id
stringlengths
1
7
title
stringlengths
2
559
article
stringlengths
0
9.99k
38094968
Subscapularis Repair Augmentation With the Long Head Biceps Tendon During Anatomic Total Shoulder Arthroplasty: The "Biceps-Subscap Sling" Technique.
Subscapularis repair failure following anatomic total shoulder arthroplasty (TSA) can compromise postoperative range of motion and joint stability, often leading to persistent pain and worse outcomes. Augmenting the subscapularis repair, particularly in at-risk patients, may provide a more robust construct and prevent subscapularis failure. The long head of the biceps tendon (LHBT) is an accessible autograft with applications previously described in several shoulder procedures. In this technical note and accompanying video, we describe LHBT augmentation of subscapularis repair following TSA. The LHBT is released from the supraglenoid tubercle and is passed through the subscapularis tendon vertically in a pulvertaft weave fashion. Transosseous sutures are used to complete the peel repair, with the LHBT acting as a rip-stop to help protect the repair from suture pullout. In addition, the incorporated LHBT remains in continuity with the remainder of the biceps distally and may act as a dynamic stabilizer. This technique, termed the "Biceps-Subscap Sling" technique, provides additional structural integrity to subscapularis repair and is a cost-effective, biologically active option.
38094969
A Minimally Invasive Technique for Harvesting Quadriceps Tendon Autograft With a Bone Plug for Anterior Cruciate Ligament Reconstruction.
Anterior cruciate ligament reconstruction (ACLR) with quadriceps tendon (QT) was first described decades ago. Recent studies have demonstrated superior graft characteristics (diameter, strength, and stiffness) and reduced postoperative morbidity. However, limited instrumentation options currently available to surgeons allow for minimally invasive QT harvest with a bone plug. As an alternative to traditional QT harvest techniques, we describe a surgical technique allowing for minimally invasive QT autograft harvest with a bone plug (QuadVantage Technologies, Inc). This approach can offer technical advantages, including efficiency of graft harvest, reproducibility of procedure, and more consistent graft sizes.
38094970
Arthroscopic Rotator Cuff Repair With Superior Fulcrum Reconstruction Using Autologous Ipsilateral Peroneus Longus Tendon for Irreparable Massive Rotator Cuff Tears.
Rotator cuff tears are still among the serious challenges encountered by sports medicine surgeons. With the development of arthroscopic technology, the treatment options for irreparable massive rotator cuff tears (IMRCTs) have gradually increased, but postoperatively, these options are prone to graft retears, reoperations, infections, revision surgical procedures, and so on. On the basis of studies on the balance of the force couples of the rotator cuff, more scholars believe that when addressing IMRCTs, attention should be paid to the reconstruction of the force couples of the rotator cuff; hence, we developed the superior fulcrum reconstruction technique. This article describes an alternative approach to IMRCT repair with superior fulcrum reconstruction using autologous ipsilateral peroneus longus tendon.
38094971
Arthroscopic Bone Block Cerclage Suture Fixation of Fresh Distal Tibial Allograft for Anterior Glenoid Reconstruction.
Glenoid bone loss in patients with recurrent anterior shoulder instability poses a unique challenge to treating surgeons. Various bone block procedures have been used to reconstruct the glenoid, including autologous coracoid transfer, iliac crest autograft, distal clavicle autograft, and distal tibia allograft. Distal tibia allograft has been increasingly used because of its advantages over autologous graft sources. Having started out as an open procedure, glenoid reconstruction with distal tibia allograft has now found its way to evolving into an arthroscopic procedure. Various techniques have been devised for arthroscopic distal tibia allograft fixation, including screw, suture anchor, and suture button. This technical note describes an arthroscopic distal tibia allograft fixation technique, using a transglenoid parallel drill guide and 2 cerclage tape sutures that are fastened using a tensioner. This technique provides strong graft fixation while avoiding the potential complications and technical challenges of metal screw fixation.
38094972
Ten Pearls for Anterior Cruciate Ligament Reconstruction.
Anterior cruciate ligament (ACL) reconstruction is a common orthopaedic procedure that has continued to evolve. Since it is a complex procedure, it carries a risk of a range of complications. To ensure optimal results, there are many important considerations to take such as the choice of graft, tunnel positioning, graft preparation, and many others. In this technical note, we elucidate our top 10 pearls to consider for a successful ACL reconstruction.
38094973
Custom, 3-Dimensional Patient-Specific Instrumentation in Anatomic Total Shoulder Arthroplasty: Part 1-Preoperative Assessment, Preoperative Planning, and Guide Design.
Successful total shoulder arthroplasty relies on a multitude of factors specific to patients, implant selection, and surgical technique. Among technical factors, correct intraoperative placement of prosthetic components is paramount. Three-dimensional computed tomography has emerged as a vital tool, allowing surgeons to measure glenoid inclination, glenoid version, and humeral head subluxation more accurately and reproducibly. Several commercial preoperative planning software resources are available to determine the optimal size and positioning of prosthetic components yet do so at significant cost and with meaningful time constraints. At our institution, we have applied the principles of these technologies to develop a custom, 3-dimensionally printed glenoid guide for accurate placement of the central pin. In this technical note, we describe our evaluation of patients with glenohumeral arthritis, as well as our step-by-step procedure for designing and printing a custom patient-specific instrumentation glenoid guide for anatomic total shoulder arthroplasty.
38094974
Transosseous Fixation with Suspensory Fixation System on Medial Meniscus Root Tears.
Medial meniscal root injury is known to cause an increase in the tibiofemoral contact pressure and results in early osteoarthritis. Several techniques have been described for transosseous suture repair. Typically, the sutures are passed through the meniscus, pulled out through a transtibial tunnel, and tied over a bone bridge, a suture button, or a screw at the anterior tibial cortex. Desired meniscus root tension may not be achieved in transosseous fixation with a suture button. The suspensory fixation technique is aimed to prevent secondary looseness in the knot attached to the button implant in the tibia and to provide the desired tension in the fixation of the button implant in different degrees of flexion of the knee.
38094975
Modified Low-Flow Arthroscopic Sandwich Technique for Complex Osteochondral Lesions of the Talus.
Treatment of osteochondral lesions of the talus proves to be challenging given the unique anatomy of the intra-articular surface and associated complexity of larger lesions. Simple bone marrow-stimulating procedures for large complex lesions often lead to poor results with increased risk of lesion progression, refractory pain, and associated functional limitations. Other methods of osteochondral autografts or allografts often require osteotomies, bone windows, or fibrin glue, which are associated with donor pain and nonunion. Thus, for larger and cystic lesions, we report our experience using a modified low-flow arthroscopic sandwich technique consisting of autologous cancellous bone graft, followed by a viable cryopreserved cartilage fiber, cartilage allograft matrix putty.
38094976
All-Arthroscopic Management of Locked Posterior Shoulder Dislocation: Reduction Under Direct Visualization and Treatment of Intra-articular Pathologies.
Locked posterior shoulder dislocation (LPSD) is a rare condition often overlooked. In most cases, the humeral head remains stuck behind the glenoid, causing an impression fracture in 40% to 90% of LPSD cases, known as a reverse Hill-Sachs lesion. The condition also affects the posterior capsulolabral complex and leads to the formation of scar tissue under the coracoid and subscapularis tendon, making it challenging to reduce without surgery. Although open treatment has been successful, it does not address the posterior capsulolabral complex. Arthroscopic-assisted reduction provides a more detailed view and better exposure to the posterior structures. This article details a reproducible arthroscopic surgical technique for treating the locked dislocation and all intra-articular pathology in a single-stage procedure for patients with less than 25% reverse Hill-Sachs bone loss.
38094977
Raman spectra and defect chemical characteristics of Sr(Ti,Fe)O<sub>3-<i>y</i></sub> solid solution of bulk pellets <i>vs.</i> thin films.
Sr(Ti,Fe)O<sub>3-<i>y</i></sub> perovskite solid solutions are relevant functional materials for energy conversion and electronic devices such as solid oxide fuel and photoelectrochemical cells, electrolyzers, oxygen sensors, resistive random access memories or synaptic transistors. The Raman spectra and vibrational characteristics of the Sr(Ti,Fe)O<sub>3-<i>y</i></sub> materials class are suitable for describing their defect chemistry and the iron valence state, which governs a multitude of its mixed ionic-electronic transport and other characteristics. We synthesize a standard range of compositions containing 1-75 mol% of iron including the end members in the form of macrocrystalline bulk pellets, nanocrystalline poly- and single crystalline thin films. Through the change in both iron substitution level and microstructure, we directly see the effect of defect chemistry such as its phase, transition metal ion valence and oxygen nonstoichiometry on the Raman spectra. These are discussed in terms of <i>in</i> and <i>ex situ</i> experiments under oxidizing/reducing atmosphere. In contrast to long range structural X-ray diffraction measurements, Raman spectroscopy provides valuable insights into oxygen vacancy ordering and oxygen nonstoichiometry for the Sr(Ti,Fe)O<sub>3-<i>y</i></sub> material class.
38094978
Neighborhood and health-related outcomes: a study of adult Latinas of Caribbean and South and Central American descent in Miami.
The present study investigated neighborhood effects on substance use, mental and medical health, and health-care access. We used data collected from a sample of adult Latinas of Caribbean and South and Central American descent in 2011. The findings indicate that for adult Latinas, concentrated disadvantage in neighborhoods is associated with increased risk of alcohol misuse and inability to obtain prescription drugs due to lack of money, while Hispanic/immigrant concentration in neighborhoods is associated with fewer mental disorder symptoms. Individual age, criminal justice involvement, religious involvement, intimate partner violence, and employment are also associated with one or more health-related outcomes. We provided practice implications for macro and micro social work practice. Future research is needed to examine the mechanism underlying the negative association between neighborhood Hispanic/immigrant concentration and mental disorder symptoms.
38094979
No dose response effect in shockwave therapy applied to bone conditions: a systematic review, meta-analysis and meta-regression.
Shock waves have been widely used to treat bone conditions, but despite the articles and meta-analyses, there are still doubts about its effectiveness, with a meta-analysis pointing to uncertain evidence of positive effects for pain and delayed or non-union, while others point to a positive effect on the same outcomes. One hypothesis for this conflict in the results is the lack of research on the relationship between the applied dose and clinical outcomes.
38094980
What's the evidence on surgical treatment for congenital brachymetatarsia: A systematic review and meta-analysis.
Brachymetatarsia is marked by the shortened length of one or more metatarsal bones. Several operative options have been suggested without demonstrating the superiority of one treatment over another. This study aims to assess the main available treatment, bone lengthening achieved, clinical outcomes, and complications pertaining to congenital brachymetatarsia interventions.
38094981
Non-compressive sleeves versus compression stockings after total knee arthroplasty: A prospective pilot study.
Compression stockings are routinely prescribed after total knee arthroplasty (TKA). Non-compressive sleeves embedded with semiconductor elements (Incrediwear) are designed to enhance blood flow. The objective of this investigation is to compare compression stockings and Incrediwear on post-TKA measures.
38094982
Performance of the automated Sysmex XN-3000 analyser for detecting white blood cell abnormalities in South Africa.
Automated haematology analysers such as the Sysmex XN-3000 (Sysmex Corporation, Kobe, Japan) utilise white blood cell (WBC) flags to identify quantitative and qualitative abnormalities. Owing to clinical and biological factors, the sensitivity and specificity of the flags vary when compared to microscopy, the gold-standard method for assessing peripheral blood smear (PBS) morphology.
38094984
Antibacterial activity of soil-isolated <i>Bacillus altitudinis/pumilus</i> complex against methicillin-resistant <i>Staphylococcus aureus</i> from Mwanza, Tanzania.
Antimicrobial resistance in methicillin-resistant <i>Staphylococcus aureus</i> and beta-lactamase-producing Gram-negative bacteria is a global health concern necessitating research and the development of effective antimicrobial agents. This study, conducted in May 2020 in Mwanza, Tanzania, aimed to determine the antibacterial activity of metabolites from soil-isolated <i>Bacillus</i> species against clinical bacterial pathogens. One soil-isolated <i>Bacillus</i> species, identified as <i>Bacillus altitudinis/pumilus</i> complex, showed antibacterial activity against Gram-positive cocci, including a methicillin-resistant <i>S. aureus</i> strain with inducible clindamycin resistance, previously isolated from a patient with osteomyelitis. <i>Bacillus altitudinis/pumilus</i> complex metabolites may be a potential source of antimicrobial agents against multidrug-resistant bacteria.
38094983
Providing specimen transport through an online marketplace in the Northern region of Ghana.
Integrated diagnostic networks, which are themselves dependent on robust specimen transport solutions, are fundamental to effective healthcare systems.
38094985
Impact of Dimensionality Reduction on Outlier Detection: an Empirical Study.
Outlier detection is a fundamental data analytics technique often used for many security applications. Numerous outlier detection techniques exist, and in most cases are used to directly identify outliers without any interaction. Typically the underlying data used is often high dimensional and complex. Even though outliers may be identified, since humans can easily grasp low dimensional spaces, it is difficult for a security expert to understand/visualize why a particular event or record has been identified as an outlier. In this paper we study the extent to which outlier detection techniques work in smaller dimensions and how well dimensional reduction techniques still enable accurate detection of outliers. This can help us to understand the extent to which data can be visualized while still retaining the intrinsic outlyingness of the outliers.
38094986
A proximal distance algorithm for likelihood-based sparse covariance estimation.
This paper addresses the task of estimating a covariance matrix under a patternless sparsity assumption. In contrast to existing approaches based on thresholding or shrinkage penalties, we propose a likelihood-based method that regularizes the distance from the covariance estimate to a symmetric sparsity set. This formulation avoids unwanted shrinkage induced by more common norm penalties, and enables optimization of the resulting nonconvex objective by solving a sequence of smooth, unconstrained subproblems. These subproblems are generated and solved via the proximal distance version of the majorization-minimization principle. The resulting algorithm executes rapidly, gracefully handles settings where the number of parameters exceeds the number of cases, yields a positive-definite solution, and enjoys desirable convergence properties. Empirically, we demonstrate that our approach outperforms competing methods across several metrics, for a suite of simulated experiments. Its merits are illustrated on international migration data and a case study on flow cytometry. Our findings suggest that the marginal and conditional dependency networks for the cell signalling data are more similar than previously concluded.
38094987
Development of recommendations for a minimum dataset for Identifying Social factors that Stratify Health Opportunities and Outcomes (ISSHOOs) in pain research.
There is increasing recognition of the need for researchers to collect and report data that can illuminate health inequities. In pain research, routinely collecting equity-relevant data has the potential to inform about the generalisability of findings; whether the intervention has differential effects across strata of society; or it could be used to guide population targeting for clinical studies. Developing clarity and consensus on <b><i>what</i></b> data should be collected and <b><i>how</i></b> to collect it is required to prompt researchers to further consider equity issues in the planning, conduct, interpretation, and reporting of research. The overarching aim of the 'Identifying Social Factors that Stratify Health Opportunities and Outcomes' (ISSHOOs) in pain research project is to provide researchers in the pain field with recommendations to guide the routine collection of equity-relevant data. The design of this project is consistent with the methods outlined in the 'Guidance for Developers of Health Research Reporting Guidelines' and involves 4 stages: (i) Scoping review; (ii) Delphi Study; (iii) Consensus Meeting; and (iv) Focus Groups. This stakeholder-engaged project will produce a minimum dataset that has global, expert consensus. Results will be disseminated along with explanation and elaboration as a crucial step towards facilitating future action to address avoidable disparities in pain outcomes.
38094988
An improved sample container cup and its effect on NIRS of tobacco smoke for quality stability estimation.
This paper describes a design of an improved self-made Bruker NIR cup and analyzes the effect of the equipment modification to fit the Cambridge filter pad, which enhances experimental efficiency and reduces operational complexity. A self-made NIR cup based on the classical NIR cup is designed to speed up the operation process and reduce the experiment's time cost. To estimate the effect of this equipment modification, the NIR spectra from the classical sample cup and the new self-made cup are compared and analyzed. Furthermore, the quality evaluation results from NIR data of the two cups are also compared according to a distance metric chemometrics method, which shows quality analytical values between these two cups are approaching each other while the experiment efficiency is improved.•This paper introduces a newdesign of a self-made container cup improved from the Bruker's traditional sample container cup to better fit the filter pad and improve the experiment efficiency and convenience.•This paper also analyzes the effect of this container cup change by comparing the NIR spectra before and after modification.
38094989
Application of variation theory in STEM education: A comprehensive guideline for STEM teachers.
Incorporating appropriate pedagogical strategies has been instrumental in the development of a favorable learning environment for holistic learning, particularly in Science, Technology, Engineering, and Mathematics (STEM) education. However, there is growing evidence of the need to advance the existing methods, through more robust and comprehensive fieldwork grounded in design study. It has been shown that the lack of guidance in lesson planning using variation theory is also thought to require particular attention, as the accuracy of the student learning relies significantly on the planning of the lesson. However, little research has outlined the strategy to be followed for incorporating variation theory. This article proposes a method of preparing lesson plans to systematically implement the variation theory in STEM classrooms. The method seeks to design and implement current techniques as follows:•According to variation theory, teachers must create the necessary conditions for learning for the students to recognize what they are expected to learn.•To create the necessary conditions for learning, teachers define the key aspects of the topic to be covered and use different patterns of variations in teaching those contents, such as contrast, separation, generalization, and fusion.•Finally, teachers focus on the key aspects one by one or simultaneously to grab students' attention.
38094992
Peptoid-based macrodiscs of variable lipid composition for structural studies of membrane proteins by oriented-sample solid-state NMR.
Solid-state Nuclear Magnetic Resonance (NMR) in combination with magnetically aligned discoidal lipid mimics allows for studying the conformations of membrane proteins in planar, lipid-rich bilayer environments and at the physiological temperature. We have recently demonstrated the general applicability of macrodiscs composed of DMPC lipids and peptoid belts, which yield magnetic alignment and NMR spectroscopic resolution comparable or superior to detergent-containing bicelles. Here we report on a considerable improvement in the magnetic alignment and NMR resolution of peptoid-based macrodiscs consisting of a mixture of the zwitterionic and negatively charged lipids (DMPC/DMPG at the 85% to 15% molar ratio). The resulting linewidths are about 30% sharper due to the higher orientational order parameter likely arising from the stabilizing electrostatic repulsion between the discs. Moreover, highly aligned, detergent-free macrodiscs can be formed with a longer-chain lipid, DPPC. Interestingly, the spectra of Pf1 in the two lipid mimetics are almost indistinguishable, which would mean that the overall transmembrane helix tilt might be governed not only by the hydrophobic matching but also possibly by the interactions of the flanking lysine and arginine residues at the membrane interface.
38094991
Quality of Life and Psychometric Characteristics of Syrian Refugee Physicians Who Migrated to Turkey: A Cross-Sectional Study.
The concept of migration comes with various problems, affecting the quality of life and psychological state of immigrants. This study aimed to investigate the quality of life and depression and anxiety states of physicians who immigrated to Turkey after the civil war that started in Syria in 2011.
38094993
Time to Reconsider Ejection Fraction in Heart Failure: Reclassification Needed Beyond Ejection Fraction.
38094995
Impact of Physical Activity on Clinical Outcomes in AF Patients Undergoing Catheter Ablation.
38094994
Disparities in Representation of Asian Participants and Investigators in Cardiometabolic Trials.
38094996
Asia-Pacific Investigators and Asian Enrollment in Cardiometabolic Trials: Insights From Publications Between 2011 and 2020.
A lack of geographic and racial diversity in clinical trial populations may arise from a disproportionate focus on the United States and Europe for trial leadership and conduct. Inadequate diversity may compromise the external validity to the Asia-Pacific (APAC) region, where 60% of global cardiometabolic disease exists.
38094998
Reducing the Risk of Dementia in Atrial Fibrillation.
38094997
Short-Term Outcomes Following Transcatheter Edge-to-Edge Repair: Insights From the OCEAN-Mitral Registry.
Transcatheter edge-to-edge repair (TEER) is a less invasive treatment for patients with mitral regurgitation (MR). Limited safety and efficacy data of TEER with MitraClip, including the fourth-generation (G4) system, in a large cohort, are available.
38094999
Fatal Arrhythmic Risks in Cardiac Sarcoidosis With Mildly Impaired Cardiac Function.
The prognosis and later fatal arrhythmia in cardiac sarcoidosis (CS) with relatively preserved cardiac function were unclear.
38095000
The ABC-Death Score for Mortality Prediction in Patients With Atrial Fibrillation Undergoing Catheter Ablation.
Data on the performance of risk scores in predicting mortality risk after atrial fibrillation (AF) ablations are limited.
38094990
Neurofilament light chain levels in serum among a large mixed memory clinic cohort: Confounders and diagnostic usefulness.
Early and accurate diagnosis of neurocognitive disorders including neurodegenerative dementia remains challenging. This study explores the impact of biological factors on serum neurofilament light chain (NfL) levels and clinical usefulness for the detection of neurocognitive disorders in a mixed memory clinic.
38095001
Up-to-Date Clinical Practice of Transcatheter Edge-to-Edge Repair in Asia: Challenges and Opportunities.
38095002
Atrial Fibrillation Ablation and the ABC-Death Score: Beyond Rhythm Outcomes.
38095003
<i>RNF213</i> p.R4810K Variant Increases the Risk of Vasospastic Angina.
38095004
Dementia Risk of Direct Oral Anticoagulants Versus Warfarin for Atrial Fibrillation: Systematic Review and Meta-Analysis.
Direct-acting oral anticoagulants (DOACs) have demonstrated superior efficacy in preventing stroke and death compared with warfarin in patients with atrial fibrillation (AF), but their influence on dementia risk remains unclear.
38095006
Management of Cardiac Sarcoidosis With Mildly Impaired Cardiac Function.
38095005
Practical Application of Coronary Physiologic Assessment: Asia-Pacific Expert Consensus Document: Part 1.
Coronary physiologic assessment is performed to measure coronary pressure, flow, and resistance or their surrogates to enable the selection of appropriate management strategy and its optimization for patients with coronary artery disease. The value of physiologic assessment is supported by a large body of evidence that has led to major recommendations in clinical practice guidelines. This expert consensus document aims to convey practical and balanced recommendations and future perspectives for coronary physiologic assessment for physicians and patients in the Asia-Pacific region based on updated information in the field that including both wire- and image-based physiologic assessment. This is Part 1 of the whole consensus document, which describes the general concept of coronary physiology, as well as practical information on the clinical application of physiologic indices and novel image-based physiologic assessment.
38095007
Direct Oral Anticoagulant Dosing in Patients With Atrial Fibrillation: An Asian Perspective.
Optimal dosing of direct oral anticoagulants (DOACs) for stroke prevention in "gray area" patients with atrial fibrillation (AF) remains a challenge for clinicians. In Asia, this is concerning in patients who are very elderly, have low body weight, and are at a high risk of bleeding. This review aims to summarize the dose reduction criteria for DOACs, discuss the evidence on dosing of DOACs across Asian regions, and collate opinions from authors across Asia. Nonrecommended dosing of DOACs is common in Asia, primarily due to the fear of bleeding, with the total clinical benefit of higher dosing being overlooked. The ELDERCARE-AF (Edoxaban Low-Dose for Elder Care-Atrial Fibrillation Patients) trial and real-world case studies provide some evidence on the use of low-dose DOACs in gray area patients. Opinions on dose adjustment guidance, concomitant medication adjustments, and therapeutic drug monitoring were collated. Research is needed to fill the evidence gaps on optimal DOAC doses for gray area patients.
38095008
Clinical Features of Heart Failure With Normal Ejection Fraction: Insights From the ASIAN-HF Registry.
Heart failure and left ventricular ejection fraction in the normal range (HFnEF) (left ventricular ejection fraction [LVEF] of ≥55% for men and ≥60% for women) is understudied.
38095009
Cryoablation: Nitrogen or Nitrous Oxide? Balloon or Nonballoon?
38095010
Liquid Nitrogen Cryoballoon Ablation System for Paroxysmal Atrial Fibrillation: A Multicenter, Prospective, Single-Arm Clinical Trial.
Cryoballoon ablation (CBA) has emerged as an effective treatment for atrial fibrillation (AF).
38095011
Protein Engineering Technologies for Development of Next-Generation Genome Editors.
Base editors and prime editors have emerged as promising tools for the modeling and treatment of genetic diseases due to their ability to introduce targeted modifications in the genomic DNA of living cells. Several engineering approaches have been applied to improve their performance, ranging from simple protein design approaches to complex directed evolution schemes that can probe a vast landscape of mutational variants with minimal user intervention. These extensive efforts have led to new generations of editors with enhanced properties such as increased editing activity, tailored editing windows, increased targetability, smaller construct size for viral delivery, and decreased off-target effects. In this manuscript we review protein engineering technologies that have been recently utilized to create an ever-evolving landscape of high-performance gene editing tools specifically designed for genetic targets of interest and that have redefined what is possible in the field of precision medicine.
38095013
The selective cyclooxygenase-2 inhibitor NS398 ameliorates cisplatin-induced impairments in mitochondrial and cognitive function.
Chemobrain is a condition that negatively affects cognition in cancer patients undergoing active chemotherapy, as well as following chemotherapy cessation. Chemobrain is also known as chemotherapy-induced cognitive impairment (CICI) and has emerged as a significant medical contingency. There is no therapy to ameliorate this condition, hence identification of novel therapeutic strategies to prevent CICI is of great interest to cancer survivors. Utilizing the platinum-based chemotherapy cisplatin in an investigative approach for CICI, we identified increased expression of cyclooxygenase-2 (COX-2) and prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) in the adult mouse hippocampus, and in human cortical neuron cultures derived from induced pluripotent stem cells (iPSCs). Notably, administration of NS398, a selective COX-2 inhibitor, prevented CICI <i>in vivo</i> without negatively affecting the antitumor efficacy of cisplatin or potentiating tumor growth. Given that dysfunctional mitochondrial bioenergetics plays a prominent role in CICI, we explored the effects of NS398 in cisplatin-induced defects in human cortical mitochondria. We found that cisplatin significantly reduces mitochondrial membrane potential (MMP), increases matrix swelling, causes loss of cristae membrane integrity, impairs ATP production, as well as decreases cell viability and dendrite outgrowth. Pretreatment with NS398 in human cortical neurons attenuated mitochondrial dysfunction caused by cisplatin, while improving cell survival and neurite morphogenesis. These results suggest that aberrant COX-2 inflammatory pathways may contribute in cisplatin-induced mitochondrial damage and cognitive impairments. Therefore, COX-2 signaling may represent a viable therapeutic approach to improve the quality of life for cancer survivors experiencing CICI.
38095012
Health Poverty Alleviation Project in Rural China: Impact on Poverty Vulnerability, Health Status, Healthcare Utilization, Health Expenditures.
China has lead to the inception of the Health Poverty Alleviation Project (HPAP) in 2015. While the previous studies suggest that, despite its apparent reduction in patients' financial strain, the long-term poverty reduction effects are yet to be fully elucidated. This study explores HPAP's enduring impact on poverty reduction and the potential moral hazards.
38095014
The Role of TFE3 in Mediating Skeletal Muscle Mitochondrial Adaptations to Exercise Training.
TFE3 is a transcription factor that activates the expression of lysosomal genes involved in the clearance of dysfunctional mitochondria, termed mitophagy. With exercise, TFE3 is presumed to optimize the mitochondrial pool through the removal of organelles via lysosomes. However, the molecular mechanisms of the involved pathways remain unknown. Wild-type (WT) and TFE3 knockout (KO) mice were subjected to 6 weeks of voluntary wheel running as an endurance training regimen. This was followed by a 45-minute bout of <i>in situ</i> stimulation of the sciatic nerve innervating hindlimb muscles to evaluate muscle fatigue and contractile properties. A subset of animals was treated with colchicine to measure autophagy and mitophagy flux. Fatigability during stimulation was reduced with training in WT animals, as seen by a 13% increase in percent of maximum force at 5 minutes of stimulation, and a 30% increase at 30 minutes. Permeabilized fiber oxygen consumption was also improved with training. Concurrent with improved muscle and mitochondrial function, COX activity and COX I protein expression were increased in trained WT animals compared to untrained animals, signifying an increase in mitochondrial content. These training adaptations were abolished with the loss of TFE3. Surprisingly, the absence of TFE3 did not affect lysosomal content, nor did it blunt the induction of mitophagy flux with contractile activity compared to WT mice. Our results suggest that the loss of TFE3 compromises beneficial training adaptations that lead to improved muscle endurance and mitochondrial function.
38095016
Fast and Slow Muscle Fiber Transcriptome Dynamics with Lifelong Endurance Exercise.
We investigated fast and slow muscle fiber transcriptome exercise dynamics among three groups of men: Lifelong exercisers (LLE, n=8, 74±1 y), old healthy non-exercisers (OH, n=9, 75±1 y), and young exercisers (YE, n=8, 25±1 y). Muscle biopsies were obtained pre- and 4h post-resistance exercise (3x10 knee extensions, 70% 1-RM). Fast and slow fiber size and function were assessed pre-exercise with fast and slow RNA-seq examined pre- and post-exercise. LLE fast fiber size was similar to OH, which were ~30% smaller than YE (P<0.05) with contractile function variables among groups resulting in lower power in LLE (P<0.05). LLE slow fibers were ~30% larger and more powerful compared to YE and OH (P<0.05). At the transcriptome level, fast fibers were more responsive to resistance exercise compared to slow fibers among all three cohorts (P<0.05). Exercise induced a comprehensive biological response in fast fibers (P<0.05) including transcription, signaling, skeletal muscle cell differentiation, and metabolism with vast differences among the groups. Fast fibers from YE exhibited a growth and metabolic signature, with LLE being primarily metabolic, and OH showing a strong stress related response. In slow fibers, only LLE exhibited a biological response to exercise (P<0.05), which was related to ketone and lipid metabolism. The divergent exercise transcriptome signatures provide novel insight into the molecular regulation in fast and slow fibers with age and exercise and suggest that the ~5% weekly exercise time commitment of the lifelong exercisers provided a powerful investment for fast and slow muscle fiber metabolic health at the molecular level.
38095015
Upper airway imaging and function in obstructive sleep apnea in people with and without HIV.
Obstructive sleep apnea (OSA) is common in people living with HIV (PLWH), but the underlying mechanisms are unclear. With improved long-term survival among PLWH, aging and obesity are increasingly prevalent in this population. These are also strong risk factors for the development of obstructive sleep apnea. We used magnetic resonance imaging (MRI) to measure upper airway (UA) anatomy and tongue fat content in PLWH with OSA (PLWH+OSA, N=9) and in age-, sex-, and BMI-matched OSA controls (OSA, N=11). We also quantified change in UA dimension during tidal breathing (during wakefulness and natural sleep) at four anatomical levels from the hard palate to the epiglottis along with synchronous MRI-compatible electroencephalogram and nasal flow measurements. All participants underwent on a separate night a baseline polysomnogram to assess OSA severity and an additional overnight physiological sleep study to measure OSA traits. We found no difference between the PLWH+OSA and the OSA control group in UA volume (PLWH+OSA: 12.8 ml (10.1-17.0), OSA: 14.0 ml (13.3-17.9), median (IQR)) or tongue volume (PLWH+OSA: 140.2 ml (125.1-156.9), OSA: 132.4 ml (126.8-154.7)) and a smaller tongue fat content in PLWH+OSA (11.2% (10.2-12.4)) than in the OSA controls (14.8% (13.2-15.5), p=0.046). There was no difference in the dynamic behavior of the UA between the two groups. When pooled together, both static and dynamic imaging metrics could be correlated with measures of UA mechanical properties. Our data suggest similar underlying UA physiology in OSA in subjects with and without HIV.
38095017
ABHD5 protects cardiac function in alcoholic cardiomyopathy via HDAC4-NT to inhibit CAMKII/MEF2 axis.
Excessive intake of Alcohol is associated with a high incidence of alcoholic cardiomyopathy (ACM), which may impair cardiac function. In our study, we explored the Abhydrolase Domain Containing 5 (ABHD5) mechanism in ACM about histone deacetylase 4 (HDAC4) and CaM-CaMKII/MEF2 signaling pathway. Rat models of ACM were established in Wistar rats, and in vitro cell models were constructed in rat cardiomyocytes H9C2 utilizing 12-h of treatment of Alcohol (200 mM) to study the regulatory role of ABHD5 in ACM with the involvement of HDAC4 and CaM-CaMKII/MEF2 signaling pathway, as evidenced by determination of cardiac function, myocardial fibrosis, apoptosis of cardiomyocytes and oxidative stress condition. We found that both ABHD5 mRNA and protein expression was significantly lower in the ACM rats and rat cardiomyocytes H9C2. ACM rats with oe-ABHD5 injection showed repressed myocardial hypertrophy and myocardial fibrosis. Also, overexpression of ABHD5 reduced apoptosis and oxidative stress in H9C2 cells. Mechanistic studies demonstrated that ABHD5 via HDAC4-NT inhibits CAMKII/MEF2 axis. This study highlighted that ABHD5 decreased cardiac hypertrophy and myocardial fibrosis and limited cardiomyocyte apoptosis and oxidative stress injury in ACM.
38095018
Computed tomography -defined sarcopenia is associated with long-term survival among patients undergoing open thoracic aortic reconstruction.
As markers of sarcopenia, psoas muscle areas and indexes measured from computed tomography images have been found to predict long-term mortality in cardiothoracic as well as other surgical cohorts. Our objective was to investigate the association between psoas muscle status, taking into account muscle density in addition to area, and survival among patients undergoing open thoracic aortic reconstruction.
38095019
Differentiated neuroblastoma cells remain epigenetically poised for de-differentiation to an immature state.
Neuroblastoma is the most common extracranial solid tumor of childhood and accounts for a significant share of childhood cancer deaths. Prior studies utilizing RNA sequencing of bulk tumor populations showed two predominant cell states characterized by high and low expression of neuronal genes. Although cells respond to treatment by altering their gene expression, it is unclear whether this reflects shifting balances of distinct subpopulations or plasticity of individual cells. Using neuroblastoma cell lines lacking MYCN amplification, we show that the antigen CD49b distinguishes these subpopulations. CD49b expression marks proliferative cells with an immature gene expression program, while CD49b-negative cells express differentiated neuronal marker genes and are non-cycling. Sorted populations spontaneously switch between CD49b expression states in culture, and CD49b-negative cells can generate rapidly growing, CD49b-positive tumors in mice. Though doxorubicin treatment selectively kills CD49b-positive cells in culture, the CD49b-positive population recovers when treatment is withdrawn. We profiled H3K27ac to identify enhancers and super enhancers that are specifically active in each population and find that CD49b-negative cells maintain the priming H3K4me1 mark at elements that are active in CD49b-high cells. Improper maintenance of primed enhancer elements thus may underlie cellular plasticity in neuroblastoma, representing potential therapeutic targets for this lethal tumor.
38095020
DNA methylation regulates RNA m<sup>6</sup> A modification through transcription factor SP1 during the development of porcine somatic cell nuclear transfer embryos.
Epigenetic modifications play critical roles during somatic cell nuclear transfer (SCNT) embryo development. Whether RNA N6-methyladenosine (m<sup>6</sup> A) affects the developmental competency of SCNT embryos remains unclear. Here, we showed that porcine bone marrow mesenchymal stem cells (pBMSCs) presented higher RNA m<sup>6</sup> A levels than those of porcine embryonic fibroblasts (pEFs). SCNT embryos derived from pBMSCs had higher RNA m<sup>6</sup> A levels, cleavage, and blastocyst rates than those from pEFs. Compared with pEFs, the promoter region of METTL14 presented a hypomethylation status in pBMSCs. Mechanistically, DNA methylation regulated METTL14 expression by affecting the accessibility of transcription factor SP1 binding, highlighting the role of the DNA methylation/SP1/METTL14 pathway in donor cells. Inhibiting the DNA methylation level in donor cells increased the RNA m<sup>6</sup> A level and improved the development efficiency of SCNT embryos. Overexpression of METTL14 significantly increased the RNA m<sup>6</sup> A level in donor cells and the development efficiency of SCNT embryos, whereas knockdown of METTL14 suggested the opposite result. Moreover, we revealed that RNA m<sup>6</sup> A-regulated TOP2B mRNA stability, translation level, and DNA damage during SCNT embryo development. Collectively, our results highlight the crosstalk between RNA m<sup>6</sup> A and DNA methylation, and the crucial role of RNA m<sup>6</sup> A during nuclear reprogramming in SCNT embryo development.
38095021
Effect of a single methyl substituent on the electronic structure of cobaltocene studied by computationally assisted MATI spectroscopy.
Metallocenes represent archetypical organometallic compounds playing key roles in various fields of fundamental and applied chemistry. Many of their unique properties arise from low ionization energies (IE) which can be tuned by introducing substituents into the rings. Here we report the first mass-analyzed threshold ionization (MATI) spectrum of a methylmetallocene, (Cp')(Cp)Co (Cp' = &#951;<sup>5</sup>-C<sub>5</sub>H<sub>4</sub>Me, Cp = &#951;<sup>5</sup>-C<sub>5</sub>H<sub>5</sub>). The presence of a single Me group allows us to study the "pure" effect of methylation without the mutual influence of substituents. The MATI technique provides an extremely high accuracy in determining the adiabatic IE of (Cp')(Cp)Co which equals 5.2097(6) eV. The effect of a Me group on the IE of cobaltocene appears to be 36% stronger than that in bis(&#951;<sup>6</sup>-benzene)chromium. The MATI spectrum of (Cp')(Cp)Co shows a rich vibronic structure from which vibrational frequencies of the free ion are determined. This information provides a solid basis for testing the quality of quantum chemical calculations. Various levels of the DFT and coupled cluster computations are used to describe the structural and electronic transformations accompanying the detachment of an elctron from (Cp')(Cp)Co. New aspects of the methyl substituent influence on the potential energy surfaces, as well as on the inhomogeneous changes in charge density and electrostatic potential caused by ionization, are discussed.
38095022
Clinical validation of NerveTrend versus conventional i-IONM mode of NIM Vital in prevention of recurrent laryngeal nerve events during bilateral thyroid surgery: A randomized controlled trial.
The aim of this study was to test the hypothesis that use of NerveTrend™ mode of intermittent neuromonitoring (i-IONM) during thyroidectomy may identify and prevent impending recurrent laryngeal nerve (RLN) injury.
38095023
L-carnitine pretreatment ameliorates heat stress-induced acute kidney injury by restoring mitochondrial function of tubular cells.
A major complication of heat-related illness is the development of acute kidney injury (AKI) and damage to kidney tubular cells. Because kidney tubular cells utilize fatty acids as a major energy source, impaired fatty acid oxidation (FAO) may be associated with kidney injury due to heat stress. Carnitine is essential in the transportation of fatty acid into mitochondria for FAO. To date, there has been little attention given to the role of carnitine in heat-related illness and AKI. To evaluate the relationship between carnitine inadequacy and heat-related illness severity or AKI, we examined serum carnitine levels in patients with heat-related illness. We also used heat-stressed mice, to investigate the effect of L-carnitine pre-treatment on various kidney functions such as mitochondrial activity, proinflammatory changes in kidney macrophages, and histological damage. We observed an elevation in serum acylcarnitine levels, indicating carnitine insufficiency in patients with severe heat-related illness and/or AKI. L-carnitine pretreatment ameliorated ATP production in murine tubular cell mitochondria and prevented a change in the kidney macrophage population dynamics observed in AKI - a decrease in tissue resident macrophages, influx of bone marrow-derived macrophages, and change toward pro-inflammatory M1 polarization. In conclusion, carnitine insufficiency may be closely associated with severe heat-related illness and related AKI. Enhancement of the FAO pathway by L-carnitine pretreatment may prevent heat stress-induced AKI by restoring mitochondrial function.
38095024
Beast of (renal) Burden? Bst1 expressing neutrophils in kidney injury.
38095025
A Combination of ß-Hydroxybutyrate and Citrate Ameliorates Disease Progression in a Rat Model of Polycystic Kidney Disease.
Our research has shown that interventions producing a state of ketosis are highly effective in rat, mouse, and cat models of polycystic kidney disease (PKD), preventing and partially reversing cyst growth and disease progression. The ketone ß-hydroxybutyrate (BHB) appears to underlie this effect. Additionally, we have demonstrated that naturally formed microcrystals within kidney tubules trigger a renoprotective response that facilitates tubular obstruction clearance in healthy animals but, alternatively, leads to cyst formation in PKD. The administration of citrate prevents microcrystal formation and slows PKD progression. Juvenile Cy/+ rats, a non-orthologous PKD model, were supplemented from 3 to 8 weeks of age with water containing titrated BHB, citrate, or in combination to find minimal effective and optimal dosages, respectively. Adult rats were given a reduced BHB/Citrate combination or equimolar control K/NaCl salts from 8 to 12 weeks of age. Additionally, adult rats were placed in metabolic cages following BHB, citrate, and BHB/Citrate administration to determine the impact on mineral, creatinine, and citrate excretion. BHB or citrate alone effectively ameliorates disease progression in juvenile rats, decreasing markers of cystic disease and, in combination, producing a synergistic effect. BHB/Citrate leads to partial disease regression in adult rats with established cystic disease, inhibiting cyst formation and kidney injury. BHB/Citrate confers benefits via multiple mechanisms, increases creatinine and citrate excretion, and normalizes mineral excretion. BHB and citrate are widely available and generally recognized as safe compounds and, in combination, exhibit high promise for supporting kidney health in polycystic kidney disease.
38095026
The risk assessment of imminent inpatient aggression: A cross-cultural validation study of the dynamic appraisal of situational aggression in Estonia.
The reason for this study was void of a data-driven imminent risk assessment instrument for aggression in psychiatry clinics in Estonia. The predictive accuracy of the observer-rated Dynamic Assessment of Situational Aggression (DASA) has been repeatedly demonstrated. However, the research gap remains regarding a deeper conceptual understanding of the underlying latent structure of the DASA.
38095027
Glatiramer acetate induces mast cell degranulation via MRGPRX2, implications for local and systemic adverse reactions.
38095028
Are Members of Political Out-Groups More Morally or Physically Disgusting?
Recent research has found that Americans are disgusted by anonymous members of their political out-group. Determining whether the disgust elicited by political out-group members is more physical or moral may contribute to the understating of what enables its elicitation and regulation. Building on research showing the experience of moral disgust involves relatively abstract construal and the experience of physical disgust involves relatively concrete construal, we predicted that disgust experienced toward political out-group members is more moral than physical. Two preregistered experiments (total <i>N</i>=854) found that (a) the effect of level of construal on the intensity of disgust from political out-group members is more similar to the effect of level of construal on moral disgust than on physical disgust, and (b) the appraisal underlying disgust from political out-group members involves more abstract than concrete construal, similar to moral disgust. We discuss implications of these findings for intergroup relations and emotion regulation.
38095029
[Postoperative pulmonary torsion after upper lobectomy by thoracotomy].
The aim of this case report is to describe a lobar torsion after elective pulmonary resection. This is a rare but potentially fatal condition in which the lung rotates on its own axis. Although this condition may occur spontaneously, it most often follows lobectomy. Early diagnosis and prompt surgical intervention are essential to prevent complications. Treatment is surgical, and involves repositioning the lung in a physiological position. However, the presence of ischaemic lesions may lead to the resection of the lung portion concerned.
38095030
[Multifocal cerebral venous thrombosis].
Cerebral venous thrombosis is a rare condition and represents a neurological emergency. It is a particular subtype of stroke, characterized by a huge diversity of neurological symptoms. Due to the diversity of its potential clinical presentations, medical imaging plays an important role in its early detection, even on non-dedicated examinations often performed in search of another acute neurological pathology. The aim of this case report is to illustrate the different radiological signs of cerebral venous thrombosis and to discuss the difficulties in diagnosing it by imaging at the acute stage.
38095031
[Febrile cervicalgia revealing infectious epiduritis : a case report].
Infectious epiduritis and epidural abscesses are relatively rare pathologies but with important neurological consequences. A low incidence associated with an insidious clinical presentation leads to frequent delays in diagnosis, which worsen the prognosis of patients with the development of neurological deficits. While the evaluation of risk factors, a careful clinical examination and biological tests can guide to the diagnosis, the key examination remains magnetic resonance imaging (MRI) while lumbar puncture remains contraindicated. Although surgery (spinal decompression) has long been the treatment of choice, the current management of patients with infectious epiduritis is debated between surgery and conservative treatment with systemic antibiotic therapy.
38095032
[Aortic stenosis : new developments in management].
Aortic stenosis (AS) is the most common valve disease in our countries; most often of degenerative origin, its prevalence is constantly increasing due to the aging of the population. Its development is a continuum ranging from aortic sclerosis to severe aortic stenosis, the diagnosis of which is essentially based on transthoracic echocardiography, which will allow classification into subcategories. Even if today no treatment makes it possible to prevent the progression of the disease, the management has clearly evolved with an increasingly important place for new approaches to valve replacement by the percutaneous route, and an indication of management at an increasingly early stage.
38095033
[Cardio-oncology and cardio-obstetrics : crucial role of a multidisciplinary approach].
In this clinical case, we describe the cardio-oncological history and the complexity of the management of a patient presenting a breast cancer diasgnosed during pregnancy followed by a postpartum cardiomyopathy. A multidisciplinary approach is mandatory.
38095034
[Iatrogenic colitis following immunotherapy : monocentric retrospective study at the University Hospital of Liège].
Checkpoint inhibitor colitis is a complication that is often underestimated when it is slow-grade, and results in relatively few hospital admissions compared to its frequency of occurrence. A strict history-taking approach, combined with an endoscopic work-up in cases of severity, is recommended. The use of the fecal calprotectin may also be useful. When used appropriately, the various lines of treatment are generally effective, and second-line therapies (biotherapies) are rarely used. However, recent evidence suggests that patients with severe symptoms should be treated more rapidly with biological therapies, especially if severity is endoscopically confirmed, as corticosteroids carry a greater risk of infection. The objective of this study is to demonstrate the efficacy of non-symptomatic, first and second line therapies for immunotherapy-related colitis in a population of patients at the CHU of Liège.
38095035
[Renal manifestations of syphilis].
Syphilis is an acquired or congenital systemic pathology, currently on the rise in Europe. The clinical manifestations of syphilis are not very specific and variable over time. In this case report, we describe two renal presentations of syphilis in patients followed in a Pre-Exposure Prophylaxis (PrEP) program for the prevention of HIV infection. The specificity of the renal involvement of syphilis, the diagnostic and the therapeutic management will be discussed in this article.
38095036
[Study on the occurrence of adverse health events in nursing homes : contributions from the Liège SENIOR cohort].
The SENIOR study followed a cohort of older people living in nursing homes for 8 years and examined their adverse health events. The results were analysed after 1, 3 and 8 years to identify predictive factors and improve care. After 1 year, residents with poorer motor and muscle function had a higher incidence of adverse health events such as death and falls. Sarcopenia predicted mortality, while poor physical performance was associated with falls. At 3 years, poor nutritional status and poor balance were important predictors of mortality, falls and loss of independence. At 8 years, younger age, higher body mass index, and good physical and cognitive performance were associated with longer survival. The study also examined the impact of the COVID-19 pandemic in nursing homes and found no significant association between frailty, nutrition, muscle strength and COVID-19. In conclusion, functional capacity and nutrition play a crucial role in predicting adverse events in nursing home residents. The results will guide public health policies and clinical interventions to improve quality of life.
38095037
[Encopresis in children, the view of child psychiatry].
The article aims to provide a state of knowledge in the literature on encopresis in the child psychiatric population. The general definition of the symptom and its analysis are presented according to different approaches. Then, the clinic of encopresis is described according to its specificities. The main associated disorders and psychiatric/psychosocial risk factors are discussed in detail. Regarding patient care, the multidisciplinary approach, including the complementarity with the paediatrician, is essential in a number of cases. Finally, family approach and the impact of trauma would be interesting research perspectives.
38095038
[Finerenone (Kerendia®), a new weapon against the chronic kidney disease of a patient with type 2 diabetes].
Finerenone, a new nonsteroidal mineralocorticoid receptor antagonist, showed a significant reduction in a primary composite renal outcome in FIDELIO-DKD and a significant reduction in a primary composite cardiovascular outcome in FIGARO-DKD in patients with type 2 diabetes (T2D) and a chronic kidney disease (CKD). In a subsequent analysis that combined these two clinical trials (FIDELITY), the reduction becomes statistically significant when compared to placebo for both outcomes, with a hazard ratio of 0.86 (95 % confidence interval 0.78-0.95; P = 0.0018) for the cardiovascular outcome and 0.77 (0.67-0.88; P = 0.0002) for the renal outcome. Furthermore, all renal events occurred less frequently with finerenone than with placebo, including the progression to end-stage CKD independently of the baseline levels of glomerular filtration rate and albuminuria and regardless of associated medications (including gliflozins). The safety profile was excellent. However, a significant increase in serum potassium level was observed. Even if it is less pronounced than the increase usually seen with spironolactone, the risk of hyperkalemia requires some caution regarding both patient selection and monitoring. Finerenone (Kerendia®) is indicated in the treatment of CKD with albuminuria in adult patients with T2D. In Belgium, it is reimbursed with conditions in combination with a renin-angiotensin blocker.
38095039
[The management of gout].
We describe the case of a patient with a history of gout, who presents with a new episode of acute gout. Based on this clinical case, we will discuss the management of acute gout. We will then address the management of chronic gout, i.e., the indications for a hypouricemic treatment and the caution required when starting this treatment. Finally, we will address the need for a holistic care, discussing the change of certain co-medications, screening for cardiovascular comorbidities and providing diet and life-style recommendations.
38095040
Windows Scanning Multiomics: Integrated Metabolomics and Proteomics.
Metabolomics and proteomics offer significant advantages in understanding biological mechanisms at two hierarchical levels. However, conventional single omics analysis faces challenges due to the high demand for specimens and the complexity of intrinsic associations. To obtain comprehensive and accurate system biological information, we developed a multiomics analytical method called Windows Scanning Multiomics (WSM). In this method, we performed simultaneous extraction of metabolites and proteins from the same sample, resulting in a 10% increase in the coverage of the identified biomolecules. Both metabolomics and proteomics analyses were conducted by using ultrahigh-performance liquid chromatography mass spectrometry (UPLC-MS), eliminating the need for instrument conversions. Additionally, we designed an R-based program (WSM.R) to integrate mathematical and biological correlations between metabolites and proteins into a correlation network. The network created from simultaneously extracted biomolecules was more focused and comprehensive compared to those from separate extractions. Notably, we excluded six pairs of false-positive relationships between metabolites and proteins in the network established using simultaneously extracted biomolecules. In conclusion, this study introduces a novel approach for multiomics analysis and data processing that greatly aids in bioinformation mining from multiomics results. This method is poised to play an indispensable role in systems biology research.
38095041
Fall 2023 ACIP Update on Meningococcal, RSV, COVID-19, and Other Pediatric Vaccines.
The Advisory Committee on Immunization Practices (ACIP), a group of medical and public health experts that provides advice to the Centers for Disease Control and Prevention (CDC), normally meets three times per year to develop US vaccine recommendations. The ACIP met October 25-26, 2023, to discuss meningococcal vaccines, mpox vaccines, respiratory syncytial virus (RSV) vaccines, influenza vaccines, COVID-19 vaccines, and the combined pediatric and adult immunization schedules for 2024. The ACIP also held special meetings on September 12th and September 22nd to discuss COVID-19 2023-2024 vaccine recommendations and RSV immunization in pregnant women. This update summarizes the proceedings of these meetings that are most relevant to the pediatric population. Major updates for pediatric clinicians include recommendations for XBB monovalent COVID-19 immunization for the 2023-2024 respiratory season, the recently licensed pentavalent MenABCWY meningococcal vaccine and mpox vaccination in high-risk young adults and discussion regarding the parallel strategies of protection against RSV disease in infants via maternal immunization during pregnancy or direct prophylaxis of infants with nirsevimab.
38095043
Resveratrol alleviates imidacloprid-induced mitochondrial apoptosis, necroptosis, and immune dysfunction in chicken lymphocyte lines by inhibiting the ROS/MAPK signaling pathway.
Imidacloprid (IMI) is a neonicotinoid insecticide with the highest global market share, and IMI exposure in the environment can negatively affect many nontarget organisms (a general term for organisms affected by drugs other than target organisms). Resveratrol (RSV), a non-flavonoid polyphenolic organic compound derived from peanuts, grapes, and other plants, has anti-inflammatory and antioxidant effects. It is currently unclear how RSV protects against cell damage caused by IMI. Therefore, we established an experimental model of chicken lymphocyte lines exposed to 110 μg/mL IMI and/or 0.5 μM RSV for 24 h. According to the experimental results, IMI markedly raised intracellular reactive oxygen species levels and diminished the activity of the cellular antioxidant enzymes (CAT, SOD, and GPx), leading to MDA accumulation and decreased T-AOC. JNK, ERK, and P38, the essential components of the mitogen-activated protein kinase (MAPK) signaling pathway, were also expressed more when IMI was present. Additionally, IMI resulted in upregulation of mitochondrial apoptosis (Caspase 3, Caspase 9, Bax, and Cyt-c) and necroptosis (Caspase 8, RIPK1, RIPK3, and MLKL) related factors expression, downregulation of Bcl-2 expression, induction of upregulation of cytokine IL-6 and TNF-α expression, and downregulation of IFN-γ expression. The combined treatment of RSV and IMI significantly reduced cellular oxidative stress levels, inhibited the MAPK signaling pathway, and alleviated IMI-induced mitochondrial apoptosis, necroptosis, and immune dysfunction. To summarize, RSV antagonized IMI-induced mitochondrial apoptosis, necroptosis, and immune dysfunction in chicken lymphocyte lines by inhibiting the ROS/MAPK signaling pathway.
38095042
Unveiling the role of MGMT and DAPK hypermethylation in response to anti-EGFR agents: Molecular insights for advancing HNSCC treatment.
Epidermal growth factor receptor (EGFR) is frequently activated in head and neck squamous cell carcinoma (HNSCC) and serves as a valuable target for therapy. Despite the availability of the EGFR inhibitors Cetuximab, Afatinib, and Allitinib, there are limited predictive markers for their response. Understanding molecular aberrations in HNSCC could facilitate the identification of new strategies for patient clinical and biological classification, offering novel therapeutic avenues.
38095044
What Domains of Belgian Euthanasia Practice are Governed and by Which Sources of Regulation: A Scoping Review.
Multiple sources of regulation seek to shape euthanasia practice in Belgium, including legislation and training. This study comprehensively mapped which of these sources govern which domains of euthanasia practice, such health professionals' obligations, or managing patient requests.
38095046
A case of haemolytic disease of the fetus and newborn attributed to a novel antigen in the RHAG blood group system.
A newborn presented with jaundice in Thailand. The cord red cells tested positive by direct antiglobulin test (DAT) for an unknown maternal red cell antibody. Initial blood group sequencing suggested that the infant carried a novel variant RHAG c.140T>C, responsible for a low-prevalence antigen in the RHAG blood group system (ISBT 030). We report here on testing of samples from the infant's parents and older sibling to define a new antigen in the RHAG system.
38095045
Maternal care in wild toque macaques (Macaca sinica) involves prolonged lactation and interbirth intervals as adaptations to reduce maternal depletion and infant mortality in harsh environments.
Weaning age in primates has been challenging to measure and new methods, involving molecular biomarkers in feces, tissue, or teeth have contributed to a solution. Here, we used a direct approach by briefly anesthetizing 442 female toque macaques (Macaca sinica) of Sri Lanka (over a 17-year period) and manually testing their mammary tissue for the presence or absence of milk. Milk tests were related to known offspring ages and maternal care behaviors and indicated that older infants suckled milk well past the weaning age of 7 months that is often reported for food-provisioned primates. Mothers strongly rejected their infants' nursing attempts in two phases, the first at 7 months as an honest signal "giving notice" promoting a shift to greater independence from milk to solid food, and when "shutting down" at final weaning after 12-18 months. The shift to supplementary lactation coincided also with the cessation of mothers carrying their infants and a resumption of cycling. All infants up to 7.2 months suckled milk, 91% of them did up to 18 months, this continued for 42% of infants beyond 18 months, and normally none received milk after 22 months. Lactation extended into 2.2% of cycling and 10.7% of pregnant females (up to 50% of gestation). The interbirth interval was prolonged by factors predicted to draw on female metabolic energy reserves and included the duration of lactation, growth among primiparas, and dietary limitations. The last also increased menarche. Females offset the metabolic costs of lactation with increased foraging and catabolism, but infants died when lactation costs seemingly compromised maternal condition. The prolonged lactation and slowed reproduction are considered adaptations to promote infant survival and growth in an environment where the natural food supply limits population growth and competition for food and water impacts the mortality of the youngest the most.
38095049
Brief video training for suicide prevention in veterans: A randomized controlled trial of VA S.A.V.E.
VA S.A.V.E. (Signs; Ask; Validate; Encourage/Expedite) is a gatekeeper training developed by the Department of Veterans Affairs (VA) that teaches individuals to identify and assist veterans at risk for suicide. Although VA S.A.V.E. has been widely disseminated, rigorous evaluation is lacking.
38095050
Wall-associated kinase GhWAK13 mediates arbuscular mycorrhizal symbiosis and Verticillium wilt resistance in cotton.
The cell wall is the major interface for arbuscular mycorrhizal (AM) symbiosis. However, the roles of cell wall proteins and cell wall synthesis in AM symbiosis remain unclear. We reported that a novel wall-associated kinase 13 (GhWAK13) positively regulates AM symbiosis and negatively regulates Verticillium wilt resistance in cotton. GhWAK13 transcription was induced by AM symbiosis and Verticillium dahliae (VD) infection. GhWAK13 is located in the plasma membrane and expressed in the arbuscule-containing cortical cells of mycorrhizal cotton roots. GhWAK13 silencing inhibited AM colonization and repressed gene expression of the mycorrhizal pathway. Moreover, GhWAK13 silencing improved Verticillium wilt resistance and triggered the expression of immunity genes. Therefore, GhWAK13 is considered an immune suppressor required for AM symbiosis and disease resistance. GhWAK7A, a positive regulator of Verticillium wilt resistance, was upregulated in GhWAK13-silenced cotton plants. Silencing GhWAK7A improved AM symbiosis. Oligogalacturonides application also suppressed AM symbiosis. Finally, GhWAK13 negatively affected the cellulose content by regulating the transcription of cellulose synthase genes. The results of this study suggest that immunity suppresses AM symbiosis in cotton. GhWAK13 affects AM symbiosis by suppressing immune responses.
38095052
Neurophobia among resident physicians in the emergency service.
Neurophobia is defined as the fear towards clinical neurology caused by the inability to apply theoretical knowledge to practical clinical situations. This phenomenon is not restricted to medical students and has never been studied before in the Emergency Department. We aimed to study how resident doctors perceive their knowledge in neurology and urgent neurological conditions as well as possible causes for said fears.
38095048
Pre-erythrocytic malaria vaccines: RTS,S, R21, and beyond.
38095051
Unexpected Low Temperature Activity with Low N2O Emission of Stabilized Al-rich Zeolite Beta for Selective Catalytic Reduction of NOx.
The low temperature activity of Fe-loaded zeolites as selective catalytic reduction of NOx by NH3 (NH3-SCR) catalysts is a critical drawback for practical application. Here, we found unexpected improvement of low temperature activity by our proposed postsynthetic treatment. An Al-rich zeolite beta (Si/Al = 5) is employed as the catalyst support, and the parent sample is dealuminated for higher hydrothermal stability, followed by the liquid-mediated stabilization treatment and impregnation. It is found that stabilized samples feature excellent low temperature activity and high N2 selectivity even for a long-term operation, along with the ability to maintain high NOx conversion after aging. The improved SCR activity should be attributed to abundant acid sites in Al-rich framework and better stabilization of monomeric iron species after the stabilization treatment. Furthermore, the low yield of side product N2O is probably due to the absence of the generation of NH4NO3 during NH3-SCR catalyzed by Fe-loaded zeolites.
38095053
[Clinical profile and non-recreational methamphetamine abuse (shabu) among stroke patients in the Philippine population].
Chronic non-recreational use of methamphetamine (shabu) is increasing among the Filipino population in Barcelona. The Asian population presents a different stroke pattern, with a higher incidence of haemorrhage, and different vascular risk factors and health behaviours. The objective of this study is to describe the stroke profile and incidence of methamphetamine use in patients of Filipino origin admitted to our centre.
38095055
[Occupational performance skills in Parkinson's disease: relationship with health-related quality of life and caregiver burden. Letter].
38095054
[Review of a series of cases of Creutzfeldt-Jakob disease in a tertiary care hospital].
We analysed a series of patients with sporadic Creutzfeldt-Jakob disease in our setting.
38095057
Self-Assembled Core-Shell Structure MgO@TiO<sub>2</sub> as a K<sub>2</sub>CO<sub>3</sub> Support with Superior Performance for Direct Air Capture CO<sub>2</sub>.
Traditional carbon capture and storage technologies for large point sources can at best slow the rate of increase in atmospheric CO<sub>2</sub> concentrations. In contrast, direct capture of CO<sub>2</sub> from ambient air, or "direct air capture" (DAC), offers the potential to become a truly carbon-negative technology. Composite solid adsorbents fabricated by impregnating a porous matrix with K<sub>2</sub>CO<sub>3</sub> are promising adsorbents for the adsorption capture of CO<sub>2</sub> from ambient air. Nevertheless, the adsorbent can be rapidly deactivated during continuous adsorption/desorption cycles. In this study, MgO-supported, TiO<sub>2</sub>-stabilized MgO@TiO<sub>2</sub> core-shell structures were prepared as supports using a novel self-assembled (SA) method and then impregnated with 50 wt % K<sub>2</sub>CO<sub>3</sub> (K<sub>2</sub>CO<sub>3</sub>/MgO@TiO<sub>2</sub>, denoted as SA-KM@T). The adsorbent exhibits a high CO<sub>2</sub> capture capacity of &#8764;126.6 mg CO<sub>2</sub>/g sorbent in direct air adsorption and maintained a performance of 20 adsorption/desorption cycles at 300 &#176;C mid-temperature, which was much better than that of K<sub>2</sub>CO<sub>3</sub>/MgO. Analysis proved that the core-shell structure of the support effectively inhibited the reaction between the active component (K<sub>2</sub>CO<sub>3</sub>) and the main support (MgO) by the addition of TiO<sub>2</sub>, resulting in higher reactivity, thermal stability, and antiagglomeration properties. This work provides an alternative strategy for DAC applications using adsorbents.
38095056
HERTHENA-Lung02: phase III study of patritumab deruxtecan in advanced <i>EGFR</i>-mutated NSCLC after a third-generation EGFR TKI.
After disease progression on EGFR tyrosine kinase inhibitor (TKI) therapy, patients with <i>EGFR</i>-mutated NSCLC who are then treated with platinum-based chemotherapy (PBC) obtain only limited clinical benefit with transient responses. Therapies with greater efficacy and tolerable safety profiles are needed in this setting. The receptor tyrosine kinase HER3 is widely expressed in NSCLC, and increased expression is associated with poor treatment outcomes. In the U31402-A-U102 phase I trial, HER3-DXd showed promising antitumor activity with manageable safety in heavily pre-treated patients with <i>EGFR</i>-mutated NSCLC across a range of tumor HER3 expression levels and EGFR TKI resistance mechanisms. HERTHENA-Lung02 is the first phase III trial to evaluate the safety and efficacy of HER3-DXd versus PBC in patients with progression on a third-generation EGFR TKI. <b>Clinical Trial Registration:</b> NCT05338970&#160;(clinicaltrials.gov); 2021-005879-40 (EudraCT Number).
38095058
The multifunctional role of intrinsic disorder in NF-κB signaling.
The nuclear factor-κB (NF-κB) transcription activation system involves disordered regions of both the NF-κB dimers and their inhibitors, the IκBs. The system is well-studied both at the cellular and biophysical levels affording a unique opportunity to compare and contrast the conclusions from both types of experiments. Through a combination of both experiments and theory, we have discovered that the RelA/p50 heterodimer and its inhibitor IκBα operate under kinetic control. Intrinsically disordered parts of both proteins are directly involved in temporal control and their folding and unfolding determines the rates of various processes. In this review, we show how the dynamic state of the intrinsically disordered sequences define the rates of intracellular processes.
38095059
Unveiling breast cancer risk profiles: a survival clustering analysis empowered by an online web application.
<b>Aim:</b> To develop a shiny app for doctors to investigate breast cancer treatments through a new approach by incorporating unsupervised clustering and survival information. <b>Materials &amp; methods:</b> Analysis is based on the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset, which contains 1726 subjects and 22 variables. Cox regression was used to identify survival risk factors for K-means clustering. Logrank tests and C-statistics were compared across different cluster numbers and Kaplan-Meier plots were presented. <b>Results &amp; conclusion:</b> Our study fills an existing void by introducing a unique combination of unsupervised learning techniques and survival information on the clinician side, demonstrating the potential of survival clustering as a valuable tool in uncovering hidden structures based on distinct risk profiles.
38095060
The PDLIM family of actin-associated proteins and their emerging role in membrane trafficking.
The PDZ and LIM domain (PDLIM) proteins are associated with the actin cytoskeleton and have conserved in roles in metazoan actin organisation and function. They primarily function as scaffolds linking various proteins to actin and its binding partner α-actinin via two conserved domains; an N-terminal postsynaptic density 95, discs large and zonula occludens-1 (PDZ) domain, and either single or multiple C-terminal LIN-11, Isl-1 and MEC-3 (LIM) domains in the actinin-associated LIM protein (ALP)- and Enigma-related proteins, respectively. While their role in actin organisation, such as in stress fibres or in the Z-disc of muscle fibres is well known, emerging evidence also suggests a role in actin-dependent membrane trafficking in the endosomal system. This is mediated by a recently identified interaction with the sorting nexin 17 (SNX17) protein, an adaptor for the trafficking complex Commander which is itself intimately linked to actin-directed formation of endosomal recycling domains. In this review we focus on the currently understood structural basis for PDLIM function. The PDZ domains mediate direct binding to distinct classes of PDZ-binding motifs (PDZbms), including α-actinin and other actin-associated proteins, and a highly specific interaction with the type III PDZbm such as the one found in the C-terminus of SNX17. The structures of the LIM domains are less well characterised and how they engage with their ligands is completely unknown. Despite the lack of experimental structural data, we find that recently developed machine learning-based structure prediction methods provide insights into their potential interactions and provide a template for further studies of their molecular functions.
38095061
Atopic Dermatitis in the Elderly Population.
Atopic dermatitis is a common inflammatory disease with a chronic and relapsing course. Although considered a childhood disease, it is now evident that atopic dermatitis is also common in adulthood and in the elderly population. Atopic dermatitis typically manifests with bilateral and symmetrical eczematous lesions on the face, trunk and skin folds. Itch is invariably present and may be very severe, markedly  affecting daily life and sleep. In older adults, atopic dermatitis may have a high level of impact on quality of life, frequently burdening an already complex comorbid situation. The full assessment of disease burden (localizations, itch severity, sleep alterations, impact on quality of life, disease history, comorbidities) is crucial to identify the most appropriate treatment. In many cases, moderate-to-severe atopic dermatitis in the elderly population can be successfully and safely treated with biological agents inhibiting the interleukin-4/-13 pathway, whereas the use of Janus kinase inhibitors may pose concerns about the safety profile.
38095063
Identification of Structural Motifs Critical for Human G6PC2 FunctionInformed by Sequence Analysis and an AlphaFold2-Predicted Model.
G6PC2 encodes a glucose-6-phosphatase (G6Pase) catalytic subunit, primarily expressed in pancreatic islet beta cells, that modulates the sensitivity of insulin secretion to glucose and thereby regulates fasting blood glucose (FBG). Mutational analyses were conducted to validate an AlphaFold2 (AF2)-predicted structure of human G6PC2 in conjunction with a novel method to solubilize and purify human G6PC2 from a heterologous expression system. These analyses show that residues forming a predicted intramolecular disulfide bond are essential for G6PC2 expression and that residues forming part of a type 2 phosphatidic acid phosphatase (PAP2) motif are critical for enzyme activity. Additional mutagenesis shows that residues forming a predicted substrate cavity modulate enzyme activity and substrate specificity and residues forming a putative cholesterol recognition amino acid consensus (CRAC) motif influence protein expression or enzyme activity. This CRAC motif begins at residue 219, the site of a common G6PC2 non-synonymous single nucleotide polymorphism (SNP), rs492594 (Val219Leu), though the functional impact of this SNP is disputed. In microsomal membrane preparations, the L219 variant has greater activity than the V219 variant, but this difference disappears when G6PC2 is purified in detergent micelles. We hypothesize that this was due to a differential association of the two variants with cholesterol. This concept was supported by the observation that the addition of cholesteryl hemi-succinate to the purified enzymes decreased the Vmax of the V219 and L219 variants ~8-fold and ~3 fold, respectively. We anticipate that these observations should support the rational development of G6PC2 inhibitors designed to lower FBG.
38095062
Leptin and adiposity measures from birth to later childhood: Findings from the Hyperglycemia and Adverse Pregnancy Outcomes Follow-Up Study.
Cord blood (CB) leptin is positively associated with adiposity at birth, but the association with child adiposity is unclear.
38095064
Case report: ocular manifestations of a gain-of-function mutation in <i>CLCN6</i>, a newly diagnosed disease.
Label="BACKGROUND" NlmCategory="UNASSIGNED">In 2020, a new disease was reported by Polovitskaya et al., caused by a monoallelic, gain-of-function mutation in <i>CLCN6</i>, encoding the ClC-6 Cl-/H&#177;exchanger.
38095065
Correlates of malnutrition in patients with heart failure: the role of social support.
Heart failure (HF) is a major public health challenge. Malnutrition has a significant effect on HF prognosis. Understanding the impact of social and clinical factors on the risk of malnutrition is necessary because it may aid in improving the health status of HF patients.
38095066
[Adherence to the Mediterranean diet and eating behaviour in Spanish schoolchildren].
eating behaviors may modulate or influence diet quality and the degree of adherence to the Mediterranean diet in children and adolescents.
38095067
Efficacy of Intravenous Nitrates for the Prevention of Coronary Artery Spasm During Pulsed Field Ablation of the Mitral Isthmus.
38095068
Current Status and Principles for the Treatment and Prevention of Diabetic Foot Ulcers in the Cardiovascular Patient Population: A Scientific Statement From the American Heart Association.
Despite the known higher risk of cardiovascular disease in individuals with type 2 diabetes, the pathophysiology and optimal management of diabetic foot ulcers (DFUs), a leading complication associated with diabetes, is complex and continues to evolve. Complications of type 2 diabetes, such as DFUs, are a major cause of morbidity and mortality and the leading cause of major lower extremity amputation in the United States. There has recently been a strong focus on the prevention and early treatment of DFUs, leading to the development of multidisciplinary diabetic wound and amputation prevention clinics across the country. Mounting evidence has shown that, despite these efforts, amputations associated with DFUs continue to increase. Furthermore, due to increasing patient complexity of management secondary to comorbid conditions, such as cardiovascular disease, the management of peripheral artery disease associated with DFUs has become increasingly difficult, and care delivery is often episodic and fragmented. Although structured, process-specific approaches exist at individual institutions for the management of DFUs in the cardiovascular patient population, there is insufficient awareness of these principles in the general medicine communities. Furthermore, there is growing interest in better understanding the mechanistic underpinnings of DFUs to better define personalized medicine to improve outcomes. The goals of this scientific statement are to provide salient background information on the complex pathogenesis and current management of DFUs in cardiovascular patients, to guide therapeutic and preventive strategies and future research directions, and to inform public policy makers on health disparities and other barriers to improving and advancing care in this expanding patient population.