IntelliCage: the development and perspectives of a mouse- and user-friendly automated behavioral test system.

IntelliCage for mice is a rodent home-cage equipped with four corner structures harboring symmetrical double panels for operant conditioning at each of the two sides, either by reward (access to water) or by aversion (non-painful stimuli: air-puffs, LED lights). Corner visits, nose-pokes and actual licks at bottle-nipples are recorded individually using subcutaneously implanted transponders for RFID identification of up to 16 adult mice housed in the same home-cage. This allows for recording individual in-cage activity of mice and applying reward/punishment operant conditioning schemes in corners using workflows designed on a versatile graphic user interface.

Gross Hematuria Associated with Anticoagulants and Antiplatelet Drugs: Analysis of Current Treatment Standards and Relevance of Co-medication and Pharmacological Interactions.

Background: Anticoagulants and antiplatelet drugs are risk factors for gross hematuria (GH). Moreover, co-medication and drug-drug interactions (DDIs) may influence GH and its clinical course.

Objective: To investigate the relationship between GH and administration of oral anticoagulants and antiplatelet drugs.

SB8, an approved bevacizumab biosimilar based on totality of evidence: scientific justification of extrapolation.

SB8 is a biosimilar of bevacizumab based on its similarity demonstrated by physicochemical, functional, non-clinical and clinical studies. Supported by the concept of extrapolation, SB8 was authorized and is used in a similar manner across all types of tumors as reference bevacizumab. Furthermore, SB8 offers convenience with prolonged stability compared with reference bevacizumab in diluted form.

Recording electrical activity from the brain of behaving octopus.

Octopuses, which are among the most intelligent invertebrates, have no skeleton and eight flexible arms whose sensory and motor activities are at once autonomous and coordinated by a complex central nervous system. The octopus brain contains a very large number of neurons, organized into numerous distinct lobes, the functions of which have been proposed based largely on the results of lesioning experiments. In other species, linking brain activity to behavior is done by implanting electrodes and directly correlating electrical activity with observed animal behavior.

Behavior is movement only but how to interpret it? Problems and pitfalls in translational neuroscience-a 40-year experience.

Translational research in behavioral neuroscience seeks causes and remedies for human mental health problems in animals, following leads imposed by clinical research in psychiatry. This endeavor faces several problems because scientists must read and interpret animal movements to represent human perceptions, mood, and memory processes. Yet, it is still not known how mammalian brains bundle all these processes into a highly compressed motor output in the brain stem and spinal cord, but without that knowledge, translational research remains aimless.

[Pharmaceutical residues in aquatic compartments : Status quo and perspectives].

Meanwhile, more than 600 different pharmaceuticals have been detected in surface water, with diclofenac, ethinylestradiol and cotrimoxazole as the frequently dominating substances. The highest concentrations of parent compounds, metabolites and transformation products were measured particularly in urban wastewater discharges, in liquid manure from animal husbandries and aquaculture facilities; however, the levels of certain psychopharmaceuticals and estrogen effective substances in surface water have been associated with behavioral changes and reproduction toxicity in fish species. As a consequence, in the near future measures must be implemented that noticeably reduce the discharge of pharmaceuticals into the environment.

[Vaccines against coronavirus disease 2019 (COVID-19) : Efficacy comparison, safety aspects, and current challenges].

Several RNA-, vector-, and protein-based coronavirus disease 2019 (COVID-19) vaccines are currently available in order to achieve high titers of neutralizing antibodies against the spike protein as well as strongly activated CD4+- and CD+ T‑cells. However, there are formulation-specific advantages and disadvantages with regard to physicochemical stability, spectrum of adverse effects, need for adjuvants or adaptability to potentially novel viral variants. Whereas children and pregnant women now have access to COVID-19 vaccines, it often remains difficult to achieve sufficient cellular and humoral immunity in heavily immunocompromised patients.

How Do Hospital Pharmacists Approach Substitution of Nanomedicines? Insights from a Qualitative Pilot Study and a Quantitative Market Research Analysis in Five European Countries.

We conducted research to assess hospital pharmacists' familiarity with/interpretation of data requirements for the different regulatory approval frameworks and the impact of this on their approach to substitution in the formulary. The online questionnaire included a small molecule (acetylsalicylic acid-follow-ons approved via the generic pathway), two biologic drugs (insulin glargine and etanercept-follow-ons approved via the biosimilar pathway), a non-biologic complex drug (NBCD; glatiramer acetate-follow-ons approved via the hybrid pathway) and a nanomedicine, ferric carboxymaltose (no follow-ons approved as yet). The study was conducted in two phases: an initial qualitative pilot study with 30 participants, followed by a quantitative stage involving 201 pharmacists from five European countries.

Chronic fluoxetine treatment impairs motivation and reward learning by affecting neuronal plasticity in the central amygdala.

Background And Purpose: The therapeutic effects of fluoxetine are believed to be due to increasing neuronal plasticity and reversing some learning deficits. Nevertheless, a growing amount of evidence shows adverse effects of this drug on cognition and some forms of neuronal plasticity.

Experimental Approach: To study the effects of chronic fluoxetine treatment, we combine an automated assessment of motivation and learning in mice with an investigation of neuronal plasticity in the central amygdala and basolateral amygdala.

IntelliCage as a tool for measuring mouse behavior - 20 years perspective.

Since the 1980s, we have witnessed the rapid development of genetically modified mouse models of human diseases. A large number of transgenic and knockout mice have been utilized in basic and applied research, including models of neurodegenerative and neuropsychiatric disorders. To assess the biological function of mutated genes, modern techniques are critical to detect changes in behavioral phenotypes.

A new formulation of levothyroxine engineered to meet new specification standards.

Small variations in the dose of levothyroxine have been associated with marked variations in thyroid function in people with hypothyroidism. Accordingly, regulators have identified levothyroxine as a "narrow therapeutic index" drug subject to more stringent regulations compared with other drugs, in terms of the accuracy and stability of the amount of active drug in each tablet (typically required to be 95-105% of the labelled amount over its full shelf life), and its bioavailability geometric mean ratios (90% confidence intervals between 90-111.1%, including 100%).

Precipitation strengthening in Cu-Ni-Si alloys modeled with ab initio based interatomic potentials.

Effective interaction potentials suitable for Cu/δ-NiSi and Cu/β-NiSi are developed. We optimise the potential parameters of an embedded atom method potential to reproduce forces, energies, and stresses obtained from ab initio calculations. Details of the potential generation are given, and its validation is demonstrated.

[Pulmonary infiltrates in haematological patients].

Background: Pulmonary complications are frequent in haematologic patients.

Method: This review article summarizes the outcome of a discussion that took place during an expert meeting on the subject of pulmonary infiltrates.

Results And Conclusions: The most common causes of pulmonary infiltrates in haematologic patients are bacterial infections.

Safety of intranasal human insulin: A review.

Aims: To conduct a review in order to assess the safety of intranasal human insulin in clinical studies as well as the temporal stability of nasal insulin sprays.

Material And Methods: An electronic search was performed using MEDLINE. We selected original research on intranasal human insulin without further additives in humans.

Safety of shortened infusion times for combined ipilimumab and nivolumab.

Background: Combined ipilimumab and nivolumab induces encouraging response rates in patients with unresectable or metastatic melanoma. However, the approved protocol for dual checkpoint inhibition (3 mg/kg ipilimumab over 90 min and 1 mg/kg nivolumab over 60 min) is time-intensive and several trials have shown that both single agents can be safely administered at faster infusion rates.

Aim: To investigate whether combined checkpoint inhibition with 3 mg/kg ipilimumab and 1 mg/kg nivolumab can be safely administered over 30 min per agent.

Automated dissection of permanent effects of hippocampal or prefrontal lesions on performance at spatial, working memory and circadian timing tasks of C57BL/6 mice in IntelliCage.

To evaluate permanent effects of hippocampal and prefrontal cortex lesion on spatial tasks, lesioned and sham-operated female C57BL/6 mice were exposed to a series of conditioning schemes in IntelliCages housing 8-10 transponder-tagged mice from each treatment group. Sequential testing started at 51-172days after bilateral lesions and lasted for 154 and 218days in two batches of mice, respectively. Spontaneous undisturbed behavioral patterns clearly separated the three groups, hippocampals being characterized by more erratic hyperactivity, and strongly impaired circadian synchronization ability.

How to select a nanosimilar.

Nanomedicines in the class of nonbiological complex drugs (NBCDs) are becoming increasingly available. Up to 23 nanomedicines have been approved, and approximately 50 are in clinical development. Meanwhile, the first nanosimilars have entered the market through the generic approval pathway, but clinical differences have been observed.

[Treatment and Secondary Prevention of Venous Thromboembolism - Change in Oral Anticoagulation].

With the recent approval of the fourth direct non vitamin K dependent oral anticoagulant (NOAC) edoxaban the range of available NOACs for the treatment of venous thromboembolism (VTE) has expanded. Shortly thereafter, two updated guidelines for the prevention and treatment of VTE have been published. In these NOACs are listed as equal anticoagulants to low-molecular weight heparin (LMWH), or fondaparinux (FDX), and VKA for the initial or maintenance treatment of VTE.

Combined treatment with ipilimumab and intratumoral interleukin-2 in pretreated patients with stage IV melanoma-safety and efficacy in a phase II study.

Treatment of advanced melanoma patients with ipilimumab results in improved survival. However, only about 20% of treated patients experience long-term benefit. Combining treatment of ipilimumab with other drugs may improve immune activation and potentially enhance clinical efficacy.

Eco-HAB as a fully automated and ecologically relevant assessment of social impairments in mouse models of autism.

Eco-HAB is an open source, RFID-based system for automated measurement and analysis of social preference and in-cohort sociability in mice. The system closely follows murine ethology. It requires no contact between a human experimenter and tested animals, overcoming the confounding factors that lead to irreproducible assessment of murine social behavior between laboratories.

The ability to solve elementary logic tasks in mice with the knockout of sodium-calcium exchanger gene 2 (NCX2).

Mice with a knockout of the sodium-calcium exchanger 2 (NCX2) gene were statistically significantly more successful than wild-type controls in the solution of two cognitive tasks, the test for the capacity to extrapolate the direction of the stimulus movement and the "puzzle-box" test for the capacity to find a hidden route to safe environment, which were based on food and aversive motivations, respectively. In both tests, the success of task solution was based on the animal's ability to use the object's "permanence" rule (according to J. Piaget).