Volumetric and Asymmetric Index Analysis of Subcortical Structures in Multiple Sclerosis Patients: A Retrospective Study Using volBrain Software.

Introduction Multiple sclerosis (MS) is a chronic and autoimmune disease that has a significant influence on the central nervous system, such as the brain and spinal cord, affecting millions of individuals globally. Understanding the connection between subcortical brain regions and MS is crucial for effective diagnostic and therapeutic approaches for treating this disabling disease. This study explores the relationship between volume and contours of asymmetry index of subcortical brain regions in individuals with MS using volBrain software (https://www.volbrain.net; developed by José V. Manjón (Valencia Polytechnic University, Valencia, Spain) and Pierrick Coupé (University of Bordeaux, Bordeaux, France)). Methods In our retrospective investigation, we admitted 100 Turkish individuals, comprising 50 patients diagnosed with relapsing-remitting MS (RRMS) (24 (48%) males and 26 (52%) females) and 50 healthy controls (23 (46%) males and 27 (54%) females), registered between October 2017 and February 2022 for five years and underwent assessment in the radiology department at the Teaching and Research Hospital of Kocaeli University; 1,150 Turkish patients were excluded from our study based on our exclusion criteria. We used magnetic resonance imaging with a 3-Tesla (3T) scanner and volBrain software to assess volumes (cm3) and asymmetry indexes due to asymmetry for different levels of atrophy of total intracranial, total brain, gray matter, white matter, and subcortical regions, the most affected regions in MS patients for both patient and control cohorts. Results Statistical analysis revealed a significant difference between patient and control groups (p < 0.001), with patient group mean age at 38.32 years and control group mean age at 32.88 years. Patient group exhibited lower values for total intracranial, total brain, gray matter, white matter, and cerebrospinal fluid volume compared to control group (p < 0.05). The results indicated a statistically significant decrease (p < 0.05) in the values for total intracranial and total brain volume, whereas all other values remained unchanged. We compared volumes of subcortical structures on the right and left sides and found that the putamen, thalamus, and globus pallidus had statistically lower values in the patient group than in the control group (p < 0.001), apart from the lateral ventricle. Furthermore, our retrospective investigation demonstrated a statistically significant difference in the globus pallidus asymmetry index, indicating a preference for the patient group (p < 0.05). A lower asymmetry index value signifies a larger volume for the right side of the subcortical regions of the brain when compared to the left side. Conclusion Brain atrophy, although characterized by irreversible tissue damage, is targeted by therapeutic interventions to prevent progression. It is, therefore, imperative to develop a universally accepted measurement standard for subcortical structures that also considers the inherent variability present within each structure. Our findings serve as an important basis and indicator for the determination of subcortical atrophy and asymmetry in MS, the prognosis of the disease, and the etiology of clinical symptoms. Subsequent research may benefit by adopting the novel approach of considering brain atrophy as an outcome rather than a predictor, thereby facilitating the elucidation of the intricate biological mechanisms that give rise to volume loss.

Surgical outcomes and follow-up results of 53 pediatric craniopharyngioma cases: a single-center study.

OBJECTIVE: Craniopharyngiomas are locally invasive neoplasms, and they cause potential lifelong morbidity because of their tendency for local recurrence. Despite advancements in endoscopic techniques, gross-total resection (GTR) of tumors with invasion or adhesion to important surrounding anatomical structures is extremely difficult. The authors present a single-center study that evaluated the impact of the endoscopic endonasal approach (EEA) on the surgical outcomes of pediatric craniopharyngiomas, the factors affecting the resection rate, and recurrence. METHODS: A total of 44 pediatric patients (age ≤ 18 years) who were treated via the EEA for craniopharyngioma from August 1997 to June 2022, as well as their 53 operations, were included in this study. The preoperative radiological configuration and surgical data of these cases were assessed. Also, preoperative and postoperative clinical (endocrinologic, neurological, and ophthalmological), hypothalamic, physical and social development, and neurocognitive assessment data were described. RESULTS: In total, 37 cases (69.8%) had no history of operation beforehand. The most common symptoms at presentation were endocrine disturbances (98.1%), headache without vomiting (84.3%), and visual disturbance (51%). Cases were classified as infrasellar (1.9%), sellar (32.1%), sellar-suprasellar (52.8%), and suprasellar (13.2%) localization. GTR was achieved in 34/53 cases (64.1%). The rate of GTR was higher in infrasellar and sellar tumors compared with sellar-suprasellar and suprasellar tumors (p = 0.003), and preoperative hypothalamic involvement was associated with lower likelihood of GTR (p = 0.024). Moreover, with experience, the rate of GTR increased (p = 0.037). Postoperative complications, other than endocrine impairment, occurred in 10/53 cases (18.9%). The mean duration of follow-up was 53.57 months. At follow-up, 21/53 (39.6%) cases presented with tumor recurrence. The 5-year progression-free survival (PFS) rate was 48.5%. There was a statistically significant difference between the GTR and other-than-GTR groups in terms of PFS (p < 0.001). According to univariate analysis, smaller tumor (p = 0.017), infrasellar and sellar localization (p = 0.031), and GTR (p < 0.001) were significantly associated with decreased rate of recurrence. Also, there was a statistically significant association between the recurrence rate and adhesion strength of the tumor (p < 0.001). CONCLUSIONS: This retrospective cohort study revealed surgical indications for EEA, as well as factors affecting the resection rate, recurrence, and quality of life during the follow-up period of the included cases. The authors believe that GTR should be the goal for craniopharyngioma treatment, but the authors' treatment approach was to provide a balance between radical surgery with maximum safety and adjuvant treatment for long-term disease control.

ARID3A and ARID3B exert direct regulatory control over the long non-coding RNAs (lncRNAs) MALAT1 and NORAD within the context of non-small cell lung cancer (NSCLC).

Lung cancer, known for its high mortality rates and poor prognosis, remains one of the most prevalent cancer types. Early detection and effective treatment methods are crucial for improving survival rates. Non-small cell lung cancer (NSCLC) accounts for approximately 85 % of all lung cancer cases. Long non-coding RNAs (lncRNAs), which play vital roles in various biological processes, have been implicated in the development of cancer and can impact key therapeutic targets in different cancer types. In NSCLC, the dysregulation of specific lncRNAs, such as MALAT1 and NORAD, has been associated with neoplastic initiation, progression, metastasis, tumor angiogenesis, chemoresistance, and genomic instability. Both MALAT1 and NORAD directly regulate the expression of the transcription factor E2F1, thereby influencing cell cycle progression. Additionally, MALAT1 has been reported to affect the expression of p53 target genes, leading to cell cycle progression through the repression of p53 promoter activity. NORAD, on the other hand, is indirectly regulated by p53. The AT-rich interaction domain (ARID) family of DNA-binding proteins, particularly ARID3A and ARID3B, are involved in various biological processes such as cell proliferation, differentiation, and development. They also play significant roles in E2F-dependent transcription and are transcriptional targets of p53. The intricate balance between promoting cellular proliferation through the pRB-E2F pathway and inducing growth arrest through the p53 pathway underscores the crucial regulatory role of ARID3A, ARID3B, and their interaction with lncRNAs MALAT1 and NORAD. In this study, we aimed to investigate the potential interactive and functional connections among ARID3A, ARID3B, MALAT1, and NORAD in NSCLC, considering their involvement in the pRB-E2F and p53 pathways. Our findings strongly suggest that ARID3A and ARID3B play a regulatory role in controlling MALAT1 and NORAD in NSCLC. Specifically, our study demonstrates that the activities of MALAT1 and NORAD were markedly increased upon the overexpression of ARID3A and ARID3B. Therefore, we can conclude that ARID3A and ARID3B likely contribute significantly to the oncogenic functions of MALAT1 and NORAD in NSCLC. Consequently, targeting ARID3A and ARID3B could hold promise as a therapeutic approach in NSCLC, given their direct control over the expression of MALAT1 and NORAD.

A reference center study in thyrotropin-secreting pituitary adenomas: clinicopathological, therapeutic and long-term follow-up outcomes.

PURPOSE: This study aims to analyze the clinicopathological features, diagnostic steps, and therapeutic results of TSHomas and to reveal the effective factors on remission. METHODS: The clinical, radiological, and pathological features and surgical and endocrinological results of 41 TSHoma cases followed between 2005 and 2022 were retrospectively analyzed. The factors affecting the surgical cure were investigated by comparing the groups with and without remission. RESULTS: A total of 41 patients (23 male,18 female) were included in the study and the mean age was 42 (31.5-49). Palpitation and headache were the most common complaints. The time from the onset of symptoms to diagnosis was 8 (3-20) months. There were 8 patients with a preoperative clinical and biochemical diagnosis of TSH + GH co-secretion. In the TRH stimulation test, a blunted TSH response was obtained in 18 patients (90.0%). Complete suppression could not be obtained in any of the patients who underwent the T3 suppression test. The median maximum tumor diameter was 19.0 mm (6.8-41). There was microadenoma in 4 (9.8%) patients and macroadenoma in 37 patients (92.8%). Remission was achieved in 31 (75.6%) of 40 patients who underwent endoscopic transsphenoidal surgery (eTSS). The Ki-67 labeling index was 2% (1.00-4.00) in the entire patient group. Preoperative use of antithyroid drugs appears to be significantly associated with surgical cure. CONCLUSION: Diagnosis of TSHoma is still full of challenges and dynamic tests remain important. Recognition and good management of inappropriate TSH secretion states affect subsequent surgical outcomes.

Correction to: Efects of AGEs, sRAGE and HMGB1 on Clinical Outcomes in Multiple Myeloma.

[This corrects the article DOI: 10.1007/s12288-022-01574-6.].

Investigation of CD56, ADAM17 and FGF21 Expressions in the Placentas of Preeclampsia Cases.

Objective: In the present study, we investigated the expression of CD56, ADAM17 and FGF21 antibodies (Ab), which we think have an effect on the pathophysiology of preeclampsia (PE), in pregnant patients with healthy placentas and placentas with PE. The expression of these antibodies has been investigated in a limited amount of former research, but their role in PE has not yet been clarified. With this study, we aimed to contribute to the elucidation of the pathophysiology of PE and the detection of new target molecules for treatment. Materials and Methods: Parturients with singleton pregnancy at 32 weeks or above without any maternal or fetal pathology who were admitted to the Department of Obstetrics and Gynecology, Zonguldak Bülent Ecevit University Practice and Research Hospital between 11 January 2020 and 7 January 2022 were included in the present study. Pregnant women with coexisting disease or a pathology related to the placenta (ablation placenta, vasa previa, hemangioma, etc.) were excluded. CD56, ADAM17 and FGF21 antibodies were histopathologically and immunohistochemically detected in 60 placentas with PE (study group) and 43 healthy placentas (control group). Results: CD56, ADAM17 and FGF21 proteins were all more intensely expressed in preeclamptic placentas and a statistically significant difference was found between the two groups for all three antibodies (p < 0.001). Deciduitis, perivillous fibrin deposition, intervillous fibrin, intervillous hemorrhage, infarct, calcification, laminar necrosis and syncytial node were found to be significantly more common in the study group (p < 0.001). Conclusions: We observed that CD56, ADAM17 and FGF21 expressions increased in preeclamptic placentas. These Ab may be responsible for the pathogenesis of PE, which can be illuminated with further studies.

Thirst intensity survey in ADPKD patients.

INTRODUCTION: With increased fluid intake and tolvaptan treatment, the growth rate of cysts can be theoretically decelerated in autosomal polycystic kidney disease. In this prospective study, it was planned to evaluate thirst sensation in these patients and the parameters affecting its intensity. METHODS: Forty-one ADPKD patients on tolvaptan and 40 ADPKD patients not on tolvaptan as the control group were evaluated for thirst distress sensation and intensity. The feeling of thirst and the discomfort caused by excessive fluid intake was assessed with Thirst Distress Scale-HF 12 questions (60/12). Thirst intensity was evaluated with a 100 mm visual scale. RESULTS: Of the whole group, 35.8% (29) were males, and 64.2% (52) were females. The mean age of the tolvaptan group was 39.17 ± 9.35 years and for the control group, it was 41.95 ± 12.29 years. There was a negative correlation between the thirst distress score of the patients and an increase in creatinine level after a year of tolvaptan treatment (r = - 0.335, p = 0.035). The patients not taking thiazide had higher thirst intensity scores (p = 0.004). There was no impact of tolvaptan dosage, total kidney volume, serum sodium, urinary osmolarity or eGFR on thirst distress and thirst intensity scores. DISCUSSION/CONCLUSION: Only thiazide co-treatment had a positive impact on thirst distress and intensity when given tolvaptan. Thirst Distress Scale for ADPKD patients can be used to classify patients before and during tolvaptan treatment.

An unusual manifestation in a pediatric patient with MAFB mutation: Sacroiliitis in multicentric carpotarsal osteolysis syndrome.

Multicentric carpotarsal osteolysis (MCTO) syndrome, is typically characterized by progressive bone resorption in especially carpal and tarsal bones, in addition to abnormal facial appearance and proteinuria. This disorder is caused by monoallelic pathogenic MAFB mutations, which result in excessive osteoclastogenesis via aberrant receptor activator of nuclear factor kappa-B ligand activation. Most cases are sporadic with de-novo mutations, and it is still unclear why carpal and tarsal bones are predominantly affected. The early phases of MCTO resemble juvenile idiopathic arthritis (JIA) with ankle and wrist swelling and pain, even with inflammatory changes in magnetic resonance imaging. Herein we report a pediatric patient, previously treated with antirheumatic drugs, and eventually diagnosed with MCTO. This case was a descriptive case with exophthalmos, significant proteinuria, and total loss of carpal and tarsal bones at the time of genetic diagnosis. Similar to the literature, our case had typical radiological findings despite methotrexate and anti-tumor necrosis factor-alpha treatment. However, while arthritis affecting joints other than wrists and ankles has not been reported so far in the literature, our case had bilateral sacroiliitis which completely resolved after adalimumab treatment. We cannot be sure if sacroiliitis was incidental or occurred as a component of the disease, nonetheless, we think that sharing our experience may lead to easy and early recognition of MCTO, with more knowledge on rare manifestations of MCTO, and thus we may be able to clarify the benefits of denosumab, which is the most promising agent in early phases of the disease.

Effects of AGEs, sRAGE and HMGB1 on Clinical Outcomes in Multiple Myeloma.

Purpose: The receptor for advanced glycation end products (RAGE) upregulated during the onset and progression of cancer and bone-related pathologies. In this study, we aimed to investigate the role of serum advanced glycation end products (AGEs), soluble RAGE (sRAGE) and high mobility group box 1 (HMGB1), in multiple myeloma (MM). Methods: AGEs, sRAGE and HMGB1 concentrations of 54 newly diagnosed MM patients and 30 healthy volunteers were measured by ELISA. The estimations were done only once at diagnosis. The medical records of the patients were evaluated. Results: There was no significant difference between the AGEs and sRAGE levels between the patient and control groups (p = 0.273, p = 0.313). In ROC analysis, a HMGB1 cutoff value of > 9170 pg/ml accurately discriminated MM patients (AUC = 0.672, 95% CI 0.561-0.77, p = 0.0034). AGEs level was found to be significantly higher in early-stage disease and HMGB1 in advanced disease (p = 0.022, p = 0.026). High HMGB1 levels were detected in patients whose with better first-line treatment response (p = 0.019). At 36 months, 54% of patients with low AGE were alive, compared to 79% of patients with high AGE (p = 0.055). Patients with high HMGB1 levels tended to have a longer PFS (median 43 mo [95% CI; 20.68-65.31] ) compared to patients with low HMGB1 levels (median 25 mo [95% CI; 12.39-37.6], p = 0.054). Conclusion: In this study, a significant elevation of serum HMGB1 level was found in MM patients. In addition, the positive effects of RAGE ligands on treatment response and prognosis were determined.

Eating Disorder-15: Factor Structure, Psychometric Properties, Validity, and Reliability of the Turkish Version for Clinical and Non-Clinical Samples. / Yeme Bozuklugu-15: Klinik ve Klinik Olmayan Örneklemler için Türkçe Versiyonun Faktör Yapisi, Psikometrik Özellikleri, Geçerligi ve Güvenilirligi.

OBJECTIVE: Eating Disorder-15 (ED-15) is a self-report scale recommended for use to evaluate weekly progress and treatment results in eating disorders. This research aims to examine the factor structure, psychometric properties, validity, and reliability of the Turkish version of ED-15 (ED-15-TR) for clinical and non-clinical samples. METHOD: Translation-back translation method was used for language equivalence of ED-15-TR. The research was conducted with a total of 1049 volunteers, with two sample groups as non-clinical (n=978) and clinical (n=71). The participants completed an information form, ED-15-TR, Eating Disorder Examination Scale (EDE-Q), and Beck Depression Inventory (BDI). Three hundred fifty-two participants from the non-clinical group and 18 from the clinical group completed ED-15-TR again within a week. RESULTS: Factor analysis confirmed the two-factor structure of ED-15- TR. Cronbach's alpha value was 0.911 (0.773, and 0.904 for the two subscales respectively), the intraclass correlation coefficient for testretest reliability was 0.943 in the clinical group (0.906, and 0.942 for the two subscales respectively); 0.777 (0.699, and 0.776 for the two subscales respectively) in the non-clinical group (for all p<0.001). The high level of a positive correlation between ED-15-TR and EDE-Q supported concurrent validity. CONCLUSION: This research indicates that ED-15-TR is an acceptable, valid, and reliable self-report scale for Turkish society.

The holistic approach to the CHRNA7 gene, hsa-miR-3158-5p, and 15q13.3 hotspot CNVs in migraineurs.

Migraine is a neurological disease characterized by severe headache attacks. Combinations of different genetic variations such as copy number variation (CNV) in a gene and microRNA (miRNA) expression can provide a holistic approach to the disease as a pathophysiological, diagnostic, and therapeutic target. CNVs, the Cholinergic Receptor Nicotinic Alpha 7 Subunit (CHRNA7) gene, and expression of gene-targeting miRNAs (hsa-miR-548e-5p and hsa-miR-3158-5p) in migraineurs (n = 102; with aura, n = 43; without aura, n = 59) and non-migraines (n = 120) aged 15-60 years, comparative, case-control study was conducted. Genetic markers were compared with biochemical parameters (BMI, WBC, Urea, GFR, ESR, CRP, HBG). All analyzes were performed by quantitative Real-Time PCR (q-PCR) and fold change was calculated with the 2-ΔΔCT method. The diagnostic power of the CHRNA7 gene, CNV, and miRNAs were analyzed with the receiver operating curve (ROC). CHRNA7 gene and hsa-miR-3158-5p are down-regulated in migraineurs and the gene is controlled by this miRNA via CNVs (p < .05). Both deletion and duplication were detected in patients with migraine for CVN numbers (p = .05). The number of CNV deletions was higher than duplications. When CHRNA7-CNV-hsa-miR-3158-5p was modeled together in the ROC analysis, the area under the curve (AUC) was 0.805, and the diagnostic power was "good". In migraineurs, the CHRNA7 gene can be controlled by hsa-miR-3158-5p via CNVs to modulate the mechanism of pain. These three genetic markers have diagnostic potential and may be used in antimigraine treatments.

Okadaic Acid-Induced Alzheimer's in Rat Brain: Phytochemical Cucurbitacin E Contributes to Memory Gain by Reducing TAU Protein Accumulation.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive memory loss and cognitive decline, with hallmark pathologies related to amyloid beta (Aß) and TAU. Natural phytochemicals show promise for drug discovery to fill the current therapeutic innovation gap in AD. This study investigated the effect of cucurbitacin E (CuE), one of the bioactive components of Ecballium elaterium, on TAU fibril formation in okadaic acid-induced AD in rats. In a randomized design, we assigned 30 female Sprague Dawley rats to one of five experimental groups: (1) control, (2) stereotaxic surgery, (3) stereotaxic surgery + artificial cerebrospinal fluid, (4) stereotaxic surgery + okadaic acid (AD model), and (5) stereotaxic surgery + okadaic acid + CuE treatment. For experimental groups 4 and 5, rats were administered OKA-ICV (200 ng/kg) followed by CuE (4 mg/[kg·day], intraperitoneally) for 20 days. Expression of the MAPK1/3 and MAPK14 genes associated with TAU metabolism, hippocampal protein levels of these genes, cognitive functions of the rats, and histological accumulation of TAU in the brain were evaluated. Our findings in this preclinical model collectively suggest that phytochemical CuE contributes to memory gain by reducing TAU protein accumulation, which warrants further evaluation in future in vitro and in vivo studies.

Effects of antidiabetics and exercise therapy on suppressors of cytokine signaling-1, suppressors of cytokine signaling-3, and insulin receptor substrate-1 molecules in diabetes and obesity.

OBJECTIVE: Pathological destruction of insulin signaling molecules such as insulin receptor substrate, especially due to the increase in suppressors of cytokine signaling molecules, has been demonstrated in experimental diabetes. The contribution of suppressors of cytokine signaling proteins to the development of insulin resistance and the effects of antidiabetic drugs and exercise on suppressors of cytokine signaling proteins are not clearly known. METHODS: A total of 48 Wistar albino adult male rats were divided into six groups: control group, obese group with diabetes, obese diabetic rats treated with metformin, obese diabetic rats treated with pioglitazone, obese diabetic rats treated with exenatide, and obese diabetic rats with applied exercise program. Immunohistochemical staining was performed in both the liver and adipose tissue. RESULTS: There was a statistically significant decrease in suppressors of cytokine signaling-1, a decrease in suppressors of cytokine signaling-3, an increase in insulin receptor substrate-1, and a decrease in immunohistochemical staining in the obese group treated with metformin and exenatide compared to the obese group without treatment in the liver tissue (p<0.05). A statistically significant decrease in immunohistochemical staining of suppressors of cytokine signaling-1 and suppressors of cytokine signaling-3 was found in the obese group receiving exercise therapy compared to the obese group without treatment in visceral adipose tissue (p<0.05). Likewise, no significant immunohistochemistry staining was seen in diabetic obese groups. CONCLUSION: Metformin or exenatide treatment could prevent the degradation of insulin receptor substrate-1 protein by reducing the effect of suppressors of cytokine signaling-1 and suppressors of cytokine signaling-3 proteins, especially in the liver tissue. In addition, exercise can play a role as a complementary therapy by reducing suppressors of cytokine signaling-1 and suppressors of cytokine signaling-3 proteins in visceral adipose tissue.

Association of childhood asthma with Gasdermin B (GSDMB) and Oromucoid-like 3 (ORMDL3) genes.

OBJECTIVE: Genome-length association studies have shown that Gasdermin B (GSDMB) and Orosomucoid-like 3 (ORMDL3) genes located on the long arm of chromosome 17 are associated with asthma. In this study, it was aimed to determine the possible relationship between asthma control test (ACT), exercise provocation test (ECT), and fractional nitric oxide (FENO) levels and GSDMB and ORMDL3 gene expressions. METHODS: 59 asthmatic and 38 non-asthmatic children were included in the study. We divided the patient group into two subgroups as mild persistent asthma (29 patients) and moderate persistent asthma (30 patients). ORMDL3, GSDMB gene expression levels, ECT, total IgE levels, and eosinophil counts were measured in all cases. In addition, ACT and FeNO levels were measured in children with asthma. Afterward, the relationship of ORMDL3 and GSDMB gene expression coefficient changes with ECT, ACT, and FeNO was examined. RESULTS: When patients with ACT ≤15 were compared with patients with ACT ≥20, ORMDL3 and GSDMB gene expressions were increased 6.74 and 11.74 times, respectively. Comparing patients with ACT ≥20 and ACT ≤15 in terms of coefficient changes (ΔCq), higher change values were observed for ΔCq ORMDL3 in patients with ACT ≤15 (p=0.015). Similarly, when patients with FENO ≤25 ppb were compared with patients with FENO >25 ppb, ORMDL3 and GSDMB gene expressions were increased by 2.93 and 3.56 times, respectively. When the coefficient changes were compared, no significant difference was found between FENO≤25 and FENO >25 patients. There was a slight negative correlation between ΔCq values and ACT score (p=0.003, r=-0.418 for ORMDL3, and p=0.016, r=-0.345 for GSDMB). In addition, we observed a statistically significant positive correlation between ORMDL3 and GSDMB gene expressions (r=0.80, p<0.001). CONCLUSION: We showed that increased ORMDL3 and GSDMB gene expression levels may be associated with ACT scores, FeNO and ECT in asthma. These findings may encourage future studies with larger numbers of subjects that can use gene expression levels in various asthma phenotypes for prognostic prediction.

Macular and peripapillary vessel density alterations in a large series of patients with systemic lupus erythematosus without ocular involvement.

PURPOSE: The aim of this study was to investigate changes in both macular and peripapillary retinal microcirculation in the subclinical period of systemic lupus erythematosus (SLE) patients and to assess the relationship of these changes with disease activity, damage index, renal involvement, and use of hydroxychloroquine (HCQ). METHODS: Sixty eyes of 60 SLE patients and 60 age-matched, healthy controls were evaluated with optical coherence tomography angiography (OCTA). Vessel densities, structural parameters, and foveal avascular zone (FAZ) assesments were made. RESULTS: There was no significant correlation between activity and damage index and all regions of both superficial (SCP-VD) and deep capillary plexus vessel densities (DCP-VD) in the SLE group. There were no significant difference between groups in terms of FAZ, structural parameters, and radial peripapillary capillary vessel densities (RPC-VD). The mean SCP-VD and DCP-VD of most regions showed a significant decrease in the SLE group, except for parafovea superior and parafovea temporal. The decrease in vessel density (VD) in the perifoveal regions of DCP-VD in SLE patients was remarkable. DCP-VD showed good specifity and sensitivity in detecting vascular changes in SLE patients with whole image area under the curve (AUC) = 0.671, p < 0.001, odds ratio (OR) = 0.909, p = 0.009, and perifovea AUC = 0.671, p < 0.001, OR = 0.918, p = 0.012. Similarly, the SCP-VD whole image AUC = 0.609, p = 0.037, and OR = 0.825, p = 0.018 and perifovea AUC = 0.608, p = 0.037, and OR = 0.918, p = 0.012. The DCP-VD of perifovea superior showed a diagnostic accuracy for discrimination between SLE patients with and without nephritis (AUC = 0.671, p = 0.016). The SCP-VD and cumulative dose of HCQ demonstrated significant negative correlation in the SLE group (whole image, r = - 0.332, p = 0.010). CONCLUSIONS: SLE patients without ocular involvement had vascular changes that were particularly evident in the DCP and primarily in the perifovea. The perifovea superior of DCP had diagnostic utility in patients with nephropathy.

Programmed Cell Death Ligand 1 Expression Level and Prognostic Significance in Acute Myeloid Leukemia.

Purpose: We aimed to evaluate the expression level of programmed death ligand-1 (PD-L1) and its effects on prognosis in acute myeloid leukemia. Methods: The flow cytometry was used to detect PD-L1 expression on leukemic cells of 86 de novo acute myeloid leukemia patients with longitudinal follow-up. Results: Median follow-up was 13 (0-73) months. The mean of expression level was 3.22 ± 0.47 at diagnosis and ranged from 0 to 28%. PD-L1 expression tended to be lower in patients with acute promyelocytic leukemia (2.47 ± 1.08, p = 0.09) but there was no significant difference between neither diagnostic nor cytogenetic subgroups. There was no difference in PD-L1 levels between the patients who achieved complete remission (3.4 ± 0.61) and those who did not (2.91 ± 0.72, p = 0.94). The patients with low PD-L1 at diagnosis (median 25 mo [95% CI; 0-56.7]) had a longer overall survival compared with high PD-L1 (median 13 mo [95% CI; 5.52-25.17], p = 0.079). PD-L1 expression was lower at relapse (2.04 ± 0.79) compared to initial diagnosis (4.52 ± 0.93, p = 0.049). The patients who had overall survival longer than 1 year showed lower PD-L1 expression at relapse (0.66 ± 0.93) compared with who had not (5.06 ± 4.28, p = 0.052). A negative correlation between CD33 and PD-L1 (r = - 0.303, p = 0.005) was detected. Conclusion: Despite its low expression levels, PD-L1 appears to be a clinically important prognostic factor. The negative correlation determined between PD-L1 and CD33 supports the combination approach of PD-L1 inhibitors and CD33 targeted immunotherapies. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-021-01473-2.

Neonatal Tactile Stimulation Downregulates Dendritic Spines in Layer V Pyramidal Neurons of the WAG/Rij Rat Somatosensory Cortex.

Objective: The aim of our study is to examine the effects of neonatal tactile stimulations on the brain structures that previously defined as the focus of epilepsy in the Wistar-Albino-Glaxo from Rijswijk (WAG/Rij) rat brain with genetic absence epilepsy. Methods: In the present research, morphology and density of dendritic spines were analyzed in layer V pyramidal neurons of the somatosensory cortex (SoCx) of WAG/Rij rats (nonstimulated control, tactile-stimulated, and maternal separated rats) and healthy Wistar (nonepileptic) rats. To achieve this, a Golgi-Cox method was used. Results: Dendritic spine number in layer V of the SoCx has been detected significantly higher in adult WAG/Rij rats at postnatal day 150 in comparison to nonepileptic adult control Wistar rats (p < 0.001). Moreover, quantitative analyses of dendrite structure in adult WAG/Rij rats showed a decrease in dendrite spine density of pyramidal neurons of SoCx which occurred in early neonatal exposure to maternal separation (MS) and tactile stimulation (TS) (p < 0.001). Conclusions: Our findings provide the first evidence that tactile stimulations during the early postnatal period have a long-term impact on dendrite structure in WAG/Rij rat's brain and demonstrate that neonatal tactile stimulation can regulate dendritic spines in layer V in pyramidal neurons of SoCx in epileptic brains.

The effects of metformin, pioglitazone, exenatide and exercise on fatty liver in obese diabetic rats: the role of IRS-1 and SOCS-3 molecules.

BACKGROUND: Obesity-induced inflammation mechanism is seen as a mechanism that may be the cause of insulin resistance and non-alcoholic fatty liver disease (NAFLD). Pathological destruction of insulin signaling molecules such as insulin receptor substrate proteins (IRS), especially due to the increase of cytokine signal suppressors (SOCS), has been demonstrated in experimental diabetes. The aim of this study was to determine the effects of metformin, pioglitazone, exenatide and exercise treatments used in type 2 diabetes on fatty liver and the role of Irs-1 and Socs3 molecules in this process in obese diabetic rats. METHODS: The study was conducted on 48 Wistar albino adult male rats weighing 180-220 g and randomly divided into 6 groups. The obese rat model with fatty liver was formed with a 60% fat diet for 4 weeks. Afterwards, drug treatment with metformin (Ob + D + M), pioglitazone (Ob + D + P), exenatide (Ob + D + ExA)) or exercise (Ob + D + ExE) was applied for 4 weeks to these obese groups, in which diabetes was induced by streptozocin (STZ). At the end of the experimental protocol, liver tissue samples were taken from all rat groups and histopathological and genetic analyses were performed. RESULTS: The mean steatosis degrees of the Ob + D + ExA and Ob + D + ExE groups were statistically significantly decreased compared to the obese diabetic group (p < 0.001). The group with the lowest mean steatosis grade was the Ob + D + ExE. Decrease in SOCS-3 expression was significant in Ob + D + M and Ob + D + P groups than other groups (p < 0.05). Mean staining intensities of Ob + D + Ex group, Ob + D + ExE group and Ob + D + P group according to IRS-1 expression statistically significantly increased compared to obese diabetic group (p < 0.05). Average staining intensity of Ob + D + ExE group according to IRS-1 expression was significant than other groups. CONCLUSION: Exercise and exenatide treatments seemed to be the prominent treatment methods by showing a statistically significant effect in decreasing the degree of steatosis, decreasing the Socs3 expression level and increasing the Irs-1 expression level.

Endoscopic approach for giant pituitary adenoma: clinical outcomes of 205 patients and comparison of two proposed classification systems for preoperative prediction of extent of resection.

OBJECTIVE: Giant pituitary adenoma is considered a challenging pathology for surgery owing to its complications and low resection rate. In this study, the authors present their experience of using the endoscopic endonasal approach to treat patients with giant pituitary adenoma, and they aimed to develop a classification system for prediction of extent of resection. METHODS: The institutional medical records of patients diagnosed with giant pituitary adenoma who underwent endoscopic endonasal transsphenoidal surgery between August 1997 and December 2019 were retrospectively reviewed. Surgical and clinical outcomes were evaluated in detail. The effects of tumor characteristics on extent of resection were analyzed. The findings were used to develop two classification systems that could preoperatively predict extent of resection. Morphological score was based on tumor characteristics, and landmark-based classification was defined according to surgical zones based on neurovascular landmarks. The effects of change in surgical strategy, which aimed to maximize tumor resection and capsule dissection, on rates of resection and complications were evaluated before and after 2017. RESULTS: This study included 205 patients, with a mean patient age of 46.95 years and mean preoperative tumor diameter of 46.56 mm. Gross-total resection (GTR) was achieved in 35.12% of patients, near-total resection (NTR) in 39.51%, and subtotal resection (STR) in 25.36%. Extent of resection differed significantly between the grades and zones of the classification systems (p < 0.001 for both). Among patients with grade 3 tumor, 75.75% of patients achieved STR, 21.21% achieved NTR, and 3.03% achieved GTR. Among patients with zone 3 tumor, 65.75% achieved STR, 32.87% achieved NTR, and 1.36% achieved GTR. Both grade 3 and zone 3 indicated limited extent of resection. The mean (range) follow-up duration was 50.16 (9-247) months. Postoperative recovery of at least one hormone axis was seen in 15.24% of patients with pituitary deficiency, and development of new hormonal deficiency was observed in 22.43% of patients. Complications included permanent diabetes insipidus (7.80%), cerebrospinal fluid leakage (3.90%), postoperative apoplexy (3.90%), meningitis (3.41%), and epistaxis (3.41%). The surgical mortality rate was 1.46%. Among 85 patients treated before 2017, 27.05% of patients achieved GTR, 37.64% achieved NTR, and 35.29% achieved STR; among 120 patients treated after 2017, 40.83% achieved GTR, 40.83% achieved NTR, and 18.33% achieved STR. Seven patients in the pre-2017 cohort had postoperative apoplexy versus only 1 patient in the post-2017 cohort. There were no statistically significant differences between the two periods in terms of the incidence rates of other complications. CONCLUSIONS: Capsule dissection and GTR are valuable for preventing serious complications and reducing recurrence of giant adenoma. Treatment of giant pituitary adenoma may be better managed with the help of a classification system that provides information about extent of resection that can be achieved with an endoscopic approach.