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Strategies of Well-being Training and Resilience
Walters DM and Maddaus M
As cardiothoracic surgeons, we face frequent challenges to our well-being and our ability to function as our best selves. Building personal resilience is an important way to help us manage these challenges. Here, the authors outline the scope of the problem, the consequences of burnout, and offer 4 strategies to train ourselves to be more resilient: (1) Pursuit of fulfillment, (2) Cultivation of community and belonging, (3) Mitigation of microstresses and avoiding feelings of overwhelm, and (4) Building a "resilience bank account."
Current Advances in the Management of Congenital Adrenal Hyperplasia
Bouliari A, Bullard F, Lin-Su K and Lekarev O
Congenital adrenal hyperplasia (CAH) is an autosomal recessive genetic condition caused by various enzyme deficiencies that result in disruptions of pathways of adrenal steroidogenesis. 21-hydroxylase deficiency is the most common form of CAH and has a variable phenotype which ranges a spectrum, from the most severe salt-wasting type to the simple-virilizing type and the least severe nonclassical form. Patients with CAH are at risk for various comorbidities due to the underlying adrenal hormone production imbalance as well as the treatment of the condition, which typically includes supraphysiologic glucocorticoid dosing. Children and adults require frequent monitoring and careful medication dosing adjustment. However, there are multiple novel therapies on the horizon that offer promise to patients with CAH in optimizing their treatment regimens and reducing the risk of comorbidities.
Pectus Disorders: Excavatum, Carinatum and Arcuatum
Notrica DM, McMahon LE and Jaroszewski DE
This article reviews pectus excavatum, carinatum, and arcuatum. Topics covered include etiology, epidemiology, associated syndromes, physiologic impact, workup, indications for treatment, surgical and nonsurgical therapy, results, complications, and emerging therapies. Pectus excavatum is an inward deformation of the sternum and/or anterior chest wall. Pectus carinatum is ether an outward protrusion or tilt of the sternum with potential psychological impact, but no demonstrated physiologic impact. Nonoperative compression bracing is successful in carinatum patients with chest wall flexibility who are compliant with a bracing program. Pectus arcuatum is an abnormally short, fully fused sternum with a high anterior protrusion.
Common Pediatric Urologic Conditions: Contemporary Management of Cryptorchidism, the Retractile Testis, and Phimosis
Huen K and Richardson S
Undescended testis is the most common genital disorder identified at birth. Boys who do not have spontaneous descent of the testis at 6 months of age, adjusted for gestational age, should be referred to pediatric urology for timely orchiopexy. Retractile testes are at risk for secondary ascent of the testes and should be monitored by physical examination annually. If there is concern for ascent of the testis, pediatric urology referral is recommended. Most cases of phimosis can be managed medically with topical corticosteroids and manual retraction of the foreskin.
Understanding the Negative Effect of Stigma: A Pediatrician's Guide to Employing Anti-stigma Language/Care to Improve Engagement and Outcomes
Deall T and Wright T
A primer for pediatric providers on understanding stigma in health care, the terminology and types of stigma, the conditions commonly faced with stigma in pediatrics, the components of evidence-based anti-stigma initiatives, and guidance to effect change within a pediatric practice. The authors outline the negative effects of stigma in pediatrics and how to combat the problem at the source, and explore self-stigma, public stigma, and structural stigma and how it applies to weight, diabetes, disability, HIV, mental health, and substance use in pediatrics.
Etiology of the Neonatal Hypoglycemias
Stanley CA and De Leon DD
To provide a more appropriate foundation for dealing with the problem of hypoglycemia in newborn infants, this article focuses on the mechanisms which underlie the various forms of neonatal hypoglycemia and discusses their implications for newborn care. Evidence indicates that all of the major forms of neonatal hypoglycemia are the result of hyperinsulinism due to dysregulation of pancreatic islet insulin secretion. Based on these observations, the authors propose that routine measurement of B-hydroxybutyrate should be considered an essential part of glucose monitoring in newborn infants.
Novel Approaches to Patients with Differences of Sex Development
Ochoa B, Weidler EM, Parks MA, Speck KE and van Leeuwen K
Patients with differences of sex development (DSDs) have complex anatomy and surgical needs related to both Mullerian and non-Mullerian structures. Approaches to vaginal reconstruction for these conditions are guided by individual anatomy, with the goal of establishing unobstructed outflow for the reproductive, urinary, and gastrointestinal tracts. Patients may have anatomy requiring vaginoplasty for either outflow tract obstruction or chosen sexual function. In this article, the authors focus on management of differences in vaginal anatomy with delayed vaginoplasty for the newborn with DSD.
Providing Compassionate, Evidence-Based Care for Refugee, Immigrant, and Migrant Children
Ibrahim A, Linton JM and Dawson-Hahn E
Immigrant children experience diverse migration paths to the United States facing unique challenges that impact their health and well-being. This article provides an overview of the pathways to health care and physical, mental, and behavioral health considerations for refugee and immigrant children. Health equity and cultural humility frameworks are reviewed. Approach to care guidance and clinical pearls are provided for the initial medical assessment in addition to medical screening, mental health, education, and developmental health. The importance of health literacy and advocacy are highlighted, emphasizing their ability to address health inequities and improve care.
Respiratory Syncytial Virus: Epidemiology, Burden of Disease, and Clinical Update
Rago ARP, D'Arrigo SF, Osmani M, Espinosa CM and Torres CM
Respiratory syncytial virus (RSV) is a common viral pathogen that accounts about 33 million cases of acute lower respiratory tract infection (LRTI) worldwide in children under the age of 5 years each year. High-risk populations, particularly preterm infants, those with underlying chronic lung disease, congenital heart disease, or compromised immune systems, are afflicted most significantly. RSV infection is characterized by significant amount of mucus and submucosal edema in the respiratory tract, leading to congestion and, oftentimes, significant respiratory distress. Antigen- and PCR-based testing are used to diagnose RSV infection.
Financial Well-Being for Thoracic Surgeons
Chai LF, Salna MP and Stanifer BP
The authors provide a brief overview for thoracic surgeons in topics essential to achieving financial well-being as a student, trainee, practicing surgeon, and beyond. While broad in nature, the authors' article is comprehensive, and they cover topics including student loans, asset and wealth management, investment opportunities, financial and estate planning, and insurances. It is hoped that the information provided will allow thoracic surgeons to become more familiar with the financial topics that pertain to thoracic surgeons and provide an introduction to explore financial wellness and literacy more thoroughly.
Hobbies, Distractions, Obsessions, and Addictions
Gulati S and Marshall MB
A career in cardiothoracic surgery takes a psychological and emotional toll, which is likely increased by recent changes in our health care environment. The benefits of leisure pursuits are severalfold, one of which includes supporting physician wellness. However, we are at risk of relying on unhealthy mechanisms to provide relief. The incidence of addiction and substance abuse is high, particularly among women surgeons. There are a variety of opportunities to help ourselves and support our colleagues. We need to promote healthy activities outside of our profession for the long-term well-being of cardiothoracic surgeons and our specialty.
Abuse, Bullying, Harassment, Discrimination, and Allyship in Cardiothoracic Surgery
Contreras N, Essig R, Magarinos J and Pereira S
Abuse, bullying, harassment, and discrimination are prominent workplace occurrences within cardiothoracic (CT) surgery that cause burnout and threaten the well-being of surgeons. Under-represented and marginalized groups experience higher incidences of these negative events, and CT surgery is one of the least diverse specialties. The CT surgery workforce and institutional leadership must prioritize mentorship, sponsorship, and allyship to promote a diverse and healthy specialty for surgeon recruitment, growth, and job satisfaction.
Approach to Constipation in Children: Recommendations for Evaluation and Management
Maselli KM, Shah NR and Speck KE
Constipation is common in childhood, and most patients can be successfully managed by their primary care provider. However, some patients will require more specialized management either due to an underlying congenital colorectal disorder such as Hirschsprung disease or anorectal malformation or due to severe functional constipation that is refractory to medical management.
Overview of Systemic Autoinflammatory Diseases
Nazzar Romero S and McCurdy D
Systemic autoinflammatory diseases (SAID) are a growing family of disorders of the innate immune system. Over the years, there have been changes in the definition, classification and nomenclature of SAID as new syndromes and pathophysiologic mechanisms continue to be described. Recognizing the clinical manifestations of SAID is important for their early diagnosis and management. The field continues to advance with potential new therapies underway.
Managing Career Transitions in Cardiothoracic Surgery
Hui DS, Espinosa JA and Carpenter AJ
Transitions during a career in cardiothoracic surgery include transition to practice following residency, multiple transitions over the course of the career, and transition to retirement. Each carries some degree of uncertainty and stress, and early preparation for each transition is key to success. A clear understanding of both professional and personal goals drives decisions and choices along the course of a career. It is crucial to seek legal counsel with expertise in physician employment contracts. Developing collegial and collaborative relationships should be a focus throughout one's career. This article outlines the key elements to successful career progression.
Personal Relationships and Well-being for Cardiothoracic Surgeons
Ungerleider JD, Jones-Ungerleider KC, Ungerleider GD and Ungerleider RM
This article summarizes relevant research on relational psychology and interpersonal neurobiology and how it applies to cardiothoracic surgeons, their partners and their children. It also provides a synopsis of data retrieved from a well-being survey of cardiothoracic surgeons in the AATS, as well as a separate survey of the well-being experiences of their significant others. Additionally, the article makes recommendations for improving the well-being of cardiothoracic surgeons, as well as their relationships with their partners and children.
Monochorionic Twin Complications and Fetoscopic Interventions
Gebb JS, Khalek N, Whitehead MT and Oliver ER
Monochorionic twins are at risk for complications due to the presence of placental vascular anastomoses, including twin-twin transfusion syndrome, twin anemia-polycythemia sequence, selective fetal growth restriction, and twin reversed arterial perfusion sequence. While ultrasound is the primary modality to screen for the development of these complications, MRI plays an important role in assessing monochorionic twin pregnancies for the development of other complications, such as neurologic injury. In this article, the authors review the ultrasound imaging findings associated with monochorionic twin complications, management options, and the role for MRI in these pregnancies.
Safety and Optimizing Ergonomics for Cardiothoracic Surgeons
Venkateswaran S, Wang D, Potter AL and Jeffrey Yang CF
Cardiothoracic surgery, demanding in nature, often results in surgeons suffering from musculoskeletal injuries, causing chronic pain and leading to premature retirement. A significant majority report experiencing pain, exacerbated by minimally invasive techniques such as video-assisted thoracoscopic surgery. Despite this, many surgeons delay seeking medical assistance. To mitigate these risks, preventative strategies such as strength exercises, stretching during operations, and taking brief breaks are crucial. However, the surgical community faces a shortage of institutional support and comprehensive ergonomic education. Advancements in technology, including artificial intelligence and virtual reality, could offer future solutions.
Sleep, Nutrition, and Health Maintenance in Cardiothoracic Surgery
Obeid JM, Sadeghi JK, Wolf AS and Bremner RM
Cardiothoracic surgeons work in high-intensity environments starting in surgical training and throughout their careers. They deal with critical patients. Their routine procedures are delicate, require extensive attention to detail, and can have detrimental effects on patients' lives. Cardiothoracic surgeons are required to perform at their best capacity incessantly. To do this, they must safeguard their mental and physical well-being. Preserving health through sleep, nutrition, exercise, and routine medical checkups ensures a cardiothoracic surgeon's well-being. Great personal effort and discipline is required to maintain health in a busy schedule. We offer our best recommendations from expert peers in the field.
Wellness Strategies Among Bad Outcomes and Complications
Bostock IC and Antonoff MB
Surgery of the chest is high stakes, and adverse events are common. Given the frequency and severity of such complications, cardiothoracic surgeons are at particularly high risk of becoming second victims. Even though our primary commitment as doctors is to take care of our patients, surgeons may fall into the emotional and intellectual trap of taking on the whole responsibility of a patient's poor outcome. This viewpoint may lead the physician to develop a heightened self-doubt, greater insecurity, and imposter syndrome, further affecting their ability to prevent complications and tackle difficult cases in the future.
Caring for Patients and Populations: A Political or Medical Platform
Berkowitz CD
Fetal Head and Neck Imaging
Patino M, Jaimes C and Robson CD
Prenatal MRI plays an essential role in the evaluation of the head and neck. This article overviews technical considerations and both isolated and syndromic anomalies of the fetal calvarium, globes and orbits, ears, maxilla, mandible, and neck.
Eating Disorders: All that a Pediatrician Should Know
Adams KN and Hovel E
Eating Disorders are psychiatric conditions that can manifest clinically as malnutrition due to restrictive eating and weight control behaviors or obesity due to binge eating. Eating disorders such as anorexia and bulimia nervosa have peak onset during adolescence and young adulthood. This population is at the highest risk due to psychosocial changes surrounding identity development and body image that occurs during this life-stage. Though binge eating disorder and avoidant/restrictive food intake disorder are not characterized by body image overvaluation, peak onset is also during adolescence and young adulthood.
Preventing Behavioral Human Immunodeficiency Virus Infections in Adolescents and Young Adults
Ryan RL, Emmanuel PJ and Sanders LJ
HIV prevention in adolescents and young adults (AYA) requires a multi-pronged strategy encompassing behavioral, biologic, and structural approaches. This article reviews the epidemiology of HIV infection in the United States and its pathogenesis and transmission. Prevention approaches are discussed in more detail, with an emphasis on how each approach is relevant to AYA populations. Information is summarized in a resource table with links to references and in-depth discussions of the topics reviewed in this article.
Maternal Postpartum Depression Screening and Early Intervention in the Neonatal Intensive Care Unit
Hukill JF, Blanco MA, ElSeed Peterson EE and Torres CM
Families with infants admitted to the neonatal intensive care unit (NICU) are at a markedly increased risk of developing postpartum depression (PPD) because of the stressors they experience by having an infant in this intensive setting. Routine screening for PPD is not regularly performed for these families because many NICUs do not offer it and well-child visits are missed while the infant is hospitalized. Because the identification and treatment of PPD is often missed in these families, screening needs to be administered in the NICU to ensure improved outcomes.
A Review of Community-Based Gun Violence Prevention Programs and the Physician's Role
DeBlieux PJ, Alexander LF, Nookala N and Nereim C
Gun violence (GV) and safety is a contentious topic in the United States, despite increasing morbidity and mortality among children and adolescents. It is important for physicians to take a role in preventing future GV. This article aims to present several methods that physicians can use to prevent GV in their own communities, ranging from implementation of large-scale intervention programs to simple screenings and anticipatory guidance. As the problem of GV persists, it is important for physicians to use their role to identify individuals who are at high-risk and advocate for changes that will benefit their future health.
Childhood Behind Bars: Children and the US Juvenile Legal System
Barnert ES
This article examines the epidemiology of the US juvenile legal system, which disproportionately impacts youth with multiple marginalized identities and exacerbates health inequities. Policy changes that can improve the treatment of children who display disruptive behavior are highlighted, so as to lay out a path forward for supporting children and enhancing health equity while bolstering public safety. Finally, this article concludes that the systemic racism pervasive in the juvenile legal system signals an important role for pediatrics to advance racial equity and transform our approach to childhood.
Pediatric Immune Thrombocytopenia
Gotesman M, Shear M, Raheel S, Procassini M and Panosyan EH
Pediatric immune thrombocytopenia (ITP) is a fairly common bleeding disorder PRESENTING with a decreased number of platelets. The typical clinical presentation involves mild bleeding symptoms with bruising and petechiae and occasional mucosal bleeding. ITP is thought to be an autoimmune disorder and more recently other mechanisms have been described. Most cases resolve spontaneously and can undergo watchful waiting as the platelet count improves. Initially, steroids or intravenous immunoglobulin G (IVIg) can be used to increase platelets. For those cases that do not resolve and become persistent or chronic, there are multiple treatment options, with new agents being studied in adults that will hopefully make it to clinical trials in pediatrics in the future.
Optimizing Advanced Imaging of the Pediatric Patient in the Emergency Department: Policy Statement
, , , Marin JR, Lyons TW, Claudius I, Fallat ME, Aquino M, Ruttan T and Daugherty RJ
Advanced imaging, including ultrasonography, computed tomography, and magnetic resonance imaging (MRI), is an integral component to the evaluation and management of ill and injured children in the emergency department. As with any test or intervention, the benefits and potential impacts on management must be weighed against the risks to ensure that high-value care is being delivered. There are important considerations specific to the pediatric patient related to the ordering and interpretation of advanced imaging. This policy statement provides guidelines for institutions and those who care for children to optimize the use of advanced imaging in the emergency department setting and was coauthored by experts in pediatric and general emergency medicine, pediatric radiology, and pediatric surgery. The intent is to guide decision-making where children may access care.
Cost-Consequence Analysis of Deprescribing to Optimize Health Outcomes for Frail Older People: A Within-Trial Analysis
Worz C
Optimizing Advanced Imaging of the Pediatric Patient in the Emergency Department: Technical Report
, , , Marin JR, Lyons TW, Claudius I, Fallat ME, Aquino M, Ruttan T and Daugherty RJ
Advanced diagnostic imaging modalities, including ultrasonography, computed tomography, and magnetic resonance imaging (MRI), are key components in the evaluation and management of pediatric patients presenting to the emergency department. Advances in imaging technology have led to the availability of faster and more accurate tools to improve patient care. Notwithstanding these advances, it is important for physicians, physician assistants, and nurse practitioners to understand the risks and limitations associated with advanced imaging in children and to limit imaging studies that are considered low value, when possible. This technical report provides a summary of imaging strategies for specific conditions where advanced imaging is commonly considered in the emergency department. As an accompaniment to the policy statement, this document provides resources and strategies to optimize advanced imaging, including clinical decision support mechanisms, teleradiology, shared decision-making, and rationale for deferred imaging for patients who will be transferred for definitive care.
Characteristics, trends, and management of Penile cancer in the United States: A population-based study
Bologna E, Licari LC, Franco A, Ditonno F, Manfredi C, De Nunzio C, Perdona S, Brassetti A, Leonardo C, Coogan CL, Cherullo EE and Autorino R
Penile cancer (PeCa) is a rare disease. HPV infection, smoking, phimosis, and lichen sclerosus represent well-known associated risk factors.
Relationship between first trimester physical activity and premature rupture of membranes: a birth cohort study in Chinese women
Lv C, Lu Q, Zhang C, Yan S, Chen H, Pan XF, Fu C, Wang R and Song X
This study aimed to examine prospective associations of different intensity levels and types of physical activity (PA) in early pregnancy with premature rupture of membranes (PROM) among Chinese pregnant women.
Biomarkers of mortality in adults and adolescents with advanced HIV in sub-Saharan Africa
Riitho V, Connon R, Gwela A, Namusanje J, Nhema R, Siika A, Bwakura-Dangarembizi M, Musiime V, Berkley JA, Szubert AJ, Gibb DM, Walker AS, Klein N and Prendergast AJ
One-third of people with HIV in sub-Saharan Africa start antiretroviral therapy (ART) with advanced disease. We investigated associations between immune biomarkers and mortality in participants with advanced HIV randomised to cotrimoxazole or enhanced antimicrobial prophylaxis in the Reduction of Early Mortality in HIV-Infected Adults and Children Starting Antiretroviral Therapy (REALITY) trial (ISRCTN43622374). Biomarkers were assayed using ELISA and Luminex. Associations between baseline values and all-cause 24-week mortality were analysed using Cox models, and for cause-specific mortality used Fine & Gray models, including prophylaxis randomisation, viral load, CD4, WHO stage, age, BMI, and site as covariates; and weighted according to inverse probability of selection into the substudy. Higher baseline CRP, IFN-γ, IL-6 and IP-10 were associated with higher all-cause mortality; and higher IL-23, IL-2 and RANTES with lower all-cause mortality. Associations varied by cause of death: tuberculosis-associated mortality was most strongly associated with higher CRP and sST2, and cryptococcosis-associated mortality with higher IL-4 and lower IL-8. Changes in I-FABP (p = 0.002), faecal alpha-1 antitrypsin (p = 0.01) and faecal myeloperoxidase (p = 0.005) between baseline and 4 weeks post-ART were greater in those receiving enhanced versus cotrimoxazole prophylaxis. Our findings highlight how the immune milieu shapes outcomes following ART initiation, and how adjunctive antimicrobials can modulate the gut environment in advanced HIV.
Metaproteomic portrait of the healthy human gut microbiota
Tanca A, Palomba A, Fiorito G, Abbondio M, Pagnozzi D and Uzzau S
Gut metaproteomics can provide direct evidence of microbial functions actively expressed in the colonic environments, contributing to clarify the role of the gut microbiota in human physiology. In this study, we re-analyzed 10 fecal metaproteomics datasets of healthy individuals from different continents and countries, with the aim of identifying stable and variable gut microbial functions and defining the contribution of specific bacterial taxa to the main metabolic pathways. The "core" metaproteome included 182 microbial functions and 83 pathways that were identified in all individuals analyzed. Several enzymes involved in glucose and pyruvate metabolism, along with glutamate dehydrogenase, acetate kinase, elongation factors G and Tu and DnaK, were the proteins with the lowest abundance variability in the cohorts under study. On the contrary, proteins involved in chemotaxis, response to stress and cell adhesion were among the most variable functions. Random-effect meta-analysis of correlation trends between taxa, functions and pathways revealed key ecological and molecular associations within the gut microbiota. The contribution of specific bacterial taxa to the main biological processes was also investigated, finding that Faecalibacterium is the most stable genus and the top contributor to anti-inflammatory butyrate production in the healthy gut microbiota. Active production of other mucosal immunomodulators facilitating host tolerance was observed, including Roseburia flagellin and lipopolysaccharide biosynthetic enzymes expressed by members of Bacteroidota. Our study provides a detailed picture of the healthy human gut microbiota, contributing to unveil its functional mechanisms and its relationship with nutrition, immunity, and environmental stressors.
Unlock the potential: Auditory-evoked event-related potential (ERP) as a treatment-responsive biomarker for Rett syndrome
Medina J and Zhou Z
Pulmonary metastatic gestational choriocarcinoma following an uncomplicated term pregnancy: a case report
Jafari-Nozad AM and Jahani N
Choriocarcinoma is a highly malignant pregnancy-related trophoblastic neoplasm, characterized by early metastasis to the lungs. Therefore, patients may manifest nongynecological symptoms owing to distant metastases. The incidence of choriocarcinoma after a term pregnancy is really rare (1/160,000 pregnancies).
A Comparison of CT-Based Pancreatic Segmentation Deep Learning Models
Suri A, Mukherjee P, Pickhardt PJ and Summers RM
Pancreas segmentation accuracy at CT is critical for the identification of pancreatic pathologies and is essential for the development of imaging biomarkers. Our objective was to benchmark the performance of five high-performing pancreas segmentation models across multiple metrics stratified by scan and patient/pancreatic characteristics that may affect segmentation performance.
Fluorescence-activated nuclear sorting (FANS) of nuclei from in vitro-generated syncytiotrophoblast
Khan T, Whyte JJ, Schulz LC and Roberts RM
Large, multinucleated cells, like syncytiotrophoblasts (STB), are not readily analyzed by standard methods used for single cells, such as single-cell RNA-sequencing and fluorescence-activated cellular sorting (FACS). Here we have demonstrated that fluorescence-activated nuclear sorting (FANS) is suitable to analyze nuclei from STB. Human pluripotent stem cells (PSCs) can be differentiated into a mixed trophoblast populations comprising approximately 20 % STB by treatment with BMP4 (Bone Morphogenetic Protein-4), plus A83-01 and PD173074, inhibitors of activin and FGF2 signaling, respectively (the BAP model) in about a week. Here we demonstrate that FANS can be used to separate two types of STB nuclei from the nine different clusters of trophoblast nuclei previously identified in the BAP model by single nucleus RNA sequencing (snRNAseq). Rather than using cell surface markers, as in FACS, transcription factors in various combinations were employed to target specific nuclear types. Nuclei were isolated at d 8 of BAP differentiation of H1 human embryonic stem cells and fixed in 4 % paraformaldehyde. After permeabilization in 0.1 % triton X-100, nuclei were incubated for 3 and 1 h at 4 °C with primary and secondary antibodies respectively and nuclear samples were then subjected to FANS. By using markers identified by snRNA and immunohistochemistry, nuclei were first sorted into a Topoisomerase-1, or TOP1, bright population and then into the two STB subpopulations by using antibodies to JUNB (Jun B Proto-Oncogene) and TFCP2L1 (Transcription Factor CP2 Like 1). The protocol established here is simple, straightforward, and efficient and can be used on a relatively large scale to sort individual subtypes of nuclei from mixed populations of trophoblasts for further analysis.
Total Body PET/CT: A Role in Musculoskeletal Diseases
Katal S, Patel P, Lee J, Taubman K and Gholamrezanezhad A
Recent advancements in PET technology have culminated in the development of total-body PET (TB-PET) systems, which overcome many limitations of traditional scanners. These TB-PET scanners, while still becoming widely available, represent the forefront of clinical imaging across numerous medical institutions worldwide. Early clinical applications have demonstrated their enhanced image quality, precise lesion quantification, and overall superior performance relative to conventional scanners. The capabilities of TB-PET technology, including extended scan range, ultrahigh sensitivity, exceptional temporal resolution, and dynamic imaging, offer significant potential to tackle unresolved clinical challenges in medical imaging. In this discussion, we aim to explore the emerging applications, opportunities, and future perspectives of TB-PET/CT in musculoskeletal disorders (MSDs). Clinical applications for both oncologic and non-oncologic musculoskeletal diseases are discussed, including inflammatory arthritis, infections, osteoarthritis, osteoporosis, and skeletal muscle disorders. From the ability to visualize small musculoskeletal structures and the entire axial and appendicular skeleton, TB-PET shows significant potential in the diagnosis and management of MSD conditions as it becomes more widely available.
India's forgotten children
Bawaskar HS
Multi-system involvement-including purpura fulminans-as an adverse effects of immune checkpoint inhibitor therapy for clear cell renal cell carcinoma
Wirbel C, Breton AL, Donzier L, Tartas S, Curings P, Pariset C and Berthoux E
Approach to duodenal pathology in bariatric surgery: Transit bipartition as an option
Sanchez-Cordero S, Lopez-Gonzalez R, Pujol-Gebellí J and Castellvi-Valls J
Transit bipartition (TB) emerges as a bariatric surgery alternative to Duodenal Switch (DS), emphasizing complete intestinal access and reduced malabsorption. By directly stimulating the distal ileum, TB promotes weight loss while preserving endoscopic duodenal access. This technique enhances anorexigenic hormones, aiding in satiety and weight loss, with lower malnutrition risks than DS. TB shows favorable short-term outcomes in weight management and comorbidity reduction, serving as a simpler, less malabsorptive option than DS. Nonetheless, long-term studies are essential for comprehensive efficacy assessment.
Patient perspectives on personalised medicine for obesity: An IMI2 SOPHIA Study
Farrell E, le Roux CW, Hollmann E, Nadglowski J and McGillicuddy D
Personalised medicine is seen as an exciting opportunity to improve the health outcomes of people with obesity. As research on phenotyping and personalised treatment for obesity rapidly advances, this study sought to understand patient preferences and perspectives on personalised medicine for obesity.
Toward personalized medicine in patients with familial hypercholesterolemia
Tada H and Takamura M
The dual benefits of laparoscopic gastrectomy combined with Roux-en-Y anastomosis in patient with type 2 diabetes and gastric schwannoma
Zhang L, Zhou B, Li Z and Meng H
Have outcomes following colectomy in the United States improved over time?
Kane WJ, Kuron M, Gooding JL, Hoang SC, Friel CM, Jin R, Turrentine FE and Hedrick TL
There has been tremendous effort to improve quality following colorectal surgery, including the proliferation of minimally invasive techniques, enhanced recovery protocols, and surgical site infection prevention bundles. While these programs have demonstrated improved postoperative outcomes at the institutional level, it is unclear whether similar benefits are present on a national scale.
Bacterial cellulose microfilament biochar-architectured chitosan/polyethyleneimine beads for enhanced tetracycline and metronidazole adsorption
Mosaffa E, Ramsheh NA, Banerjee A and Ghafuri H
This study investigates the potential applications of incorporating 2D bacterial cellulose microfibers (BCM) biochar into chitosan/polyethyleneimine beads as a semi-natural sorbent for the efficient removal of tetracycline (TET) and metronidazole (MET) antibiotics. Batch adsorption experiments and characterization techniques evaluate removal performance and synthesized adsorbent properties. The adsorbent eliminated 99.13 % and 90 % of TET and MET at a 10 mg.L concentration with optimal pH values of 8 and 6, respectively, for 90 min. Under optimum conditions and a 400 mg.L concentration, MET and TET have possessed the maximum adsorption capacities of 691.325 and 960.778 mg.g, respectively. According to the isothermal analysis, the adsorption of TET fundamentally follows the Temkin (R = 0.997), Redlich-Peterson (R = 0.996), and Langmuir (R = 0.996) models. In contrast, the MET adsorption can be described by the Langmuir (R = 0.997), and Toth (R = 0.991) models. The pseudo-second-order (R = 0.998, 0.992) and Avrami (R = 0.999, 0.999) kinetic models were well-fitted with the kinetic results for MET and TET respectively. Diffusion models recommend that pore, liquid-film, and intraparticle diffusion govern the rate of the adsorption process. The developed semi-natural sorbent demonstrated exceptional adsorption capacity over eleven cycles due to its porous bead structure, making it a potential candidate for wastewater remediation.
Rewinding the Clock: Preparing the Next Generation of Radiology Residents for Oral Boards
Sheng M, Ritchie B, Ramaiya N and Mohamed I
The replacement of the ABR in-person oral examination with the DR certifying examination affected approximately 15,000 radiologists, spanning from 2013 to 2027. This decision was motivated by better aligning with the timing of other American Board of Medical Specialty (ABMS) members, more closely reflecting real-world practice of radiology and narrowing training geared towards the trainee's subspecialty preference. However, in retrospect, this change may have subtracted from the quality and value of diagnostic radiology training as a whole with the de-emphasis on competence in general radiology, communication skills, and cognitive reasoning. In this paper, the authors lay out a blueprint necessary in order to rewind the clock of how diagnostic radiology programs can prepare their trainees for the new DR oral examination. Such a change will require substantial redactions affecting all designations, including radiology faculty, education teams, departmental leadership, academic institutions, ACGME, and ABR. The authors believe that implementing these modifications will not only effectively equip radiology candidates for the new DR oral examination but will also augment the significance of radiologists as indispensable members of multidisciplinary teams. The authors also outline the challenges that could emerge from these changes and speculate on the anticipated role of AI in future oral board examinations.
Opportunities and challenges to the development and deployment of vaccines for pregnant women in Germany
Pley C and Kampmann B
Maternal immunisation is a powerful tool to protect both pregnant women and their children. A new maternal RSV vaccine holds promise to protect newborns from RSV-associated illness in the first few months of life, but no official recommendation has been made in Germany. Since RSV causes a significant burden of paediatric hospital admissions, we consider it a pertinent opportunity to review barriers to maternal vaccination in Germany, which might also apply to other settings. Access to vaccination for pregnant women in Germany is shaped by an interplay of legal, regulatory, institutional, and sociocultural factors, with a less permissive clinical research environment, delays in recommendation and roll-out, and lower acceptance by healthcare professionals and the population. Actionable recommendations to improve availability and uptake include coordination with other national regulatory bodies to reduce delays, awareness and literacy campaigns for health professionals and the general public, and capacity building for vaccine clinical research.
Clinically Available and Reproducible Prediction Models for IDH and CDKN2A/B Gene Status in Adult-type Diffuse Gliomas
Zhu M, Han F, Gao J, Yang J, Yin L, Du Z and Zhang J
Isocitrate dehydrogenase (IDH) and cyclin-dependent kinase inhibitor (CDKN) 2A/B status holds important prognostic value in diffuse gliomas. We aimed to construct prediction models using clinically available and reproducible characteristics for predicting IDH-mutant and CDKN2A/B homozygous deletion in adult-type diffuse glioma patients.
COVID-19 vaccine immunogenicity and safety surrounding fourth and subsequent vaccine doses in patients with hematologic malignancies
Bhella S, Wilkin AM, Hueniken K, Vijenthira A, Sebag M, Wang P, Hicks LK, Hay AE, Assouline S, Fraser G, Balitsky A, Mangel J, Owen C, Reiman A, Sehn L, Sutherland H, Zhang T, Arnold C, Leite T, McCarthy E, Cooper C, Langlois MA, Arianne Buchan C and
Immune response to COVID-19 vaccine is diminished in patients with hematologic malignancy. There is limited data regarding response to vaccine doses in these patients.
Heatwave frequency and disability status: Thermal inequities in the U.S. South
Chakraborty J
Although extreme heat has been found to be disproportionately distributed with respect to socially disadvantaged and marginalized groups, persons with disabilities have received limited attention in previous research on heat exposure disparities.
Intradermal fractional dose vaccination as a method to vaccinate individuals with suspected allergy to mRNA COVID-19 vaccines
Roozen GVT, Granger A, van Binnendijk RS, den Hartog G, Roestenberg M, Visser LG and Roukens AHE
Suspected allergic reactions after mRNA COVID-19 vaccination withheld multiple individuals from getting fully vaccinated during the pandemic. We vaccinated adults who had experienced possible allergic symptoms after their first intramuscular dose of a COVID-19 mRNA vaccine with a 1/5th fractional intradermal test dose of the mRNA-1273 (Moderna) COVID-19 vaccine. No anaphylactic reactions were observed after intradermal vaccination (n = 56). Serum anti-S1 IgG concentrations were measured using a bead-based multiplex assay four weeks after vaccinations. Antibody concentrations were compared with a previously collected nationwide cohort that had received two intramuscular doses of mRNA-1273. Antibody responses in all subjects tested (n = 47) were comparable to standard of care intramuscular dosing. Fractional intradermal dosing of mRNA COVID-19 vaccines may provide a pragmatic solution that is safe, time efficient compared to skin prick testing, dose sparing and immunogenic in individuals with suspected vaccine allergy.
COVID-19 vaccination and major cardiovascular and haematological adverse events in Abu Dhabi: retrospective cohort study
Pimentel MAF, Shaikh M, Al Safi M, Naqvi Y and Khan S
The widespread administration of COVID-19 vaccines has prompted a need to understand their safety profile. This investigation focuses on the safety of inactivated and mRNA-based COVID-19 vaccines, particularly concerning potential cardiovascular and haematological adverse events. A retrospective cohort study was conducted for 1.3 million individuals residing in Abu Dhabi, United Arab Emirates, who received 1.8 million doses of the inactivated BBIBP CorV (by SinoPharm) and mRNA-based BNT162b2 (Pfizer-BioNTech) vaccines between June 1, 2021, and June 30, 2022. The study's primary outcome was to assess the occurrence of selected cardiovascular and haematological events leading to hospitalization or emergency room visits within 21 days post-vaccination. Results showed no significant increase in the incidence rates of these events compared to the subsequent 22 to 42 days following vaccination. Analysis revealed no elevated risk for adverse outcomes following first (IRR 1·03; 95% CI 0·82-1·31), second (IRR 0·92; 95% CI 0·72-1·16) and third (IRR 0·82; 95% CI 0·66-1·00) doses of either vaccine. This study found no substantial link between receiving either mRNA and inactivated COVID-19 vaccines and a higher likelihood of cardiovascular or haematological events within 21 days after vaccination.
Generation of a novel attenuated IBDV vaccine strain by mutation of critical amino acids in IBDV VP5
Gao H, Zhang S, Chang H, Guo Y, Li Z, Wang Y, Gao L, Li X, Cao H and Zheng SJ
Infectious bursal disease virus (IBDV) is an acute and highly infectious RNA virus known for its immunosuppressive capabilities, chiefly inflicting rapid damage to the bursa of Fabricius (BF) of chickens. Current clinical control of IBDV infection relies on vaccination. However, the emergence of novel variant IBDV (nVarIBDV) has posed a threat to the poultry industry across the globe, underscoring the great demand for innovative and effective vaccines. Our previous studies have highlighted the critical role of IBDV VP5 as an apoptosis-inducer in host cells. In this study, we engineered IBDV mutants via a reverse genetic system to introduce amino acid mutations in VP5. We found that the mutant IBDV-VP5/3m strain caused reduced host cell mortality, and that strategic mutations in VP5 reduced IBDV replication early after infection, thereby delaying cell death. Furthermore, inoculation of chickens with IBDV-VP5/3m effectively reduced damage to BF and induced neutralizing antibody production comparable to that of parental IBDV WT strain. Importantly, vaccination with IBDV-VP5/3m protected chickens against challenges with nVarIBDV, an emerging IBDV variant strain in China, reducing nVarIBDV loads in BF while alleviating bursal atrophy and splenomegaly, suggesting that IBDV-VP5/3m might serve as a novel vaccine candidate that could be further developed as an effective vaccine for clinical control of IBD. This study provides a new clue to the development of novel and effective vaccines.
Stratification tools in the follow-up of persons living with HIV, are they necessary and applicable?
Mena Á
Epicardial adipose tissue attenuation on computed tomography in women with coronary microvascular dysfunction: A pilot, hypothesis generating study
Patel NH, Dave EK, Fatade YA, De Cecco CN, Ko YA, Chen Y, Sharma A, Rashid F, Vatsa N, Samady H, Toleva O, Quyyumi A, Mehta PK and Stillman AE
Patients with myocardial ischemia without obstructive coronary artery disease often have coronary microvascular dysfunction (CMD) and associated increased risk of cardiovascular (CV) events and anginal hospitalizations. Epicardial adipose tissue (EAT) covers much of the myocardium and coronary arteries and when dysfunctional, secretes proinflammatory cytokines and is associated with CV events. While oxidative stress and systemic inflammation are associated with CMD, the relationship between EAT and CMD in women is not well known.
The Efficacy of Voice Therapy via Hybrid Group Telepractice Program with Asynchronous Components for Primary School Teachers: A Pilot Study
Jaroentonyakorn P, Chinchai S, Bunrayong W, Wanicharoen N and Shibamoto I
To determine the efficacy of a hybrid group telepractice program in voice therapy for primary school teachers.
Azithromycin sequential therapy plus inhaled terbutaline for Mycoplasma Pneumoniae pneumonia in children: a systematic review and meta-analysis
Sheng Y, Liang Y, Zhao C, Kang D and Liu X
An improper host immune response to Mycoplasma pneumoniae generates excessive inflammation, which leads to the impairment of pulmonary ventilation function (PVF). Azithromycin plus inhaled terbutaline has been used in the treatment of Mycoplasma pneumoniae pneumonia (MPP) in children with impaired pulmonary function, but previous randomized controlled trials (RCTs) showed inconsistent efficacy and safety. This study is aimed to firstly provide a systematic review of the combined therapy.
Ferroptosis Pathways: Unveiling the Neuroprotective Power of Cistache Deserticola Phenylethanoid Glycosides
Zhang X, Liu Z, Li Z, Qi L, Huang T, Li F, Li M, Wang Y, Ma Z and Gao Y
Cistanche deserticola is a kind of parasitic plant living in the roots of desert trees. It is a rare Chinese medicine, which has the effect of tonifying kidney Yang, benefiting essence and blood and moistening the intestinal tract. Cistache deserticola phenylethanoid glycoside (PGS), an active component found in Cistanche deserticola Ma, have potential kidney tonifying, intellectual enhancing, and neuroprotective effects. Cistanche total glycoside capsule has been marketed to treat vascular dementia disease.
Healthcare utilisation and quality of life according to atrial fibrillation burden, episode frequency and duration
Frausing MHJP, Van De Lande M, Linz D, Crijns HJGM, Tieleman RG, Hemels MEW, De Melis M, Schotten U, Kronborg MB, Nielsen JC, Van Gelder I and Rienstra M
We aimed to evaluate the association between atrial fibrillation (AF) burden, duration and number of episodes with healthcare utilisation and quality of life in patients with early paroxysmal AF without a history of AF.
Echocardiographic assessment for cardiopulmonary function in patients with congenital heart disease-related pulmonary arterial hypertension
Yang L, Luo D, Huang T, Li X, Zhang G, Zhang C and Fei H
For patients with congenital heart disease-related pulmonary arterial hypertension (CHD-PAH), cardiopulmonary exercise testing (CPET) can reflect cardiopulmonary reserve function. However, CPET may not be readily accessible for patients with high-risk conditions or limited mobility due to disability. Echocardiography, on the other hand, serves as a widely available diagnostic tool for all CHD-PAH patients. This study was aimed to identify the parameters of echocardiography that could serve as indicators of cardiopulmonary function and exercise capacity.
Decoding mitochondrial quality control mechanisms: Identifying treatment targets for enhanced cellular health
Wankhede NL, Rajendra Kopalli S, Dhokne MD, Badnag DJ, Chandurkar PA, Mangrulkar SV, Shende PV, Taksande BG, Upaganlawar AB, Umekar MJ, Koppula S and Kale MB
Mitochondria are singular cell organelles essential for many cellular functions, which includes responding to stress, regulating calcium levels, maintaining protein homeostasis, and coordinating apoptosis response. The vitality of cells, therefore, hinges on the optimal functioning of these dynamic organelles. Mitochondrial Quality Control Mechanisms (MQCM) play a pivotal role in ensuring the integrity and functionality of mitochondria. Perturbations in these mechanisms have been closely associated with the pathogenesis of neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Compelling evidence suggests that targeting specific pathways within the MQCM could potentially offer a therapeutic avenue for rescuing mitochondrial integrity and mitigating the progression of neurodegenerative diseases. The intricate interplay of cellular stress, protein misfolding, and impaired quality control mechanisms provides a nuanced understanding of the underlying pathology. Consequently, unravelling the specific MQCM dysregulation in neurodegenerative disorders becomes paramount for developing targeted therapeutic strategies. This review delves into the impaired MQCM pathways implicated in neurodegenerative disorders and explores emerging therapeutic interventions. By shedding light on pharmaceutical and genetic manipulations aimed at restoring MQCM efficiency, the discussion aims to provide insights into novel strategies for ameliorating the progression of neurodegenerative diseases. Understanding and addressing mitochondrial quality control mechanisms not only underscore their significance in cellular health but also offer a promising frontier for advancing therapeutic approaches in the realm of neurodegenerative disorders.
Antiviral susceptibility of SARS-CoV-2 and influenza viruses from 3 co-infected pediatric patients
Takashita E, Ichikawa M, Fujisaki S, Morita H, Nagata S, Miura H, Watanabe S, Hasegawa H and Kawaoka Y
In Japan, influenza activity was low throughout the COVID-19 pandemic until the 2022-23 season, when the first influenza outbreak occurred since the 2020-21 season. In our influenza surveillance during the COVID-19 pandemic, co-infection with SARS-CoV-2 and influenza virus had not been detected; however, in January 2024, we identified three pediatric outpatients co-infected with these viruses: one with SARS-CoV-2 Omicron EG.5 sublineage HK.3 and influenza A(H3N2) and two with SARS-CoV-2 Omicron BA.2.86 sublineage JN.1.5 and influenza A(H1N1)pdm09. We evaluated the susceptibility of SARS-CoV-2 against RNA-dependent RNA polymerase inhibitors (remdesivir and molnupiravir) and 3C-like protease inhibitors (nirmatrelvir and ensitrelvir), and that of influenza viruses against neuraminidase inhibitors (oseltamivir, peramivir, zanamivir, and laninamivir) and the cap-dependent endonuclease inhibitor baloxavir. All viruses tested were susceptible to these antiviral drugs and did not possess amino acid substitutions associated with reduced antiviral susceptibility. The patients were treated with anti-influenza drugs and did not develop severe symptoms despite the co-infection. Since SARS-CoV-2 and influenza viruses continue to evolve, continuous monitoring of their circulation remains essential to assess public health measures and support clinical management.
Research progress in the treatment of schistosomiasis with traditional Chinese medicine
Xiang F, Zhang Z, Li Y, Li M, Xie J, Sun M, Peng Q and Lin L
Schistosomiasis, caused by infection with organisms of the Schistoma genus, is a parasitic and infectious disease that poses a significant risk to human health. Schistosomiasis has been a widespread issue in China for at least 2,000 years. Traditional Chinese medicine (TCM) has a rich history of treating this disease, and the significant theoretical and practical knowledge attained therein may be useful in modern practice.
Neuropeptides and receptors in the cephalochordate: a crucial model for understanding the origin and evolution of vertebrate neuropeptide systems
Su L, Li G, Chow BKC and Cardoso JCR
Genomes and transcriptomes from diverse organisms are providing a wealth of data to explore the evolution and origin of neuropeptides and their receptors in metazoans. While most neuropeptide-receptor systems have been extensively studied in vertebrates, there is still a considerable lack of understanding regarding their functions in invertebrates, an extraordinarily diverse group that account for the majority of animal species on Earth. Cephalochordates, commonly known as amphioxus or lancelets, serve as the evolutionary proxy of the chordate ancestor. Their key evolutionary position, bridging the invertebrate to vertebrate transition, has been explored to uncover the origin, evolution, and function of vertebrate neuropeptide systems. Amphioxus genomes exhibit a high degree of sequence and structural conservation with vertebrates, and sequence and functional homologues of several vertebrate neuropeptide families are present in cephalochordates. This review aims to provide a comprehensively overview of the recent findings on neuropeptides and their receptors in cephalochordates, highlighting their significance as a model for understanding the complex evolution of neuropeptide signaling in vertebrates.
Mitochondrial DNA transcription and mitochondrial genome-encoded long noncoding RNA in diabetic retinopathy
Kumar J and Kowluru RA
In diabetic retinopathy, mitochondrial DNA (mtDNA) is damaged and mtDNA-encoded genes and long noncoding RNA cytochrome B (LncCytB) are downregulated. LncRNAs lack an open reading frame, but they can regulate gene expression by associating with DNA/RNA/protein. Double stranded mtDNA has promoters on both heavy (HSP) and light (LSP) strands with binding sites for mitochondrial transcription factor A (TFAM) between them. The aim was to investigate the role of LncCytB in mtDNA transcription in diabetic retinopathy. Using human retinal endothelial cells incubated in high glucose, the effect of regulation of LncCytB on TFAM binding at mtDNA promoters was investigated by Chromatin immunoprecipitation, and binding of LncCytB at TFAM by RNA immunoprecipitation and RNA fluorescence in situ hybridization. High glucose decreased TFAM binding at both HSP and LSP, and binding of LncCytB at TFAM. While LncCytB overexpression ameliorated decrease in TFAM binding and transcription of genes encoded by both H- and L- strands, LncCytB-siRNA further downregulated them. Maintenance of mitochondrial homeostasis by overexpressing mitochondrial superoxide dismutase or Sirtuin-1 protected diabetes-induced decrease in TFAM binding at mtDNA and LncCytB binding at TFAM, and mtDNA transcription. Similar results were obtained from mouse retinal microvessels from streptozotocin-induced diabetic mice. Thus, LncCytB facilitates recruitment of TFAM at HSP and LSP, and its downregulation in diabetes compromises the binding, resulting in the downregulation of polypeptides encoded by mtDNA. Regulation of LncCytB, in addition to protecting mitochondrial genomic stability, should also help in maintaining the transcription of mtDNA encoded genes and electron transport chain integrity in diabetic retinopathy.
The Urological Tribulations of Michel de Montaigne: How the Essayist's Stones Influenced His Writings
Sitharthan D and Mitterdorfer A
To explore how Michel de Montaigne's battle with urolithiasis influenced his writings and philosophical outlook during the Renaissance period.
Computational model of the cancer necrotic core formation in a tumor-on-a-chip device
Bonifácio ED, Araújo CA, Guimarães MV, de Souza MP, Lima TP, de Avelar Freitas BA and Torres LAG
The mechanisms underlying the formation of necrotic regions within avascular tumors are complex and poorly understood. In this paper, we investigate the formation of a necrotic core in a 3D tumor cell culture within a microfluidic device, considering oxygen, nutrients, and the microenvironment acidification by means of a computational-mathematical model. Our objective is to simulate cell processes, including proliferation and death inside a microfluidic device, according to the microenvironmental conditions. We employed approximation utilizing the finite element models taking into account glucose, oxygen, and hydrogen ions diffusion, consumption and production, as well as cell proliferation, migration and death, addressing how tumor cells evolve under different conditions. The resulting mathematical model was examined under different scenarios, being capable of reproducing cell death and proliferation under different cell concentrations, and the formation of a necrotic core, in good agreement with experimental data reported in the literature. This approach not only advances our fundamental understanding of necrotic core formation but also provides a robust computational platform to study personalized therapeutic strategies, offering an important tool in cancer research and treatment design.
A novel L-shaped ortho-quinone analog suppresses glioblastoma progression by targeting acceleration of AR degradation and regulating PI3K/AKT pathway
Zhang T, Pan W, Tan X, Yu J, Cheng S, Wei S, Fan K, Wang L, Luo H and Hu X
Glioblastoma (GBM) is a primary intracranial malignant tumor with the highest mortality and morbidity among all malignant central nervous system tumors. Tanshinone IIA is a fat-soluble active ingredient obtained from Salvia miltiorrhiza, which has an inhibitory effect against various cancers. We designed and synthesized a novel L-shaped ortho-quinone analog TE5 with tanshinone IIA as the lead compound and tested its antitumor activity against GBM. The results indicated that TE5 effectively inhibited the proliferation, migration, and invasion of GBM cells, and demonstrated low toxicity in vitro. We found that TE5 may bind to androgen receptors and promote their degradation through the proteasome. Inhibition of the PI3K/AKT signaling pathway was also observed in TE5 treated GBM cells. Additionally, TE5 arrested the cell cycle at the G2/M phase and induced mitochondria-dependent apoptosis. In vivo experiments further confirmed the anti-tumor activity, safety, and effect on androgen receptor level of TE5 in animal models of GBM. Our results suggest that TE5 may be a potential therapeutic drug to treat GBM.
Immunomodulatory effects of antiangiogenic tyrosine kinase inhibitors in renal cell carcinoma models: Impact on following anti-PD-1 treatments
Fumarola C, La Monica S, Bonelli M, Zoppi S, Alfieri R, Galetti M, Gnetti L, Campanini N, Pozzi G, Cavazzoni A, Mazzaschi G, Silini EM, Buti S and Petronini PG
The approval of immune checkpoint inhibitors (ICIs) has revolutionized the management of metastatic renal cell carcinoma (RCC), introducing several ICI-based combinations as the new standard of care for affected patients. Nonetheless, monotherapy with antiangiogenic tyrosine kinase inhibitors (TKIs), such as pazopanib or sunitinib, still represents a first-line treatment option for selected patients belonging to the favorable risk group according to the International mRCC Database Consortium (IMDC) model. After TKI monotherapy, the main second-line option is represented by ICI monotherapy with the anti-Programmed Death Receptor 1(PD-1) nivolumab To date, the expected clinical outcomes are similar with pazopanib or sunitinib and there is no clear indication for selecting one TKI over the other. Moreover, their impact on subsequent ICI treatment outcomes is not well defined, yet. Based on these premises, we investigated the immunomodulatory activity of these drugs in vitro and in vivo.Both TKIs induced Programmed Cell Death Ligand-1 (PD-L1) expression and soluble PD-L1 release in RCC cells, and hampered T cell activation, reducing cytokine production and the proportion of activated T cells. Nevertheless, in a syngeneic co-culture system with peripheral blood mononuclear cells (PBMCs) and tumor cells, incubation with anti-PD-1 antibody following TKIs treatment significantly restored T cell function, potentiating the cytotoxic effects against tumor cells. Pazopanib and sunitinib followed by anti-PD-1 antibody produced a comparable inhibition of tumor growth in a RCC syngeneic mouse model. Our findings suggest that pazopanib and sunitinib, showing similar immunomodulatory effects, may have a comparable impact on the subsequent effectiveness of PD-1/PD-L1 blockade.
Up-regulation of BRD4 contributes to gestational diabetes mellitus-induced cardiac hypertrophy in offspring by promoting mitochondria dysfunction in sex-independent manner
Huang C, Liu Z, Chen M, Zhang H, Mo R, Chen R, Liu Y, Wang S and Xue Q
Gestational diabetes mellitus (GDM) is associated with cardiovascular disease in postnatal life. The current study tested the hypothesis that GDM caused the cardiac hypertrophy in fetal (ED18.5), postnatal day 7 (PD7), postnatal day 21 (PD21) and postnatal day 90 (PD90) offspring by upregulation of BRD4 and mitochondrial dysfunction. Pregnant mice were divided into control and GDM groups. Hearts were isolated from ED18.5, PD7, PD21 and PD90. GDM increased the body weight (BW) and heart weight (HW) in ED18.5 and PD7, but not PD21 and PD90 offspring. However, HW/BW ratio was increased in all ages of GDM offspring compared to control group. Electron microscopy showed disorganized myofibrils, mitochondrial swelling, vacuolization, and cristae disorder in GDM offspring. GDM resulted in myocardial hypertrophy in offspring, which persisted from fetus to adult in a sex-independent manner. Echocardiography analysis revealed that GDM caused diastolic dysfunction, but had no effect on systolic function. Meanwhile, myocardial BRD4 was significantly upregulated in GDM offspring and BRD4 inhibition by JQ1 alleviated GDM-induced myocardial hypertrophy in offspring. Co-immunoprecipitation showed that BRD4 interacted with DRP1 and there was an increase of BRD4 and DRP1 interaction in GDM offspring. Furthermore, GDM caused the accumulation of damaged mitochondria in hearts from all ages of offspring, including mitochondrial fusion fission imbalance (upregulation of DRP1, and downregulation of MFN1, MFN2 and OPA1) and myocardial mitochondrial ROS accumulation, which was reversed by JQ1. These results suggested that the upregulation of BRD4 is involved in GDM-induced myocardial hypertrophy in the offspring through promoting mitochondrial damage in a gender-independent manner.
Perceived physical literacy in children and early adolescents: two valid and reliable versions of the PL-C Quest
Ortega-Benavent N, Menescardi C, Romero-Martínez J, Barnett LM and Estevan I
Perceived physical literacy contributes to the understanding of individuals' physical activity (PA) engagement. It is important a scale is validated in the population of interest. Also, the type of administration may affect reliability and validity. So, the aim of this study was twofold: 1) to examine evidence of validity and reliability of the Spanish version of the Physical Literacy for Children Questionnaire (PL-C Quest) in a cohort of children and adolescents and 2) to assess two versions of administering the scale. The study was conducted in two stages, depending on the administration format of the PL-C Quest (double-dichotomous, and four-point response style) in a cohort of 2004 (n=916; n=1088) students. In both administration forms, evidence of validity (relation with other variables, i.e., concurrent and predictive, and structural validity), invariance (between boys and girls) and reliability (test-retest and internal consistency) were examined. There was evidence of validity for both administration types, with adequate reliability and good to excellent test-retest reliability for both administration forms. Both methods of administration for the PL-C Quest can capture perceived physical literacy in Spanish 8- to 14-year-old children and early adolescents.
High-resolution single-particle imaging at 100-200 keV with the Gatan Alpine direct electron detector
Chan LM, Courteau BJ, Maker A, Wu M, Basanta B, Mehmood H, Bulkley D, Joyce D, Lee BC, Mick S, Czarnik C, Gulati S, Lander GC and Verba KA
Developments in direct electron detector technology have played a pivotal role in enabling high-resolution structural studies by cryo-EM at 200 and 300 keV. Yet, theory and recent experiments indicate advantages to imaging at 100 keV, energies for which the current detectors have not been optimized. In this study, we evaluated the Gatan Alpine detector, designed for operation at 100 and 200 keV. Compared to the Gatan K3, Alpine demonstrated a significant DQE improvement at these voltages, specifically a ∼ 4-fold improvement at Nyquist at 100 keV. In single-particle cryo-EM experiments, Alpine datasets yielded better than 2 Å resolution reconstructions of apoferritin at 120 and 200 keV on a ThermoFisher Scientific (TFS) Glacios microscope fitted with a non-standard SP-Twin lens. We also achieved a ∼ 3.2 Å resolution reconstruction for a 115 kDa asymmetric protein complex, proving its effectiveness with complex biological samples. In-depth analysis revealed that Alpine reconstructions are comparable to K3 reconstructions at 200 keV, and remarkably, reconstruction from Alpine at 120 keV on a TFS Glacios surpassed all but the 300 keV data from a TFS Titan Krios with GIF/K3. Additionally, we show Alpine's capability for high-resolution data acquisition and screening on lower-end systems by obtaining ∼ 3 Å resolution reconstructions of apoferritin and aldolase at 100 keV and detailed 2D averages of a 55 kDa sample using a side-entry cryo holder. Overall, we show that Gatan Alpine performs well with the standard 200 keV imaging systems and may potentially capture the benefits of lower accelerating voltages, possibly bringing smaller sized particles within the scope of cryo-EM.
A critical appraisal of the role of metabolomics in breast cancer research and diagnostics
Gadwal A, Panigrahi P, Khokhar M, Sharma V, Setia P, Vishnoi JR, Elhence P and Purohit P
Breast cancer (BC) remains the most prevalent cancer among women worldwide, despite significant advancements in its prevention and treatment. The escalating incidence of BC globally necessitates continued research into novel diagnostic and therapeutic strategies. Metabolomics, a burgeoning field, offers a comprehensive analysis of all metabolites within a cell, tissue, system, or organism, providing crucial insights into the dynamic changes occurring during cancer development and progression. This review focuses on the metabolic alterations associated with BC, highlighting the potential of metabolomics in identifying biomarkers for early detection, diagnosis, treatment and prognosis. Metabolomics studies have revealed distinct metabolic signatures in BC, including alterations in lipid metabolism, amino acid metabolism, and energy metabolism. These metabolic changes not only support the rapid proliferation of cancer cells but also influence the tumour microenvironment and therapeutic response. Furthermore, metabolomics holds great promise in personalized medicine, facilitating the development of tailored treatment strategies based on an individual's metabolic profile. By providing a holistic view of the metabolic changes in BC, metabolomics has the potential to revolutionize our understanding of the disease and improve patient outcomes.
Molecular detection of Colpodella sp. and other tick-borne pathogens in ticks of ruminants, Italy
Jimale KA, Bezerra-Santos MA, Mendoza-Roldan JA, Latrofa MS, Baneth G and Otranto D
Colpodella species are close relatives of Apicomplexan protozoa. Although most species of this genus are free-living organisms that feed on other protists and algae, reports indicate their occurence in ticks and human patients, including an individual with a history of tick bite manifesting neurological symptoms. During an investigation of tick-borne pathogens (TBPs) in blood samples of cattle, goats, and in ticks collected on them, Colpodella sp. DNA was detected in a Rhipicephalus bursa tick collected from cattle, while of Theileria sergenti/buffeli/orientalis, Babesia bigemina, Sarcocystis cruzi, Babesia spp., and Rickettsia spp. were molecularly detected in cattle, goats, and ticks in southern Italy. Data herein reported highlight the unprecedented presence of Colpodella sp. in ticks in Italy, raising concern due to the potential pathogenic role of this less known protozoan. This finding advocates for performing routine epidemiological surveys to monitor potential emerging vector-borne pathogens.
Structural characterization of cholesterol-rich nanoemulsion (LDE)
Perez AS, Morikawa AT, Maranhão RC and Figueiredo Neto AM
Cholesterol-rich nanoemulsion (LDE) can carry chemotherapeutic agents in the circulation and can concentrate those agents in the neoplastic and inflammatory tissues. This method improves the biodistribution of the drug and reduces toxicity. However, the structural stability of LDE particles, without or with associated drugs, has not been extensively investigated. The aim of the present study is to investigate the structural stability of LDE and LDE associated to paclitaxel, etoposide or methotrexate in aqueous solution over time by small-angle X-ray scattering (SAXS and Ultra SAXS) and dynamic light scattering (DLS). The results show that LDE and LDE associated with those chemotherapeutic agents had reproducible and stable particle diameter, physical structure, and aggregation behavior   over 3-month observation period. As estimated from both DLS and Ultra-SAXS methods, performed at pre-established intervals, the average particle diameter of LDE alone was approx. 32nm, of LDE-paclitaxel was 31nm, of LDE-methotrexate was 35nm and of LDE-etoposide was 36nm. Ultra-SAXS analysis showed that LDE nanoparticles were quasi-spherical, and SAXS showed that drug molecules inside the particles showed a layered-like organization. Formulations of LDE with associated PTX, ETO or MTX were successfully tested in animal experiments and in patients with cancer or with cardiovascular disease, showing markedly low toxicity, good tolerability and possible superior pharmacological action. Our results may be useful for ensuing clinical trials of this novel Nanomedicine tool, by strengthening the knowledge of the structural aspects of those LDE formulations.
PI3K/AKT signaling alters glucose metabolism in uterine microenvironment of women with idiopathic recurrent spontaneous miscarriage
Doma Sherpa D, Dasgupta S, Mitra I, Kanti Das T, Chakraborty P, Joshi M, Sharma S, Kalapahar S and Chaudhury K
This study aims to identify metabolomic signatures in uterine fluid of women with idiopathic recurrent spontaneous miscarriage (IRSM) during window of implantation (WOI). Also, glucose transporters GLUT3 and GLUT4 and proteins of PI3K-Akt signaling pathway in endometrial tissue are assessed.
Unveiling therapeutic potential: Adipose tissue-derived mesenchymal stem cells and their exosomes in the management of diabetes mellitus, wound healing, and chronic ulcers
Ahmadieh-Yazdi A, Karimi M, Afkhami E, Hajizadeh-Tafti F, Kuchakzadeh F, Yang P and Sheykhhassan M
Diabetes mellitus (DM) is a pervasive global health issue with substantial morbidity and mortality, often resulting in secondary complications, including diabetic wounds (DWs). These wounds, arising from hyperglycemia, diabetic neuropathy, anemia, and ischemia, afflict approximately 15% of diabetic patients, with a considerable 25% at risk of lower limb amputations. The conventional approaches for chronic and diabetic wounds management involves utilizing various therapeutic substances and techniques, encompassing growth factors, skin substitutes and wound dressings. In parallel, emerging cell therapy approaches, notably involving adipose tissue-derived mesenchymal stem cells (ADMSCs), have demonstrated significant promise in addressing diabetes mellitus and its complications. ADMSCs play a pivotal role in wound repair, and their derived exosomes have garnered attention for their therapeutic potential. This review aimed to unravel the potential mechanisms and provide an updated overview of the role of ADMSCs and their exosomes in diabetes mellitus and its associated complications, with a specific focus on wound healing.
Identification of N-(((1S,3R,5S)-adamantan-1-yl)methyl)-3-((4-chlorophenyl)sulfonyl)benzenesulfonamide as novel Nav1.8 inhibitor with analgesic profile
Song C, Qiu J, Luo M, Fu Y, Hu S, Liu W, Zhang D, Chen M, Cao Z, Yang X and Ke B
Chronic pain is a common and challenging clinical problem that significantly impacts patients' quality of life. The sodium channel Nav1.8 plays a crucial role in the occurrence and development of chronic pain, making it one of the key targets for treating chronic pain. In this article, we combined virtual screening with cell membrane chromatography techniques to establish a novel method for rapid high-throughput screening of selective Nav1.8 inhibitors. Using this approach, we identified a small molecule compound 6, which not only demonstrated high affinity and inhibitory activity against Nav1.8 but also exhibited significant inhibitory effects on CFA-induced chronic inflammatory pain. Compared to the positive drug VX-150, compound 6 showed a more prolonged analgesic effect making it a promising candidate as a Nav1.8 inhibitor with potential clinical applications. This discovery provides a new therapeutic option for the treatment of chronic pain.
Joint response from Latin American, European Obstetric Violence Observatories and others organizations all over Europe to the Joint Position Statement on Substandard and Disrespectful Care in Labour - Because Words Matter
Brigidi S, Battisti A, Skoko E, Santos C, Morais L, Sadler M, Candia M, Brocker Á, Contreras L, Trouvé A, Bish S, Gonzaléz C, Rossel J, Yáñez F, Werner L, Mena-Tudela D, Villegas A, Galliardo R and Fernandez S
The issue of obstetric violence is internationally acknowledged as a serious violation of human rights. First identified by the Committee of Experts of the Inter-American Belém do Pará Convention in 2012, it is recognized as a form of gender-based violence that infringes upon women's rights during childbirth. Nations such as Argentina, Mexico, Venezuela, and certain regions in Spain have implemented laws against it, highlighting its severity and the need for protective legislation. Major international organizations, including WHO and the Council of Europe, advocate for the elimination of disrespectful and abusive treatment in maternity care. In 2019, the UN Special Rapporteur on violence against women called on states to protect women's human rights in reproductive services by enforcing laws, prosecuting perpetrators, and providing compensation to victims. However, despite advances, there remains institutional and systemic resistance to recognizing obstetric violence, which undermines trust in healthcare and impacts women's quality of life. Addressing this violence is imperative, requiring education and training in women's human rights for all healthcare professionals. As part of the coalition of experts from various organizations (InterOVO), we respond to the publication by EAPM, EBCOG, and EMA: "Joint Position Statement: Substandard and Disrespectful Care in Labor - Because Words Matter." We are committed to preventing and mitigating obstetric violence and improving care for women and newborns.
Evaluating Danish Breast Cancer Group locoregional radiotherapy guideline adherence in clinical treatment data 2008-2016: The DBCG RT Nation study
Refsgaard L, Skarsø Buhl E, Yates E, Maae E, Berg M, Al-Rawi S, Saini A, Vestmø Maraldo M, Boye K, Louise Holm Milo M, Jensen I, Wichmann Matthiessen L, Nørring Bekke S, Holck Nielsen M, Laugaard Lorenzen E, Bech Jellesmark Thorsen L, Sofia Korreman S and Vrou Offersen B
Guideline adherence in radiotherapy is crucial for maintaining treatment quality and consistency, particularly in non-trial patient settings where most treatments occur. The study aimed to assess the impact of guideline changes on treatment planning practices and compare manual registry data accuracy with treatment planning data.
Locoregional Versus General Anesthesia for Carotid Artery Stenting in the American College of Surgeons National Surgical Quality Improvement Project
Koleilat I, Denesopolis J, Parides M, MacCallum KP and Lipsitz E
Carotid artery stenting (CAS) may be performed by transfemoral or transcervical (TCAR) approaches and with a variety of anesthetic techniques. No current literature clearly supports one anesthetic method over another. We therefore sought to evaluate the outcomes of CAS procedures based on anesthetic approach.
[Thinking about family carers in terms of their experiential knowledge]
Jodet S, Charles J and Longuechaud C
Despite well-established recommendations and psycho-education programmes, the health of family carers is most often impaired, which means that the support they provide is seen only in terms of burden. A phenomenological approach based on strength-based care shows that they develop skills and strategies for the well-being of their loved one, and are nurtured by a sense of hope that enables them to acquire experiential knowledge.
ARHGAP29 Is Involved in Increased Invasiveness of Tamoxifen-resistant Breast Cancer Cells and its Expression Levels Correlate With Clinical Tumor Parameters of Breast Cancer Patients
Kansy M, Wert K, Kolb K, Gallwas J and Gründker C
Aggressive breast cancer (BC) cells show high expression of Rho GTPase activating protein 29 (ARHGAP29), a negative regulator of RhoA. In breast cancer cells in which mesenchymal transformation was induced, ARHGAP29 was the only one of 32 GTPase-activating enzymes whose expression increased significantly. Therefore, we investigated whether there is a correlation between expression of ARHGAP29 and tumor progression in BC. Since tamoxifen-resistant BC cells exhibit increased mesenchymal properties and invasiveness, we additionally investigated the relationship between ARHGAP29 and increased invasion rate in tamoxifen resistance. The question arises as to whether ARHGAP29 is a suitable prognostic marker for the progression of BC.
[The place and function of the gender of child psychiatric carers]
Naturel L and Prevost C
In a child psychiatry unit, where it is said that men are reassuring and women are mothering, the group experience of carers on the function of their gender in child care was explored. Gender is relevant to institutional care, but creates a divide. Representations focus on fear, sexuality, violence and fragility. Caregivers, ambivalent about neutralising gender, suffer from representations of what it does to children and to the institution.
[Peer support, a vector for transforming psychiatric practices]
de Salle J and Choppin A
Peer support is based on the mirror effect between the peer carer and the person being supported, which is a powerful lever for recovery. Through their work, peer helpers also hold up a mirror to "non-peer" carers. The reflection they see is a litmus test that can lead to changes in care practices, but it can also generate defensive reactions.
[Not Available]
Cudennec T
[The contribution of a mental health patient trainer to carers]
Verbeck E
As peer support becomes more professional, it is becoming increasingly recognised and diversified. When a mental health patient-trainer works with psychiatric carers, the latter gain a better understanding of the patient's point of view. In addition, valuing their experiential knowledge can support peer helpers in their recovery. However, we mustn't forget that these are fragile people and that their past can come back to haunt them if they are not careful. Testimonial.
[Staff hebdomadaire qualité et gestion des risques en gériatrie: un outil d'appropriation de la démarche qualité pour le management des unités]
Lô Strauss B, Garnier V, Demichelis A, Vanvert C, Ducki S and Couturier P
The quality approach has become essential in geriatric hospital services, but also in the medico-social sector. This process is continuous and shared by all those in charge of the care units, to facilitate unit management and support caregivers in this approach. The weekly structured quality staff meeting is a relevant tool to facilitate the understanding and appropriation of this approach by the medical and nursing managers of the care units.
[Setting up a training program in a geriatric short-stay department]
Jauniot Gibert C and Ducloux Brion F
As the department's team had been renewed in less than two years, it was necessary to invent a method to improve cohesion and communication, and to enhance the skills of professionals. This led to the creation of a training program using a variety of methods (theoretical training, care approaches and quality coffees).
[Refusal of care by the elderly]
Maeker E and Maeker-Poquet B
Refusal of care is a frequent occurrence in geriatric medicine, especially among people with neurocognitive diseases, particularly in the advanced stages. These refusals of care are a daily burden, not only for the patients themselves, but also for their carers and caregivers. Although they can be prevented, the absence of a single, simple strategy for overcoming them is a real challenge for professionals and carers alike. Their management calls for an approach that is essentially non-pharmacological, always interdisciplinary, humanistic and ethically grounded.
[Not Available]
Conti C, Casciari D, Aderomou L and Cudennec T
[Not Available]
Sorrieul B
[Dermatoses of elderly inpatients in Casablanca: epidemiology and factors associated with length of stay]
Ngouele A, Traoré B, Belemsigri D, Hali F, Hassoune S and Chiheb S
Geriatric in-patient dermatoses are diverse. Few data in Morocco describe the epidemiological profile and factors associated with average length of stay (LOS). Our aim was to identify these dermatoses and determine the factors associated with LOS.
[Recognition of caregivers by people with severe neurocognitive disorders]
Hennebert I, Darnaud T and Cuervo-Lombard CV
The recognition of caregivers working with elderly people with neuro-evolutionary diseases is a fact. The caregivers interviewed for this study reported that they felt recognized and identified by these elderly people, who were considered to be prosopagnosic. The caregivers were even able to show that this recognition was possible, even during changes in appearance.
[Design of information tools on technical aids for front-line professionals working with people losing their autonomy]
Blavette L, Rigaud AS, Dacunha S and Pino M
The use of technical aids has a positive impact on the autonomy and quality of life of elderly or disabled people, and is also beneficial for the caregivers and professionals who support them. Nevertheless, there are still major obstacles to their use, notably a general lack of information on technical aids. This observation led us to produce a set of information tools to help people better understand these aids and how to use them.
[Samii: a robotic mediation application to improve geriatric care]
Rampeneaux C, Abci B, Blavette L, Tamou B and Pino M
The emergence of social robots in gerontology has introduced new playful and reassuring media into nursing homes and geriatric wards. Despite promising results, their complexity hinders their widespread adoption. The Intelligent Interactive Care System aims to remedy these limitations by offering interactive therapeutic workshops. This study evaluates residents' involvement in these workshops within an adapted activity and care center, revealing a high level of involvement and satisfaction.
[Healthcare professionals' perception of advanced nursing practice in Ehpad with regard to the risk of drug iatrogenicity in heart failure patients]
Suciu S
Medication iatrogenia is a real public health problem. Elderly people are particularly at risk, due to their multiple pathologies, including heart failure; residents of residential care facilities for the dependent elderly (Ehpad) are no exception. Studies show that this risk is avoidable in 60% of cases, and that advanced practice nurses (APNs) can play a pivotal role in preventive measures. How would the role of the APN be perceived by other healthcare professionals working with these heart failure patients institutionalized in Ehpad?
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