Relationship Between Fear of Cancer Recurrence and Quality of Life in Patients Undergoing Active Cancer Treatment: The Mediating Role of Social Support.

INTRODUCTION: Socio-psychological factors such as fear of recurrence and presence of social support may affect quality of life (QOL) of cancer patients. Identifying mediating factors that impact QOL are crucial for targeting vulnerability in patients undergoing cancer treatments. The study purpose was therefore to determine relationships between presence of fear of cancer recurrence and QOL of patients, with the mediating role of social support. METHODS: A predictive correlational design was used to conduct the study with 300 patients with cancer who were undergoing chemotherapy, radiotherapy, or surgery at two medical centers in Tehran. Measures included a demographic information form, the Fear of Cancer Recurrence Inventory (FCRI), the European Organization for Research and Treatment of Cancer QOL Questionnaire (EORTC QLQ-C30), and the Multidimensional Scale of Perceived Social Support (MSPSS). Data analyses included descriptives, and path analysis analyses. RESULTS: Higher fear of cancer recurrence predicted lower QOL (ß = -0.60, p < 0.001). Moreover, individuals with lower fear of cancer recurrence also perceived higher social support (ß = 0.32, p < 0.001). Additionally, individuals with higher perceived social support also reported better QOL (ß = 0.30, p < 0.001). CONCLUSION: Perceived social support plays a significant mediating role in the relationship between the fear of cancer recurrence and QOL in patients undergoing active cancer treatment. Enhancing social support among cancer patients may contribute to enhanced QOL, and as does reducing fears associated with disease recurrence.

Percutaneous Coronary Intervention Associated with a Higher Risk of Hypoxemia and COVID-19 Severity.

OBJECTIVE: The primary goal of the present study was to measure the implications of hypoxemia in COVID-19 patients with a history of coronary artery disease (CAD). METHODS: A systematic search of the literature published from November 1, 2019 to May 1, 2021, was conducted on PubMed/MEDLINE, Embase, and Web of Science databases. Afterwards, an observational study was designed based on the electronic health records of COVID-19 patients hospitalized in a tertiary referral hospital during the same period. A total of 179 COVID-19 cases were divided into two groups: cases with a history of CAD and percutaneous coronary intervention (CAD/PCI+, n = 89) and controls (n = 90). Clinical data were extracted from the electronic database of the hospital and statistically analyzed. RESULTS: After the application of inclusion/exclusion criteria, only three studies were deemed eligible, one of which was concerned with the impact of CAD on the all-cause mortality of COVID-19. Results from our observational study indicated that the cases were older (median age: 74 vs. 45) and more likely to develop hypoxemia (25.8% vs. 8.8%) than the controls. CAD/PCI+ was correlated with a more severe COVID-19 (11% vs. 1%). Age was a moderately significant independent predictor of increased COVID-19 severity, while hypoxemia was not. CONCLUSION: Considering the negative impact of hypoxemia on the prognosis of COVID-19 and its higher prevalence among COVID-19 patients with underlying CAD, further research is warranted to unravel the negative effects of COVID-19 on the mechanisms of gas exchange and delivery in patients with pre-existing CAD.

Lenalidomide improves NKG2D-based CAR-T cell activity against colorectal cancer cells invitro.

Introduction: Although CAR-based immunotherapy is viewed as a promising treatment for tumors, particularly hematological malignancies, solid tumors can pose challenges. It has been suggested that the immunomodulatory medication Lenalidomide (LEN) may increase the effectiveness of CAR T cells in the treatment of solid tumors. The purpose of our study was to investigate the effect of NKG2D-based CAR T cell therapy on colorectal cancer cell lines, and then we assessed combinatorial therapy using NKG2D CAR T cells and lenalidomide in vitro. Methods and results: To prepare NKG2D CAR T cells, a second-generation NKG2D-CAR construct was designed and transfected into the T cells using a lentiviral system. The NKG2D CAR T cells showed significantly higher cytotoxic activity against colorectal cancer cell lines, HCT116 and SW480, compared to untransduced T cells. In addition, our data demonstrated that the cytotoxicity and cytokine secretion of NKG2D CAR T cells significantly increased in the presence of higher doses of lenalidomide. Conclusions: The study findings suggest that combinational therapy, utilizing NKG2D-based CAR T cells and lenalidomide, has a high potential for effectively eliminating tumor cells in vitro.

Postesophagectomy chylothorax: a review of the risk factors, diagnosis, and management.

Chylothorax is a crucial postoperative complication of esophagectomy. Characterized by the leakage of chyle and lymphatic fluid through the thoracic duct, chylothorax could result in pleural effusion, respiratory distress, shortness of breath, cardiac arrhythmia, electrolyte imbalance, and malnutrition. Postesophagectomy chylothorax is associated with high morbidity and mortality, and its diagnosis and management require prompt and accurate identification of risk factors and treatment strategies. A variety of strategies are available to treat postesophagectomy chylothorax, ranging from conservative management to pharmacological, lymphangiographic, and surgical treatments. This study reviews the physio-anatomical basis, disease presentation, diagnostic methods, risk factors, and management options for postesophageal chylothorax, filling the literature gap, and highlighting the importance of early recognition and timely intervention in improving patient outcomes.

Resveratrol as an antitumor agent for glioblastoma multiforme: Targeting resistance and promoting apoptotic cell deaths.

Glioblastoma multiforme (GBM) is one of the most aggressive brain and spinal cord tumors. Despite the significant development in application of antitumor drugs, no significant increases have been observed in the survival rates of patients with GBM, as GBM cells acquire resistance to conventional anticancer therapeutic agents. Multiple studies have revealed that PI3K/Akt, MAPK, Nanog, STAT 3, and Wnt signaling pathways are involved in GBM progression and invasion. Besides, biological processes such as anti-apoptosis, autophagy, angiogenesis, and stemness promote GBM malignancy. Resveratrol (RESV) is a non-flavonoid polyphenol with high antitumor activity, the potential of which, regulating signaling pathways involved in cancer malignancy, have been demonstrated by many studies. Herein, we present the potential of RESV in both single and combination therapy- targeting various signaling pathways- which induce apoptotic cell death, re-sensitize cancer cells to radiotherapy, and induce chemo-sensitizing effects to eventually inhibit GBM progression.

An updated overview of the application of CAR-T cell therapy in neurological diseases.

Genetically modified immune cells, especially CAR-T cells, have captured the attention of scientists over the past 10 years. In the fight against cancer, these cells have a special place. Treatment for hematological cancers, autoimmune disorders, and cancers must include CAR-T cell therapy. Determining the therapeutic targets, side effects, and use of CAR-T cells in neurological disorders, including cancer and neurodegenerative diseases, is the goal of this study. Due to advancements in genetic engineering, CAR-T cells have become crucial in treating some neurological disorders. CAR-T cells have demonstrated a positive role in treating neurological cancers like Glioblastoma and Neuroblastoma due to their ability to cross the blood-brain barrier and use diverse targets. However, CAR-T cell therapy for MS diseases is being researched and could be a potential treatment option. This study aimed to access the most recent studies and scientific articles in the field of CAR-T cells in neurological diseases and/or disorders.

A hierarchical framework for distributed resilient control of islanded AC microgrids under false data injection attacks.

In this paper, we propose a control scheme to ensure the microgrid control layers are resilient to cyberattacks. The studied microgrid consists of several distributed generation (DG) units and we consider the hierarchical control structure that is common for microgrids. The use of communication channels among DGs has made microgrids more vulnerable and this is where cybersecurity issues arise. In this work we added three algorithms, reputation-based, Weighted Mean Subsequence Reduced (W-MSR) and Resilient Consensus Algorithm with Trusted Nodes (RCA-T), to the secondary control layer of the microgrid and made them resilient to false data injection (FDI) attacks. In reputation-based control, some procedures are used for detecting the attacked DGs and isolating them from the others. W-MSR and RCA-T are Mean Subsequence Reduced (MSR)-based algorithms that fade the effect of attacks without finding them. These algorithms use a simple strategy that ignores some extreme values of neighboring agents, so an attacker can simply get ignored. Our analysis of the reputation-based algorithm is based on scrambling matrices, so the communication graph can switch in a prescribed set. In each of the above cases, to evaluate the performance of the designed controllers, in addition to theoretical analysis, we evaluated and compared the controllers using simulation.

Crosslinking strategies for biomimetic hydrogels in bone tissue engineering.

Bone tissue engineering has become a popular area of study for making biomimetic hydrogels to treat bone diseases. In this work, we looked at biocompatible hydrogels that can be injected into bone defects that require the smallest possible surgery. Mineral ions can be attached to polymer chains to make useful hydrogels that help bones heal faster. These ions are very important for the balance of the body. In the chemically-triggered sector, advanced hydrogels cross-linked by different molecular agents have many advantages, such as being selective, able to form gels, and having mechanical properties that can be modified. In addition, different photo-initiators can be used to make photo cross linkable hydrogels react quickly and moderately under certain light bands. Enzyme-triggered hydrogels are another type of hydrogel that can be used to repair bone tissue because they are biocompatible and gel quickly. We also look at some of the important factors mentioned above that could change how well bone tissue engineering works as a therapy. Finally, this review summarizes the problems that still need to be solved to make clinically relevant hydrogels.

High activity and high functional connectivity are mutually exclusive in resting state zebrafish and human brains.

BACKGROUND: The structural connectivity of neurons in the brain allows active neurons to impact the physiology of target neuron types with which they are functionally connected. While the structural connectome is at the basis of functional connectome, it is the functional connectivity measured through correlations between time series of individual neurophysiological events that underlies behavioral and mental states. However, in light of the diverse neuronal cell types populating the brain and their unique connectivity properties, both neuronal activity and functional connectivity are heterogeneous across the brain, and the nature of their relationship is not clear. Here, we employ brain-wide calcium imaging at cellular resolution in larval zebrafish to understand the principles of resting state functional connectivity. RESULTS: We recorded the spontaneous activity of >12,000 neurons in the awake resting state forebrain. By classifying their activity (i.e., variances of ΔF/F across time) and functional connectivity into three levels (high, medium, low), we find that highly active neurons have low functional connections and highly connected neurons are of low activity. This finding holds true when neuronal activity and functional connectivity data are classified into five instead of three levels, and in whole brain spontaneous activity datasets. Moreover, such activity-connectivity relationship is not observed in randomly shuffled, noise-added, or simulated datasets, suggesting that it reflects an intrinsic brain network property. Intriguingly, deploying the same analytical tools on functional magnetic resonance imaging (fMRI) data from the resting state human brain, we uncover a similar relationship between activity (signal variance over time) and functional connectivity, that is, regions of high activity are non-overlapping with those of high connectivity. CONCLUSIONS: We found a mutually exclusive relationship between high activity (signal variance over time) and high functional connectivity of neurons in zebrafish and human brains. These findings reveal a previously unknown and evolutionarily conserved brain organizational principle, which has implications for understanding disease states and designing artificial neuronal networks.

Brain-wide perception of the emotional valence of light is regulated by distinct hypothalamic neurons.

Salient sensory stimuli are perceived by the brain, which guides both the timing and outcome of behaviors in a context-dependent manner. Light is such a stimulus, which is used in treating mood disorders often associated with a dysregulated hypothalamic-pituitary-adrenal stress axis. Relationships between the emotional valence of light and the hypothalamus, and how they interact to exert brain-wide impacts remain unclear. Employing larval zebrafish with analogous hypothalamic systems to mammals, we show in free-swimming animals that hypothalamic corticotropin releasing factor (CRFHy) neurons promote dark avoidance, and such role is not shared by other hypothalamic peptidergic neurons. Single-neuron projection analyses uncover processes extended by individual CRFHy neurons to multiple targets including sensorimotor and decision-making areas. In vivo calcium imaging uncovers a complex and heterogeneous response of individual CRFHy neurons to the light or dark stimulus, with a reduced overall sum of CRF neuronal activity in the presence of light. Brain-wide calcium imaging under alternating light/dark stimuli further identifies distinct and distributed photic response neuronal types. CRFHy neuronal ablation increases an overall representation of light in the brain and broadly enhances the functional connectivity associated with an exploratory brain state. These findings delineate brain-wide photic perception, uncover a previously unknown role of CRFHy neurons in regulating the perception and emotional valence of light, and suggest that light therapy may alleviate mood disorders through reducing an overall sum of CRF neuronal activity.

Non-opioid Intravenous Drugs for Pain Management in Patients Presenting with Acute Migraine Pain in the Emergency Department: A Comprehensive Literature Review.

Context: Migraine is one of the most common causes of disability worldwide and the sixth cause of loss of life years due to disability. Migraine is reported mainly in young and middle-aged people, so it can cause a person to face many problems in doing daily tasks. The emergency department annually accepts 1.2 million patients with migraine. Therefore, timely diagnosis of the disease, knowledge of valuable drugs in an emergency, knowing how to use them, and finally, early treatment can play an essential and decisive role in improving patients' symptoms and reducing the disability caused by the disease. An essential and valuable drug category in the emergency department to manage pain is non-opioid intravenous (IV) drugs. Therefore, this study aimed to evaluate non-opioid IV drugs to manage pain in patients with acute migraines in the emergency department. Method: This study conducted a comprehensive literature review to access the latest scientific studies and documents using keywords (acute migraine, non-opioid IV drugs, pain management) in reliable databases such as PubMed, Scopus, Web of Science, Cochrane, and Google Scholar. We reviewed 87 articles, 53 of which were evaluated and compared. Results: A review study considers intravenous acetaminophen as a suitable option for the first-line treatment of acute migraine in the emergency department if the patient does not tolerate aspirin and non-steroidal anti-inflammatory drugs (NSAIDs). Various studies have obtained positive effects of NSAIDs and dihydroergotamine (DHE) in treating acute migraine. Prescribing anti-dopaminergic drugs can effectively reduce associated symptoms such as nausea and vomiting. Dexamethasone and magnesium sulfate are effective in preventing migraine and severe attacks. Intravenous sodium valproate is effective in moderate to severe migraine attacks or treatment-resistant migraines. In the emergency department, prescribing intravenous haloperidol, lidocaine, and propofol can help manage migraine and improve other associated symptoms, such as nausea or vomiting. Conclusions: Non-opioid IV drugs are essential to manage pain and improve other migraine symptoms in the emergency setting. Knowing the above drugs and their optimal use has a decisive role in managing patients with acute migraine in the emergency department.

THC-induced behavioral stereotypy in zebrafish as a model of psychosis-like behavior.

High doses of the Cannabis constituent Δ9-tetrahydrocannabinol (THC) increase the risk of psychosis in humans. Highly accessible animal models are needed to address underlying mechanisms. Using zebrafish with a conserved endocannabinoid system, this study investigates the acute effects of THC on adult zebrafish behavior and the mechanisms involved. A concentration-dependent THC-induced behavioral stereotypy akin to THC's effect in rats and the psychotropics phencyclidine and ketamine in zebrafish was established. Distinctive circular swimming during THC-exposure was measured using a novel analytical method that we developed, which detected an elevated Repetition Index (RI) compared to vehicle controls. This was reduced upon co-administration of N-methyl-D-aspartate (NMDA) receptor agonist NMDA, suggesting that THC exerts its effects via biochemical or neurobiological mechanisms associated with NMDA receptor antagonism. Co-treatment of γ-aminobutyric acid receptor antagonist pentylenetetrazol also showed signs of reducing the RI. Since THC-induced repetitive behavior remained in co-administrations with cannabinoid receptor 1 inverse agonist AM251, the phenotype may be cannabinoid receptor 1-independent. Conversely, the inverse cannabinoid receptor 2 agonist AM630 significantly reduced THC-induced behavioral stereotypy, indicating cannabinoid receptor 2 as a possible mediator. A significant reduction of the THC-RI was also observed by the antipsychotic sulpiride. Together, these findings highlight this model's potential for elucidating the mechanistic relationship between Cannabis and psychosis.

The Effect of Peppermint (Mentha piperita) Extract on the Severity of Nausea, Vomiting and Anorexia in Patients with Breast Cancer Undergoing Chemotherapy: A Randomized Controlled Trial.

Background and Objective: Nausea, vomiting, and anorexia are the most common side effects reported in cancer patients undergoing chemotherapy. The present study aimed to determine the effect of peppermint extract on the severity of nausea, vomiting, and anorexia in patients with breast cancer undergoing chemotherapy. Methods and Materials: In this randomized controlled trial, we selected 84 patients with breast cancer undergoing chemotherapy. They were then assigned to 2 groups of experimental and control (n = 42, each) using block randomization. Patients in the experimental group received 40 drops of peppermint extract mixed in 20 cc of tap water every 8 hours, while patients in the control group received 40 drops of distilled water mixed in 20 cc of tap water every 8 hours. The severity of nausea, vomiting, and anorexia was measured and recorded before the intervention, and immediately, 24 and 48 hours after the chemotherapy using the Visual Analogue Scale. Statistical analysis of the data was conducted using SPSS software version 21. Results: The results of the present study revealed that there was a significant difference between the 2 groups at 24 and 48 hours after the chemotherapy (P < .05), so that the mean score of the severity of nausea, vomiting, and anorexia in the experimental group was lower than in the control group (P < .05). Conclusion: The use of peppermint as a method in complementary medicine may improve nausea, vomiting, and anorexia in patients with breast cancer undergoing chemotherapy. Further studies with greater sample size and longer follow-up period are needed to confirm the current findings.

Selective Inhibition of Esophageal Cancer Stem-like Cells with Salinomycin.

BACKGROUND: Targeting Cancer Stem-Like Cells (CSLCs) can provide promising new therapeutic strategies to inhibit cancer progression, metastasis and recurrence. Salinomycin (Sal), an antibacterial ionophore, has been shown to inhibit CSCs specifically. Recently, it has been reported that Sal can destabilize TAZ, the hypo pathway transducer in CSLCs. OBJECTIVES: Here, in the current study, we aimed to assess the differential toxicity of Sal in esophageal CSLCs and its relation to TAZ gene expression. METHODS: The esophageal cancer cell line, KYSE-30, was used for the enrichment of CSLCs. The expression of TAZ was knocked down using specific siRNA transfection and then the cytotoxicity of Sal was measured using XTT assay. The qRT-PCR method was used for gene expression assessment and the sphere formation ability was monitored using light microscopy. RESULTS: Our findings showed that esophageal CSLCs over-express stemness-associated genes, including SOX2, OCT4 as well as TAZ (~14 fold, P value=0.02) transcription coactivator. We found Sal can selectively inhibit KYSE-30 CSLCs viability and sphere formation ability; however, TAZ knockdown does not change its differential toxicity. CONCLUSION: Overall, our results indicated that Sal can selectively decrease the viability of esophageal CSLCs in a TAZ-independent manner.

Heritable natural variation of light/dark preference in an outbred zebrafish population.

Anxiety is a fear-like response to stimuli perceived to be threatening. Excessive or uncontrollable anxiety is a debilitating psychiatric disorder which affects many people throughout their lifetime. In unravelling the complex genetic and environmental regulations of anxiety-like phenotypes, models measuring the natural dark avoidance of larval zebrafish have shed light on the individual variation and heritability of this anxiety-related trait. Using the light/dark choice paradigm and selective breeding, this study aims to validate previous findings of the variable (VDA) and strong dark aversion (SDA) heritability in AB-WT larval zebrafish using the outbred zebrafish strain EK, which offers more genetic diversity to aid in future molecular mapping efforts. 190 larvae (6 days post fertilization [dpf] and 7 dpf) were tested across four trials and divided into variable (VDA), medium (MDA) and strong (SDA) dark aversion for further in-crosses. VDA and MDA larvae became more explorative with time, whereas SDA larvae rarely left the preferred light zone. The SDA and VDA in-crosses significantly increased the respective phenotypes in the second generation of larvae, whereas VDA × MDA inter-crosses did not. For the second-generation SDA cohort, dark aversion correlated with increased thigmotaxis, which reinforces SDA as an anxiety-like phenotype. Our finding that the dark aversion trait and SDA and VDA phenotypes are heritable in an outbred zebrafish population lays an important foundation for future studies of genetic underpinnings using whole-genome mapping methods. This conserved fear/anxiety-like response in a highly accessible model organism also allows for further pharmacological and behavioral studies to elucidate the etiology of anxiety and the search for novel therapeutics for anxiety disorders.

Sulfasalazine induces mitochondrial dysfunction and renal injury.

Sulfasalazine is a commonly used drug for the treatment of rheumatoid arthritis and inflammatory bowel disease. There are several cases of renal injury encompass sulfasalazine administration in humans. The mechanism of sulfasalazine adverse effects toward kidneys is obscure. Oxidative stress and its consequences seem to play a role in the sulfasalazine-induced renal injury. The current investigation was designed to investigate the effect of sulfasalazine on kidney mitochondria. Rats received sulfasalazine (400 and 600 mg/kg/day, oral) for 14 consecutive days. Afterward, kidney mitochondria were isolated and assessed. Sulfasalazine-induced renal injury was biochemically evident by the increase in serum blood urea nitrogen (BUN), gamma-glutamyl transferase (γ-GT), and creatinine (Cr). Histopathological presentations of the kidney in sulfasalazine-treated animals revealed by interstitial inflammation, tubular atrophy, and tissue necrosis. Markers of oxidative stress including an increase in reactive oxygen species (ROS) and lipid peroxidation (LPO), a defect in tissue antioxidant capacity, and glutathione (GSH) depletion were also detected in the kidney of sulfasalazine-treated groups. Decreased mitochondrial succinate dehydrogenase activity (SDA), mitochondrial depolarization, mitochondrial GSH depletion, increase in mitochondrial ROS, LPO, and mitochondrial swelling were also evident in sulfasalazine-treated groups. Current data suggested that oxidative stress and mitochondrial injury might be involved in the mechanism of sulfasalazine-induced renal injury.

Ammonia-induced mitochondrial dysfunction and energy metabolism disturbances in isolated brain and liver mitochondria, and the effect of taurine administration: relevance to hepatic encephalopathy treatment.

INTRODUCTION: Ammonia-induced oxidative stress, mitochondrial dysfunction, and energy crisis are known as some the major mechanisms of brain injury in hepatic encephalopathy (HE). Hyperammonemia also affects the liver and hepatocytes. Therefore, targeting mitochondria seems to be a therapeutic point of intervention in the treatment of HE. Taurine is an abundant amino acid in the human body. Several biological functions including the mitochondrial protective properties are attributed to this amino acid. The aim of this study is to evaluate the effect of taurine administration on ammonia-induced mitochondrial dysfunction. MATERIAL AND METHODS: Isolated mice liver and brain mitochondria were exposed to different concentrations of ammonia (1, 5, 10, and 20 mM) and taurine (1, 5, and 10 mM), and several mitochondrial indices were assessed. RESULTS: It was found that ammonia inhibited mitochondrial dehydrogenases activity caused collapse of mitochondrial membrane potential (MMP), induced mitochondrial swelling (MPP), and increased reactive oxygen species (ROS) in isolated liver and brain mitochondria. Furthermore, a significant amount of lipid peroxidation (LPO), along with glutathione (GSH) and ATP depletion, was detected in ammonia exposed mitochondria. Taurine administration (5 and 10 mM) mitigated ammonia-induced mitochondrial dysfunction. CONCLUSIONS: The current investigation demonstrates that taurine is instrumental in preserving brain and liver mitochondrial function in a hyperammonemic environment. The data suggest taurine as a potential protective agent with a therapeutic capability against hepatic encephalopathy and hyperammonemia.

Carnosine ameliorates liver fibrosis and hyperammonemia in cirrhotic rats.

AIM: Chronic liver injury and cirrhosis leads to liver failure. Hyperammonemia is a deleterious consequence of liver failure. On the other hand, oxidative stress seems to play a pivotal role in the pathogenesis of liver fibrosis as well as in the cytotoxic mechanism of ammonia. There is no promising therapeutic agent against ammonia-induced complications. The present study was conducted to evaluate the role of carnosine (CA) administration on liver pathological changes, elevated plasma ammonia, and its consequent events in cirrhotic rats. METHODS: Bile duct ligated (BDL) rats were used as a model of cirrhosis. CA (250, 500, and 1000mg/kg, daily, i.p) was administered for 28 consecutive days to BDL animals. At the end of treatments, markers of oxidative stress and liver fibrosis was determined in liver and serum biomarkers of liver injury and plasma ammonia was assessed. Moreover, changes in animals' locomotor activity were monitored. RESULTS: Severe bridging fibrosis, inflammation, and necrosis in liver, along with elevated serum biomarkers of liver injury were evident in BDL animals. Furthermore, plasma ammonia was drastically elevated in cirrhotic rats and animals' locomotor activity was suppressed. It was found that CA (250, 500, and 1000mg/kg, daily, i.p) significantly alleviated liver injury and its consequent events in cirrhotic rats. The data suggested that CA is not only a useful and safe agent to preserve liver function, but also prevented hyperammonemia and brain damage as a deleterious consequence of cirrhosis and liver failure.