Aim: The study's long-term goals, such as determining supratherapeutic ranges according to age distributions
specific to the country, adjusting dosages for additional drugs used by patients in different disease
groups, and providing the opportunity for etiological studies in the light of diagnosis and drug metabolism
perspective, are of great importance in defining the study. Method: Population pharmacokinetics is a
method expressed to evaluate processes such as absorption, distribution, metabolism, and elimination of a
drug from an individual's blood-plasma concentration. In drug pharmacokinetic experiments, generating
data without considering any pharmacokinetic differences among patients prevents the measurement or
observation of variability among individuals in the population as a simple approach. The dose-concentration
relationship is crucial for individualized dose adjustment. Additionally, the impact of other drugs used
by the individual on metabolite levels and the metabolic interactions between drugs play a critical role in
the development of personalized treatments. Population approaches provide a foundation that benefits the
observation of these effects. The variability in drug metabolism among individuals forms one of the fundamental
building blocks of personalized treatment approaches, specifically through Therapeutic Drug Monitoring
(TDM), which plays an important role in determining the therapeutic range of drugs. Materials:
In this study, drug metabolism findings of patients served at NP Istanbul Brain Hospital between 2010 and
2022 were examined within the repository created along with other patient-specific parameters. Results
and Conclusion: The analysis results have been followed up longitudinally, partially demographically,
and retrospectively. Thanks to the repository of NP Istanbul Brain Hospital, population pharmacokinetic
analyses aimed in this study are being conducted for the first time globally and nationally in terms of
scope. The repository has been studied with TDM for individualized treatment methods, and within this
project, it is anticipated to perform phenotyping with the population pharmacokinetic approach.

Background: Lead acetate (Pb) exposure during frontal cortex development is associated with developmental
toxicity later in life, causing both morphological and functional alterations. Curcuma longa,
however, has been suggested to possess neuroprotective qualities that could lessen these adverse effects.
Objective: Assessed the frontal cortex following treatment with Curcuma longa. Materials and Methods:
Twenty adult female Wistar rats and ten adult male Wistar rats were matched during the proestrous phase
of the estrous cycle in order to mate and create five groups of six (n=6) in a 4:2 (4 females to 2 males)
ratio. Gestational day 0 was marked as the confirmation of pregnancy based on if sperm is present and a
vaginal plug in the vaginal smear. Four (n=4) pregnant Wistar rats were put together. Group 1 (control) rats
were given 2 milliliters per kilogram of distilled water. Pb was given at a dose of 120 mg/kg to Group 2.
Group 3 rats were given 120 mg/kg of lead and 100 mg/kg of vitamin C. The animals in Group 4 received
750 mg/kg of Curcuma longa and 120 mg/kg of Pb. The animals in Group 5 rats were given 1500 mg/kg
of Curcuma longa and 120 mg/kg of Pb. From gestational day 7 to day 21 (14 days), the medication was
administered orally. The animals were allowed to litter naturally. At postnatal day (PND) 1, some pups
were euthanized using chloroform inhalation and their brains were harvested for Oxidative stress markers,
histology, histochemical assessments. While some pups were kept for Cliff avoidance test at PND 4-7.
Results: The study found that lead acetate (Pb) exposure during gestation significantly decreased the mean
turning latency in the cliff avoidance test and increased lipid peroxidation (MDA) levels, while decreasing
antioxidant enzyme levels (SOD, CAT, GSH) compared to the control group. These neurological and oxidative
changes were mitigated by co-administration of Curcuma longa, with a notable improvement in the
cliff avoidance test performance and restoration of the altered histological and histochemical markers. The
results suggest that Curcuma longa, a natural antioxidant, has neuroprotective properties that can counteract
the adverse effects of lead toxicity during gestational development. Conclusion: N-Butanol Fraction
of Curcuma Longa ameliorated lead-induced neurotoxicity in rat pups.

Background: Benzodiazepines (BZDs) are a class of depressant drugs that have enjoyed widespread use
in conventional clinical management of anxiety-related conditions such as panic disorders that require
therapeutic central relaxation and sedation. Meanwhile, prolonged administration of benzodiazepines even
at low doses has however been linked to variety of undesirable effects such as discontinuation relapse with
the associated risk of abuse and dependency. Aim: This study investigated the behavioral, histological
and biochemical outcomes of long-term low dose diazepam use and explored the potential role of nigella
sativa oil (NSO) in the amelioration of the associated side effects. Methods: Adult Wistar rats (n=32)
were randomized into four groups that received normal saline; diazepam; diazepam + NSO; or NSO only,
respectively for 14 days. At the end of the period of the various exposures, the rats were taken through
behavioral paradigms after which they were sacrificed for chemical and histological profiling. Results:
diazepam-exposed rats exhibited stress-related manifestations with relatively poor performance in memory-
related tasks. Repeated diazepam ingestion reduced brain antioxidant biomarkers while causing elevation
of brain oxidative stress markers. On histological observation, mild degenerative changes were evident
in the various brain regions of the diazepam-exposed rats. Conclusion: Interventional nigella sativa oil
administration showed therapeutic potentials by mitigating and reversing the observed effects of diazepam,
largely due to its antioxidant and anti-inflammatory effects as observed in the present study.

Background: Pyrethroids pose health risks to humans. Therefore, it is imperative to assess the preventive
benefits of thymoquinone against neurotoxicity induced by cypermethrin- in the hippocampal dentate
gyrus. Methods: Forty male adult Wistar rats with an average weight of 180-200g were randomly allocated
to five (5) groups, and each comprising eight rats (n=8 per group). The groups were designated
as follows, through oral administrations for 14 days: 0.5ml phosphate- buffered saline (PBS) was given
to group one; Group two received 20mg/kg of cypermethrin (CYM); Group three received 10 mg/kg of
thymoquinone (THQ); Group four received 20 mg/kg of cypermethrin followed by 10mg/kg of thymoquinone
(CYM-10mgTHQ); and Group five received 20 mg/kg and 5mg/kg cypermethrin and thymoquinone
respectively (CYM-5 mgTHQ). Behavioral, histological, immunohistochemical, and biochemical analyses
were conducted post-treatment. Results: Cypermethrin administration caused the rise in pro-inflammatory
cytokine TNF-α, Nuclear Factor-kappa B (NF-κB) and increased expression of astrocytes, microglia, and
pro-apoptotic protein Bax. Additionally, cypermethrin reduced levels of anti-inflammatory cytokine IL-10
and acetylcholinesterase (AChE) activity. Cytoarchitectural disruption of dentate gyrus were observed.
Cognitive deficits were evident. Thymoquinone treatment attenuated TNF-α and NF-κB elevation, reduced
astrocyte, microglial, and Bax expression, and increased IL-10 and AChE. Conclusion: Thymoquinone
demonstrated anti-inflammatory and anti-apoptotic effects against cypermethrin-induced neurotoxicity,
improving cognitive function in rats.

Aim: Emergentism as an ontology of consciousness leaves unanswered the question as to its
mechanism. I aim to solve the body–mind problem by explaining how conscious organisms
emerged on an evolutionary basis at various times in accordance with an accepted scientific
principle through a mechanism that cannot be understood, in principle. Proposal: The reason for
this cloak of secrecy is found in a seeming contradiction in the behavior of information with respect
to the first two laws of thermodynamics. Information, the microstate of particles within an isolated
system’s macrostate, can, like first‑law energy, be neither created nor destroyed, yet the information
in the system, like second‑law entropy, will inevitably increase. To explain information increasing
without being created, Laplace’s demon is invoked, able to predict where each particle is destined.
This doesn’t work for emerging events like consciousness, which are unpredictable. This can be
understood in terms of the derivation of entropy, and the emergence of classical physics, from the
Relativistic Transactional Interpretation of Quantum Mechanics. I propose that the increased entropy
in a time‑irreversible, unpredictable (emergent) isolated system requires the simultaneous deletion
of information concerning the steps, or calculations, involved. Conclusion: Thus, the steps leading
to consciousness are immediately destroyed and must remain a mystery. Implications include that
entropy, not panpsychism, is the universal principle generative of consciousness, that our being
conscious proves that we are not predetermined, and that consciousness requires assuming an
“entropy debt” that can only be repaid by living organisms, prohibiting the emergence of conscious
machines.

Background: Epilepsy is a neurological illness that disturbs the central nervous system and is
characterized by regular convulsions. Over 70 million people worldwide are thought to have
epilepsy, with the prevalence rate estimated to be around 1%. Aims: The objective of this study
was to assess antiepileptic activities and histological changes after Mentat administration in the
hippocampus of pentylenetetrazole (PTZ)‑induced seizure mice. Materials and Methods: Twenty
Swiss albino mice (18–28 g) were divided into four groups (n = 5) and were given the following
intraperitoneally, 2 ml/kg distilled water and 50 mg/kg PTZ to Groups 1 and 2 animals, respectively.
Groups 3 and 4 animals were given 200 mg/kg and 400 mg/kg of Mentat, respectively, 1 h before
the administration of PTZ and were observed for 300 s. After the experiment, all surviving animals
in the various groups were humanely sacrificed and the brains were harvested and preserved in
10% buffered formalin. The brain tissues were processed using routine histological procedures
and stained with hematoxylin and eosin. Results: Results of this revealed that Mentat was able to
delay the onset time of seizure and offered quantal protection to the animals. Mentat also showed
a dose‑dependent ameliorative effect against histological changes following PTZ administration in
mice. Conclusion: Mentat attenuates PTZ‑induced seizure in mice.