Transient global amnesia and hippocampal diffusion restriction: an overlooked radiological finding.

Transient global amnesia (TGA) is characterized by isolated sudden anterograde amnesia. Diffusion restriction can be observed in the hippocampus on DWI-MRI at varying rates in TGA patients. This study analyzes the prevalence and characteristics of the hippocampal diffusion restriction (HDR), its relationship with vascular risk factors, and the prevalence of lesions overlooked in routine reports. 91 patients diagnosed with TGA at a tertiary hospital between 2011 and 2022 were evaluated retrospectively. The mean age was 64.8 ± 7.3 years, and 63.7% of patients were female. 75.8% of the patients had at least one vascular risk factor. Focal diffusion restriction was detected in 17 patients (18.5%) on DWI-MRI, with only one being extra-hippocampal. 81.2% of HDR was detected when DWI-MRI scan was performed between 12 and 96 h after the onset of symptoms. HDR was detected most when the imaging was performed in 24 to 48 h (p = 0.03). There was no correlation between the duration of symptoms and the detection rates of HDR (p = 0.55). In 9 patients (53% of 17) diffusion restriction was not specified in routine radiology reports. Although focal ischemia, venous flow abnormalities, migraine and epileptic phenomena have been suggested in its etiology, TGA is a clinical condition of which pathophysiology has not been determined clearly. Signal changes observed in DWI-MRI has led to discussions that cerebrovascular etiology may play a role, yet more comprehensive studies are required to prevent and manage TGA. HDRs can be overlooked in routine reports. Therefore, the DWI-MRI images of patients with TGA should be examined vigilantly.

Optimizing SH-SY5Y cell culture: exploring the beneficial effects of an alternative media supplement on cell proliferation and viability.

In the quest to unravel the mysteries of neurological diseases, comprehending the underlying mechanisms is supreme. The SH-SY5Y human neuroblastoma cell line serves as a crucial tool in this endeavor; however, the cells are known for its sensitivity and slow proliferation rates. Typically, this cell line is cultured with 10% Fetal Bovine Serum (FBS) supplement. Nu-Serum (NuS), a low-protein alternative to FBS, is promising to advance cell culture practices. Herein, we evaluated the substitution of NuS for FBS to test the hypothesis that an alternative serum supplement can aid and promote SH-SY5Y cell proliferation and differentiation. Our findings revealed that the NuS-supplemented group exhibited a notable increase in adhered cells compared to both the FBS and serum-free (SF) groups. Importantly, cell viability remained high in both sera treated groups, with the NuS-supplemented cells displaying significantly larger cell sizes compared to the SF-treated group. Furthermore, cell proliferation rates were higher in the NuS-treated group, and neuroblast-like morphology was observed earlier than FBS group. Notably, both FBS and NuS supported the differentiation of these cells into mature neurons. Our data supports NuS as an alternative for SH-SY5Y cell culture, with the potential to elevate the quality of research in the neuroscience field.

Intra-prostatic tumour evolution, steps in metastatic spread and histogenomic associations revealed by integration of multi-region whole-genome sequencing with histopathological features.

BACKGROUND: Extension of prostate cancer beyond the primary site by local invasion or nodal metastasis is associated with poor prognosis. Despite significant research on tumour evolution in prostate cancer metastasis, the emergence and evolution of cancer clones at this early stage of expansion and spread are poorly understood. We aimed to delineate the routes of evolution and cancer spread within the prostate and to seminal vesicles and lymph nodes, linking these to histological features that are used in diagnostic risk stratification. METHODS: We performed whole-genome sequencing on 42 prostate cancer samples from the prostate, seminal vesicles and lymph nodes of five treatment-naive patients with locally advanced disease. We spatially mapped the clonal composition of cancer across the prostate and the routes of spread of cancer cells within the prostate and to seminal vesicles and lymph nodes in each individual by analysing a total of > 19,000 copy number corrected single nucleotide variants. RESULTS: In each patient, we identified sample locations corresponding to the earliest part of the malignancy. In patient 10, we mapped the spread of cancer from the apex of the prostate to the seminal vesicles and identified specific genomic changes associated with the transformation of adenocarcinoma to amphicrine morphology during this spread. Furthermore, we show that the lymph node metastases in this patient arose from specific cancer clones found at the base of the prostate and the seminal vesicles. In patient 15, we observed increased mutational burden, altered mutational signatures and histological changes associated with whole genome duplication. In all patients in whom histological heterogeneity was observed (4/5), we found that the distinct morphologies were located on separate branches of their respective evolutionary trees. CONCLUSIONS: Our results link histological transformation with specific genomic alterations and phylogenetic branching. These findings have implications for diagnosis and risk stratification, in addition to providing a rationale for further studies to characterise the genetic changes causally linked to morphological transformation. Our study demonstrates the value of integrating multi-region sequencing with histopathological data to understand tumour evolution and identify mechanisms of prostate cancer spread.

Vesicular HMGB1 release from neurons stressed with spreading depolarization enables confined inflammatory signaling to astrocytes.

The role of high mobility group box 1 (HMGB1) in inflammation is well characterized in the immune system and in response to tissue injury. More recently, HMGB1 was also shown to initiate an "inflammatory signaling cascade" in the brain parenchyma after a mild and brief disturbance, such as cortical spreading depolarization (CSD), leading to headache. Despite substantial evidence implying a role for inflammatory signaling in prevalent neuropsychiatric disorders such as migraine and depression, how HMGB1 is released from healthy neurons and how inflammatory signaling is initiated in the absence of apparent cell injury are not well characterized. We triggered a single cortical spreading depolarization by optogenetic stimulation or pinprick in naïve Swiss albino or transgenic Thy1-ChR2-YFP and hGFAP-GFP adult mice. We evaluated HMGB1 release in brain tissue sections prepared from these mice by immunofluorescent labeling and immunoelectron microscopy. EzColocalization and Costes thresholding algorithms were used to assess the colocalization of small extracellular vesicles (sEVs) carrying HMGB1 with astrocyte or microglia processes. sEVs were also isolated from the brain after CSD, and neuron-derived sEVs were captured by CD171 (L1CAM). sEVs were characterized with flow cytometry, scanning electron microscopy, nanoparticle tracking analysis, and Western blotting. We found that HMGB1 is released mainly within sEVs from the soma of stressed neurons, which are taken up by surrounding astrocyte processes. This creates conditions for selective communication between neurons and astrocytes bypassing microglia, as evidenced by activation of the proinflammatory transcription factor NF-ĸB p65 in astrocytes but not in microglia. Transmission immunoelectron microscopy data illustrated that HMGB1 was incorporated into sEVs through endosomal mechanisms. In conclusion, proinflammatory mediators released within sEVs can induce cell-specific inflammatory signaling in the brain without activating transmembrane receptors on other cells and causing overt inflammation.

Skull bone marrow channels as immune gateways to the central nervous system.

Decades of research have characterized diverse immune cells surveilling the CNS. More recently, the discovery of osseous channels (so-called 'skull channels') connecting the meninges with the skull and vertebral bone marrow has revealed a new layer of complexity in our understanding of neuroimmune interactions. Here we discuss our current understanding of skull and vertebral bone marrow anatomy, its contribution of leukocytes to the meninges, and its surveillance of the CNS. We explore the role of this hematopoietic output on CNS health, focusing on the supply of immune cells during health and disease.

Lung cancer from suspicion to treatment: An indicator of healthcare access in Turkey.

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths worldwide. Before beginning lung cancer treatment, it is necessary to complete procedures such as suspecting lung cancer, obtaining a pathologic diagnosis, and staging. This study aimed to investigate the processes from suspicion of lung cancer to diagnosis, staging, and treatment initiation. METHODS: The study was designed as a multicenter and cross-sectional study. Patients with lung cancer from various health institutions located in all geographic regions of Turkey were included in the study. The sociodemographic and clinical characteristics of the patients, the characteristics of the health institutions and geographic regions, and other variables of the lung cancer process were recorded. The time from suspicion of lung cancer to pathologic diagnosis, radiologic staging, and treatment initiation, as well as influencing factors, were investigated. RESULTS: The study included 1410 patients from 29 different medical centers. The mean time from the initial suspicion of lung cancer to the pathologic diagnosis was 48.0 ± 52.6 days, 39.0 ± 52.7 days for radiologic staging, and 74.9 ± 65.5 days for treatment initiation. The residential areas with the most suspected lung cancer cases were highly developed socioeconomic zones. Primary healthcare services accounted for only 0.4% of patients with suspected lung cancer. The time to pathologic diagnosis was longer in the Marmara region, and the wait time for staging and treatment initiation was longer in Eastern and Southeastern Anatolia. Patients who presented to chest disease referral hospitals with peripheral lesions, those with early-stage disease, and those who were diagnosed surgically had significantly longer wait times. CONCLUSION: The time between pathologic diagnosis, staging, and treatment initiation in lung cancer was longer than expected. Increasing the role of primary healthcare services and distributing socioeconomic resources more equally will contribute to shortening the time to diagnosis and improve treatment processes for lung cancer.

Honokiol decreases alpha-synuclein mRNA levels and reveals novel targets for modulating alpha-synuclein expression.

Background: Intracytoplasmic inclusions comprised of aggregated alpha-synuclein (αsyn) represent a key histopathological feature of neurological disorders collectively termed "synucleinopathies," which includes Parkinson's disease (PD). Mutations and multiplications in the SNCA gene encoding αsyn cause familial forms of PD and a large body of evidence indicate a correlation between αsyn accumulation and disease. Decreasing αsyn expression is recognized as a valid target for PD therapeutics, with down-regulation of SNCA expression potentially attenuating downstream cascades of pathologic events. Here, we evaluated if Honokiol (HKL), a polyphenolic compound derived from magnolia tree bark with demonstrated neuroprotective properties, can modulate αsyn levels in multiple experimental models. Methods: Human neuroglioma cells stably overexpressing αsyn, mouse primary neurons, and human iPSC-derived neurons were exposed to HKL and αsyn protein and SNCA messenger RNA levels were assessed. The effect of HKL on rotenone-induced overexpression of αsyn levels was further assessed and transcriptional profiling of mouse cortical neurons treated with HKL was performed to identify potential targets of HKL. Results: We demonstrate that HKL can successfully reduce αsyn protein levels and SNCA expression in multiple in vitro models of PD with our data supporting a mechanism whereby HKL acts by post-transcriptional modulation of SNCA rather than modulating αsyn protein degradation. Transcriptional profiling of mouse cortical neurons treated with HKL identifies several differentially expressed genes (DEG) as potential targets to modulate SNCA expression. Conclusion: This study supports a HKL-mediated downregulation of SNCA as a viable strategy to modify disease progression in PD and other synucleinopathies. HKL has potential as a powerful tool for investigating SNCA gene modulation and its downstream effects.

Post-inflammatory administration of N-acetylcysteine reduces inflammation and alters receptor levels in a cellular model of Parkinson's disease.

Parkinson's disease (PD) is a complex, multifactorial neurodegenerative disease with a prevalence of 1% over the age of 55. Neuropathological hallmarks of PD include the loss of dopaminergic neurons in the substantia nigra pars compacta and the accumulation of Lewy bodies that contain a variety of proteins and lipids including alpha-synuclein (α-syn). Although the formation of α-syn occurs intracellularly, it can also be found in the extracellular space where it can be taken up by neighboring cells. Toll-like receptor 2 (TLR2) is an immune system receptor that has been shown to recognize extracellular α-syn and modulate its uptake by other cells. Lymphocyte-activation gene 3 (LAG3), an immune checkpoint receptor, has also been proposed to play a role in extracellular α-syn internalization; however, a recent study has disputed this role. Internalized α-syn can trigger expression and secretion of inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-1ß, IL-2, and IL-6 and induce neuroinflammation, apoptosis, and mitophagy that results in cellular death. In this study, we tested if N-acetylcysteine (NAC), an anti-inflammatory and anti-carcinogenic drug, can circumvent the detrimental effects of neuroinflammation and induce an anti-inflammatory response by modulating transcription and expression of TLR2 and LAG3 receptors. Cells overexpressing wild-type α-syn were treated with TNF-α to induce inflammation followed by NAC to inhibit the deleterious effects of TNF-α-induced inflammation and apoptosis. SNCA gene transcription and α-syn protein expression were validated by q-PCR and Western blot (WB), respectively. Cell viability was measured, and apoptosis was evaluated by WB and terminal deoxynucleotidyl transferase nick end labeling methods. Alterations in LAG3 and TLR2 receptor levels were evaluated by immunofluorescent labeling, WB, and q-PCR. TNF-α not only increased inflammation but also increased endogenous and overexpressed α-syn levels. NAC treatment decreased expression of TLR2 and increased transcription of LAG3 receptor and diminished inflammation-mediated toxicity and cell death. Here, we demonstrate that NAC can reduce neuroinflammation that occurs as a result of alpha-synuclein overexpression, via a TLR2-associated pathway, making it a promising candidate for therapeutic intervention. Further studies are needed to elucidate molecular mechanisms and pathways related to neuroinflammation in PD and to develop possible new therapeutic approaches to slow the clinical progression of PD.

Comparing therapeutic effects of alternate day versus daily oral iron in women with iron deficiency anemia: A retrospective cohort study.

In order to replenish iron stores and bring hemoglobin (Hb) levels back to normal, oral iron is the primary treatment option for women with iron deficiency anemia (IDA). This study investigated the efficacy and side effects of daily versus alternate-day, given single doses versus double doses oral iron supplementation for treating IDA. A retrospective cohort study was performed between 2021 and 2022, including 120 patients. Study group were divided into 4 age-sex-matched groups; Group I (n = 30) and Group II (n = 30) which were received ferrous sulphate tablets daily in single or double doses, respectively, containing 60 mg of elemental iron each. Groups III (n = 30) and IV (n = 30) were received a single and double dose on alternate days, respectively. The primary outcome was the mean difference in Hb from baseline at week 4. Gastrointestinal (GI) side effects were accepted as a secondary outcome. The daily single dose and alternate day double dose groups had median Hb changes of 2.3 (2.1) and 2.6 (1.8) g/dL. The differences in Hb between Groups I and II, I and III, and Groups IV and II, IV and III were significant (P < .001, P = .001, P < .001, and P < .001, respectively). There is no significant difference between groups regarding improving iron parameters such as serum iron, total iron binding capacity, transferrin saturation, and ferritin. The incidence of GI side effects were greater in double doses than in single doses of daily or alternate-day therapies (43.3% and 30% vs 10% and 3.3%). Daily or alternate-day double dose resulted in more side effects but less therapeutic efficacy in women with IDA. To find the best supplementation method, randomized controlled trials with a larger sample of participants, longer study lengths, and various iron doses may be helpful.

Preclinical characterization of ISB 1342, a CD38 × CD3 T-cell engager for relapsed/refractory multiple myeloma.

Although treatment of multiple myeloma (MM) with daratumumab significantly extends the patient's lifespan, resistance to therapy is inevitable. ISB 1342 was designed to target MM cells from patients with relapsed/refractory MM (r/r MM) displaying lower sensitivity to daratumumab. ISB 1342 is a bispecific antibody with a high-affinity Fab binding to CD38 on tumor cells on a different epitope than daratumumab and a detuned scFv domain affinity binding to CD3ε on T cells, to mitigate the risk of life-threatening cytokine release syndrome, using the Bispecific Engagement by Antibodies based on the TCR (BEAT) platform. In vitro, ISB 1342 efficiently killed cell lines with different levels of CD38, including those with a lower sensitivity to daratumumab. In a killing assay where multiple modes of action were enabled, ISB 1342 showed higher cytotoxicity toward MM cells compared with daratumumab. This activity was retained when used in sequential or concomitant combinations with daratumumab. The efficacy of ISB 1342 was maintained in daratumumab-treated bone marrow patient samples showing lower sensitivity to daratumumab. ISB 1342 induced complete tumor control in 2 therapeutic mouse models, unlike daratumumab. Finally, in cynomolgus monkeys, ISB 1342 displayed an acceptable toxicology profile. These data suggest that ISB 1342 may be an option in patients with r/r MM refractory to prior anti-CD38 bivalent monoclonal antibody therapies. It is currently being developed in a phase 1 clinical study.

Predictors of 3-month mortality with muscle ultrasound and palliative prognostic tools among patients admitted to palliative care units.

BACKGROUND/AIMS: Prognostic factors are an important issue in progressive and life-limiting diseases. This study evaluate 3-month mortality in patients admitted to the palliative care unit (PCU). METHODS: In this study, the patient's demographics, comorbidities, nutritional status, and laboratory values were recorded. The palliative performance scale (PPS), the palliative prognostic index (PPI), and the palliative prognostic (PaP) score were calculated. The rectus femoris (RF) cross-sectional area (CSA), RF muscle thickness, gastrocnemius (GC) medialis muscle thickness, pennation angle and fascicle length of the GC were measured by ultrasound for survival prediction. RESULTS: A total of 88 patients enrolled during the study period, with a mean age of 73.6 ± 13.3 years and a 3-month mortality rate of 59.1%. The findings of a multivariable Cox proportional hazards regression model based on age, gender, C-reactive protein level and Nutrition Risk Screening 2002 scores as covariates revealed the PPI and the PaP score to be significant predictors of 3-month mortality. In addition, in the unadjusted Cox proportional hazard regression analysis, the CSA of the RF muscle was also found to be a significant predictor of 3-month mortality. CONCLUSION: Findings revealed that the combined use of the CSA of the RF, the PPI, and the PaP score are reliable predictors of mortality in patients admitted to the PCU.

Evaluation of EfficientNet models for COVID-19 detection using lung parenchyma.

When the COVID-19 pandemic broke out in the beginning of 2020, it became crucial to enhance early diagnosis with efficient means to reduce dangers and future spread of the viruses as soon as possible. Finding effective treatments and lowering mortality rates is now more important than ever. Scanning with a computer tomography (CT) scanner is a helpful method for detecting COVID-19 in this regard. The present paper, as such, is an attempt to contribute to this process by generating an open-source, CT-based image dataset. This dataset contains the CT scans of lung parenchyma regions of 180 COVID-19-positive and 86 COVID-19-negative patients taken at the Bursa Yuksek Ihtisas Training and Research Hospital. The experimental studies show that the modified EfficientNet-ap-nish method uses this dataset effectively for diagnostic purposes. Firstly, a smart segmentation mechanism based on the k-means algorithm is applied to this dataset as a preprocessing stage. Then, performance pretrained models are analyzed using different CNN architectures and with our Nish activation function. The statistical rates are obtained by the various EfficientNet models and the highest detection score is obtained with the EfficientNet-B4-ap-nish version, which provides a 97.93% accuracy rate and a 97.33% F1-score. The implications of the proposed method are immense both for present-day applications and future developments.

The effect of a combined treatment of foot soak and lavender oil inhalation therapy on the severity of insomnia of patients with cancer: Randomized interventional study.

OBJECTIVES: This three-arm randomized intervention study was carried out with the aim to evaluate the effects of a combined foot soak and lavender oil inhalation therapy on the severity of insomnia of patients with cancer. METHOD: This research was carried out in oncology and palliative services. Forty-five patients were randomly assigned to three groups. Throughout a 14-day period, 20 min of foot soak treatment was applied to the patients in the F group, patients in the L group were applied lavender oil inhalation therapy for 5 min and a combined treatment of foot soak and lavender oil inhalation therapy were applied to the patients in the FL group. Insomnia severity of the patients in all groups were evaluated twice using the Insomnia Severity Index at the baseline and on the fifteenth day. RESULTS: The severity of the insomnia of the patients in all groups was found to be moderate. The severity of the insomnia in the second evaluation was found to be statistically significantly lower in the L and FL groups (p<0.05) compared to the baseline evaluation within the group, however no significant difference was found in the F group (p>0.05). The effect size of a combined treatment of foot soak and lavender oil inhalation therapy on the severity of insomnia of patients in the FL group was higher and moderate (d = 0.684) compared to merely foot soak and merely lavender oil inhalation therapy. CONCLUSION: A combined treatment of foot soak and lavender oil inhalation therapy shall mitigate the severity of a moderate level of insomnia of patients with cancer.

Metabolic profiling of prostate cancer in skeletal microenvironments identifies G6PD as a key mediator of growth and survival.

The spread of cancer to bone is invariably fatal, with complex cross-talk between tumor cells and the bone microenvironment responsible for driving disease progression. By combining in silico analysis of patient datasets with metabolomic profiling of prostate cancer cells cultured with bone cells, we demonstrate the changing energy requirements of prostate cancer cells in the bone microenvironment, identifying the pentose phosphate pathway (PPP) as elevated in prostate cancer bone metastasis, with increased expression of the PPP rate-limiting enzyme glucose-6-phosphate dehydrogenase (G6PD) associated with a reduction in progression-free survival. Genetic and pharmacologic manipulation demonstrates that G6PD inhibition reduces prostate cancer growth and migration, associated with changes in cellular redox state and increased chemosensitivity. Genetic blockade of G6PD in vivo results in reduction of tumor growth within bone. In summary, we demonstrate the metabolic plasticity of prostate cancer cells in the bone microenvironment, identifying the PPP and G6PD as metabolic targets for the treatment of prostate cancer bone metastasis.

Confocal reflectance microscopy for metal and lipid nanoparticle visualization in the brain.

Aim: A requirement for nanoparticle (NP) research is visualization of particles within cells and tissues. Limitations of electron microscopy and low yields of NP fluorescent tagging warrant the identification of alternative imaging techniques. Method: Confocal reflectance microscopy (CRM) in combination with fluorescence imaging was assessed for visualizing rhodamine B-conjugated silver and fluorescein isothiocyanate-conjugated lipid core-stearylamine NP uptake in vitro and in vivo. Results: CRM successfully identified cellular uptake and blood-brain barrier penetration of NPs owing to their distinguishing refractive indices. NP-dependent reflectance signals in vitro were dose and incubation time dependent. Finally, CRM facilitated the distinction between nonspecific fluorescence signals and NPs. Conclusion: These findings demonstrate the value of CRM for NP visualization in tissues, which can be performed with a standard confocal microscope.

Nanoparticles (NPs) are extremely small materials utilized in the healthcare sector mainly for the delivery of drugs into tissues that are not easily accessible with regular pharmaceuticals. One such tissue is the brain, which has a barrier between it and the bloodstream that prevents the passage of most drugs. For NP research, the successful entry of NPs into target tissues must be demonstrated, but this is complicated by the small size and weak labeling of NPs. In this article, the authors demonstrate a low-cost, complementary microscopy technique that is readily available in most biological research laboratories and that can be used to detect and analyze the entry of different NP types into brain tissue and their uptake by brain tumor cells. These data create new opportunities for research on NP-assisted drug delivery to the central nervous system.

Parenchymal neuroinflammatory signaling and dural neurogenic inflammation in migraine.

BACKGROUND: Pain is generally concomitant with an inflammatory reaction at the site where the nociceptive fibers are activated. Rodent studies suggest that a sterile meningeal inflammatory signaling cascade may play a role in migraine headache as well. Experimental studies also suggest that a parenchymal inflammatory signaling cascade may report the non-homeostatic conditions in brain to the meninges to induce headache. However, how these signaling mechanisms function in patients is unclear and debated. Our aim is to discuss the role of inflammatory signaling in migraine pathophysiology in light of recent developments. BODY: Rodent studies suggest that a sterile meningeal inflammatory reaction can be initiated by release of peptides from active trigeminocervical C-fibers and stimulation of resident macrophages and dendritic/mast cells. This inflammatory reaction might be needed for sustained stimulation and sensitization of meningeal nociceptors after initial activation along with ganglionic and central mechanisms. Most migraines likely have cerebral origin as suggested by prodromal neurologic symptoms. Based on rodent studies, a parenchymal inflammatory signaling cascade has been proposed as a potential mechanism linking cortical spreading depolarization (CSD) to meningeal nociception. A recent PET/MRI study using a sensitive inflammation marker showed the presence of meningeal inflammatory activity in migraine with aura patients over the occipital cortex generating the visual aura. These studies also suggest the presence of a parenchymal inflammatory activity, supporting the experimental findings. In rodents, parenchymal inflammatory signaling has also been shown to be activated by migraine triggers such as sleep deprivation without requiring a CSD because of the resultant transcriptional changes, predisposing to inadequate synaptic energy supply during intense excitatory transmission. Thus, it may be hypothesized that neuronal stress created by either CSD or synaptic activity-energy mismatch could both initiate a parenchymal inflammatory signaling cascade, propagating to the meninges, where it is converted to a lasting headache with or without aura. CONCLUSION: Experimental studies in animals and emerging imaging findings from patients warrant further research to gain deeper insight to the complex role of inflammatory signaling in headache generation in migraine.

DNA binding alters ARv7 dimer interactions.

Androgen receptor (AR) splice variants are proposed to be a potential driver of lethal castration-resistant prostate cancer. AR splice variant 7 (ARv7) is the most commonly observed isoform and strongly correlates with resistance to second-generation anti-androgens. Despite this clinical evidence, the interplay between ARv7 and the highly expressed full-length AR (ARfl) remains unclear. In this work, we show that ARfl/ARv7 heterodimers readily form in the nucleus via an intermolecular N/C interaction that brings the four termini of the proteins in close proximity. Combining fluorescence resonance energy transfer and fluorescence recovery after photobleaching, we demonstrate that these heterodimers undergo conformational changes following DNA binding, indicating dynamic nuclear receptor interaction. Although transcriptionally active, ARv7 can only form short-term interactions with DNA at highly accessible high-occupancy ARfl binding sites. Dimerization with ARfl does not affect ARv7 binding dynamics, suggesting that DNA binding occupancy is determined by the individual protein monomers and not the homodimer or heterodimer complex. Overall, these biophysical studies reveal detailed properties of ARv7 dynamics as both a homodimer or heterodimer with ARfl.

Evaluation of parents' knowledge, attitudes, and practices regarding self-medication for their children's dental problems during the COVID-19 pandemic: a cross-sectional survey.

BACKGROUND: Self-medication refers to taking medicine without consultation with a doctor or dentist, and it is an important health issue, especially during the COVID-19 pandemic. There are no data about parents' SM practices for their children's dental problems during the COVID-19 pandemic. The present study aims to evaluate parents' knowledge, attitudes, and practices regarding self-medication for their children's dental problems during the COVID-19 pandemic in Northern Turkey. METHODS: A cross-sectional survey was carried out in the pediatric dental clinic at Ondokuz Mayis University, Faculty of Dentistry, Department of Pediatric Dentistry, immediately after the COVID-19 lockdown ended. A total of 389 parents who agreed to participate in the study completed the questionnaire from July 1 to October 1. A questionnaire with 18 items was designed to collect information on the parents' knowledge and attitudes regarding when, why, and how to use drugs and on their practices on medicating their children. The collected data were analyzed using descriptive and analytical statistics (chi-square test). RESULTS: The majority of parents (n = 273; 70.2%) practiced self-medication for their children's dental problems. Self-medication with a previously prescribed medications was usually preferred by parents (n = 179; 62.2%). Analgesics (98%) were the most commonly used medicines by parents in their self-medication for their children's dental problems. CONCLUSION: Prevalence of self-medication practices for children's dental problems is high in Turkey during the COVID-19 pandemic. Therefore, new healthcare services, such as teledentistry, may be useful to overcome problems related to the self-medication of children during times when the ability to reach healthcare providers is limited, such as during pandemics.

Non-hexagonal neural dynamics in vowel space.

Are the grid cells discovered in rodents relevant to human cognition? Following up on two seminal studies by others, we aimed to check whether an approximate 6-fold, grid-like symmetry shows up in the cortical activity of humans who "navigate" between vowels, given that vowel space can be approximated with a continuous trapezoidal 2D manifold, spanned by the first and second formant frequencies. We created 30 vowel trajectories in the assumedly flat central portion of the trapezoid. Each of these trajectories had a duration of 240 milliseconds, with a steady start and end point on the perimeter of a "wheel". We hypothesized that if the neural representation of this "box" is similar to that of rodent grid units, there should be an at least partial hexagonal (6-fold) symmetry in the EEG response of participants who navigate it. We have not found any dominant n-fold symmetry, however, but instead, using PCAs, we find indications that the vowel representation may reflect phonetic features, as positioned on the vowel manifold. The suggestion, therefore, is that vowels are encoded in relation to their salient sensory-perceptual variables, and are not assigned to arbitrary grid-like abstract maps. Finally, we explored the relationship between the first PCA eigenvector and putative vowel attractors for native Italian speakers, who served as the subjects in our study.

KCl-induced cortical spreading depression waves more heterogeneously propagate than optogenetically-induced waves in lissencephalic brain: an analysis with optical flow tools.

Although cortical spreading depolarizations (CSD) were originally assumed to be homogeneously and concentrically propagating waves, evidence obtained first in gyrencephalic brains and later in lissencephalic brains suggested a rather non-uniform propagation, shaped heterogeneously by factors like cortical region differences, vascular anatomy, wave recurrences and refractory periods. Understanding this heterogeneity is important to better evaluate the experimental models on the mechanistics of CSD and to make appropriate clinical estimations on neurological disorders like migraine, stroke, and traumatic brain injury. This study demonstrates the application of optical flow analysis tools for systematic and objective evaluation of spatiotemporal CSD propagation patterns in anesthetized mice and compares the propagation profile in different CSD induction models. Our findings confirm the asymmetric angular CSD propagation in lissencephalic brains and suggest a strong dependency on induction-method, such that continuous potassium chloride application leads to significantly higher angular propagation variability compared to optogenetically-induced CSDs.