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The Impact of Emergency Room Overcrowding on the Incidence of Healthcare-Acquired Infections Among Patients
Full text linkEmergency department (ED) visits are vital components of healthcare delivery, serving as the primary site for acute medical care, particularly for individuals with urgent medical needs. The ED is among the most crowded hospital units. The fast-paced setting and over-crowdedness of an emergency room have become the reality of every hospital across the United States. Overcrowding causes problems for patients and staff, which include the risk of contracting healthcare-acquired infections. This is due to several factors that in most cases lead to an increase in the number of people within the ED, an increase in mortality and morbidity, and a decrease in the ability to provide critical services promptly to patients suffering from medical emergencies. Although the causes of ED overcrowding are complex, the main cause is inadequate inpatient capacity for a patient population with an increasing severity of illness. This study focuses on the over-crowded environment of an Emergency department and the relationship it may have to the increasing number of avoidable health care-acquired infections
Investigating PINCH-1 in Glioblastoma Multiforme: A Potential Adjuvant Therapy Target to Improve Treatment Outcomes
Full text linkGliomas account for approximately 80% of all brain cancers and 30% of central nervous system tumors. Glioblastoma multiforme (GBM), the most common, is unfortunately, the most aggressive glioma cancer type. Despite treatment efforts such as surgery, radiation, and chemotherapy, nearly all low-grade astrocytoma progress to GBM without complete surgical resection. Achieving full surgical removal is typically impossible, leading to an almost 100% recurrence rate of GBM after 9 months with a median survival of approximately 15 months. This poor prognosis is due to its high invasiveness and resistance to therapy. Therefore, improved therapeutic approaches are needed to reduce recurrence and prevent progression of astrocytoma into GBM. This research investigated how the particularly interesting new cysteine-histidine-rich protein 1 (PINCH-1) protein may lead to a potential adjuvant therapy to supplement surgery, radiation, and chemotherapy. The PINCH protein is highly expressed during development for cytoskeletal organization, cell migration, extracellular matrix and focal adhesion interactions, as well as, cell survival. However, after birth, PINCH-1 is nearly undetectable in healthy cells, but resurges in cancer cells. Though PINCH-1 has been linked to various cancers by several studies, little is known about the mechanistic and signaling pathways whereby PINCH contributes to the development and recurrence of GBM and resistance of cancer cells to therapeutic intervention. Our study investigated the consequences of changes in PINCH-1 protein expression, cell cycle alterations, post-translational modifications, and cell survival in GBM cell sensitivity to chemotherapeutic agents. Further studies are required to identify potential pathways to modify PINCH1 for use as an adjuvant therapy to accompany surgical, chemotherapeutic, and radiation treatment
A Better Road to Recovery- Effectiveness of Osteopathic Manipulative Treatment Compared to Conventional Methods on Post-Concussion Patients
Full text linkBackground:
Concussion, a form of traumatic brain injury, often presents with sleep disturbances, headache, confusion, and memory impairment. Current treatment includes reduced screen time, physical activity, and increased rest. For decades, these treatment options have demonstrated improvement in symptoms. Recently, there is growing interest in whether using osteopathic manipulative treatment (OMT) to target structural dysfunctions is more effective. This review compares OMT to conventional treatment methods in post-concussion patients.
Methods:
This literature review uses data from clinical trials, randomized controlled trials, observational studies, and case reports within the past 10-15 years. It includes adolescents, adults, elderly, athletes, and non-athletes while excluding data involving non-human/animal studies. The comparison takes into account symptom reduction, recovery time, and quality of life.
Results:
Compared to conventional treatment, OMT shows a statistically significant improvement (p-value
Conclusion:
Overall, OMT shows promising results in treating concussion patients. However, further research using a larger sample size, standardized treatments, and long-term follow-ups is needed to better understand the effectiveness of OMT compared to conventional treatment in post-concussion patients
Effects of the Non-Stimulant Norepinephrine Reuptake Inhibitor, Atomoxetine, on Cognitive Flexibility in Healthy Adult Long-Evans Rats
Full text linkExecutive function is the control of multiple higher order cognitive processes that include attention, working memory, and cognitive flexibility. Cognitive flexibility is the ability to shift behavioral strategies
in response to changing environmental demands and task complexity. This cognitive modality is often impaired in many neuropsychiatric disorders like attention deficit hyperactivity disorder (ADHD). Deficits in cognitive flexibility are associated with dysregulation of the catecholamines, norepinephrine (NE) and dopamine (DA) within the prefrontal cortex (PFC). Atomoxetine (ATX), a non-stimulant NE reuptake inhibitor, elevates levels of NE and DA in the PFC by inhibiting the norepinephrine transporter (NET). ATX is used to treat ADHD and improves components of cognitive flexibility in rodent models of cognitive disorder. However, the effects of ATX on cognitive flexibility in healthy adult rats have not been demonstrated. Within the current study, an automated operant strategy shifting task (SST) of cognitive flexibility was used to examine the effects of ATX (0.3-1mg/kg) on performance in male and female Long-Evans rats. Rats initially acquired a visual cue strategy to collect sucrose reward pellets. Twenty-four hours after initial acquisition, rats were assessed for retrieval of the visual cue strategy followed by a series of strategy shifting and reversal learning challenges
Direct Synthesis of Cerium Oxide Nanoparticles in Reducing Sugars: Enhanced Ce3+ Surface Density for Biological Application
Full text linkCerium oxide nanoparticles (CNPs) are recognized for their ability to scavenge reactive oxygen species (ROS), making them promising candidates for mitigating oxidative damage in biomedical applications. However, many conventional synthesis methods limit the formation of Ce³⁺ states, which are critical for this antioxidant function. Building upon previous findings that glucose can promote Ce³⁺ formation, this study investigates the broader impact of both reducing (glucose, fructose, galactose) and non-reducing (dextran, sucrose, cyclodextrin) natural sugars on CNP synthesis. CNPs were synthesized in the presence of these sugars, and the surface densities of Ce³⁺ were measured. Results showed that reducing sugars significantly increased Ce³⁺ surface density compared to controls, enhancing the redox-active nature of the nanoparticles. Superoxide dismutase (SOD) assays further demonstrated a correlation between higher Ce³⁺ ratios and increased biological activity, affirming the functional importance of redox modulation. Biological evaluation in human bone marrow-derived mesenchymal stem cells (hMSCs) revealed no cytotoxic effects from any CNP formulation. Notably, sugar-modified CNPs at low concentrations enhanced alkaline phosphatase (ALP) activity and calcium deposition, as confirmed by ALP and Alizarin Red S (ARS) assays, key indicators of osteogenic differentiation. Overall, the study underscores the therapeutic potential of Ce³⁺-rich, sugar-modified CNPs for promoting bone growth and broadens their applicability in regenerative medicine
Hypoxia Induced Ribosomal RNA Fragmentation Mediated by RNase L
Full text linkIschemic injury contributes to a range of global pathologies. Ischemia/Reperfusion Injury (IRI) is a paradoxical phenomenon that involves an initial restriction of blood flow followed by a sudden restoration of perfusion. This type of injury takes place in conditions such as myocardial infarction, acute kidney disease, and ischemic stroke and often leads to cellular death. Additionally, IRI exacerbates post-surgical outcomes and plays a role in graft dysfunction and transplant rejection. Despite efforts to develop therapies targeting known IRI pathways, clinical trials have largely been unsuccessful, underscoring the need for alternative mechanisms and biomarkers associated with IRI-induced apoptosis. Reactive oxygen species (ROS) generated during IRI-induced apoptosis inflict damage on proteins, lipids, and nucleic acids, including ribosomal RNA (rRNA), which is vital for ribosome function. Our cell culture studies uncovered distinct rRNA fragmentation patterns under oxidative stress and metal homeostasis defects, which differ from those observed in hypoxia/reoxygenation scenarios. This indicates that a unique mechanism is involved in IRI-induced apoptosis. One potential contributor to these rRNA alterations is ribonuclease activity. RNase-L, an interferon-associated ribonuclease, is upregulated during low-oxygen states and may be responsible for rRNA cleavage in hypoxia/reoxygenation conditions. Northern blot analysis revealed specific rRNA cleavages in wild-type (WT) A549 cells that were absent in RNase-L knockout (KO) A549 cells. Furthermore, WT cells exhibited significant morphological changes following hypoxia, while KO cells remained indistinguishable from control samples. These findings suggest a link between RNase-L and the unique rRNA cleavages observed during IRI-induced apoptosis. Further investigation into IRI-specific rRNA alterations, including fragmentation patterns and nucleotide modifications, could yield valuable insights into ischemic pathology. If validated, rRNA changes may serve as biomarkers for IRI, which can be used to enhance diagnostic capabilities and guide therapeutic development
Religion and Attitudes Toward Xenotransplantation: Results of a Nationwide Survey in the United States.
Full text linkReligious viewpoints have been shown to influence the ways in which many persons approach medical decision-making and have been noted as a potential barrier to xenotransplantation acceptance. This study sought to explore how attitudes toward xenotransplantation differ among various religious beliefs. A national Likert-scale survey was conducted in 2023 with a representative sample in the United States. Religious belief was self-reported. Regression analysis was used to identify associations with religious belief and hesitations about xenotransplantation. Five thousand and eight individuals across the United States responded to the survey. The two biggest concerns about xenotransplantation across religious groups were the current lack of evidence about success and the risk of xenozoonosis. Although they still expressed concerns about certain issues, Catholic and Muslim respondents were most comfortable with xenotransplantation for all. On average, the risk of xenozoonosis was a concern among 25% across all religious beliefs (
Comprehensive SUMO Proteomic Analyses Identify HIV Latency-Associated Proteins in Microglia.
Full text linkSUMOylation, the post-translational modification of proteins by small ubiquitin-like modifiers, plays a critical role in regulating various cellular processes, including innate immunity. This modification is essential for modulating immune responses and influencing signaling pathways that govern the activation and function of immune cells. Recent studies suggest that SUMOylation also contributes to the pathophysiology of central nervous system (CNS) viral infections, where it contributes to the host response and viral replication dynamics. Here, we explore the multifaceted role of SUMOylation in innate immune signaling and its implications for viral infections within the CNS. Notably, we present novel proteomic analyses aimed at elucidating the role of the small ubiquitin-related modifier (SUMO) in human immunodeficiency virus (HIV) latency in microglial cells. Our findings indicate that SUMOylation may regulate key proteins involved in maintaining viral latency, suggesting a potential mechanism by which HIV evades immune detection in the CNS. By integrating insights from proteomics with functional studies, we anticipate these findings to be the groundwork for future studies on HIV-host interactions and the mechanisms that underlie SUMOylation during latent and productive infection
BEHAVIORAL AND NEUROACTIVATIONAL CORRELATES OF PSYCHOSOCIAL STRESS-INDUCED COCAINE SEEKING IN THE RAT
No full textAbstract Nicole Maria Hinds BEHAVIORAL AND NEUROACTIVATIONAL CORRELATES OF PSYCHOSOCIAL STRESS-INDUCED COCAINE SEEKING IN THE RAT 2024 Molecular Cell Biology & Neuroscience Doctor of Philosophy Cocaine Use Disorder is characterized by a high risk for relapse that can persist over extended periods of abstinence. Psychosocial stressors are well-established to promote drug craving and relapse in humans but have rarely been employed in preclinical relapse models. Consequently, the underlying neural circuitry by which these stressors drive cocaine seeking has not yet been thoroughly explored. This project aimed to identify brain regions recruited during psychosocial stress-induced cocaine seeking in rats, with a focus on the ventromedial hypothalamus and periaqueductal gray, two critical components of the brain’s medial hypothalamic defense network. Male and female Long-Evans rats were trained to self-administer cocaine (0.5 mg/kg/inf, IV) in 2-h daily sessions for 20 sessions. On sessions 11, 14, 17, and 20, a discrete tactile cue was presented in the operant chamber that signaled impending social defeat stress, nonsocial footshock stress, or a no-stress control condition, each in separate groups of rats. Responding was then extinguished, and rats were then either re-exposed to the cue that signaled their assigned stress/no-stress post session event, or subjected to another extinction session, and reinstatement of cocaine seeking was measured. Immunohistochemical detection of c-Fos expression was then employed to examine patterns of neural activation in brain regions of interest that coincided with cocaine-seeking behavior. Re-exposure to the tactile cue reinstated cocaine seeking in both males and females in all groups. Moreover, predilection to display active-defense coping strategies during social threat was positively correlated with cocaine-seeking magnitude. Neuronal activation of the rostrolateral periaqueductal gray (rPAGl) during psychosocial stress-induced cocaine seeking was significantly and positively correlated with the tendency to display active-defense coping responses during social defeat stress and with psychosocial stress-induced cocaine-seeking behavior, as well as with levels of neural activation in the prelimbic prefrontal cortex and lateral hypothalamus/perifornical area, associations that were driven by males. Finally, retrograde tract-tracing studies revealed a negative correlation between psychosocial stress-induced cocaine seeking and the number of rPAGl/vl-projecting cells in the prelimbic prefrontal cortex and anterior cingulate cortex, including the subpopulation of these cells that were Fos-positive. Collectively, these results indicate for the first time that the rPAGl may play an important role in the expression of psychosocial stress-induced cocaine-seeking behavior, and that its contributions may be modulated by top-down inhibition from frontal cortical regions
Inhibition of Lysine Deacetylase Activity Impacts Formation of the Vitamin D Receptor Activation Complex
Full text linkThe vitamin D endocrine system is responsible for the regulation of many biological processes including bone metabolism, calcium homeostasis, cell proliferation and cell differentiation. Alterations to the vitamin D signaling pathway are associated with several diseases including bone diseases, diabetes, cardiovascular diseases, autoimmune diseases, and cancer. Vitamin D precursors are chemically modified to become the biologically active hormone, calcitriol. Calcitriol binds to the vitamin D receptor (VDR), a member of the nuclear hormone receptor (NHR) superfamily. VDR forms a heterodimer with retinoid X receptor (RXR) and together they bind to promoters containing vitamin D response elements (VDREs) to activate transcription of target genes. Other NHRs have been shown to be post-translationally modified that can either increase or decrease their transcriptional output through alterations in protein-protein or protein-DNA interactions. I have generated evidence that two lysines on VDR are likely to be targets of acetylation, and alterations to lysine deacetylase activity impacts VDR transcriptional output through changes in co-activator and co-repressor binding. Together, these data suggest a novel way for the cell to modulate the response of VDR to available vitamin D