Carthamus Tinctorius L. (Safflower) extracts inhibit expression of metastatic genes of MDA-MB-231 breast cancer cells.

Breast cancer is the most common type of cancer in women and the second  cause of cancer-related death after lung cancer. Although the common methods used in the treatment of breast cancer are chemotherapy, radiotherapy and surgery, the search for alternative treatments continues.  The leading  alternative treatments are medicinal plants which actually inspire the production of many cancer drugs. In this study, the proliferative and metastatic effects of Carthamus tinctorius L., known for its many therapeutic properties, on metastatic breast cancer were investigated. Here, intending to evaluate the the content and actions of different extracts of safflower leaves extracts were prepared by extracting in water, alcohol and oil and analysed by FTIR. Their antioxidant effect was tested and then the extracts were applied to metastatic breast cancer cells. FTIR spectrums of all three extracts have revealed the presence of organic compounds.  It is found that all extracts but mostly the oil extract has antioxidant property. MTT assay, wound healing assay and gene expression analysis were performed to assess the antiproliferative and anti metastatic effects of the extracts on breast cancer cells. It is found that, there is no significant antiproliferative effect of extracts on MDA-MB-231 cells except the alcohol extract. However, all safflower extracts, especially the oil extract, significantly reduced the metastatic potential of breast cancer cells. It is concluded that safflower contents are potent chemicals which inhibit the cellular mechanisms underlying the spreading of cancer cells and further analysis may lead to new initiatives in drug design research.

Revisiting the Radical Radiotherapy-Radiochemotherapy Results in Anal Canal Cancers: (TROD Gastrointestinal Group Study 02-005).

BACKGROUND AND AIM: This study aimed to determine treatment outcomes and factors affecting prognosis in patients diagnosed with anal canal cancer who received radical radiotherapy (RT) or radiotherapy combined with chemotherapy (CT-RT) in radiation oncology centers in Turkey and compare the results with literature. MATERIAL AND METHOD: The study included 193 patients with anal canal cancer reported between 1995 and 2019, of which 162 had complete data. The study was conducted in 11 radiation oncology centers, and a joint database was shared among them. Patients received radiotherapy doses of 45 Gy to 60 Gy. Data analysis was done using SPSS for Windows version 20. RESULTS: Median follow-up was 48.51 months (2-214). All patients received radiotherapy, and 140 (86.4%) received concurrent chemotherapy. Radiotherapy doses of 50.4 Gy to 60 Gy were administered to 74 patients (45.7%) using 2-dimensional-3-dimensional (2D-3D) conformal therapy and 70 patients (43.2%) using intensity modulated radiotherapy technique (IMRT). Acute phase hematologic toxicity was observed in 62 patients (38.3%), and nonhematologic toxicity in 123 patients (75.9%). The 5-year overall survival (OS) rate was 75.1% and disease-specific survival (DSS) rate was 76.4%. OS without colostomy was achieved in 79,8 % at 5 years, and complete response in 112 patients (69.1%). OS rate was significantly higher in 142 patients with positive response (P < .000) and 112 with complete response (P < .000). Anemia (P < .002), local progression, and systemic progression (P < .000) resulted in lower OS (P < .002). In univariate analysis, factors affecting OS rate were: gender, age, stage, lymph node status, T stage, RT treatment duration, and treatment planning with PET fusion, which were found to be statistically significant. Completing radiotherapy in less than 45 days, concurrent chemotherapy, and continued administration of mitomycin and 5 FU as chemotherapy had a significant positive effect on overall survival. OS rate was higher in patients receiving RT dose of 58 Gy or less and undergoing IMRT planning in radiotherapy. IMRT was associated with lower acute and late side effects. CONCLUSION: Radiochemotherapy is the primary treatment for anal canal cancer and advanced radiotherapy techniques may increase survival by reducing side effects and improving treatment continuation. Higher treatment doses require further investigation. The efficacy of treatment can be improved by including patients treated with modern radiotherapy techniques in multicenter prospective studies using new and more effective chemotherapy and immunotherapy agents.

The role of breast milk beta-endorphin and relaxin-2 on infant colic.

BACKGROUND: The relationship between infant colic and breast milk beta-endorphin (BE) and relaxin-2 (RLX-2) has not been studied before. METHODS: Thirty colic infants and their mothers constituted the study group, and the same sex, similar age and healthy infants and their mothers formed the control group. Maternal predisposing factors were analysed with questionnaires. RESULTS: The frequency of headache and myalgia in the mothers was significantly higher in the study group compared to the control group. Sleep quality of mothers in the study group was worse than in the control group (p = 0.028). While breast milk RLX-2 level in the study group was not different from the control group, breast milk BE level in the study group was significantly higher than the control group (p = 0.039). A positive correlation was found between breast milk BE levels and crying times, and between sleep quality scores and crying times. Headache, myalgia, sleep quality and breast milk BE levels were found to have a significant effect on infant colic. CONCLUSIONS: Breast milk RLX-2 has no role on infant colic. Breast milk BE may act as a biological mediator in transmitting of maternal predisposing factors such as poor sleep quality, headache and myalgia from mother to infant. IMPACT: The relationship between infant colic and breast milk beta-endorphin (BE) and elaxin-2 (RLX-2) has not been studied before. Maternal sleep quality, headache, and myalgia are predisposing factors associated with infant colic. Breast milk RLX-2 has no effect on infant colic. Breast milk BE may play a role as a biological mediator in transmitting the effects of predisposing factors from mother to infant. Breast milk BE may be a mediator in biological communication between mother and infant.

Trimodality therapy of malignant pleural mesothelioma with helical tomotherapy.

OBJECTIVE: The purpose of this study was to determine the efficacy and tolerability of hemithoracic radiotherapy implemented with helical tomotherapy (HTT) in malignant pleural mesothelioma (MPM) patients. METHODS: Between October 2018 and December 2020, data from 11 MPM patients who received trimodality therapy, including lung-sparing surgery (pleurectomy-decortication, P/D), adjuvant chemotherapy (cisplatin+ pemetrexed), and radiotherapy, were retrospectively reviewed. HTT was used to deliver a total of 30 Gy, 50-54 Gy or 59.4-60 Gy to R2 disease with 1.8-2 Gy daily doses. Descriptive data are presented in number (percentage) or median (minimum- maximum). The Kaplan-Meier method was used to calculate survival data. In patients with toxicities, the risk organ doses were compared using the Mann-Whitney U test. RESULTS: The median follow-up was 20.5 (12-30) months. Two-year local control, disease-free, and overall survival rates were 48.5%, 49%, and 77.9%, respectively. The median prescribed dose for planning target volume (PTV) was 50.4±8.7 (30-60) Gy. Mean dose (Dmean) of total lung was 19.9±6 (10.4-26) Gy; the V20 (%) of ipsilateral and contralateral lungs were 89.±11.2 (62.7-100) and 0.7±2.1 (0.49-5.9), respectively. Esophageal Dmean and maximum doses (Dmax) were found as 21.7±8.4 (7.4-34) and 53.1±10.4 (25.4-64.4) Gy, respectively. V30 (%) and Dmean of heart were 22.3%±13.4% (3.9-47) and 21±5.7 (10.8-29.3) Gy, respectively. Dmax of medulla spinalis (MS) was 38.6± 1.3 (13.7-48) Gy. Grade 1-2 radiation pneumonitis (RP) developed in 4 (36.4%) and esophagitis in 2 (18.2%) patients. RP was found to be associated with MS and esophageal doses (p<0.05). Myelitis was diagnosed in 1 (9.1%) patient (MS Dmax: 29 Gy). CONCLUSION: HTT can be used as part of trimodality therapy for MPM patients with acceptable toxicities. MS and esophageal doses should be considered for radiation pneumonitis risk, and new dose constraints for these organs should be defined.

Clinical and Laboratory Findings by Serum Vitamin D Levels in Children with COVID-19.

OBJECTIVE: The studies on children with COVID-19 are very limited. The aim of this study is to reveal the effect of serum 25-hydroxy vitamin D level on clinical and laboratory parameters. MATERIALS AND METHODS: The study included 74 children (35 boys and 39 girls) diagnosed with COVID-19. The retrospective data were obtained from the file records of the patients. Seventy-four patients were divided into 3 groups (group 1, deficient; group 2, insufficient; and group 3, sufficient) according to their serum 25-hydroxy vitamin D levels. RESULTS: The mean age of all patients was 113.25 ± 64.55 months. The mean leucocyte count was substantially higher in group 3 compared to groups 1 and 2 (P = .05 and P = .002, respectively). The mean lymphocyte and platelet count in group 3 was remarkably higher than both groups 1 and 2 (P = .001 and P = .002; and P = .04 and P = .01, respectively). The mean serum parathyroid hormone concentration in group 1 was markedly higher than both groups 2 and 3 (P=.003 and P = .002, respectively) while the mean serum 25-hydroxy vitamin D level in group 1 was remarkably lower than both groups 2 and 3 (P=.001 and P=.001, respectively). Serum 25-hydroxy vitamin D concentrations were positively correlated with leucocyte, lymphocyte, and platelet counts (r=0.221, P=.05; r=0.396, P=.001; and r=0.249, P=.03, respectively) while there was a negative correlation with parathyroid hormone concentrations (r=-0,436, P=.001). CONCLUSION: This study suggests that COVID-19 has a benign course in children and that serum 25-hydroxy vitamin D concentration may have a role in the lymphocyte count.

Comparison of Serum Adropin Levels in Patients with Diabetes Mellitus, COVID-19, and COVID-19 with Diabetes Mellitus.

OBJECTIVE: In the present study, the relationship between a poor prognosis and adropin levels in diabetic patients with coronavirus disease 2019 was investigated by measuring serum adropin levels and levels of D-dimer, C-reactive protein, and ferritin, which are considered prognostic factors for coronavirus disease 2019. MATERIALS AND METHODS: Hundred volunteer participants treated in the Erzurum Regional Training and Research Hospital were included in this study. Serum adropin levels were measured by enzyme-linked immunosorbent assay. The relationship between serum adropin level and C-reactive protein, ferritin, and D-dimer levels was analyzed by correlation analysis. RESULTS: The participants' serum adropin levels differed between the groups (P = .0007). The control group had the highest adropin levels among groups. The lowest adropin levels were in the COVID + diabetes mel- litus group. Adropin levels of diabetes mellitus, COVID, and diabetes mellitus+COVID groups were sig- nificantly decreased when compared to the control (P < .05). There was a significant negative correlation between adropin and C-reactive protein, D-dimer, and ferritin. CONCLUSION: Adropin can be used as an auxiliary biomarker, a prognostic factor in the early management of coronavirus disease 2019 patients with diabetes mellitus. We think that our study will guide future studies conducted in this field.

Plasma renin, aldosterone, and urinary prostaglandin E2 levels in children with hypocalcemia due to vitamin D deficiency rickets.

We investigated the effect of hypocalcemia on plasma renin, aldosterone, and urine PGE2 levels in children with vitamin D deficiency rickets (VDDR). In the study group, 25 patients with VDDR-induced hypocalcemia were treated with a single dose of 150,000-300,000 IU cholecalciferol and 50 mg/kg/day elemental Ca for 10 days. On any day between 21th and 30th days after the treatment, the patients' clinical, biochemical and radiologic findings were re-evaluated. The healthy children with the same sex and similar age as the study group comprised the control group. Plasma sodium (Na), potassium (K), calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), parathyroid hormone (PTH), 25- hydroxy vitamin D (25OHD), renin, aldosterone; and urinary Ca, creatinine (Cr) and prostaglandin E2 (PGE2) levels were measured in both the study (pre-treatment and post-treatment) and the control group. Plasma Ca, P, 25OHD and renin levels and urinary PGE2/Cr ratio in the post-treatment group were significantly higher than those in the pre-treatment group while K, ALP, and PTH concentrations were significantly lower. Plasma ALP and PTH levels in pre-treatment group were significantly higher than in the control group while Ca, P, 25OHD, aldosterone and renin concentrations and urinary PGE2/Cr ratio were significantly lower. Post-treatment plasma Ca level was significantly decreased in normal limits compared to the control group while other biochemical parameters were not different from the control group. Plasma Ca concentration was positively correlated with renin level and urinary PGE2/Cr ratio. The findings suggest that hypocalcemia may inhibit the production of renin, aldosterone and PGE2 and a blunt aldosterone secretion may develop even after recovery from hypocalcemia.

The Successful Treatment of Deep Soft-tissue Calcifications with Topical Sodium Thiosulphate and Acetazolamide in a Boy with Hyperphosphatemic Familial Tumoral Calcinosis due to a Novel Mutation in FGF23

Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare autosomal recessive disorder. Topical sodium thiosulfate (STS) and acetazolamide can be a safe and effective treatment for patients who do not respond to conventional therapy for ectopic calcifications. We report the successful treatment of deep soft-tissue calcifications with topical STS and acetazolamide in a boy diagnosed with HFTC due to a novel homozygous mutation of FGF23.

The genetics and clinical manifestations of patients with vitamin D dependent rickets type 1A.

OBJECTIVES: Vitamin D dependent rickets type 1A (VDDR-1A) is a very rare autosomal recessive disorder caused by mutations in the CYP27B1, which encodes vitamin D 1α-hydroxylase. We report the genetics and clinical manifestations of nine patients with VDDR-1A and compare our patients to other cases with the same mutations in the literature. METHODS: The clinical presentations, clinical and laboratory findings and treatment modalities of the patients were evaluated retrospectively. RESULTS: The mean age of the patients at the time of diagnosis was 39.9 months (range: 4.5-111). At the time of diagnosis, six patients had received stoss vitamin D therapy. Clinical findings related to rickets were obvious in seven patients and unclear in two patients. Except for one case, all patients had laboratory findings of rickets. A novel variant and four previously reported mutations in CYP27B1 were identified. The mean calcitriol and elemental calcium dose were 45.5 ng/kg/day (range: 20-70) and 75.6 mg/kg/day (range: 45-125), respectively. CONCLUSIONS: We found a novel compound heterozygous mutation consisting of a reported duplication [(p.F443Pfs*24 (c.1319_1325 dup CCCACCC)] in exon 8 and a novel deletion [p.D507Efs*34 (c.1521 delC)] in exon 9. Our study suggests that the clinical manifestations and laboratory findings of the patients with VDDR1A are variable even among the patients with the same mutation.

Two novel CYP2R1 mutations in a family with vitamin D-dependent rickets type 1b.

PURPOSE: Vitamin D-dependent rickets type 1b (VDDR1b) is a very rare autosomal recessive disorder caused by mutations in CYP2R1 that produces 25-hydroxylase. To date only five mutations in CYP2R1 have been identified. This study has reported the genetic results and the clinical characteristics of a family with VDDR1b and compared this family to the other families with VDDR1b in literature. METHODS: After two probands were diagnosed with VDDR1b, all other family members were evaluated. Serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone, 25-hydroxy vitamin D, and 1.25-dihydroxy vitamin D levels were measured in all family members. All individuals were evaluated radiographically, and a genetic analysis was done in all family members. The other families with VDDR1b in literature were reviewed. RESULTS: Two novel mutations [c.367 + 1G > C and p.E339Q (c.1015G > C)] were identified. The clinic and laboratory findings were strikingly different among the members of this family regardless of the mutation and the number of alleles affected. The families having different mutations in literature had also extensive variation in both the clinical and the laboratory findings. CONCLUSION: The current study further expands CYP2R1 mutation spectrum. The findings of both the current and the previous studies suggest that VDDR1b is a more complex disorder than the known autosomal recessive inheritance model and the phenotype may show an extensive variation regardless of the mutation type and the gene dosage.

Sclerosing bone dysplasias with hallmarks of dysosteosclerosis in four patients carrying mutations in SLC29A3 and TCIRG1.

The osteopetroses and related sclerosing bone dysplasias can have a broad range of manifestations. Especially in the milder forms, sandwich vertebrae are an easily recognizable and reliable radiological hallmark. We report on four patients from three families presenting with sandwich vertebrae and platyspondyly. The long bone phenotypes were discordant with one patient showing modeling defects and patchy osteosclerosis, while the second displayed only metaphyseal sclerotic bands, and the third and fourth had extreme metaphyseal flaring with uniform osteosclerosis. Two of the four patients had experienced pathological fractures, two had developmental delay, but none showed cranial nerve damage, hepatosplenomegaly, or bone marrow failure. According to these clinical features the diagnoses ranged between intermediate autosomal recessive osteopetrosis and dysosteosclerosis. After exclusion of mutations in CLCN7 we performed gene panel and exome sequencing. Two novel mutations in SLC29A3 were found in the first two patients. In the third family a TCIRG1 C-terminal frameshift mutation in combination with a mutation at position +4 in intron 2 were detected. Our study adds two cases to the small group of individuals with SLC29A3 mutations diagnosed with dysosteosclerosis, and expands the phenotypic variability. The finding that intermediate autosomal recessive osteopetrosis due to TCIRG1 splice site mutations can also present with platyspondyly further increases the molecular heterogeneity of dysosteosclerosis-like sclerosing bone dysplasias.

[Evaluation of epidemiologic and clinical features of oropharyngeal tularemia patients in the Eastern Anatolia Region of Turkey]. / Dogu Anadolu Bölgesi'nden hastanemize basvuran orofarengeal tularemi olgularinin epidemiyolojik ve klinik özelliklerinin degerlendirilmesi.

Tularemia is a zoonotic infectious disease caused by Francisella tularensis. Tularemia is endemic in the northern hemisphere and is usually seen in North America, Europe and Asia. Although the ulceroglandular tularemia is the most common form in these regions, the oropharyngeal form is more prevalent in Eastern Europe, including Turkey. The disease has importance in Turkey due to its wide geographic distribution and periodic outbreaks. The aim of this study was to determine the demographic, clinical and epidemiological characteristics of oropharyngeal tularemia patients. The demographic, clinical, epidemiological and laboratory findings of 26 tularemia patients admitted to our hospital from Erzurum and 5 neighbour provinces were analyzed retrospectively. Francisella tularensis microagglutination test (MAT) was performed for all patients whose clinical symptoms were consistent with tularemia and MAT titers ≥ 1/160 were considered positive. Twenty-six oropharyngeal tularemia patients (13 males and 13 females) were included in the study. All of the patients had cervical lymphadenopathy (LAP) at least one month period. Twenty (76.9%) of the patients included in the study were living in rural areas, and 17 (65.4%) were dealing with livestock. It was determined that 9 (34.6%) of the patients used water from municipal water supply, 9 (34.6%) of the patients used water from natural water supply and 8 (30.8%) of the patients used both of the water supplies. The most common symptoms among the patients in the study were fever in 23 (88.5%) patients, sore throat in 24 (92.3%) patients, and cervical LAP in all of the patients. Thirteen (50%) of the patients were treated with streptomycin, 7 (26.9%) with doxycycline and 6 (23.1%) with gentamicin. This is the first study showing that tularemia is present in Erzincan, Agri, Igdir as well as Erzurum provinces, and it provides that the incidence has increased in this region. Tularemia diagnosis is generally underestimated due to the lack of specific symptoms. Therefore, tularemia should also be considered in patients who have complaints of sore throat and cervical LAP in non-endemic regions.

The effect of the zinc concentration in breast milk on neonatal weight gain.

The change in breast milk zinc (Zn) concentration in a feeding period during lactation may affect neonatal weight gain. The aim of this study was to determine how to change the Zn concentrations in breast milk during a feeding period in early and late lactation periods and identify the relationship between the differences in the Zn levels in breast milk during lactation and neonatal weight gain. Breast milk was collected in the early and late lactation periods with samples being obtained before (foremilk) and after (hindmilk) a feeding period. Then, we determined the Zn concentrations in the breast milk and measured the weight of the infants before and after the same feeding period. The study was composed of 37 newborns and their mothers. During the feeding period, the Zn concentrations in both the transitional and mature milk decreased significantly. During the lactation period, the Zn levels were markedly lower in only the hindmilk. The body weights of the infants both before and after feeding in the early lactation period were negatively correlated with the delta Zn concentration in the same period, but the delta body weights in the early lactation period were positively correlated with the Zn levels in the hindmilk in the same period. In addition, body weights before feeding in the late lactation period were also positively correlated with Zn levels in hindmilk in the early lactation period. This study suggests that the Zn concentrations in both the transitional and mature milk decreased, which suggests that changes in the Zn content of breast milk during lactation might play a role in the weight gain of healthy neonates.

Comparison of six-minute walking tests conducted with and without supplemental oxygen in patients with chronic obstructive pulmonary disease and exercise-induced oxygen desaturation.

BACKGROUND: There are contradictory reports in the literature on the effects of supplemental oxygen administered before or after exercise tests. In light of this, we compared the results of 6-minute walking tests performed in room-air conditions (A6MWT) and with supplemental oxygen (O6MWT) in patients with chronic obstructive pulmonary disease (COPD) and exercise-induced oxygen desaturation. PATIENTS AND METHODS: Thirty-one patients with COPD were included in the study. The A6MWT and O6MWT were performed in randomized order on each patient. During the tests, severity of dyspnea and tiring of the leg were evaluated by the Modified Borg Scale. Heart rate and pulsed oxygen saturation and blood pressure were measured by pulse oximeter. RESULTS: Walking distance was longer with the O6MWT than with the A6MWT (P=0.001). The O6MWT resulted in a smaller increase in dyspnea, leg fatigue, and heart rate and a smaller drop in pulsed saturation than the A6MWT (P<0.05). The walking distance with the O6MWT correlated with respiratory function and hemodynamic parameters (P<0.05). CONCLUSION: The O6MWT, which produced less hemodynamic stress and was safer than the A6MWT, might provide more accurate information on exercise limitation for patients with COPD. These results suggest that the O6MWT can be used as a standard walking exercise test for patients with COPD and exercise-induced oxygen desaturation.

CagA positivity and its association with gastroduodenal disease in Turkish children undergoing endoscopic investigation.

BACKGROUND: Cytotoxin-associated gene A (CagA) product is a bacterial virulence factor contributing to the pathogenicity of Helicobacter pylori (HP) infection in humans. Host factors, which vary in different countries, interact with bacterial factors to determine the disease state. Our objective was to investigate the frequency of CagA-positive HP strains and evaluate the contribution of CagA positivity to symptoms and development of mucosal lesions in HP-infected Turkish children. METHODS: We conducted a prospective clinical trial in 240 consecutive Turkish children undergoing endoscopy (110 girls, 130 boys; mean age, 8.7 +/- 4.3 years). HP infection was diagnosed on the basis of a positive rapid urease test and histology of the mucosal specimens. HP IgG and CagA IgG antibodies were measured by enzyme-linked immunosorbent assay in HP-positive children. RESULTS: The HP positivity rate was 50.4% in our study group (51 girls, 70 boys; mean age, 9.9 +/- 3.9 years). CagA was positive in 74.4%. HP infection was less common in children with vomiting (25.9%, P < 0.05). CagA positivity was not associated with any clinical symptom. HP positivity was higher in children with duodenal ulcer (80% vs. 49.1%, P = 0.05); while CagA positivity was similar. Antral nodularity was strongly associated with HP positivity and CagA positivity (30.6% vs. 3.4% and 36.7% vs. 12.9%, respectively, P < 0.05). A negative association between CagA positivity and esophagitis was observed (20% vs. 76.7%, P < 0.05). CONCLUSIONS: CagA positivity is common in HP-infected Turkish children. Esophageal lesions are less common in children infected with CagA-positive strains. Although HP is associated with duodenal ulcer disease, CagA positivity does not seem to contribute to development of ulcers in children in our series.