UBR7 acts as a histone chaperone for post-nucleosomal histone H3.

Histone chaperones modulate the stability of histones beginning from histone synthesis, through incorporation into DNA, and during recycling during transcription and replication. Following histone removal from DNA, chaperones regulate histone storage and degradation. Here, we demonstrate that UBR7 is a histone H3.1 chaperone that modulates the supply of pre-existing post-nucleosomal histone complexes. We demonstrate that UBR7 binds to post-nucleosomal H3K4me3 and H3K9me3 histones via its UBR box and PHD. UBR7 binds to the non-nucleosomal histone chaperone NASP. In the absence of UBR7, the pool of NASP-bound post-nucleosomal histones accumulate and chromatin is depleted of H3K4me3-modified histones. We propose that the interaction of UBR7 with NASP and histones opposes the histone storage functions of NASP and that UBR7 promotes reincorporation of post-nucleosomal H3 complexes.

Evidence Base Update on the Assessment of Irritability, Anger, and Aggression in Youth.

OBJECTIVE: Irritability, anger, and aggression have garnered significant attention from youth mental health researchers and clinicians; however, fundamental challenges of conceptualization and measurement persist. This article reviews the evidence base for assessing these transdiagnostic constructs in children and adolescents. METHOD: We conducted a preregistered systematic review of the evidence behind instruments used to measure irritability, anger, aggression, and related problems in youth. Searches were conducted in PsycINFO and PubMed, identifying 4,664 unique articles. Eligibility criteria focused on self- and proxy-report measures with peer-reviewed psychometric evidence from studies in English with youths ages 3-18. Additional measures were found through ancillary search strategies (e.g. book chapters, review articles, test publishers). Measures were screened and coded by multiple raters with acceptable reliability. RESULTS: Overall, 68 instruments met criteria for inclusion, with scales covering irritability (n = 15), anger (n = 19), aggression (n = 45), and/or general overt externalizing problems (n = 27). Regarding overall psychometric support, 6 measures (8.8%) were classified as Excellent, 46 (67.6%) were Good, and 16 (23.5%) were Adequate. Descriptive information (e.g. informants, scales, availability, translations) and psychometric properties (e.g. reliability, validity, norms) are summarized. CONCLUSIONS: Numerous instruments for youth irritability, anger, and aggression exist with varying degrees of empirical support for specific applications. Although some measures were especially strong, none had uniformly excellent properties across all dimensions, signaling the need for further research in particular areas. Findings promote conceptual clarity while also producing a well-characterized toolkit for researchers and clinicians addressing transdiagnostic problems affecting youth.

Conditional genetic screen in Physcomitrella patens reveals a novel microtubule depolymerizing-end-tracking protein.

Our ability to identify genes that participate in cell growth and division is limited because their loss often leads to lethality. A solution to this is to isolate conditional mutants where the phenotype is visible under restrictive conditions. Here, we capitalize on the haploid growth-phase of the moss Physcomitrella patens to identify conditional loss-of-growth (CLoG) mutants with impaired growth at high temperature. We used whole-genome sequencing of pooled segregants to pinpoint the lesion of one of these mutants (clog1) and validated the identified mutation by rescuing the conditional phenotype by homologous recombination. We found that CLoG1 is a novel and ancient gene conserved in plants. At the restrictive temperature, clog1 plants have smaller cells but can complete cell division, indicating an important role of CLoG1 in cell growth, but not an essential role in cell division. Fluorescent protein fusions of CLoG1 indicate it is localized to microtubules with a bias towards depolymerizing microtubule ends. Silencing CLoG1 decreases microtubule dynamics, suggesting that CLoG1 plays a critical role in regulating microtubule dynamics. By discovering a novel gene critical for plant growth, our work demonstrates that P. patens is an excellent genetic system to study genes with a fundamental role in plant cell growth.

Congenitally Absent Left Circumflex Artery.

Congenital coronary anomalies are uncommon with rarest being absent left circumflex artery (LCX) having prevalence of 0.003%. We report a case of a 68 year old male having acute coronary syndrome and left ventricular dysfunction whose coronary angiogram showed an absent LCX with super dominant right coronary artery (RCA). Precise morphological evaluation is needed for best suited management strategy.

Susceptibility Weighted With Quantitative Phase Magnetic Resonance Imaging in Differentiation of Various Stages of Hemorrhage and Calcification in Female Pelvic Pathologies: A Preliminary Study.

BACKGROUND: The purposes of this study were to assess the value of phase for characterization of female pelvic lesions with hemorrhage in various stages and to differentiate them from calcified lesions at 3.0-T magnetic resonance imaging (MRI). METHODS: Forty-four female patients with hemorrhagic (n = 37) or calcified (n = 7) pelvic pathology underwent conventional MRI including susceptibility-weighted imaging with phase information. Hemorrhagic lesions were grouped into acute, subacute, and chronic, and calcified lesions were detected on the basis of conventional imaging findings. Phase quantification of these hemorrhagic and calcified lesions was performed. RESULTS: The phase values significantly differed (P < 0.001) among various stages of hemorrhage, as well as calcification (chronic hemorrhage, -65.09 ± 9.09 degrees; subacute hemorrhage, -11.41 ± 4.4 degrees; acute hemorrhage, -42.30 ± 5.20 degrees; and calcified lesions, 117.55 ± 12.93 degrees). CONCLUSIONS: Quantitative phase imaging has the potential to differentiate various stages of hemorrhagic and calcified pathologies. This may add value to the conventional MRI in improved characterization of these entities in female pelvic pathologies.

Contribution of CENP-F to FOXM1-Mediated Discordant Centromere and Kinetochore Transcriptional Regulation.

Proper chromosome segregation is required to ensure chromosomal stability. The centromere (CEN) is a unique chromatin domain defined by CENP-A and is responsible for recruiting the kinetochore (KT) during mitosis, ultimately regulating microtubule spindle attachment and mitotic checkpoint function. Upregulation of many CEN/KT genes is commonly observed in cancer. Here, we show that although FOXM1 occupies promoters of many CEN/KT genes with MYBL2, FOXM1 overexpression alone is insufficient to drive the FOXM1-correlated transcriptional program. CENP-F is canonically an outer kinetochore component; however, it functions with FOXM1 to coregulate G2/M transcription and proper chromosome segregation. Loss of CENP-F results in altered chromatin accessibility at G2/M genes and reduced FOXM1-MBB complex formation. We show that coordinated CENP-FFOXM1 transcriptional regulation is a cancer-specific function. We observe a small subset of CEN/KT genes including CENP-C, that are not regulated by FOXM1. Upregulation of CENP-C in the context of CENP-A overexpression leads to increased chromosome missegregation and cell death suggesting that escape of CENP-C from FOXM1 regulation is a cancer survival mechanism. Together, we show that FOXM1 and CENP-F coordinately regulate G2/M genes, and this coordination is specific to a subset of genes to allow for maintenance of chromosome instability levels and subsequent cell survival.

The Role of Telemedicine in Enhancing Chronic Kidney Disease (CKD) Management and Dialysis Care.

Telemedicine has emerged as a transformative solution in the realm of healthcare, particularly in addressing the complexities and challenges associated with chronic kidney disease (CKD) and dialysis care. This editorial explores the potential of telemedicine in revolutionizing the management and treatment of kidney diseases, highlighting its role in mitigating the burdens faced by healthcare systems worldwide. With the advent of high-quality audio and visual platforms, telemedicine has facilitated remote healthcare delivery, enabling healthcare professionals to provide exceptional care from a distance. This is particularly relevant in the context of CKD and end-stage kidney disease (ESKD) patients, where the need for continuous care and monitoring is critical. This editorial underscored the escalating incidence of ESKD, driven by prevalent risk factors, such as diabetes, hypertension, and obesity, and the disparities in access to treatments among different populations. The integration of telemedicine in CKD and dialysis care presents a pathway toward a more accessible, efficient, and cost-effective healthcare delivery. It offers numerous benefits, including the convenience of remote monitoring, enhanced patient compliance, reduced healthcare costs, and improved patient satisfaction and quality of life. Telemedicine facilitates a multidisciplinary approach to care, allowing for timely intervention and follow-ups, which are crucial for patients undergoing dialysis. Moreover, the COVID-19 pandemic has accelerated the adoption of telemedicine, showcasing its effectiveness in maintaining continuity of care amid restrictions on patient contact. Despite its promising potential, its implementation of telemedicine faces several challenges, including regulatory hurdles, concerns about the security of medical information, and the adequacy of virtual platforms to capture crucial health indicators. In addition, the financial implications of telemedicine and its long-term sustainability remain areas requiring further investigation. In conclusion, telemedicine holds significant promise in enhancing the care and management of CKD and dialysis patients. It offers a vital solution to overcome the geographical barrier, improve access to care, and alleviate the strain on healthcare systems. However, further research is needed to fully understand its benefits compared to traditional care models and to address the challenges associated with implementation. The expansion of telemedicine in kidney care signifies a step toward a more inclusive, efficient, and patient-centered healthcare future.

Advancing Healthcare Equity in Nephrology: Addressing Racial and Ethnic Disparities in Research Trials and Treatment Strategies.

Within the healthcare sector, especially in the field of nephrology, the matter of gender and racial inequalities continues to be a critical concern that requires immediate focus. Women, particularly those of underrepresented racial groups, face significant challenges due to a lack of representation in research studies, leading to a deficit in knowledge about how kidney diseases affect them differently. These challenges are exacerbated by systemic biases in the healthcare system, which manifest in both gender and racial dimensions, hindering access to and the quality of care for kidney diseases. Addressing these complex disparities requires a recalibration of risk stratification models to include both gender- and race-specific factors and a transformation of healthcare policies to facilitate a more inclusive and sensitive approach. Essential to this transformation is the empowerment of women of all races to actively participate in their healthcare decisions and the strengthening of support systems to help them navigate the complexities of the healthcare environment. Furthermore, education programs must be designed to be culturally competent and address the unique needs and concerns of women across different racial backgrounds. Promoting a collaborative patient-provider relationship is crucial in fostering an environment where equity, dignity, and respect are at the forefront. The path to equitable nephrology care lies in a concerted, collective action from researchers, healthcare providers, policymakers, and patients, ensuring that every individual receives the highest standard of care, irrespective of gender or race.

Gender Disparity in Leading Authorship of Critical Care Clinical Trials: A Systematic Review and Meta-Analysis.

In critical care medicine, research trials serve as crucial avenues for disseminating knowledge, influencing clinical practices, and fostering innovation. Notably, a significant gender imbalance exists within this field, potentially mirrored in the authorship of critical care research. This study aimed to investigate an exploration to ascertain the presence and extent of female representation in first and senior authorship roles within critical care literature. To this end, a systematic search was conducted across PubMed, Google Scholar, and Web of Science databases for original articles published up to February 2024, coupled with a methodological quality assessment via the Newcastle-Ottawa Scale (NOS) and statistical analyses through Review Manager software (RevMan, version 5.4.1, The Cochrane Collaboration, 2020). The study's findings, distilled from seven studies included in the final analysis, reveal a pronounced gender disparity. Specifically, in critical care literature examining mixed populations, female first authors were significantly less common than their male counterparts, with an odds ratio (OR) of 4.25 (95% confidence interval (CI): 3.18-5.68; p < 0.00001). Conversely, pediatric critical care studies did not show a significant difference in gender distribution among first authors (OR: 1.37; 95% CI: 0.31-6.10; p = 0.68). The investigation also highlighted a stark underrepresentation of female senior authors in critical care research across both mixed (OR: 11.67; 95% CI: 7.76-17.56; p < 0.00001) and pediatric populations (OR: 5.41; 95% CI: 1.88-15.56; p = 0.002). These findings underscore the persistent underrepresentation of women in critical care literature authorship and their slow progression into leadership roles, as evidenced by the disproportionately low number of female senior authors.

Multi-year population-based analysis of Asian patients with acute decompensated heart failure and advanced chronic kidney disease.

BACKGROUND: Data on disparities in outcomes and risk factors in Asian patients with advanced chronic kidney disease admitted for heart failure are scare. METHODS: This was a retrospective cohort study that utilized data from the National Inpatient Sample between January 2016 and December 2019. Patients who had a primary diagnosis of acute decompensated heart failure and a concomitant diagnosis of advanced CKD were included. The primary outcome of interest was in-hospital mortality. Secondary outcomes include hospital cost, length of stay, and other clinical outcomes. Weighted multivariable logistic regression was used to adjust for comorbidities. RESULTS: There were 251,578 cases of ADHF with advanced CKD, out of which 2.6 % were from individuals of Asian ethnicity. Asian patients exhibited a higher burden of comorbidities in comparison to other UREM patients, but a lower burden than White patients. Regardless of differences in comorbidity burden, Asian patients exhibited a higher likelihood of experiencing severe consequences. After adjusting for comorbidies, White (OR:1.11; 95 % CI 1.03-1.20;0.009) patients had higher odds of mortality than Asian patients. However, Blacks (OR: 0.58; 95 % CI 0.53 to 0.63; p < 0.001) and Hispanics (OR: 0.69; 95 % CI 0.62 to 0.78; p < 0.001) had lower odds of mortality. CONCLUSION: This first population-based studies shows that Asian patients with advanced CKD admitted for ADHF have greater comorbidity burden and poorer outcomes Black and Hispanic patients. This data underscores the importance of comprehensive approaches in phenotyping, and ethnic specific interventions.

Cancer as an Individual Risk Factor for Heart Failure: A Review of Literature.

The intricate relationship between cancer and cardiovascular diseases (CVD), notably heart failure (HF), is gaining attention in the medical field. This literature review explores the intricate interplay between cancer and CVD, particularly HF, emphasizing their significant impact on global mortality and comorbidity. While preventive measures have contributed to reducing their incidence, challenges persist in predicting and managing cancer-related complications. This review article delves into various risk factors associated with both cancer and HF, including lifestyle factors, genetic predispositions, and immune system dysregulation. It highlights emerging evidence suggesting a direct interaction between cancer and HF, with studies indicating an elevated risk of mortality from cancer in patients with HF and vice versa. Pathological mechanisms such as inflammation, oxidative stress, and tissue hypoxia are implicated in cancer-induced cardiac dysfunction, underscoring the need for comprehensive clinical investigations and ethical considerations in patient care. The review also discusses the potential role of biomarkers in risk assessment, early detection of cardiotoxicity, and understanding common pathophysiological links between cancer and HF, paving the way for multifaceted preventive and therapeutic approaches.

A Systematic Review of Gender Disparity in the Authorship of Clinical Trials and Clinical Practice Guidelines in Various Medicine Subspecialties.

Authorship in clinical trials and clinical practice guidelines is considered prestigious and is associated with broader peer recognition. This systematic review investigated female representation among studies reporting authorship trends in clinical trials or clinical practice guidelines in different medicine subspecialties. Our search strategy yielded 836 articles, of which 30 met the inclusion criteria. Our findings indicate that females are severely underrepresented in authorship of clinical trials and clinical practice guidelines. Although the proportions of females may have improved in the past decade, the gains are marginal. Notably, studies in this domain predominantly focus on first/last authorship positions, and whether females are underrepresented in other positions as collaborative partners is currently unknown. Also, authorship trends in clinical trials or clinical practice guidelines of most medicine subspecialties besides cardiovascular medicine remain under-researched. Hence, standardizing the methodology for studying gender disparity in research output for comparative analysis between different subspecialties is as urgent as addressing the gender disparity in authorship.

Chunky Mitral Annular Calcification: Caseoma or a Tumor?

Mitral annular calcification (MAC) is relatively common in clinical practice. Females are more often affected than males. Patients with end-stage renal disease have MAC relatively more commonly than the general population. Patients with MAC often develop conduction system disturbances, including advanced atrioventricular blocks. They are also more likely to develop various arrhythmias, including atrial fibrillation. Caseous mitral annulus calcification is a variant of MAC that often looks like a cardiac tumor on an echocardiogram and needs to be differentiated.

Unlocking the Hidden Pathway: A Rare Encounter With Right Coronary Artery Fistula to Coronary Sinus and Right Ventricle.

Coronary artery fistulas (CAFs) are rare vascular anomalies characterized by abnormal connections between coronary arteries and cardiac chambers or adjacent structures. Advances in cardiac interventions have led to an increasing recognition of acquired CAFs, which are typically congenital. We present a case of a 62-year-old male with a complex medical history, including hypertension, atrial fibrillation, and heart failure, who presented with exertional chest pain and palpitations. Diagnostic evaluation revealed a significant CAF originating from the right coronary artery (RCA) and terminating into the coronary sinus and right ventricle. Despite the absence of significant coronary artery occlusions, the fistula was deemed clinically significant due to its potential to cause myocardial ischemia. Management involved guideline-directed medical therapy and lifestyle modifications. This case underscores the importance of early recognition and appropriate management of CAFs to optimize patient outcomes. Further research is needed to better understand the natural history and optimal management strategies of CAFs.

Contribution of CENP-F to FOXM1-mediated discordant centromere and kinetochore transcriptional regulation.

Proper chromosome segregation is required to ensure genomic and chromosomal stability. The centromere is a unique chromatin domain present throughout the cell cycle on each chromosome defined by the CENP-A nucleosome. Centromeres (CEN) are responsible for recruiting the kinetochore (KT) during mitosis, ultimately regulating spindle attachment and mitotic checkpoint function. Upregulation of many genes that encode the CEN/KT proteins is commonly observed in cancer. Here, we show although that FOXM1 occupies the promoters of many CEN/KT genes with MYBL2, occupancy is insufficient alone to drive the FOXM1 correlated transcriptional program. We show that CENP-F, a component of the outer kinetochore, functions with FOXM1 to coregulate G2/M transcription and proper chromosome segregation. Loss of CENP-F results in alteration of chromatin accessibility at G2/M genes, including CENP-A, and leads to reduced FOXM1-MBB complex formation. The FOXM1-CENP-F transcriptional coordination is a cancer-specific function. We observed that a few CEN/KT genes escape FOXM1 regulation such as CENP-C which when upregulated with CENP-A, leads to increased chromosome misegregation and cell death. Together, we show that the FOXM1 and CENP-F coordinately regulate G2/M gene expression, and this coordination is specific to a subset of genes to allow for proliferation and maintenance of chromosome stability for cancer cell survival.

PET/CT and SPECT/CT Imaging of HER2-Positive Breast Cancer.

HER2 (Human Epidermal Growth Factor Receptor 2)-positive breast cancer is characterized by amplification of the HER2 gene and is associated with more aggressive tumor growth, increased risk of metastasis, and poorer prognosis when compared to other subtypes of breast cancer. HER2 expression is therefore a critical tumor feature that can be used to diagnose and treat breast cancer. Moving forward, advances in HER2 in vivo imaging, involving the use of techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT), may allow for a greater role for HER2 status in guiding the management of breast cancer patients. This will apply both to patients who are HER2-positive and those who have limited-to-minimal immunohistochemical HER2 expression (HER2-low), with imaging ultimately helping clinicians determine the size and location of tumors. Additionally, PET and SPECT could help evaluate effectiveness of HER2-targeted therapies, such as trastuzumab or pertuzumab for HER2-positive cancers, and specially modified antibody drug conjugates (ADC), such as trastuzumab-deruxtecan, for HER2-low variants. This review will explore the current and future role of HER2 imaging in personalizing the care of patients diagnosed with breast cancer.

COVID-19 mRNA Vaccine-Associated Myocarditis.

Coronavirus disease 2019 (COVID-19) has been reported to cause cardiovascular complications including myocarditis, pericardial effusion, pericarditis, and arrhythmias. With the introduction of the vaccine, there have been reports of myocarditis possibly associated with the mRNA COVID-19 vaccine. We report a case of cardiac involvement following the second dose of Pfizer-BioNTech COVID-19 vaccine in a young male. A healthy 24-year-old male presented to the emergency department with complaints of non-radiating mid-sternal chest pain and pressure. He noticed his symptoms started six hours after he received the second dose of Pfizer COVID vaccine. Laboratory tests revealed elevated cardiac troponin I-CtNI levels. Computed tomography angiography of the chest did not show evidence of pulmonary embolism. Given his presentation of acute chest pain associated with elevated troponin levels, a coronary angiogram was performed which revealed normal coronary arteries. He was subsequently treated for acute peri-myocarditis with colchicine, non-steroidal anti-inflammatory drugs (NSAIDs), and beta-blockers for tachycardia and the prevention of arrhythmia. Although rare, clinicians should be aware of the risk for myocarditis and pericarditis, which should be considered in individuals presenting with chest pain within a week after vaccination, especially in the younger population. Although the long-term risk in these patients is uncertain, early diagnosis and treatment are key to minimizing complications.

Checkpoint Inhibitor Immune-Related Adverse Events: A Multimodality Pictorial Review.

Cancer immunotherapies are drugs that modulate the body's own immune system as an anticancer strategy. Checkpoint inhibitor immunotherapies interfere with cell surface binding proteins that function to promote self-recognition and tolerance, ultimately leading to upregulation of the immune response. Given the striking success of these agents in early trials in melanoma and lung cancer, they have now been studied in many types of cancer and have become a pillar of anticancer therapy for many tumor types. However, abundant upregulation results in a new class of side effects, known as immune-related adverse events (IRAEs). It is critical for the practicing radiologist to be able to recognize these events to best contribute to care for patients on checkpoint inhibitor immunotherapy. Here, we provide a comprehensive system-based review of immune-related adverse events and associated imaging findings. Further, we detail the best imaging modalities for each as well as describe problem solving modalities. Given that IRAEs can be subclinical before becoming clinically apparent, radiologists may be the first provider to recognize them, providing an opportunity for early treatment. Awareness of IRAEs and how to best image them will prepare radiologists to make a meaningful contribution to patient care as part of the clinical team.

Tirofiban: A Rare Cause of Thrombocytopenia in a Patient Undergoing Percutaneous Coronary Intervention.

Patients admitted to the hospital can develop thrombocytopenia due to multifactorial causes. It can be pseudo-thrombocytopenia or true thrombocytopenia. Among patients admitted for chest pain, coronary angiography (CAG) is a common diagnostic test to evaluate patients for coronary artery disease (CAD). Normally, patients undergoing angiogram receive antiplatelets and anticoagulants pre-catheterization, and platelet aggregation inhibitor agents are sometimes used during and after CAG like in patients with high thrombus burden. Glycoprotein IIb/IIIa receptor inhibitors are a type of platelet antiaggregant agents that can cause severe thrombocytopenia in few cases.  We present a case of a 68-year-old patient who came to the emergency department with inferior wall ST-segment elevation myocardial infarction and underwent angiography and had percutaneous coronary intervention (PCI) done. He was administered tirofiban during the angiogram that caused acute severe thrombocytopenia decreasing platelets count to 4000/microliter within one day. Patients' platelets gradually recovered after platelets transfusion.

Hyphema: A Rare Complication of Periprocedural Antiplatelets and Anticoagulants Following Percutaneous Coronary Intervention.

Hemorrhagic complications are one of the major complications encountered with reperfusion therapies. However, ocular hemorrhage, especially hyphema, i.e., bleeding into the anterior chamber of the eye is one of the rarest bleeding manifestations. Bleeding manifestations in the periprocedural period can be devastating for the patient as antiplatelets and anticoagulants may need to be stopped and this can lead to stent thrombosis. We present a case of a 55-year-old lady, who was a known diabetic and hypertensive and developed hyphema with periprocedural antiplatelets and anticoagulants following percutaneous coronary intervention (PCI). She was managed medically and the dose of antiplatelets was reduced. She was discharged once there was evidence of a reduction in hyphema. Two weeks post-discharge her hyphema had completely resolved.