Navigating the Blood-Brain Barrier: Challenges and Therapeutic Strategies in Breast Cancer Brain Metastases.

Breast cancer (BC) is the most common cancer in women, with metastatic BC being responsible for the highest number of deaths. A frequent site for BC metastasis is the brain. Brain metastasis derived from BC involves the cooperation of multiple genetic, epigenetic, angiogenic, and tumor-stroma interactions.

Observed daytime sleepiness in in-hospital geriatric patients and risk of falls.

Background: Daytime sleepiness and falls are frequent in geriatric in-hospital patients; however, the relationship between both events is not clear. To test the hypothesis that observed daytime sleepiness is associated with falls in geriatric in-hospital patients data collected from medical records of patients who were admitted to an acute geriatric department were retrospectively analyzed.

Methods: The data from the medical records of patients who were admitted to the geriatric department of the Alfried-Krupp-Hospital in Essen, Germany in the period from January 2018 to March 2020 were retrospectively analyzed.

Comparison of Fixation Methods for the Detection of Claudin 1 and E-Cadherin in Breast Cancer Cell Lines by Immunofluorescence.

The tight junction membrane protein claudin 1 and the adherens junction protein E-cadherin play critical roles in cell-cell communication and in cell signaling. As a result, their protein levels and distribution in cancer have been a focus of cancer researchers in recent years. The loss of sensitivity to contact inhibition and the establishment of invasive properties in cancer are thought to be a result of the mislocalization of these membrane proteins to the cytoplasm.

A Cardiac Mitochondrial FGFR1 Mediates the Antithetical Effects of FGF2 Isoforms on Permeability Transition.

Mitochondria, abundant organelles in high energy demand cells such as cardiomyocytes, can determine cell death or survival by regulating the opening of mitochondrial permeability transition pore, mPTP. We addressed the hypothesis that the growth factor FGF2, known to reside in intracellular locations, can directly influence mitochondrial susceptibility to mPTP opening. Rat cardiac subsarcolemmal (SSM) or interfibrillar (IFM) mitochondrial suspensions exposed directly to rat 18 kDa low molecular weight (Lo-) FGF2 isoform displayed increased resistance to calcium overload-induced mPTP, measured spectrophotometrically as "swelling", or as cytochrome c release from mitochondria.

The Breast Tumor Microenvironment: A Key Player in Metastatic Spread.

The tumor microenvironment plays a pivotal role in the tumorigenesis, progression, and metastatic spread of many cancers including breast. There is now increasing evidence to support the observations that a bidirectional interplay between breast cancer cells and stromal cells exists within the tumor and the tumor microenvironment both at the primary tumor site and at the metastatic site. This interaction occurs through direct cell to cell contact, or by the release of autocrine or paracrine factors which can activate pro-tumor signaling pathways and modulate tumor behavior.

Elimination of endogenous high molecular weight FGF2 prevents pressure-overload-induced systolic dysfunction, linked to increased FGFR1 activity and NR1D1 expression.

Fibroblast growth factor 2 (FGF2), produced as high (Hi-) and low (Lo-) molecular weight isoforms, is implicated in cardiac response to injury. The role of endogenous FGF2 isoforms during chronic stress is not well defined. We investigated the effects of endogenous Hi-FGF2 in a mouse model of simulated pressure-overload stress achieved by transverse aortic constriction (TAC) surgery.

Treatment of Post-Ablation Bronchopleural Fistula Using Percutaneous Synthetic Hydrogel Surgical Sealant: Initial Experience of Safety and Efficacy.

Purpose Bronchopleural fistula is a rare but serious complication of lung ablation, as it is difficult to treat and is associated with a high mortality rate. Standard therapy often relies on surgical pleurodesis, which can be particularly problematic in patients with poor baseline lung function. A minimally invasive treatment option for bronchopleural fistula may offer an alternative to surgery for appropriate patients.

Oxidized phospholipids in Doxorubicin-induced cardiotoxicity.

Doxorubicin (Dox), a widely used chemotherapy drug, can also cause cardiotoxic effects leading to heart failure. The excessive oxidative stress caused by Dox results in the modification of a variety of cellular molecules, including phospholipids. In cardiomyocytes, Dox increases oxidation of a species of phospholipids, phosphatidylcholine, which has been associated with increased cell death.

Elimination or neutralization of endogenous high-molecular-weight FGF2 mitigates doxorubicin-induced cardiotoxicity.

Cardiac fibroblast growth factor 2 (FGF2) exerts multiple paracrine activities related to cardiac response to injury. Endogenous FGF2 is composed of a mixture of 70% high- and 30% low-molecular-weight isoforms (Hi-FGF2 and Lo-FGF2, respectivley); although exogenously added Lo-FGF2 is cardioprotective, the roles of endogenous Hi-FGF2 or Lo-FGF2 have not been well defined. Therefore, we investigated the effect of elimination of Hi-FGF2 expression on susceptibility to acute cardiac damage in vivo caused by an injection of the genotoxic drug doxorubicin (Dox).

Non-mitogenic FGF2 protects cardiomyocytes from acute doxorubicin-induced toxicity independently of the protein kinase CK2/heme oxygenase-1 pathway.

Doxorubicin (Dox)-induced cardiotoxicity, a limiting factor in the use of Dox to treat cancer, can be mitigated by the mitogenic factor FGF2 in vitro, via a heme oxygenase 1 (HO-1)-dependent pathway. HO-1 upregulation was reported to require protein kinase CK2 activity. We show that a mutant non-mitogenic FGF2 (S117A-FGF2), which does not activate CK2, is cardioprotective against acute cardiac ischemic injury.

Fibroblast growth factor-2-mediated protection of cardiomyocytes from the toxic effects of doxorubicin requires the mTOR/Nrf-2/HO-1 pathway.

Background: Cardiotoxic side effects impose limits to the use of anti-tumour chemotherapeutic drugs such as doxorubicin (Dox). There is a need for cardioprotective strategies to prevent the multiple deleterious effects of Dox. Here, we examined the ability of administered fibroblast growth factor-2 (FGF-2), a cardioprotective protein that is synthesized as high and low molecular weight (Hi-, Lo-FGF-2) isoforms, to prevent Dox-induced: oxidative stress; cell death; lysosome dysregulation; and inactivation of potent endogenous protective pathways, such as the anti-oxidant/detoxification nuclear factor erythroid-2-related factor (Nrf-2), heme oxygenase-1 (HO-1) axis.

Integrating Quality and Safety Competencies to Improve Outcomes: Application in Infusion Therapy Practice.

Despite intense scrutiny and process improvement initiatives, patient harm continues to occur in health care with alarming frequency. The Quality and Safety Education for Nursing (QSEN) project provides a roadmap to transform nursing by integrating 6 competencies: patient-centered care, teamwork and collaboration, evidence-based practice, quality improvement, safety, and informatics. As front-line caregivers, nurses encounter inherent risks in their daily work.

A Novel Technique for Endovascular Removal of Large Volume Right Atrial Tumor Thrombus.

Venous thromboembolic disease is a significant cause of morbidity and mortality, particularly in the setting of large volume pulmonary embolism. Thrombolytic therapy has been shown to be a successful treatment modality; however, its use somewhat limited due to the risk of hemorrhage and potential for distal embolization in the setting of large mobile thrombi. In patients where either thrombolysis is contraindicated or unsuccessful, and conventional therapies prove inadequate, surgical thrombectomy may be considered.

High molecular weight fibroblast growth factor-2 in the human heart is a potential target for prevention of cardiac remodeling.

Fibroblast growth factor 2 (FGF-2) is a multifunctional protein synthesized as high (Hi-) and low (Lo-) molecular weight isoforms. Studies using rodent models showed that Hi- and Lo-FGF-2 exert distinct biological activities: after myocardial infarction, rat Lo-FGF-2, but not Hi-FGF-2, promoted sustained cardioprotection and angiogenesis, while Hi-FGF-2, but not Lo-FGF-2, promoted myocardial hypertrophy and reduced contractile function. Because there is no information regarding Hi-FGF-2 in human myocardium, we undertook to investigate expression, regulation, secretion and potential tissue remodeling-associated activities of human cardiac (atrial) Hi-FGF-2.

The FGF-2-triggered protection of cardiac subsarcolemmal mitochondria from calcium overload is mitochondrial connexin 43-dependent.

Aims: Fibroblast growth factor 2 (FGF-2) protects the heart from ischaemia- and reperfusion-induced cell death by a mechanism linked to protein kinase C (PKC)ε-mediated connexin 43 (Cx43) phosphorylation. Cx43 localizes predominantly to gap junctions, but has also been detected at subsarcolemmal (SSM), but not interfibrillar (IFM), mitochondria, where it is considered important for cardioprotection. We have now examined the effect of FGF-2 administration to the heart on resistance to calcium-induced permeability transition (mPTP) of isolated SSM vs.

Prenatal MRI characterization of brainstem glioma.

We describe a unique case of prenatally diagnosed diffuse brainstem glioma, detected during routine obstetric ultrasound and characterized with fetal magnetic resonance imaging. The diagnosis was supported by early postpartum imaging and confirmed at autopsy. Few examples of these rare lesions have been described in neonates by imaging and fewer cases have been confirmed by histopathological examination.

Calreticulin induces dilated cardiomyopathy.

Background: Calreticulin, a Ca(2+)-buffering chaperone of the endoplasmic reticulum, is highly expressed in the embryonic heart and is essential for cardiac development. After birth, the calreticulin gene is sharply down regulated in the heart, and thus, adult hearts have negligible levels of calreticulin. In this study we tested the role of calreticulin in the adult heart.

Connexin43 phosphorylation and cytoprotection in the heart.

The fundamental role played by connexins including connexin43 (Cx43) in forming intercellular communication channels (gap junctions), ensuring electrical and metabolic coupling between cells, has long been recognized and extensively investigated. There is also increasing recognition that Cx43, and other connexins, have additional roles, such as the ability to regulate cell proliferation, migration, and cytoprotection. Multiple phosphorylation sites, targets of different signaling pathways, are present at the regulatory, C-terminal domain of Cx43, and contribute to constitutive as well as transient phosphorylation Cx43 patterns, responding to ever-changing environmental stimuli and corresponding cellular needs.

Preferential accumulation and export of high molecular weight FGF-2 by rat cardiac non-myocytes.

Aims: fibroblast growth factor-2 (FGF-2), implicated in paracrine induction of cardiac hypertrophy, is translated as high molecular weight (Hi-FGF-2) and low molecular weight (Lo-FGF-2) isoforms. Paracrine activities are assigned to Lo-FGF-2, whereas Hi-FGF-2 is presumed to have nuclear functions. In this work, we re-examined the latter presumption by asking whether: cardiac non-myocytes (CNMs) accumulate and export Hi-FGF-2 in response to pro-hypertrophic [angiotensin II (Ang II)] stimuli; an unconventional secretory pathway requiring activated caspase-1 affects Hi-FGF2 export; and secreted Hi-FGF-2 is pro-hypertrophic.

Do clinicians use the American College of Radiology Appropriateness criteria in the management of their patients?

Objective: The purpose of this study was to investigate the use of the American College of Radiology (ACR) appropriateness criteria by referring physicians during decision making about imaging in the management of their patients.

Conclusion: There is a low utilization of the ACR appropriateness criteria by clinicians when ordering imaging studies for their patients. The ACR has invested a great deal of resources in these criteria and should therefore be aware of information regarding utilization.

Phosphorylation of connexin-43 at serine 262 promotes a cardiac injury-resistant state.

Aims: The cardioprotective agent fibroblast growth factor 2 (FGF-2) was found previously to promote phosphorylation of connexin-43 (Cx43) at protein kinase C (PKC) sites such as serine (S) 262 at levels above those of non-stimulated hearts. We asked if other PKC-dependent cardioprotective treatments cause a similar effect, and if Cx43 phosphorylation at S262 mediates resistance to injury.

Methods And Results: Isolated perfused adult rat hearts were subjected to the following treatments: ischaemic preconditioning (PC); diazoxide perfusion; FGF-2 pre-treatment followed by 30 min global ischaemia; 30 min global ischaemia followed by 60 min reperfusion in the presence or absence of FGF-2.

The role of connexins in controlling cell growth and gene expression.

The purpose of this paper is to provide a brief overview of current thinking on the role of connexins, in particular Cx43, in growth regulation, and a more detailed discussion as to potential mechanisms involved with an emphasis on gene expression. While the precise molecular mechanism by which connexins can affect the growth of normal or tumor cells remains elusive, a number of exciting reports have expanded our understanding and are presented in some detail. Thus, we will discuss (Section 2): the role of protein-protein interactions in integrating connexins into multiple signal transduction pathways; phosphorylation at specific sites and reversal of growth inhibition; the role of the carboxy-terminal regulatory domain as a signaling molecule.

Administration of FGF-2 to the heart stimulates connexin-43 phosphorylation at protein kinase C target sites.

Fibroblast growth factor-2 (FGF-2) confers acute, preconditioning-like cardiac resistance to ischemic injury in a protein kinase C (PKC)-dependent fashion. One of the downstream targets of PKC is the gap junction protein connexin-43 (Cx43). We thus examined the effects of FGF-2 on Cx43 phosphorylation at specific PKC sites in the adult heart.