Three years' interventional neurology experience in Turkey with the Thrombite thrombectomy device in large vessel occlusion in the anterior circulation: safety, efficacy, and clinical outcome.

Introduction: While the Thrombite device differs from the Solitare stent with its Helical open-side structure feature, it shows great similarity with its other features. We assessed the Thrombite device's effectiveness and safety in this study. Materials and methods: The study was a retrospective analysis of patients who were included in the Turkish Interventional Neurology database and who had mechanical thrombectomy with the Thrombite device as the first choice between January 2020 and January 2023. The type of study is descriptive research. Result: Using the Thrombite thrombectomy device, 525 patients received treatment. The median baseline National Institutes of Health Stroke Scale (NIHSS) score was 13, the median initial Alberta Stroke Program Early Computed Tomography (ASPECT) score was 8, and the mean patient age was 68.6+11.7 years. Between the groin puncture and the successful recanalization, the median time was 34 minutes (interquartile range [IQR]: 15-45). 48.2% (modified treatment in cerebral infarction; mTICI) 2b/3% and 33.9% (mTICI 2c/3) were the first-pass recanalization rates. In the end, 87.7% of patients had effective recanalization (thrombolysis in cerebral infarction 2b/3). In the "first-pass" subgroup, the favorable functional result (modified Rankin Scale 0-2) was 51.8%, while it was 41.6% for the entire patient population. The rate of embolization into new territory/different territory were 2.1/0.1%. 23 patients (4.5%) had symptomatic hemorrhage. Conclusion: The Thrombite device showed a good safety profile and high overall successful recanalization rates in our experience.

Evaluation of the relationship between idiopathic restless legs syndrome and serum hepcidin levels.

INTRODUCTION: The relationship between restless legs syndrome (RLS) and iron deficiency is a well-known topic. However, the etiology of the disease has not been determined. As the central iron deficiency is the most critical biological abnormality for RLS, we planned a study examining the relationship between RLS and hepcidin, which is the only regulatory hormone of iron metabolism known so far. METHODS: International Restless Legs Syndrome Study Group diagnostic criteria (2014) were taken as a basis. A total of 40 RLS patients and 40 healthy controls were included in the study. To avoid the potential variables that might cause secondary RLS, all the participants were asked to provide hemogram, ferritin, iron, thyroid function tests, and sedimentation analysis. The hepcidin levels were measured with a Human Hepcidin (Hepc 25) ELISA kit (MyBioSource). RESULTS: The statistically significant results of our analysis show that the red blood cell count, the neutrophil count, the percentage of lymphocytes and neutrophils, and, more distinctively, hepcidin levels were higher in RLS patients in comparison with the control group. CONCLUSION: In this study, no differences were found in iron and ferritin values. High levels of hepcidin, the main regulator of iron metabolism, in those with primary RLS support the possibility that hepcidin may play a role in the pathogenesis of RLS. We think that larger studies on this subject can give clearer ideas.

Can C-reactive protein/albumin ratio be a prognostic factor in acute stroke patients undergoing mechanical thrombectomy?

INTRODUCTION: C-reactive protein (CRP) and albumin are markers synthesized by the liver and may reflect inflammatory responses. CRP/Albumin ratio (CAR) serves better to reflect the inflammatory state and therefore the prognosis. Worse prognosis is reported in previous studies when CAR rate on admission is high in patients with stroke, aneurysmal subarachnoid hemorrhage, malignancy or patients followed in intensive care units. We aimed to investigate the relation of CAR with prognosis in mechanical thrombectomy performed acute stroke patients. MATERIALS AND METHODS: Stroke patients admitted to five different stroke centers between January 2021 and August 2022 undergoing mechanical thrombectomy were included and retrospectively analyzed. The CAR ratio was calculated as the ratio of CRP to albumin level in the venous blood samples. Primary outcome was the relation between CAR and functional outcome at 90 days determined by modified Rankin Scale (mRS). RESULTS: This study included 558 patients with a mean age of 66,5 ± 12.5 years (age range:18-89 years) best cutoff value of the CAR was 3.36, with 74.2 % sensitivity and 60.7 % specificity (Area under the curve: 0.774; 95 %CI: 0.693-0.794). There was no significant correlation between CAR rate and age, CAR rate and NIHSS on admission, and also between CAR rate and symptom recanalization (p > 0.05). CAR ratio in the mRS 3-6 group was statistically significantly higher (p < 0.001). In the multivariate analyses, CAR showed an association with 90-day mortality (odds ratio, 1.049; 95 % CI, 1.032-1.066) CONCLUSION: In acute ischemic stroke patients treated with mechanical thrombectomy, CAR may be one of the factors affecting poor clinical outcome and/or mortality in patients undergoing mechanical thrombectomy. Upcoming similar studies in this patient group may better clarify the prognostic role of CAR.

Anti-N-methyl D-aspartate receptor encephalitis presenting with the new-onset refractory status epilepticus.

New-onset refractory status epilepticus (NORSE) is a rare entity referring refractory status epilepticus (SE) in a patient without a history of epilepsy or an apparent cause. Herein, we report on a 31-year-old young female of anti-N-methyl D-aspartate (NMDA) receptor encephalitis admitted with NORSE. Her complaints began a week ago with a fever, meaningless movements, restlessness, and talking to herself. She had a history of operation for ovarian teratoma 10 years ago. Electrocardiography, hemogram, biochemistry, and neuroimaging were normal. Due to recurrent seizures despite intravenous diazepam infusions, phenytoin infusion was introduced, reducing the duration and frequency of seizures. Electroencephalogram (EEG) revealed a generalized slow background activity with low voltage and delta waves in left hemisphere derivatives without any epileptiform discharge. Autoimmune encephalitis panel revealed a positive anti-NMDAR receptor antibody. Intravenous immunoglobulins were given for 5 days. She was improved clinically and did not have a recurrent seizure. The history of our case emphasizes the importance of EEG and CSF antibody tests to reach the underlying etiology in patients presenting with refractory SE and neuropsychiatric symptoms of an unknown cause. Application of a proper treatment promptly with this approach could prevent the potential morbidity and mortality in these patients.

Investigation of the relationship between serum irisin level in the idiopathic restless legs syndrome: Could be a marker independent of physical activity?

INTRODUCTION: Restless legs syndrome (RLS) is a common but underdiagnosed neurological syndrome. It is characterized by the feeling of discomfort and desire to move, especially in the lower extremities, which often occurs at night, and the cure or relief of symptoms with movement. Irisin is a hormonelike polypeptide that was first identified in 2012, weighs 22 kDa, consists of 163 amino acids, and is mainly synthesized in muscle. Its synthesis increases with exercise. Here in this study, we planned to investigate the relationship among serum irisin level, physical activity, lipid profile, and RLS. MATERIAL AND METHODS: A total of 35 patients with idiopathic RLS and 35 volunteers were included in the study. Then, venous blood was taken from the participants in the morning after 12 h of night fasting. RESULTS: The mean value of serum irisin level was 16.9 ± 14.1 ng/mL in the case group and 5.1 ± 5.9 ng/mL in the control group, which was statistically quite significant (p < .001). A significant efficiency (under the curve area 0.886 [0.804-0.967]) of irisin value was observed in the differentiation of patients in the case and control groups. DISCUSSION: Serum irisin level was significantly higher in the case group than in the control group. In conclusion, we suggest that irisin may play a role in the pathophysiology of RLS independently of the intensity and duration of physical activity and anthropometric data, such as body weight, body mass index, and waist/hip ratio.

Pilot scale nanofiltration membrane fabrication containing ionic co-monomers and halloysite nanotubes for textile dye filtration.

Wastewater from the textile industry contains high concentrations of pollutants, so the wastewater must be treated before it is discharged. In addition, the reuse of treated wastewater should be considered from an environmental point of view, as large volumes of wastewater are produced. Since textile wastewater mainly contains dyestuffs, it must be treated effectively using environmentally friendly technologies. Membrane processes are widely used in textile wastewater treatment as they have distinct advantages over conventional wastewater treatment methods. This study reports the pilot-scale manufacturing and characterization of three different NF membranes. Three different types of membranes were fabricated. The fabricated membranes were compared through characterization by surface properties, chemical structure and morphology. Membranes were tested for pure water flux. Then the synthetic wastewater (SWW) was tested for flux and rejection. Lastly, the textile wastewater was tested. The textile wastewater flux of pure piperazine (PIP), 60% S-DADPS and 0.04% halloysite nanotubes (HNTs) were 22.42, 79.58 and 40.06 L m-2 h-1. It has been proven that the 60% s-DADPS membrane provides up to four times improvement in wastewater flux and simultaneously. In addition, NF membranes produced using HNT and sDADPS on a pilot scale have brought innovation to the literature with the good results obtained.

Correlates of Zonulin and Claudin-5, markers of intestinal and brain endothelial permeability, in Parkinson's Disease: A pilot study.

INTRODUCTION: Idiopathic Parkinson's Disease is a chronic, progressive, neurodegenerative disease that affects the substantia nigra pars compacta and dopaminergic neurons in the brain stem. Since zonulin and claudin-5 are involved in intestinal and brain endothelial permeability and it is hypothesized that the brain-gut axis is relevant in IPD, the aim of our study is to evaluate whether the relationship between Zonulin and Claudin-5 levels and Parkinson's Disease patients. METHODS: A total of 139 patients, including 34 mild, 33 moderate, 39 severe stage patients and 33 healthy controls were included. The patients' demographic data, age of onset, disease duration, disease type and drugs were noted. UPDRS and H&Y scores were evaluated. Prodromal stage symptoms and non-motor symptoms were noted. Zonulin and Claudin-5 levels in the serum were studied. RESULTS: The mean Zonulin value was significantly higher in the IPD group compared to the control one (16.0 ± 10.5 vs. 11.1 ± 4.3; p = 0.0012). Likewise, the mean Claudin-5 value in the IPD group was again significantly higher than in the control group (8.4 ± 5.5 vs. 6.2 ± 3.4; p = 0.0003). The combined ROC curve, though, showed only modest albeit significant discriminant ability. Moreover, neither zonulin nor claudin-5 related to age, phenotype or disease duration, and in terms of non-motor symptoms there was only a significant association between zonulin and urine problems and between claudin-5 and sleep symptoms. CONCLUSION: Our results suggest an association of these markers of intestinal and brain endothelial permeability and IPD, although these remain modest and preliminary and warrant further consideration in larger studies including prodromal cases.

Hemiballism and chorea with acute/subacute onset: a retrospective series.

INTRODUCTION: Chorea is a hyperkinetic movement disorder with sudden, irregular, random, dance-like involuntary movements, and ballism is usually one-sided, high-amplitude movements at the proximal of the extremities. In the etiology of acute chorea/hemiballismus, it is necessary to distinguish drugs first and then focus on metabolic causes. The most important etiological causes that may provoke acute/subacute onset chorea/hemiballismus are hypo-hyperglycemia and electrolyte disorders. In this study, we aim to present 19 patients who were admitted to our clinic with movement disorder with acute/subacute onset and diagnosed with chorea/hemiballismus. METHODS: The study was completed with 19 patients. Routine biochemistry, HbA1c level, hemogram, sedimentation, CRP, hepatitis panels, detailed infective parameters, HIV, vitamin B12 level, folate levels, and thyroid function tests were studied. All patients underwent neuro-imaging. RESULTS: 16(84.2%) were female and 3(15.8%) were male. The lowest age of the patients was 48 years, the highest age was 89 years, and the mean age was 72.21 years. Thirteen (68.42%) patients had a diagnosis of diabetes mellitus in their history. The blood glucose levels of these patients at the time of admission: the lowest was 99 mg/dl and the highest was 1200 mg/dl. HbA1c values of 11(84.61%) of the 13 patients were also found elevated. Thirteen (68.4%) patients had hemiballismus, 4(21.1%) patients had bilateral choreoathetosis in the four extremities, and 2(10.2%) patients had ballism limited to one upper extremity. CONCLUSIONS: Chorea/hemiballismus is a movement disorder that is rare and can occur due to a wide range of etiologies. The most common metabolic cause is NKHHS.

Comparison of the Effects of COVID-19 Pandemic on Male and Female Gender in Patients Diagnosed with Idiopathic Parkinson's Disease: A Case of Sakarya Province, Turkey.

Introduction: The study aims to evaluate the motor, non-motor, cognitive and psychiatric conditions of our patients diagnosed with Idiopathic Parkinson's Disease (IPD) before and after the COVID-19 pandemic and to investigate the effect of the pandemic on male and female genders. Methods: Ninety patients were included in the study. Demographic data such as age, gender, and duration of disease, type of disease of the patients were recorded. Patients were then divided into 2 groups: male and female. Movement disorders of both groups before the pandemic, disease stage determined by H&Y and UPDRS at the admission and after the pandemic, Levodopa equivalent dose used were recorded and all patients were surveyed to evaluate their motor, non-motor, cognitive, and psychiatric conditions during the COVID-19 pandemic. The effects of the COVID-19 pandemic on male and female genders were investigated. Results: Of the patients, 40 were male and 50 were female. Daytime drowsiness, weakness, impaired walking, constipation, sleep disorders, and inability to turn in the bed worsened compared to the period before the pandemic. Yet, of the psychiatric symptoms, boredom, unhappiness, anhedonia, irritability, and tension were found to increase during the pandemic. There was a statistically significant difference in UPDRS, H&Y and disease stages before and after the COVID-19 pandemic in both groups, especially in the female group (p<0.05). Conclusion: Although it was more pronounced in female patients with IPD diagnosis, both motor and non-motor symptoms were found to worsen during the COVID-19 pandemic in both groups.

Optic Neuritis due to Use of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide: A Case Report.

Neuroophthalmic involvement may occur in people infected with primary human immunodeficiency virus (HIV) due to the infection itself, opportunistic infections, malignancy or due to vascular causes. However, treatment-related optic neuropathy may be considered in patients receiving Antiretroviral therapy (ART), without an identified etiological cause, despite all examinations. In this case report, a near-complete recovery was observed in vision loss of a patient, whose 4-month treatment regimen of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/FTC/TAF) was replaced with a combination of tenofovir disoproxil + emtricitabine and lopinavir+ritonavir due to the development of optic neuritis. Recognition of the present symptoms rapidly and the implementation of the necessary change is extremely important for preventing permanent damage in these patients.

The Role of De Ritis Ratio as a Clinical Prognostic Parameter in COVID 19 Patients.

BACKGROUND: The study aims to investigate whether the De Ritis ratio can also be used in patients diagnosed with COVID-19 as a follow-up parameter, such as NLR, which is used in the follow-up and treatment of many diseases. METHODS: Ninety-nine patients admitted to our hospital with suspected COVID-19 were included in the study. Demographic data of the patients, their history characteristics, presenting symptoms, filiation status, duration of clinical stay, and length of stay in intensive care unit, intubation, dialysis, and plasmapheresis needs were examined. The patients were divided into two groups: PCR positive and PCR negative. The presenting, 5th day, and the clinical discharge values of AST, ALT, LDH, urea, creatine, eGFR, De Ritis ratio, procalcitonin, CRP, WBC, NLR, ferritin, lymphocyte, and D-dimer levels of the patients in both groups were studied. RESULTS: The DM and CAD presence in the histories of PCR-positive patients was found to be statistically signifi-cantly higher (p = 0.05, p = 0.03, respectively). Presenting symptoms of headache, fatigue, gastrointestinal symptoms, and taste loss were significantly higher in the PCR-positive patients (p = 0.04, p = 0.02, p = 0.03, p = 0.02, respectively). In the PCR-positive patients, a statistically significant correlation was found between the presenting De Ritis ratios and the presenting NLR, 5th day NLR, and NLR at discharge (p = 0.007, p = 0.02, p = 0.015, respectively). In the PCR-positive group, the 1st and 5th day De Ritis ratios of females were statistically significantly higher than males (p = 0.000, p = 0.006, respectively). Albumin, procalcitonin, length of stay in intensive care unit were significantly higher in the PCR-positive patients, while the presenting D-dimer, presenting WBC, and presenting and 5th day lymphocyte values were significantly higher in the PCR-negative patients. CONCLUSIONS: These findings show that the De Ritis ratios can be used in PCR-positive patients as a parameter, such as NLR, to follow-up and determine the prognosis of many diseases.

Nanofiltration membranes for salt and dye filtration: effect of membrane properties on performances.

In this study, commercial nanofiltration membranes (Toray, NF 270, Desal 5 L) were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, optical profilometry, contact angle, mechanical strength and zeta potential measurements. Filtration performance tests were conducted with distilled water, MgSO4 solution and synthetic dye solutions, respectively. Among three commercial membranes, the Toray membrane was thought to be better choice. Additional experiments were carried out for a more detailed characterization of the selected membrane. Therefore, firstly, flux and removal efficiency was monitored by using dye solutions at different pH values, and then experiments were carried out to observe the effect of different temperatures. Also, another filtration test with NaCl solution was performed for the Toray membrane. As the main purpose of this study, we aimed to establish a significant correlation between the structural properties of membranes and their performances. In light of the results obtained, it was observed that the contact angle, mechanical strength and surface roughness values of the membrane significantly affected the membrane performance. It was concluded that the most important parameter in dye removal was the zeta potential. As a result of this work, a data set of commercial membranes was created and is available to all membrane users.

Halloysite nanotube blended nanocomposite ultrafiltration membranes for reactive dye removal.

In this paper, ultrafiltration (UF) flat sheet membranes were manufactured by introducing two diverse halloysite nanotubes (HNT) size (5 µm and 63 µm) and five different (0, 0.63, 1.88, 3.13, 6.30 wt %) ratios by wet phase inversion. Some characterization methods which are contact angle, zeta potential, viscosity, scanning electron microscopy (SEM) and Young's modulus measurements were used for ultrafiltration membranes. Synthetic dye waters which were Setazol Red and Reactive Orange were used for filtration performance tests. These dye solutions were filtered in three different pH conditions and three different temperature conditions for pH and temperature resistance to understand how flux and removal efficiency change. The best water permeability results were obtained as 190.5 LMH and 192 LMH, for halloysite nanotubes (HNT) sizes of 5 µm and 63 µm respectively. The best water and dye performance of UF membrane contains 1.88% w/w ratio of HNT, which showed increased water flux and dye flux of membranes according to different HNT concentrations including ultrafiltration membranes.

HaNDL Syndrome Presenting With Confusion: A Rare Case Report.

HaNDL syndrome (Syndrome of Transient Headache and Neurologic Deficit with Cerebrospinal Fluid Lymphocytosis) characterized by sudden onset headache, transient neurological deficits, and cerebrospinal fluid (CSF) lymphocytosis, is a self-limited clinical entity that is rarely seen. In this article, we present a case with HaNDL syndrome in a 28-year-old male patient who presented with confusion and agitation after sudden onset of headache, right hemiparesis, and lymphocytosis pleocytosis.

Manufacturing, Characterisation and Mechanical Analysis of Polyacrylonitrile Membranes.

To investigate the effect of polyvinylpyrrolidone (PVP) addition and consequently porosity, two different sets of membranes are manufactured, since PVP is a widely used poring agent which has an impact on the mechanical properties of the membrane material. The first set (PAN 1) includes polyacrylonitrile (PAN) and the necessary solvent while the second set (PAN 2) is made of PAN and PVP. These membranes are put through several characterisation processes including tensile testing. The obtained data are used to model the static behaviour of the membranes with different geometries but similar loading and boundary conditions that represent their operating conditions. This modelling process is undertaken by using the finite element method. The main idea is to investigate how geometry affects the load-carrying capacity of the membranes. Alongside membrane modelling, their materials are modelled with representative elements with hexagonal and rectangular pore arrays (RE) to understand the impact of porosity on the mechanical properties. Exploring the results, the best geometry is found as the elliptic membrane with the aspect ratio 4 and the better RE as the hexagonal array which can predict the elastic properties with an approximate error of 12%.

Demographic characteristics and neurological comorbidity of patients with COVID-19.

ABSTRACT: The COVID-19 infection that started in the Wuhan Province of the People's Republic of China and has now spread throughout the world is not limited to the respiratory system, but also causes other systemic symptoms through viremia. Recent data show that the central and peripheral nervous system involvement is particularly substantial. Thus, the present study aims to investigate the current neurological comorbidities and symptoms of patients with COVID-19 who were followed up by our clinic physicians.

Effect of wetting agent on the dye filtration performance of ultrafiltration membrane.

In this study, the wet phase inversion method was used for fabrication of the flat sheet ultrafiltration (UF) membranes. Three different polymer types and two different wetting agents were used for the fabrication. The effect of polymer types and wetting agents were investigated on the structural and dye performance of casted membranes. Two different synthetic dyes, 100 ppm Setazol Red and 100 ppm Setazol Blue, were used for the performance test. Viscosity, contact angle, and molecular weight cut off (MWCO) of casted membranes were measured and an electro kinetic analyzer, dynamic mechanical analyzer (DMA) and scanning electron microscope (SEM) were used to determine the structural properties. While the highest water and dye permeability were obtained with PES-PEG membrane, PSf-plain membrane gave the highest removal efficiency for Setazol Red and Setazol Blue dyes, which was found to be 78.33% and 82.52%, respectively, in the conditions of neutral pH and ambient temperature. Addition of PVP and PEG wetting agents improved the structural properties and permeability of membranes, but the dye removal was decreased as against plain ones. As the retention of PEG and PVP-based PSf and PES membrane was calculated at an average of 50%, they could be used for dye retention separately or could be a candidate as a pretreatment membrane prior to nanofiltration or reverse osmosis to make their lifetime longer.

Demographic characteristics and neurological comorbidity of patients with COVID-19

SUMMARY ABSTRACT The COVID-19 infection that started in the Wuhan Province of the People's Republic of China and has now spread throughout the world is not limited to the respiratory system, but also causes other systemic symptoms through viremia. Recent data show that the central and peripheral nervous system involvement is particularly substantial. Thus, the present study aims to investigate the current neurological comorbidities and symptoms of patients with COVID-19 who were followed up by our clinic physicians.

RESUMO RESUMO A infecção de COVID-19 que começou na província de Wuhan, na República Popular da China, e já se espalhou por todo o mundo não se limita ao sistema respiratório, mas também causa outros sintomas sistêmicos através de viremia. Dados recentes mostram que seus efeitos no sistema nervoso central e periférico são particularmente significativos. Assim, o presente estudo tem como objetivo investigar as atuais comorbidades e sintomas neurológicos de pacientes com COVID-19 que foram acompanhados pelos médicos da nossa clínica.

A case report of Morvan syndrome.

Morvan syndrome is a rare disease characterized by peripheral nerve hyperexcitability, encephalopathy, dys-autonomia and significant insomnia. The patient, who was included in the present study, was followed-up at our clinics for confusion, myokymia, hyperhidrosis, epileptic seizures, tachycardia, agitation, hypokalemia, and hyponatremia. The cranial MRI of the patient demonstrated hyperintensities at the T2 and FLAIR sections of the medial temporal lobe and insular lobes. Electromyography and neurotransmission examination results were concordant with peripheral nerve hyperreactivity. Contactin-associated protein-like 2 antibodies and leucine-rich glioma inactivated protein 1 antibodies were detected as positive. The patient was diagnosed with Morvan syndrome; intravenous immunoglobulin and corticosteroid treatment was started. Almost full remission was achieved. This very rare syndrome implies challenges in diagnosis and treatment; however, remission can be achieved during the follow-up. In addition, caution is needed in the long-term follow-up of these patients regarding the development of malignancies.

Essential Tremor is not Only a Movement Disorder; Its Relationship with Sleep and Anxiety.

INTRODUCTION: Essential tremor (ET) is the most common movement disorder, and some studies suggest that there are non-motor symptoms as well as motor symptoms. This study aims to investigate the relationship between ET and anxiety and sleep disorder. METHODS: The study was conducted with 38 healthy individuals in the control group and 40 patients who admitted to the neurology clinic of our hospital and had definite ET according to the Consensus statement of the Movement Disorder Society on Tremor. Pittsburgh Sleep Quality Index (PSQI) and Hamilton Anxiety Rating Scale (HAM-A) were applied to both groups. Statistical analysis was carried out with SPSS 22.0 for Windows. RESULTS: The patient and control groups were similar in terms of age, gender and educational status. The PSQI and HAM-A scores in the patient group were significantly higher than the control group (p<0.000, p<0.000, respectively). Both scores were higher in female patients compared to male patients (p<0.05, p<0.05, respectively), and in married patients compared to single patients (p<0.05, p<0.05, respectively). CONCLUSION: Sleep disorder and anxiety are more common in patients with ET than in healthy individuals. We believe that more severe sleep disorders and anxiety in female and/or married patients are indicative of the psychosocial component of the disorder, and that this condition should not be overlooked and should be studied more comprehensively in this regard.