Modeling Challenges in Cost-Effectiveness Analysis of First-Line Immuno-Oncology Therapies in Non-small Cell Lung Cancer: A Systematic Literature Review.

Introduction: The introduction of immuno-oncology (IO) therapies has changed the treatment landscape of non-small cell lung cancer (NSCLC). Numerous cost-effectiveness analyses (CEAs) and technology appraisals (TAs) evaluating IO therapies have been recently published.

Objective: We reviewed economic models of first-line (1L) IO therapies for previously untreated advanced or metastatic NSCLC to identify methodological challenges associated with modeling cost effectiveness from published literature and TAs and to make recommendations for future CEAs in this disease area.

Clinical evidence for the first-line treatment of advanced urothelial carcinoma: Current paradigms and emerging treatment options.

Background: Patients with advanced urothelial carcinoma (UC) have poor outcomes, with 5-year survival rates of <5% for those with metastatic, stage IV disease. We have reviewed current treatment paradigms and emerging treatment options for these patients.

Methods: The websites of seven national or international organizations were searched for metastatic UC treatment guidelines.

Postnatal Development of the Posterior Hypothalamic Theta Rhythm and Local Cell Discharges in Rat Brain Slices.

Theta rhythms have been recorded from rat brain slices of the posterior hypothalamic area (PHa), including the supramammillary and posterior hypothalamic nuclei. Additionally, in numerous studies theta-related neurons were identified in the PHa according to the classification of Bland and Colom (Progress in Neurobiology, 41, 157-208, 1993). It is currently widely accepted that the PHa contributes to the process of HPC theta frequency programming at least in certain behavioral states.

Fullerenol C(OH) protects human erythrocyte membrane against high-energy electrons.

Fullerenols (polyhydroxylated fullerene C) are nanomaterial with potentially broad applicability in biomedical sciences with high antioxidant ability, thus, we investigated the radioprotecting potential of fullerenol C(OH) on human erythrocytes irradiated by high-energy electrons of 6 MeV. The results demonstrate that C(OH) at concentration of 150 μg/mL protects the erythrocytes against the radiation-induced hemolysis (comparing to non-protected cells, we observed 30% and 39% protection for 0.65 and 1.

Cell discharge correlates of posterior hypothalamic theta rhythm recorded in anesthetized rats and brain slices.

Kowalczyk et al. (Hippocampus 2014; 24:7-20) were probably the first to conduct a systemic study of posterior hypothalamic area (PHa) theta rhythm in anesthetized rats. They demonstrated that local PHa theta field potentials were tail-pinch resistant and could be generated in urethane-anesthetized rats independently of ongoing hippocampal formation theta rhythm.

Development of theta rhythm in hippocampal formation slices perfused with 5-HT1A antagonist, (S)WAY 100135.

Numerous studies have revealed that median raphe nuclei stimulation induces desynchronization of hippocampal field activity in vivo. Some findings provide evidence for tonic regulation of the theta oscillation of the septo-hippocampal system via the serotonergic system. To date the involvement of serotonergic transmission in theta rhythm generation in hippocampal slices has never been investigated.

Orexinergic theta rhythm in the rat hippocampal formation: In vitro and in vivo findings.

Previous in vivo data suggested that orexin neuropeptides (ORX(A) and ORX(B) ) synthetized in hypothalamic neurons were involved in the mechanism of generation of the hippocampal formation theta rhythm. Surprisingly, this suggestion has never been directly proved by experiments using intraseptal or intrahippocampal administration of orexins. In this study, involving the use of in vitro hippocampal formation slices and in vivo model of anesthetized rat, we provide the first convergent electropharmacological evidence that in the presence of both ORX(A) and ORX(B) the hippocampal formation neuronal network is capable of producing oscillations in the theta band.

Fullerenols as a new therapeutic approach in nanomedicine.

Recently, much attention has been paid to the bioactive properties of water-soluble fullerene derivatives: fullerenols, with emphasis on their pro- and antioxidative properties. Due to their hydrophilic properties and the ability to scavenge free radicals, fullerenols may, in the future, provide a serious alternative to the currently used pharmacological methods in chemotherapy, treatment of neurodegenerative diseases, and radiobiology. Some of the most widely used drugs in chemotherapy are anthracycline antibiotics.

[Fullerenol - properties and applications in biomedical sciences].

Fullerenols, the water-soluble derivatives of fullerenes, are currently being recently intensively studied in the context of the possibility of their application in the biomedicine. Due to their hydrophilic properties and the ability to eliminate free radicals, fullerenols may in the future provide a solid alternative to currently used pharmacological methods in chemotherapy, treatment of neurodegenerative diseases and radiobiology. Depending on the research protocol applied, fullerenols may also act as pro oxidants.

Development of NMDA-induced theta rhythm in hippocampal formation slices.

During the past 20 years experimental evidence has accumulated demonstrating that the appearance of theta rhythm requires a certain level of excitation of local neuronal networks. In this study we extended our earlier in vitro observations concerning the involvement of cholinergic and GABAergic neurotransmission in hippocampal theta production. Specifically, we investigated whether the hippocampal neuronal network is capable of generating theta oscillations in the presence of N-methyl-d-aspartic acid (NMDA) in a brain slice preparation.

Spatiotemporal characterization of mTOR kinase activity following kainic acid induced status epilepticus and analysis of rat brain response to chronic rapamycin treatment.

Mammalian target of rapamycin (mTOR) is a protein kinase that senses nutrient availability, trophic factors support, cellular energy level, cellular stress, and neurotransmitters and adjusts cellular metabolism accordingly. Adequate mTOR activity is needed for development as well as proper physiology of mature neurons. Consequently, changes in mTOR activity are often observed in neuropathology.

Does an anti-oxidant ascorbic acid improve the condition of hippocampal formation slice preparations? A micro-EEG approach.

The objective of this study was to assess whether ascorbic acid (AA), an intracellular anti-oxidant critical for neuronal protection, when added to artificial cerebrospinal fluid (ACSF), is able to protect hippocampal (HPC) formation slice preparations from ageing. In this research, the micro-electroencephalographic (EEG) technique was applied. Experiments were performed on 72 HPC formation slices obtained from 12 male Wistar rats.

Gap junction modulation of hippocampal formation theta and local cell discharges in anesthetized rats.

During the past decade experimental evidence has accumulated demonstrating that the electrical communication between neurons through gap junctions (GJs) is a necessary neural mechanism underlying oscillations and synchrony. Here we extended our earlier observations concerning the involvement of GJs in hippocampal theta production. Using trimethylamine, a GJ opener, we demonstrated a reversible increase in theta amplitude and power and an increase in the duration of theta epochs.

Uric acid but not apple polyphenols is responsible for the rise of plasma antioxidant activity after apple juice consumption in healthy subjects.

Objective: To determine whether (1) rapid consumption of 1 L of apple juice increases blood antioxidant capacity, measured as ferric-reducing ability of plasma (FRAP) and serum 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity, and (2) apple polyphenols or fructose-induced elevation of plasma uric acid contributes to post-juice increase of blood antioxidant activity.

Methods: The study involved 12 (mean age 32 ± 5 years, mean body weight 73 ± 7 kg) healthy nonsmoking subjects. Tested subjects consumed 1 L of clear apple juice and then FRAP; serum DPPH-scavenging activity, serum uric acid, and total plasma phenolics and quercetin levels were measured just before juice ingestion and 1, 2.