (P < 0.001) were significantly associated with high PSQI global scores (>5). However, according to the multivariate logistic regression analysis results, high (>22) SYNTAX scores were the only factor independently associated with the high (>5) PSQI global scores [odds ratio, 3.477; 95% confidence interval (CI), (2.190–5.522); P < 0.001]. Complete revascularization group had significantly higher sleep latency and sleep duration time, sleep efficiency and the percentage of patients with PSQI global score of ≤5 than the incomplete revascularization group (P < 0.001 for all).

Conclusion

Among patients with ACS, those with high SYNTAX scores should be monitored more carefully for sleep disorders that may occur later.
Cardiovascular risk profile in two cohorts of young apparently healthy South Asian descendants in the Netherlands: still a long way to go!
Authors: Gobardhan Sanjay N. , Oemrawsingh Pranobe V. , Liem Su S. , Cannegieter Suzanne C. , Schalij Martin J.
Published: April 2024

Background

Cardiovascular disease (CVD) imposes a major healthcare burden on young descendants of South Asian migrants living in the western world. In comparison to the native population, the prevalence is significantly higher and the prevalence of CVD risk factors is increasing rapidly. The cardiovascular risk profile and 10-year risk scores of South Asian descendants were evaluated in two cohorts with a 10-year time difference.

Methods

Two cross-sectional studies, conducted in 2004 and 2014, focused on asymptomatic South Asian descendants aged 18–59 years were performed. A short questionnaire, BMI, waist circumference, blood pressure, and nonfasting blood tests were obtained. The cohort of 2014 was matched with the cohort of 2004, based on age, gender, and family history of CVD.

Results

In 2014, 674 South Asians (44% men, age 38.2 ± 12.0 years) were matched with 674 South Asians (44% men, age 38.3 ± 12.1 years) included in 2004. Notably, hypertension prevalence decreased significantly in 2014 (10.6% vs 23.1% in 2004, P < 0.001), while mean BMI increased (26.1 vs 24.9, P < 0.001). The mean Framingham risk score was lower in 2014 (5.31 ± 6.19%) than in 2004 (6.45 ± 8.02%, P < 0.05).

Conclusion

This study demonstrates that South Asian descendants in 2014 have a lower but still high absolute risk for coronary events compared to 2004. Important differences in cardiovascular risk profile exist. Despite improvements, South Asian descendants in 2014 still face a high absolute risk for coronary events compared to 2004, indicating the necessity for continued primary prevention and lifestyle interventions.
Psychosocial and Support Needs of the Main Caregiver for Adolescents and Young Adults Undergoing Treatment for Cancer
Authors: Pettitt Nicola J. , Petrella Anika R. , Neilson Susan , Topping Annie , Taylor Rachel M.
Published: April 2024

Background

Family relationships and social networks are critically important to adolescents and young adults (AYAs) with cancer, impacting their experience and well-being throughout the cancer trajectory. A cancer diagnosis impacts the development of independence and an adult identity, which can present challenges to psychosocial well-being needs and relationships between caregivers and AYAs.

Objective

The aim of this study was to explore the psychosocial and support needs of the main caregivers of AYAs.

Methods

This is a secondary analysis of the BRIGHTLIGHT caregiver survey, exploring items pertaining to support offered/engaged with, appraisal of helpfulness, and caregivers’ emotional and psychological distress experience. Descriptive statistics, a correlational analysis, and a 1-way analysis of variance were conducted.

Results

There were 518 caregiver responses (62%). Over half received information about their caregiving needs, with the majority finding this very/fairly helpful. Most (80%) of those who had not received the information would have valued it. High levels of negative emotional and psychological well-being were reported, with 91% feeling depressed or anxious since the AYAs’ diagnosis and 41% always/often experiencing these feelings. Total distress was associated with being younger, a parent, female, and unemployed, and earning a below-average income.

Conclusions

The needs of caregivers are broad and multidimensional; however, some characteristics were associated with higher distress. When caregiver-specific information was provided by healthcare professionals, it was well received.

Implications for Practice

Healthcare professionals should consider caregivers’ needs individually and provide/signpost to support. Caregivers need to be involved in designing and implementing future research, given the heterogeneity of needs identified.
Mediation of Psychological Capital in Youth Experiencing Homelessness
Authors: Rew Lynn , Slesnick Natasha , Kesler Shelli , Rhee Hyekyun
Published: April 2024

Background

Youth who experience homelessness engage in behaviors that place them at high risk for disease and injury. Despite their health risk behaviors, these youth display psychological capital, positive attributes of hope, efficacy, resilience, and optimism that motivate them to engage in health-promoting behaviors such as safer sex. However, this array of positive psychological attributes has not been studied in this vulnerable population.

Objectives

The specific aim of this analysis was to determine whether factors of psychological capital mediated the relationship between background risk factors (e.g., race/ethnicity, educational attainment, reason for being homeless, sexual abuse history, and HIV status) and outcomes of condom intention, safer sex behaviors, and life satisfaction among youth who participated in a longitudinal intervention study.

Methods

Using a Solomon four-group design, 602 youth were recruited from drop-in centers in two large cities (Columbus, Ohio, and Austin, Texas) to participate in a brief intervention that included outcomes of enhanced communication skills, goal setting, safer sex behaviors, drug refusal skills, and life satisfaction. Using an autoregressive, cross-lagged, longitudinal mediation model, we tested the direct and indirect effects of background factors, psychological capital, and intervention outcomes. Models were tested for the intervention group alone and the total sample.

Results

There were no significant direct or indirect effects of background factors on intervention outcomes among the intervention group, and the model fit was poor. There were also no significant mediating paths via factors of psychological capital and poor model fit for the combined group.

Discussion

Findings provide important information about intrinsic strengths of youth experiencing homelessness and psychological capital as a significant construct for understanding health behaviors among disadvantaged and underserved youth. The lack of significant mediation effects may have been due, in part, to the lack of a robust measure of psychological capital. Further study with various background factors and outcomes would contribute further to our understanding of how best to support this population.
Is Endometrial Receptivity Affected in Women With Endometriosis? Results From a Matched Pair Case-Control Study of Assisted Reproductive Technology Treatments
Authors: Casalechi Maíra , Reschini Marco , Palermo Maria Carla , Di Stefano Giorgia , Vercellini Paolo , Benaglia Laura , Somigliana Edgardo , Vigano Paola
Published: April 2024

(Abstracted from Reprod Biomed Online 2023;47:103414

Endometriosis is a well-established risk factor for infertility due to alterations in folliculogenesis, oocyte release from the ovaries, tubal function, and oocyte fertilization. In addition, it has been hypothesized that the presence of an abnormal endometrium, a known consequence of endometriosis, may impair embryo implantation leading to impaired pregnancy outcomes.
Total worker health® based Helicobacter pylori public health prevention strategy
Authors: Fernandez-Tardon Guillermo , Gan Rick Kye , Rodriguez-Suarez Marta-Maria , Tardon Adonina , Arcos-González Pedro
Published: April 2024

Purpose of review

This review aims to explore the public health approach for Helicobacter pylori Infection Prevention within the Total Worker Health (TWH) framework strategy.

Recent findings

The review identifies certain occupations considered high-risk groups for H. pylori infection. It underscores primary, secondary, and tertiary public health preventive measures align with the TWH approach. Within this framework, the role of raising awareness, emphasizing infection control, worker hygiene, risk assessment, and ensuring healthcare accessibility is emphasized. The importance of early detection, treatment, eradication, and a TWH approach emerges as a central theme. The TWH approach offers a holistic perspective, intertwining occupation-related health risks with overall health and well being.

Adopting the TWH approach, coupled with household-based infection control and eradication strategies, can significantly reduce H. pylori prevalence, fostering a healthier workforce and diminishing long-term healthcare costs. The review underscores the importance of recognizing H. pylori as an occupational disease. It calls for further research into the “one-health” perspective on H. pylori transmission dynamics.
Characteristics of firearm injury by injury intent: The need for tailored interventions
Authors: Waddle Shelbie D. , Hink Ashley B. , Kuhls Deborah A. , Rivara Frederick P. , Sakran Joseph V. , Agoubi Lauren L. , Winchester Alex S. , Richards Jacy , Hoeft Christopher , Patel Bhavin , Michaels Holly , Nathens Avery B.
Published: April 2024

INTRODUCTION

While the United States has high quality data on firearm-related deaths, less information is available on those who arrive at trauma centers alive, especially those discharged from the emergency department. This study sought to describe characteristics of patients arriving to trauma centers alive following a firearm injury, postulating that significant differences in firearm injury intent might provide insights into injury prevention strategies.

METHODS

This was a multicenter prospective cohort study of patients treated for firearm-related injuries at 128 US trauma centers from March 2021 to February 2022. Data collected included patient-level sociodemographic, injury and clinical characteristics, community characteristics, and context of injury. The outcome of interest was the association between these factors and the intent of firearm injury. Measures of urbanicity, community distress, and strength of state firearm laws were used to characterize patient communities.

RESULTS

A total of 15,232 patients presented with firearm-related injuries across 128 centers in 41 states. Overall, 9.5% of patients died, and deaths were more common among law enforcement and self-inflicted firearm injuries (80.9% and 50.5%, respectively). These patients were also more likely to have a history of mental illness. Self-inflicted firearm injuries were more common in older White men from rural and less distressed communities, whereas firearm assaults were more common in younger Black men from urban and more distressed communities. Unintentional injuries were more common among younger patients and in states with lower firearm safety grades, whereas law enforcement–related injuries occurred most often in unemployed patients with a history of mental illness.

CONCLUSION

Injury, clinical, sociodemographic, and community characteristics among patients injured by a firearm significantly differed between intents. With the goal of reducing firearm-related deaths, strategies and interventions need to be tailored to include community improvement and services that address specific patient risk factors for firearm injury intent.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level III.
Septic Cavernous Sinus Thrombosis: Clinical Characteristics, Management, and Outcomes
Authors: Halawa Omar , Gibbons Alison , Van Brummen Alexandra , Li Emily
Published: April 2024

Background:

Septic cavernous sinus thrombosis (CST) is a rare condition traditionally associated with high morbidity and mortality. More recent case series report more favorable outcomes, including full functional recovery. A comprehensive assessment of the clinical characteristics and prognostic factors of visual and survival outcomes in septic CST is warranted to contemporize current understanding and help guide management.

Methods:

A multicentered retrospective cohort study was conducted at 2 tertiary care centers using an electronic medical record search of the term, “thrombosis of cavernous venous sinus” between January 1, 2000, and December 31, 2021. Inclusion criteria consisted of active infection and radiographic evidence of associated CST. Demographic and clinical data extracted included age at presentation, sex, infection type and extent, and ophthalmic examination findings at presentation—best-corrected visual acuity (BCVA), presence of relative afferent pupillary defect (RAPD), intraocular pressure (IOP), and extraocular motility (EOM) limitation. Management data collected consisted of type and length of antimicrobial therapy, type and length of anticoagulation administration, and surgical intervention. Primary outcomes assessed were ophthalmic examination findings at final evaluation and same-hospitalization mortality.

Results:

A total of 27 patients with imaging-confirmed septic CST were identified at 2 tertiary care centers. At presentation, 2 (8.7%) patients had no light perception (NLP) vision, 8 (29.6%) patients had RAPD, 17 (73.9%) patients had EOM limitation, and 13 (54.2%) had IOP >21 mm Hg. All patients received antimicrobial therapy, with vancomycin being the most common agent. Fifteen patients (55.6%) received anticoagulation, and 21 (81.5%) patients underwent surgical intervention. Same-hospitalization mortality was 3 (11.1%). Among the 21 patients with ophthalmic data at follow-up, 3 (16.7%) had NLP vision, 5 (23.8%) had a persistent RAPD, 7 (31.8%) had persistent EOM limitation, and no patients had IOP elevated above 21 mm Hg. Patients with RAPD at presentation had significantly worse BCVA at final evaluation (logMAR BCVA 1.43 higher on average, P = 0.01) and a significantly higher mortality rate (37.5% vs. 0.0%, P < 0.01) than non-RAPD patients. Demographic features, BCVA at presentation, EOM limitation at presentation, elevated IOP at presentation, and comorbid orbital cellulitis were not associated with worse visual or mortality outcomes.

Conclusions:

Septic CST may result in permanent ophthalmic functional deficit in almost one-third of cases and mortality in approximately 11% of patients under contemporary management. New RAPD at presentation may indicate higher risk of poor visual and survival outcomes.
The Study of Remyelinating Therapies in Multiple Sclerosis: Visual Outcomes as a Window Into Repair
Authors: Zuroff Leah R. , Green Ari J.
Published: April 2024

Introduction:

Amelioration of disability in multiple sclerosis requires the development of complementary therapies that target neurodegeneration and promote repair. Remyelination is a promising neuroprotective strategy that may protect axons from damage and subsequent neurodegeneration.

Methods:

A review of key literature plus additional targeted search of PubMed and Google Scholar was conducted.

Results:

There has been a rapid expansion of clinical trials studying putative remyelinating candidates, but further growth of the field is limited by the lack of consensus on key aspects of trial design. We have not yet defined the ideal study population, duration of therapy, or the appropriate outcome measures to detect remyelination in humans. The varied natural history of multiple sclerosis, coupled with the short time frame of phase II clinical trials, requires that we develop and validate biomarkers of remyelination that can serve as surrogate endpoints in clinical trials.

Conclusions:

We propose that the visual system may be the most well-suited and validated model for the study potential remyelinating agents. In this review, we discuss the pathophysiology of demyelination and summarize the current clinical trial landscape of remyelinating agents. We present some of the challenges in the study of remyelinating agents and discuss current potential biomarkers of remyelination and repair, emphasizing both established and emerging visual outcome measures.
Sir Geoffrey Allen. 29 October 1928—15 March 2023
Authors: Russell John
Published: April 2024

Sir Geoffrey Allen was first and foremost a very fine scientist, highly respected, especially for his expertise in polymer science and technology. Over time he built up an extensive network of scientific know-how globally, establishing on-going relationships with many key scientists that enabled him to provide vision and leadership for the scientific community in academia and the world of business. Allen's ability to give a succinct and clear summary of an issue, his view and the reasoning behind his view were remarkable. He was very supportive of younger scientists, particularly when he perceived talent, and encouraged them. He devoted much of his free time to promoting science and technology in various forums but especially that of young people, and was particularly good at motivating people, being extremely effective at all levels. He was great confidence builder in any situation.
Children’s subjective uncertainty-driven sampling behaviour
Authors: de Eccher Martina , Mundry Roger , Mani Nivedita
Published: April 2024

Are children and adults sensitive to gaps in their knowledge, and do they actively elicit information to resolve such knowledge gaps? In a cross-situational word learning task, we asked 5-year-olds, 6- to 9-year-olds and adults to estimate their knowledge of newly learned word–object associations. We then examined whether participants preferentially sampled objects they reported not knowing the label in order to hear their labels again. We also examined whether such uncertainty-driven sampling behaviour led to improved learning. We found that all age groups were sensitive to gaps in their knowledge of the word–object associations, i.e. were more likely to say they had correctly indicated the label of an object when they were correct, relative to when they were incorrect. Furthermore, 6- to 9-year-olds and adults—but not 5-year-olds—were more likely to sample objects whose labels they reported not knowing. In other words, older children and adults displayed sampling behaviour directed at reducing knowledge gaps and uncertainty, while younger children did not. However, participants who displayed more uncertainty-driven sampling behaviour were not more accurate at test. Our findings underscore the role of uncertainty in driving 6- to 9-year-olds’ and adults’ sampling behaviour and speak to the mechanisms underlying previously reported performance boosts in active learning.
Parasite-mediated predation determines infection in a complex predator–prey–parasite system
Authors: Hijar Islas Ana C. , Milne Amy , Eizaguirre Christophe , Huang Weini
Published: April 2024

The interplay of host–parasite and predator–prey interactions is critical in ecological dynamics because both predators and parasites can regulate communities. But what is the prevalence of infected prey and predators when a parasite is transmitted through trophic interactions considering stochastic demographic changes? Here, we modelled and analysed a complex predator–prey–parasite system, where parasites are transmitted from prey to predators. We varied parasite virulence and infection probabilities to investigate how those evolutionary factors determine species’ coexistence and populations’ composition. Our results show that parasite species go extinct when the infection probabilities of either host are small and that success in infecting the final host is more critical for the survival of the parasite. While our stochastic simulations are consistent with deterministic predictions, stochasticity plays an important role in the border regions between coexistence and extinction. As expected, the proportion of infected individuals increases with the infection probabilities. Interestingly, the relative abundances of infected and uninfected individuals can have opposite orders in the intermediate and final host populations. This counterintuitive observation shows that the interplay of direct and indirect parasite effects is a common driver of the prevalence of infection in a complex system.
Exceptionally preserved shark fossils from Mexico elucidate the long-standing enigma of the Cretaceous elasmobranchPtychodus
Authors: Vullo Romain , Villalobos-Segura Eduardo , Amadori Manuel , Kriwet Jürgen , Frey Eberhard , González González Margarito A. , Padilla Gutiérrez José M. , Ifrim Christina , Stinnesbeck Eva S. , Stinnesbeck Wolfgang
Published: April 2024

The fossil fishPtychodusAgassiz, 1834, characterized by a highly distinctive grinding dentition and an estimated gigantic body size (up to around 10 m), has remained one of the most enigmatic extinct elasmobranchs (i.e. sharks, skates and rays) for nearly two centuries. This widespread Cretaceous taxon is common in Albian to Campanian deposits from almost all continents. However, specimens mostly consist of isolated teeth or more or less complete dentitions, whereas cranial and post-cranial skeletal elements are very rare. Here we describe newly discovered material from the early Late Cretaceous of Mexico, including complete articulated specimens with preserved body outline, which reveals crucial information on the anatomy and systematic position ofPtychodus. Our phylogenetic and ecomorphological analyses indicate that ptychodontids were high-speed (tachypelagic) durophagous lamniforms (mackerel sharks), which occupied a specialized predatory niche previously unknown in fossil and extant elasmobranchs. Our results support the view that lamniforms were ecomorphologically highly diverse and represented the dominant group of sharks in Cretaceous marine ecosystems.Ptychodusmay have fed predominantly on nektonic hard-shelled prey items such as ammonites and sea turtles rather than on benthic invertebrates, and its extinction during the Campanian, well before the end-Cretaceous crisis, might have been related to competition with emerging blunt-toothed globidensine and prognathodontine mosasaurs.
Oral administration of PEDV-dissolved Alg-CS gel induces high and sustained mucosal immunity in mice
Authors: Zhang Jinhua , Cui Lei , Zhang Yongliang , Pan Hong , Yuan Honggen , Zhou SaiSai , Chen Huanchun , Song Yunfeng
Published: April 2024

Porcine epidemic diarrhea (PED) is a serious disease in piglets that leads to high mortality. An effective measure that provides higher IgA levels in the intestine and milk is required to decrease losses. Porcine epidemic diarrhea virus (PEDV) was dissolved in calcium alginate (Alg) and combined with chitosan (CS) via electrostatic interactions between cationic chitosan and anionic alginate to create a porous gel (Alg-CS+PEDV). The gel was used to immunize mice orally or in combination with subcutaneous injections of inactivated PEDV vaccine. At 12 and 24 days after immunization, levels of IgA and IgG in Alg-CS+PEDV were higher than with normal PEDV oral administration. At 24 days after immunization, the concentration of IFN-γ in Alg-CS+PEDV was higher than with normal PEDV oral administration. Furthermore, oral administration combining subcutaneous immunization induced higher levels of IgG and IgA than oral administration alone. Our study provides a new method for the preparation and administration of oral vaccines to achieve enhanced mucosal immunity against PEDV.
Effect of two activators on the gating of a K2Pchannel
Authors: Mendez-Otalvaro Edward , Kopec Wojciech , de Groot Bert L.
Published: April 2024

TREK1, a two-pore-domain (2P) mammalian potassium (K+) channel, regulates the resting potential across cell membranes, presenting a promising therapeutic target for neuropathy treatment. The gating of this channel converges in the conformation of the narrowest part of the pore: the selectivity filter (SF). Various hypotheses explain TREK1 gating modulation, including the dynamics of loops connecting the SF with transmembrane helices and the stability of hydrogen bond (HB) networks adjacent to the SF. Recently, two small molecules (Q6F and Q5F) were reported as activators to affect TREK1 by increasing its open probability in single-channel current measurements. Here, using molecular dynamics (MD) simulations, we investigate the effect of these ligands on the previously proposed modulation mechanisms of TREK1 gating compared to the apo channel. Our findings reveal that loop dynamics at the upper region of the SF exhibit only a weak correlation with permeation/ non-permeation events, whereas the HB network behind the SF appears more correlated. These non-permeation events arise from both distinct mechanisms: A C-type inactivation (resulting from dilation at the top of the SF), which has been described previously; and a carbonyl flipping in a SF binding site. We find that, besides the prevention of C-type inactivation in the channel, the ligands increase the probability of permeation by modulating the dynamics of the carbonyl flipping, influenced by a threonine residue at the bottom of the SF. These results offer insights for rational ligand design to optimize the gating modulation of TREK1 and related K+channels.
Yeast poly(A)-binding protein (Pab1) controls translation initiation in vivo primarily by blocking mRNA decapping and decay
Authors: Poonia Poonam , Valabhoju Vishalini , Li Tianwei , Iben James , Niu Xiao , Lin Zhenguo , Hinnebusch Alan G.
Published: April 2024

Poly(A)-binding protein (Pab1 in yeast) is involved in mRNA decay and translation initiation, but its molecular functions are incompletely understood. We found that auxin-induced degradation of Pab1 reduced bulk mRNA and polysome abundance in a manner suppressed by deleting the catalytic subunit of decapping enzyme (dcp2Δ), demonstrating that enhanced decapping/degradation is the major driver of reduced mRNA abundance and protein synthesis at limiting Pab1 levels. An increased median poly(A) tail length conferred by Pab1 depletion was also nullified bydcp2Δ, suggesting that mRNA isoforms with shorter tails are preferentially decapped/degraded at limiting Pab1. In contrast to findings on mammalian cells, the translational efficiencies (TEs) of many mRNAs were altered by Pab1 depletion; however, these changes were broadly diminished bydcp2Δ, suggesting that reduced mRNA abundance is a major driver of translational reprogramming at limiting Pab1. Thus, assembly of the closed-loop mRNP via PABP-eIF4G interaction appears to be dispensable for normal translation of most yeast mRNAs in vivo. Interestingly, histone mRNAs and proteins are preferentially diminished on Pab1 depletion dependent on Dcp2, accompanied by activation of internal cryptic promoters in the manner expected for reduced nucleosome occupancies, revealing a new layer of post-transcriptional control of histone gene expression.
Deep indel mutagenesis reveals the regulatory and modulatory architecture of alternative exon splicing
Authors: Baeza-Centurion Pablo , Miñana Belén , Faure Andre J. , Thompson Mike , Bonnal Sophie , Quarantani Gioia , Lehner Ben , Valcárcel Juan
Published: April 2024

Altered splicing is a frequent mechanism by which genetic variants cause disease and antisense oligonucleotides (AONs) that target pre-mRNA splicing have been approved as therapeutics for multiple pathologies including patient-customized treatments for rare diseases. However, the regulatory architecture of human exons remains poorly understood and AON discovery is currently slow and expensive, limiting the wider adoption of the approach. Here we show that that systematic deletion scans –which can be made experimentally at very low cost – provide an efficient strategy to chart the regulatory landscape of human exons and to rapidly identify effective splicing-modulating oligonucleotides in a fully quantitative manner. Our results suggest a mechanism for the evolutionary origins of unusually short microexons and the repression of transmembrane domain-encoding exons, and reveal a checkerboard architecture of sequential enhancers and silencers in a model alternative exon. Accurate prediction of the effects of deletions using deep learning provides a resource, DANGO, that maps the splicing regulatory landscape of all human exons and predicts effective splicing-altering antisense oligonucleotides genome-wide.
Targeted proteomics upon Tofersen identifies candidate response markers for SOD1-linked amyotrophic lateral sclerosis
Authors: Steffke Christina , Baskar Karthik , Wiesenfarth Maximilian , Dorst Johannes , Schuster Joachim , Schöberl Florian , Reilich Peter , Regensburger Martin , German Alexander , Günther René , Vidovic Maximilian , Petri Susanne , Weishaupt Jochen H. , Meyer Thomas , Hagenacker Tim , Grosskreutz Julian , Weyen Ute , Weydt Patrick , Haarmeier Thomas , Lingor Paul , Wolf Joachim , Hermann Andreas , Prudlo Johannes , Günther Kornelia , Knehr Antje , Elmas Zeynep , Parlak Özlem , Uzelac Zeljko , Witzel Simon , Ruf Wolfgang Philipp , Tumani Hayrettin , Ludolph Albert C. , Freischmidt Axel , Oeckl Patrick , Ho Ritchie , Brenner David , Catanese Alberto
Published: April 2024

Tofersen is the first effective and approved therapy for familial ALS caused by pathogenic variants in theSOD1gene. Following treatment with tofersen, neurofilaments in patients CSF and serum display a faster response than clinical parameters, underlining their importance as a biomarker for treatment response in clinical trials. This evidence led us to hypothesize that this novel treatment might represent an opportunity to identify additional therapy-responsive biomarkers for ALS. We chose the commercial NUcleic acid Linked Immuno-Sandwich Assay (NULISA™), to investigate a predefined panel of 120 neural, glial and inflammatory markers in CSF and serum samples longitudinally collected from SOD1-ALS patients at baseline and three months after tofersen treatment. We identified a set of proteins (beyond pNfH and NfL) whose levels differed between SOD1-ALS and the matched control group and that were responsive to treatment with tofersen, including Aβ42, NPY and UCHL1. Even though our results warrant validation in larger cohorts and longer follow-up time, they may pave the way for a panel of responsive proteins solidifying biomarker endpoints in clinical trials.
The SLaM Brain Health Clinic: a remote biomarker enhanced memory clinic for patients with mild cognitive impairment within an NHS mental health trust
Authors: Venkataraman Ashwin V. , Kandangwa Pooja , Lemmen Roos , Savla Rutvi , Beigi Mazda , Hammond Devon , Harwood Daniel , Sauer Justin , Velayudhan Latha , Ballard Clive , Brem Anna-Katharine , Kalafatis Chris , Aarsland Dag
Published: April 2024

Background

The novel South London and Maudsley Brain Health Clinic (SLaM BHC) leverages advances in remote consultations and biomarkers to provide a timely, cost-efficient and accurate diagnosis in mild cognitive impairment (MCI).

Aims

To describe the organisation, patient cohort, and acceptability of the remote diagnostic and interventional procedures.

Method

We describe the recruitment, consultation setup, the clinical and biomarker program, and the two online group interventions for cognitive wellbeing and lifestyle change. We evaluate the acceptability of the remote consultations, lumbar puncture (LP), saliva genotyping and remote cognitive and functional assessments.

Results

We present the results of the first 68 (mean age 73, 55% female, 43% ethnic minority) of 146 patients who enrolled for full remote clinical, cognitive, genetic, cerebrospinal fluid, and neuroimaging phenotyping. 86% were very satisfied/ satisfied with the remote service. 67% consented to LP and 95% of those were very satisfied, all having no significant complications. 93% found taking saliva genotyping very easy/easy and 93% found the cognitive assessments instructions clear. 98% were satisfied with the cognitive wellbeing groups and 90% of goals were achieved in the lifestyle intervention group.

Conclusions

The SLaM BHC provides a highly acceptable and safe clinical model for remote assessments and lumbar punctures in a representative, ethnically diverse population. This allows early and accurate diagnosis of Alzheimer’s, differentiation from other MCI causes and targets modifiable risk factors. This is crucial for future disease modification, ensuring equitable access to research, and provides precise, timely and cost-efficient diagnoses in UK mental health services.