Opposing tumor-cell-intrinsic and -extrinsic roles of the IRF1 transcription factor in antitumor immunity.

Type I interferon (IFN-I) and IFN-γ foster antitumor immunity by facilitating T cell responses. Paradoxically, IFNs may promote T cell exhaustion by activating immune checkpoints. The downstream regulators of these disparate responses are incompletely understood.

Adaptation of the Tumor Antigen Presentation Machinery to Ionizing Radiation.

Ionizing radiation (IR) can reprogram proteasome structure and function in cells and tissues. In this article, we show that IR can promote immunoproteasome synthesis with important implications for Ag processing and presentation and tumor immunity. Irradiation of a murine fibrosarcoma (FSA) induced dose-dependent de novo biosynthesis of the immunoproteasome subunits LMP7, LMP2, and Mecl-1, in concert with other changes in the Ag-presentation machinery (APM) essential for CD8+ T cell-mediated immunity, including enhanced expression of MHC class I (MHC-I), β2-microglobulin, transporters associated with Ag processing molecules, and their key transcriptional activator NOD-like receptor family CARD domain containing 5.

Blood-Based Biomarkers in Traumatic Brain Injury: A Narrative Review With Implications for the Legal System.

Traumatic brain injury (TBI) is an increasingly recognized diagnosis with significant, and often costly, associated consequences. Yet, despite their increased recognition, TBIs remain underdiagnosed. This issue is especially prominent in the context of mild TBI (mTBI), where there often exists little to no objective evidence of brain injury.

M2 isoform of pyruvate kinase rewires glucose metabolism during radiation therapy to promote an antioxidant response and glioblastoma radioresistance.

Background: Resistance to existing therapies is a significant challenge in improving outcomes for glioblastoma (GBM) patients. Metabolic plasticity has emerged as an important contributor to therapy resistance, including radiation therapy (RT). Here, we investigated how GBM cells reprogram their glucose metabolism in response to RT to promote radiation resistance.

Olanzapine-induced mania.

Olanzapine is a relatively new antipsychotic agent which appears to be effective in the treatment of both the positive and negative symptoms of schizophrenia. Reported here is the case of a patient who developed symptoms of mania secondary to treatment with olanzapine. Physicians prescribing olanzapine should be aware of this potential complication.

Inhibitory and excitatory alcohol-seeking cues distinct roles in behavior, neurochemistry, and mesolimbic pathway in alcohol preferring (P) rats.

Cues associated with alcohol use can readily enhance self-reported cravings for alcohol, which increases the likelihood of reusing alcohol. Understanding the neuronal mechanisms involved in alcohol-seeking behavior is important for developing strategies to treat alcohol use disorder. In all experiments, adult female alcohol-preferring (P) rats were exposed to three conditioned odor cues; CS+ associated with EtOH self-administration, CS- associated with the absence of EtOH (extinction training), and a CS a neutral stimulus.

NRF2 Mediates Cellular Resistance to Transformation, Radiation, and Inflammation in Mice.

Nuclear factor erythroid 2-related factor 2 (NRF2) is recognized as a master transcription factor that regulates expression of numerous detoxifying and antioxidant cytoprotective genes. In fact, models of NRF2 deficiency indicate roles not only in redox regulation, but also in metabolism, inflammatory/autoimmune disease, cancer, and radioresistancy. Since ionizing radiation (IR) generates reactive oxygen species (ROS), it is not surprising it activates NRF2 pathways.

Blood Biomarkers in Brain Injury Medicine.

Purpose Of Review: This review seeks to explore blood-based biomarkers with the potential for clinical implementation.

Recent Findings: Emerging non-proteomic biomarkers hold promise for more accurate diagnostic and prognostic capabilities, especially in the subacute to chronic phase of TBI recovery. Further, there is a growing understanding of the overlap between TBI-related and Dementia-related blood biomarkers.

Diverse experiences and approaches to tele neuropsychology: Commentary and reflections over the past year of COVID-19.

In response to the coronavirus disease 2019 (COVID-19) pandemic, neuropsychologists rapidly adopted teleneuropsychology (TeleNP) services to ensure continued clinical care. Prior to COVID-19, TeleNP was not widely used nor was it included in the majority of traditional practice or training models across graduate, internship, and postdoctoral programs. Out of necessity, the pandemic was a catalyst that promoted greater adoption of TeleNP services.

Blood and urinary cytokine balance and renal outcomes at cardiac surgery.

Background: Increased perioperative pro-inflammatory biomarkers, renal hypoperfusion and ischemia reperfusion injury (IRI) heighten cardiac surgery acute kidney injury (CS-AKI) risk. Increased urinary anti-inflammatory cytokines attenuate risk. We evaluated whether blood and urinary anti-inflammatory biomarkers, when expressed as ratios with biomarkers of inflammation, hypoperfusion and IRI are increased in CS-AKI patients.

The involvement of mesolimbic dopamine system in cotinine self-administration in rats.

Cotinine is the major metabolite of nicotine and has recently been shown to be self-administered intravenously by rats. However, mechanisms underlying cotinine self-administration remained unknown. Mesolimbic dopamine system projecting from the ventral tegmental area (VTA) to nucleus accumbens (NAC) is closely implicated in drug reinforcement, including nicotine.

Classes of Drugs that Mitigate Radiation Syndromes.

We previously reported several vignettes on types and classes of drugs able to mitigate acute and, in at least one case, late radiation syndromes in mice. Most of these had emerged from high throughput screening (HTS) of bioactive and chemical drug libraries using ionizing radiation-induced lymphocytic apoptosis as a readout. Here we report the full analysis of the HTS screen of libraries with 85,000 small molecule chemicals that identified 220 "hits.

Weak Magnetic Fields Enhance the Efficacy of Radiation Therapy.

Purpose: The clinical efficacy of radiation therapy is mechanistically linked to ionization-induced free radicals that cause cell and tissue injury through direct and indirect mechanisms. Free radical reaction dynamics are influenced by many factors and can be manipulated by static weak magnetic fields (WMF) that perturb singlet-triplet state interconversion. Our study exploits this phenomenon to directly increase ionizing radiation (IR) dose absorption in tumors by combining WMF with radiation therapy as a new and effective method to improve treatment.

Risk factors for lymphatic filariasis and mass drug administration non-participation in Mandalay Region, Myanmar.

Background: Myanmar commenced a lymphatic filariasis (LF) elimination programme in 2000. Whilst the country has made considerable progress since then, a number of districts have demonstrated persistent transmission after many rounds of mass drug administration (MDA). The causes of unsuccessful MDA have been examined elsewhere; however, there remains little information on the factors that contribute in Myanmar.

Acute kidney injury risk in orthopaedic trauma patients pre and post surgery using a biomarker algorithm and clinical risk score.

Acute kidney injury (AKI) after major trauma is associated with increased mortality. The aim of this study was to assess if measurement of blood biomarkers in combination with clinical characteristics could be used to develop a tool to assist clinicians in identifying which orthopaedic trauma patients are at risk of AKI. This is a prospective study of 237 orthopaedic trauma patients who were consecutively scheduled for open reduction and internal fixation of their fracture between May 2012 and August 2013.

Low-Dose Radiation Therapy (LDRT) for COVID-19: Benefits or Risks?

The limited impact of treatments for COVID-19 has stimulated several phase 1 clinical trials of whole-lung low-dose radiation therapy (LDRT; 0.3-1.5 Gy) that are now progressing to phase 2 randomized trials worldwide.

Atrial natriuretic peptide (ANP): A novel mechanism for reducing ethanol consumption and seeking behaviors in female alcohol preferring (P) rats.

Atrial Naturietic Peptide (ANP) is a neuropeptide that regulates function of the hypothalamic-pituitary-adrenal (HPA) axis, immune and neuroimmune system, and epigenetic factors. Research has indicated that ANP may mediate alcohol intake, withdrawal, and craving like behaviors. ANP receptors are present in the mesocorticolimbic (MCL) reward pathway of the brain, which includes the nucleus accumbens (Acb) and the ventral tegmental area (VTA).

Selective breeding for high alcohol preference is associated with increased sensitivity to cannabinoid reward within the nucleus accumbens shell.

Rationale: The rate of cannabinoid intake by those with alcohol use disorder (AUD) exceeds that of the general public. The high prevalence of co-abuse of alcohol and cannabis has been postulated to be predicated upon both a common predisposing genetic factor and the interaction of the drugs within the organism. The current experiments examined the effects of cannabinoids in an animal model of AUD.

The reinforcing effects of ethanol within the prelimbic cortex and ethanol drinking: Involvement of local dopamine D receptor-mediated neurotransmission.

Previous studies have identified important mesolimbic regions in supporting the reinforcing effects of ethanol. However, the involvement of the medial prefrontal cortex (mPFC), another key region within the mesocorticolimbic system, in ethanol reinforcement has been understudied. The objective of the current study was to examine the role of the prelimbic (PL) cortex sub-region of the mPFC in ethanol reinforcement and drinking.

The Rewarding and Anxiolytic Properties of Ethanol within the Central Nucleus of the Amygdala: Mediated by Genetic Background and Nociceptin.

In humans, alcohol is consumed for its rewarding and anxiolytic effects. The central nucleus of the amygdala (CeA) is considered a neuronal nexus that regulates fear, anxiety, and drug self-administration. Manipulations of the CeA alter ethanol (EtOH) consumption under numerous EtOH self-administration models.

Spontaneous Early Withdrawal Behaviors after Chronic 24-hour Free-Choice Access to Ethanol.

Aims: Abstinence after chronic alcohol consumption leads to withdrawal symptoms, which are exacerbated after repeated cycles of relapse. This study examined withdrawal-like behaviors after chronic ethanol drinking, with or without repeated cycles of deprivation.

Methods: Male alcohol-preferring (P) rats had access to continuous ethanol (CE), chronic ethanol with repeated deprivation (RD), or remained ethanol naïve (EN).

Identification of miRNA signatures associated with radiation-induced late lung injury in mice.

Acute radiation exposure of the thorax can lead to late serious, and even life-threatening, pulmonary and cardiac damage. Sporadic in nature, late complications tend to be difficult to predict, which prompted this investigation into identifying non-invasive, tissue-specific biomarkers for the early detection of late radiation injury. Levels of circulating microRNA (miRNA) were measured in C3H and C57Bl/6 mice after whole thorax irradiation at doses yielding approximately 70% mortality in 120 or 180 days, respectively (LD70/120 or 180).

Total laparoscopic management of spontaneous biliary perforation.

Spontaneous biliary perforation (SBP) in pediatrics is rare and historically has been treated with laparotomy for attempted repair and cholecystectomy. In recent years, management has evolved into a conservative approach, opting for cholecystostomy and peritoneal drainage over cholecystectomy. In this case, we report the first successful conservative management of SBP using an exclusively laparoscopic approach without cholecystectomy in a pediatric patient.