COMT rs4680 and DRD2 rs6275 variants and their association with YMRS scores in children with early-onset bipolar disorder

Background and objectives: Bipolar disorder (BD) is a clinical status with at least one manic, hypomanic or mixed attacks. Genetic factors take part significantly in early-onset BD (EOBD). Dopamine receptors (DRD) act in neurological mechanisms like motivation, learning, memory, and, control of neuroendocrine signaling. DRD2 receptor has been reported to influence the stability of DRD2 transcript. Catechol-O-Methyl transferase (COMT) inactivates catecholamines and Val158Met variation on COMT has effects on COMT activity. This study aims to explore DRD2 and COMT variants in the clinical development of EOBD.MethodsIn this case-control study, 102 EOBD patients and 168 healthy control subjects were used. DRD2 rs6275 and COMT Val158Met variations were detected by real-time polymerase chain reaction (RT-PCR). Young Mania Rating Scale (YMRS) was utilized to determine the EOBD severity.ResultsFor DRD2 rs6275 and COMT Val158Met polymorphisms, no significant relationship was observed in the genotype and allele frequencies between patient and control groups. Nevertheless, TT genotype carriers of DRD2 rs6275 polymorphism demonstrated significantly increased YMRS scores when compared with CC and CT genotype carriers (p = 0.039). Nevertheless, no significant difference was observed between COMT Val158Met genotypes and YMRS scores.ConclusionsWe suggest that the DRD2 rs6275 TT variant can be associated with symptom severity in children with EOBD and can have a clinical significance in EOBD pathogenesis. However, these results need to be confirmed with larger samples of patient and control groups. (AU)

Impact of systemic inflammatory markers in patients with ALK-positive non-small cell lung cancer treated with crizotinib.

OBJECTIVES: To evaluate the prognostic utility of inflammation-based prognostic scores in patients with ALK-positive metastatic or non-resectable non-small-cell lung cancer (NSCLC) treated with crizotinib. PATIENTS AND METHODS: A total of 82 patients with ALK-positive metastatic or non-resectable NSCLC who received ALK TKI crizotinib were included. Pre-treatment modified Glasgow prognostic score (mGPS), prognostic nutritional index (PNI), and systemic immune-inflammation index (SII) were calculated. Multivariable logistic regression and Cox proportional hazards models were used to assess the impact of pretreatment mGPS, PNI, and SII on overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). RESULTS: The ORR was 77.2%, while 1-year OS and PFS rates were 95.0% and 93.5%, respectively. The univariate analysis revealed significantly higher 1-year PFS (89.4 vs. 64.4%, p=0.043) and OS (92.0 vs. 83.3%, p=0.01) rates in patients with low (<934.7) vs. high (≥934.7) SII scores. Multivariate analysis revealed that PNI ≥0.09 was a significant determinant of poorer 1-year OS rates (hazard ratio [HR]: 2.46, 95% confidence interval [CI] 0.88-4.85, p=0.035). No significant difference was observed in survival rates according to gender, age, smoking status, prior lines of therapy, or mGPS scores, while higher mGPS scores (odds ratio [OR]: 0.1, 95%CI 0.16-1.04; p=0.009) and higher PNI scores (OR: 0.16, 95% CI 0.02-0.55; p=0.035) were associated with poorer ORR. CONCLUSION: Our findings indicate the prognostic significance of PNI and SII in terms of survival outcome and the impact of mGPS and PNI on treatment response in patients with ALK-positive NSCLC treated with crizotinib.

THE USE OF LOW DOSE PREDNISOLONE IN PATIENTS WITH SUBACUTE THYROIDITIS AND ITS EFFECT ON IMPAIRED LIFE AND SLEEP QUALITY.

Context: Subacute thyroiditis is an inflammatory thyroid disease, which is treated by nonsteroidal anti-inflammatory drugs (NSAIDs) or steroids. Objective: Defining characteristics of patients with subacute thyroiditis at diagnosis and during follow-up. Investigating the efficacies of NSAID and different doses of steroids and their effects on rates of relapse, recurrence, development of hypothyroidism and on quality of life and sleep parameters. Design: A 3-year observational study in a tertiary referral center. Subjects and Methods: A total of 63 patients with subacute thyroiditis were included. Clinical outcomes of patients treated with NSAIDs and NSAID unresponsive patients treated with prednisolone with initial doses of 0.5 mg/kg/day and 15 mg/day were evaluated. Results: White blood cell count at diagnosis was an independent predictor of NSAID unresponsiveness. No relapse or recurrence was observed in patients receiving low dose of steroids. Long symptom duration until diagnosis and treatment with NSAIDs were associated with development of hypothyroidism. Subacute thyroiditis caused significant deterioration in quality of life and sleep of patients and low dose of steroid was as effective as higher doses in improving these parameters. Conclusions: For patients with no response to NSAID therapy, an initial low dose of prednisolone (15 mg/day) is determined as a safe treatment method when dose reduction is performed with appropriate timing.

ASSOCIATION BETWEEN HASHIMOTO'S THYROIDITIS AND PAPILLARY THYROID CANCER: A SINGLE CENTER EXPERIENCE.

Purpose: To investigate the association between papillary thyroid cancer (PTC) and Hashimoto's thyroiditis (HT). Design: This study is a retrospective study that conducted during 7 consecutive years with a median 119.5 months follow-up. Subjects and Method: Patients who underwent thyroidectomy in Dokuz Eylül University Hospital during 7 consecutive years were included. Patients' demographics, biochemical, radiological, and pathological results were retrospectively assessed. Results: Four hundred sixty nine patients were evaluated. Among 469 patients who underwent thyroidectomy, 132 (28.1%) were malignant, while 182 patients were diagnosed with HT (38.8%). PTC was ranked first at 92.4% (n: 122). The prevalence of HT was 54.9% in patients with PTC and 33.1% in patients without PTC diagnosis (p<0.001). Younger age and the presence of HT were independently associated with PTC. The presence of HT was associated with increased risk of development of PTC (OR: 2.2, %95 CI: 1.4-3.5, p<0.001) but not with TNM stage or recurrence. Lymph node metastasis at presentation was the strongest predictor of recurrence (OR: 13.9, CI: 3.5-54.6, p<0.001). Conclusions: HT was an independent risk factor for development of PTC. According to our findings, HT patients (particularly with nodular HT) should be observed carefully and thyroid fine needle aspiration biopsy (TFNAB) should be encouraged if necessary.

Nutritional evaluation of non-traumatic patients admitted to the hospital from Emergency Department.

OBJECTIVE: Malnutrition is a common condition, especially among hospitalized patients which are overlooked by many clinicians. Malnutrition was found to be associated with increased hospitalization duration, increased admission frequency, increase in infection frequency and severity, bad wound healing, gait disturbances, fallings, and fractures. In this study, we aimed to determine malnutrition frequency in patients who were admitted to the emergency department for non-trauma causes and hospitalized. PATIENTS AND METHODS: 245 patients were admitted to the Emergency Department for non-trauma causes and hospitalized and 245 control group patients were included in this study. Hospitalized patients were assessed with NRS-2002 (Nutritional Risk Screening) and Mini Nutritional Assessment (MNA). Age, gender, height, weight, body mass index (BMI), malnutrition status, and wards of the patients were screened. RESULTS: 140 (57.1%) of the hospitalized patients had malnutrition according to NRS-2002 and MNA. There was a statistically significant difference between the control group and the hospitalized patients who were malnourished (Pearson chi-square test; p<0,001). There was a significant relation between hospitalized departments and malnutrition (p<0.05). There was a significant difference in age and height between hospitalized patients and the control group (p<0.0001) whereas no significant difference was found between the height and BMI (p>0.05). There was a significant relationship in terms of hospitalization and malnutrition. CONCLUSIONS: The nutritional state of the patients admitted to the emergency department for non-trauma conditions is an important factor and should not be overlooked.

BDNF Val66Met polymorphism is associated with negative symptoms in early-onset schizophrenia spectrum and other psychotic disorders

Abstract Background and Objectives. To investigate the clinical characteristics of adolescents with early-onset full psychotic disorders either with Brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) or DRD2/ANKK1 Taq1A (rs1800497) polymorphisms.

No association of anti-osteoporosis drugs with COVID-19-related outcomes in women: a nationwide cohort study.

This study was performed to evaluate whether the use of drugs in the treatment of osteoporosis in women is associated with COVID-19 outcomes. The results showed that the risk of hospitalization, intensive care unit admission, and mortality was not altered in individuals taking anti-osteoporosis drugs, suggesting no safety issues during a COVID-19 infection. INTRODUCTION: Whether patients with COVID-19 receiving anti-osteoporosis drugs have lower risk of worse outcomes has not been reported yet. The aim of this study was to evaluate the association of anti-osteoporosis drug use with COVID-19 outcomes in women. METHODS: Data obtained from a nationwide, multicenter, retrospective cohort of patients diagnosed with COVID-19 from March 11th to May 30th, 2020 was retrieved from the Turkish Ministry of Health Database. Women 50 years or older with confirmed COVID-19 who were receiving anti-osteoporosis drugs were compared with a 1:1 propensity score-matched COVID-19 positive women who were not receiving these drugs. The primary outcomes were hospitalization, ICU (intensive care unit) admission, and mortality. RESULTS: A total of 1997 women on anti-osteoporosis drugs and 1997 control patients were analyzed. In the treatment group, 1787 (89.5%) women were receiving bisphosphonates, 197 (9.9%) denosumab, and 17 (0.9%) teriparatide for the last 12 months. Hospitalization and mortality rates were similar between the treatment and control groups. ICU admission rate was lower in the treatment group (23.0% vs 27.0%, p = 0.013). However, multivariate analysis showed that anti-osteoporosis drug use was not an independent associate of any outcome. Hospitalization, ICU admission, and mortality rates were similar among bisphosphonate, denosumab, or teriparatide users. CONCLUSION: Results of this nationwide study showed that preexisting use of anti-osteoporosis drugs in women did not alter the COVID-19-related risk of hospitalization, ICU admission, and mortality. These results do not suggest discontinuation of these drugs during a COVID-19 infection.

The effect of halofuginone and pirfenidone on wound healing in experimental glaucoma filtration surgery.

PURPOSE: To investigate the effects of halofuginone and pirfenidone on wound healing in experimental glaucoma filtration surgery (GFS). STUDY DESIGN: Animal experimentation. METHODS: A total of 42 male New Zealand albino rabbits were separated into 6 equal groups. A limbal-based trabeculectomy was performed on 5 groups, and Group I (control group) underwent no surgery and received no postoperative medication. For Group II (sham group), 1 drop 0.9% NaCl was instilled qid for 14 days. For Group III, 1% topical corticosteroid (prednisolone acetate) was instilled 1 drop qid for 14 days. For Group IV, 0.4mg/mL mitomycin-C (MMC) was applied intraoperatively to the region of the scleral flap. For Group V, 0.5% pirfenidone was instilled 1 drop qid for 14 days postoperatively. For Group VI, a sponge soaked in 10ng/mL halofuginone was applied to the surgical region for 3 mins. In addition, 1% topical corticosteroid was instilled ×1 drop qid for 14 days postoperatively for Groups IV, V and VI. After 14 days, sections prepared from the bleb regions of the enucleated eyes were evaluated histopathologically and immunohistochemically. Statistical analyses of the study were performed with Kruskal-Wallis variance analysis and the Mann-Whitney U test. RESULTS: With regard to fibroblasts, suppression of the number of mononuclear cells and immunohistochemical staining intensity of transforming growth factor-b (TGF-ß), fibroblast growth factor-b (FGF-ß) and platelet derived growth factor (PDGF), the corticosteroid, MMC, pirfenidone and halofuginone groups were seen to exhibit more effect than the sham group (P<0.05). Compared to the pirfenidone and fuginone groups, inhibition of fibroblast and monocyte proliferation was determined to be lower in the MMC group (P<0.05). The intensity of TGF-ß and FGF-ß staining was seen to be lower in these two treatment groups than in the MMC group (P<0.05). CONCLUSIONS: Halofuginone and pirfenidone may be used as effective alternative agents in delaying wound healing in glaucoma filtration surgery.

The Effects of Lung Ischaemia/Reperfusion on TRPM Gene Expression

ABSTRACT Objective: Transient receptor potential melastatin (TRPM) are integral membrane proteins that have broad range of cellular functions. Roles of TRPM2, TRPM3, TRPM4 and TRPM7 among these channels are very important, and their roles in lung ischaemia/reperfusion injury have not been evaluated yet. The aim of this study is to investigate the contribution of these genes in lung ischaemia/reperfusion injury and evaluate histopathology of tissues. Methods: A total of 40 Wistar albino rats were enrolled for the study. Ischaemia was performed by the application of an atramvatic clamp to pulmonary artery. Gene expressions were determined by the semi-quantitative reverse transcription-polymerase chain reaction method. Histopatholical evaluations were held by a standard haematoxyline-eosin staining. Results: The major histopathological tissue damage was observed in ischaemia performed groups, and expression of TRPM channels was found to be obviously downregulated. Substantial changes were determined between TRPM2, TRPM3, TRPM4 and TRPM7 and lung ischaemia/reperfusion injury. In particular, expression of TRPM2 and TRPM7 was reversibly downregulated in ischaemia. Yet, the expression of TRPM3 and TRPM4 was irreversibly down-regulated after ischaemia. Conclusion: Consequently, these results indicate that TRPM family of cation channels may have significant roles in the lung ischaemia/reperfusion injury.

Oxidative DNA Damage Is Increased in Living Kidney Donors.

BACKGROUND: Long-term consequences of donor nephrectomy might be reduced kidney function, increased risk for cardiovascular disease, and impaired quality of life. The purpose of the current cross-sectional study was to evaluate the relationship between clinical, laboratory, and donation-specific outcomes of living kidney donors and systemic oxidative DNA damage. METHODS: We conducted a cross-sectional study and assessed retrospectively pre- and postdonation data from 60 donors who donated between 2010 and 2015. Plasma malondialdehyde levels and 8-hydroxy-2'-deoxyguanosine/deoxyguanosine ratio (8-OHdG/dG ratio) were determined as oxidative stress markers. Catalase, carbonic anhydrase, and paraoxonase (PON) activities were measured as antioxidants. RESULTS: Approximately 3 years after donation, the hypertensive donor ratio was 12%, and 11% of the donors had glomerular filtration rate <60 mL/min/1.73 m2. Mean serum urea (P = .001) and serum creatinine levels (P = .001) were increased; creatinine clearance level (126.2 ± 35.5 vs 94.6 ± 26.8, P = .001) was decreased in the postdonation period. There was a significant positive correlation between predonation serum urea and 8-0HdG/dG ratio (r = 0.338, P = .016) and predonation serum creatinine and 8-0HdG/dG ratio (r = 0.442, P = .001), while there was a significant negative correlation between serum creatinine and PON activity (r = -0.545, P < .001). CONCLUSION: Our data have demonstrated that kidney donors exhibit increased oxidative DNA damage and decreased antioxidant activity. We propose that predonation serum creatinine is positively correlated with 8-0HdG/dG ratio and negatively correlated with antioxidant PON activity. This is the first study to demonstrate that plasma oxidative DNA damage increases in healthy kidney donors.