Syringic acid guards against indomethacin-induced gastric ulcer by alleviating inflammation, oxidative stress and apoptosis.

The purpose of this study was to evaluate the effects of syringic acid, an anti-oxidant, on indomethacin induced gastric ulcers in rats. Experimental groups were control, ulcer, ulcer treated with 20 mg/kg esomeprazole (a proton pump inhibitor that reduces acid secretion), and ulcer treated with 100 mg/kg syringic acid. Rats were pretreated with esomeprazole or syringic acid two weeks before ulcer induction. Our histopathological observations showed that either syringic acid or esomeprazole attenuated the severity of gastric mucosal damage. Moreover, syringic acid and esomeprazole pretreatments alleviated indomethacin-induced damage by regulating oxidative stress, inflammatory response, the level of transforming growth factor-ß (TGF-ß), expressions of COX and prostaglandin E2, cell proliferation, apoptosis and regulation of the NF-κB signaling pathway. We conclude that either esomeprazole or syringic acid administration protected the gastric mucosa from harmful effects of indomethacin. Syringic acid might, therefore be a potential therapeutic agent for preventing and treating indomethacin-induced gastric damage.

Prognostic gene biomarkers for c-Src inhibitor Si162 sensitivity in melanoma cells.

Background/aim: Early detection and treatment are crucial in combating malignant melanoma. Src is an important therapeutic target in melanoma due to its association with cancer progression. However, developing effective Src-targeting drugs remains challenging and personalized medicine relies on biomarkers and targeted therapies for precise and effective treatment. This study focuses on Si162, a newly synthesized c-Src inhibitor, to identify reliable biomarkers for predicting Si162 sensitivity and explore associated biological characteristics and pathways in melanoma cells. Materials and methods: Primary melanoma cells (M1, M21, M24, M84, M133, M307, and M2025) were obtained from patients diagnosed with melanoma. Si162 cytotoxicity tests were performed using luminescent adenosine triphosphate detection and the half-maximal inhibitory concentration (IC50) values were calculated. Gene expression profiles were analyzed using microarray-based gene expression data. Differentially expressed genes between the resistant and sensitive groups were identified using Pearson correlation analysis. Gene coexpression, interactions, and pathways were investigated through clustering, network, and pathway analyses. Biological functions were examined using the Database for Annotation, Visualization, and Integrated Discovery. Molecular pathways associated with different responses to Si162 were identified using gene set enrichment analysis. The gene expressions were validated using reverse transcription-quantitative polymerase chain reaction. Results: The cells revealed significant differences in response to Si162 based on the IC50 values (p < 0.05). A total of 36 differentially expressed genes associated with Si162 susceptibility were identified. Distinct expression patterns between the sensitive and resistant groups were observed in 9 genes (LRBA, MGMT, CAND1, ADD1, SETD2, CNTN6, FGF18, C18orf25, and RPL13). Coexpression among the differentially expressed genes was highlighted, and 9 genes associated with molecular pathways, including EMT, transforming growth factor-beta (TGF-ß) signaling, and ribosomal protein synthesis, between groups. Genes involved in dysregulated immune response were observed in the resistant group. The involvement of 5 genes (ADD1, CNTN6, FGF18, C18orf25, and RPL13) in Si162 resistance was confirmed through qRT-PCR validation. Conclusion: These findings contribute to our understanding of the underlying biological differences among melanoma cells and suggest potential biomarkers and pathways associated with Si162 response and resistance.

The Turkish version of nursing practice readiness scale: Cross-cultural adaptation and psychometric evaluation.

AIM: This study aims to adapt the "Nursing Practice Readiness Scale" to Turkish culture, and evaluate its psychometric properties. BACKGROUND: New graduates' nursing practice readiness can impact their work adaptation and performance. DESIGN: The research employed a methodological design. METHODS: Data were collected between May and July 2022. The sample consisted of 436 newly graduated nurses. Content validity, construct validity and criterion validity were evaluated. Reliability was examined with adjusted item-total correlation, Cronbach's a coefficient, composite-reliability and split-half reliability. RESULTS: The Turkish version of Nursing Practice Readiness Scale was found to have good content and criterion validity. As a result of confirmatory factor analysis, the original five-factor structure of the scale was also confirmed for the Turkish version. The scale's overall Cronbach's α coefficient was determined to be 0.96, with subscale coefficients ranging from 0.73 to 0.94. The composite reliability values of the subscales were found between 0.75 and 0.94. In split-half reliability, the correlation coefficient between half was 0.952, with a Spearman-Brown Coefficient (Unequal Length) of 0.976. CONCLUSIONS: The Turkish version of Nursing Practice Readiness Scale is a valid and reliable measurement tool for evaluating the nursing practice readiness of newly graduated nurses.

Relationship between care dependency, adverse events, trust in nurses and satisfaction with care: The mediating role of patient-reported missed care.

AIM: The aim of the study was to investigate the mediating effect of patient-reported missed care in the relationship between care dependency, adverse events, trust in nurses and satisfaction with nursing care. DESIGN: A cross-sectional and correlational study. METHODS: A total of 374 patients were recruited from the medical and surgical inpatient units of two public university hospitals in Türkiye using a convenience sampling method from May to August 2022. The data were collected using the Care Dependency Scale, MISSCARE Survey-Patient, Trust in Nurses Scale and Newcastle Satisfaction with Nursing Care Scale. The relationships between the variables were analysed using a sequential mediation model (Model 6) in Hayes' PROCESS macro. RESULTS: Care dependency was found to have a significant negative effect on misscare-communication; however, it had no significant effect on misscare-basic care. Misscare-communication had a significant positive effect on the experience of adverse events, while misscare-basic care had no significant effect. Misscare-communication and basic care had a significant negative effect on trust in nurses and satisfaction with nursing care. Misscare-communication was found to have a partial mediating effect on the relationship between care dependency and experiencing adverse events, trust in nurses and satisfaction with nursing care. CONCLUSION: The results emphasize the importance of misscare-basic care, communication and patients' care dependency in improving patient outcomes such as experiencing adverse events, trust in nurses and satisfaction with nursing care, and they extend existing nursing studies by addressing missed care and care dependency together from the perspective of patients. IMPACT: We urge nurse managers to consider the role of misscare in the impact of patients' level of care dependency on patient outcomes. Accordingly, nurse managers should focus first on interventions to eliminate misscare-communication. Effective interventions to address factors that impact communication and fulfilment of basic care are necessary to achieve better patient outcomes. REPORTING METHOD: EQUATOR guidelines were followed using the STROBE reporting method. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. Patients only contributed to data collection. Data were obtained from patients hospitalized in the medical and surgical inpatient units of two public university hospitals.

Opinions of emergency nurses in Turkey on their work environment during the COVID-19 pandemic and its relationship with their health: A qualitative study.

Introduction: COVID-19 patients being admitted to emergency service pose a high risk of exposure and infection to emergency nurses. Therefore, one of the primary responsibilities of hospital management is to provide an appropriate work environment for nurses. Aim: To analyze the opinions of emergency nurses about their work environment, and to understand how the working environment is related to their health during the COVID-19 pandemic. Methods: The study employed a qualitative descriptive research design and purposive sampling method. It was conducted in the emergency service of a state hospital in the central Anatolia region of Turkey, which was providing COVID-19 care at the time. The data were collected through semi-structured individual interviews held between January and February 2021. Each interview was conducted only once via WhatsApp video calls. Data collection was continued to reach data saturation (n:14). The data were analyzed using Colaizzi's seven-step content analysis. The Consolidated Criteria for Reporting Qualitative (COREQ) Studies checklist was followed in the study. Results: Three themes emerged in the analysis of the data obtained from a total of 14 emergency nurses: (a) "Insufficient Physical Environment"; (b) "Inadequacies in Managerial Roles and Skills"; and (c) "The Effect of the Work Environment on Nurses' Health". It was determined that the work environment of emergency nurses was inadequate in terms of resting areas, ventilation and separation of clean and infected areas, and they stated that they had not received adequate support from their managers and encountered difficulties due to equipment shortage, particularly in the early stages of COVID-19. It was also determined that the work environment caused psychological and ergonomic health issues. Conclusions: It is important to provide adequate managerial support and to make arrangements that resolve the physical and mental obstacles in improving the work environment of emergency nurses.

The probiotic-induced disregulation of immune-related genes in colon cells and relation with colorectal cancer.

Supplemental probiotics available without a doctor's prescription have become a booming global market in past few years. Medical research has shown that probiotics may benefit both healthy people and cancer patients by improving their immune systems and digestive health. Even though they seldom produce serious side effects, it's important to note that they are generally safe to use. But further investigation into the role of probiotics and gut microbes in the etiology of colorectal cancer is required. Here we used computational methods to identify the transcriptome alterations induced by probiotic treatment of colon cells. The impacts of genes with substantially altered expression were assessed in relation to the progression of colorectal cancer. Following probiotic treatment, substantial and high-level changes in the expression of genes were determined. BATF2, XCL2/XCL1, RCVRN and, FAM46B were up-regulated while IL13RA2, CEMIP, CUL9, Cand XCL6, PTCH2 were down-regulated in probiotic-treated colonic tissue and tumor samples. Also, immune-related pathways were determined that contribute to colorectal cancer formation and progression, as well as genes with opposing roles. This suggests that the length and dosage of probiotic use, in addition to the specific bacterial strain, maybe the most important determinants in the association between probiotics and colorectal cancer.

The clinical phenotype of Koolen-de Vries syndrome in Turkish patients and literature review.

Koolen-de Vries syndrome (KdVS) is a rare multisystemic disorder caused by a microdeletion on chromosome 17q21.31 including KANSL1 gene or intragenic pathogenic variants in KANSL1 gene. Here, we describe the clinical and genetic spectrum of eight Turkish children with KdVS due to a de novo 17q21.31 deletion, and report on several rare/new conditions. Eight patients from unrelated families aged between 17 months and 19 years enrolled in this study. All patients evaluated by a clinical geneticist, and the clinical diagnosis were confirmed by molecular karyotyping. KdVS patients had some common distinctive facial features. All patients had neuromotor retardation, and speech and language delay. Epilepsy, structural brain anomalies, ocular, ectodermal, and musculoskeletal findings, and friendly personality were remarkable in more than half of the patients. Hypertension, hypothyroidism, celiac disease, and postaxial polydactyly were among the rare/new conditions. Our study contributes to the clinical spectrum of patients with KdVS, while also provide a review by comparing them with previous cohort studies.

Pathobiological alterations affecting the distinct clinical courses of pediatric versus adult COVID-19 syndrome.

Background/aim: The clinical presentation of pediatric coronavirus disease 2019 (COVID-19) is associated with a milder disease course than the adult COVID-19 syndrome. The disease course of COVID-19 has three clinicobiological phases: initiation, propagation, and complication. This study aimed to assess the pathobiological alterations affecting the distinct clinical courses of COVID-19 in pediatric age groups versus the adult population. We hypothesized that critical biogenomic marker expressions drive the mild clinical presentations of pediatric COVID-19. Materials and methods: Blood samples were obtained from 72 patients with COVID-19 hospitalized at Ankara City Hospital between March and July 2021. Peripheral blood mononuclear cells were isolated using Ficoll-Paque and density-gradient sedimentation. The groups were compared using a t-test and limma analyses. Mean standardized gene expression levels were used to hierarchically cluster genes employing Euclidean Gene Cluster 3.0. The expression levels of identified genes were determined using reverse transcription-polymerase chain reaction. Results: This study found that ANPEP gene expression was significantly downregulated in the pediatric group (p < 0.05, FC: 1.57) and IGF2R gene expression was significantly upregulated in the adult group (p < 0.05, FC: 2.98). The study results indicated that the expression of critical biogenomic markers, such as the first-phase (ACE2 and ANPEP) and second-phase (EGFR and IGF2R) receptor genes, was crucial in the genesis of mild clinical presentations of pediatric COVID-19. ANPEP gene expression was lower in pediatric COVID-19. Conclusion: The interrelationship between the ANPEP and ACE2 genes may prevent the progression of COVID-19 from initiation to the propagating phase in pediatric patients. High IGF2R gene expression could potentially contribute to a protective effect and may be a contributing factor for the mild clinical course observed in pediatric patients.

Cerebrolysin Alleviating Effect on Glutamate-Mediated Neuroinflammation Via Glutamate Transporters and Oxidative Stress.

Glutamate, one of the most important excitatory neurotransmitters, acts as a signal transducer in peripheral tissues and endocrine cells. Excessive glutamate secretion has been shown to cause excitotoxicity and neurodegenerative disease. Cerebrolysin is a mixture of enzymatically treated peptides derived from pig brain including neurotrophic factors, like brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), and ciliary neurotrophic factor (CNTF). The present study investigated the protective effects of cerebrolysin on glutamate transporters (EAAT 1, EAAT 2) and cytokines (IL-1ß and IL-10) activity in glutamate-mediated neurotoxicity. Primary cortex neuron culture was exposed to glutamate and successively treated with various cerebrolysin concentrations for 24 and 48 h. Our data showed that cerebrolysin primarily protects neurons by decreasing glutamate concentration in the synaptic cleft. In addition, Cerebrolysin can decrease oxidative stress and neuron cell damage by increasing antioxidant activity and decreasing inflammation cytokine levels.

NK-cell dysfunction of acute myeloid leukemia in relation to the renin-angiotensin system and neurotransmitter genes.

Acute myeloid leukemia (AML) is the most heterogeneous hematological disorder and blast cells need to fight against immune system. Natural killer (NK) cells can elicit fast anti-tumor responses in response to surface receptors of tumor cells. NK-cell activity is often impaired in the disease, and there is a risk of insufficient tumor suppression and progression. The aim of this study is to assess the dysfunction of NK cells in AML patients via focusing on two important pathways. We obtained single-cell RNA-sequencing data from NK cells obtained from healthy donors and AML patients. The data were used to perform a wide variety of approaches, including DESeq2 (version 3.9), limma (version 3.26.8) power differential expression analyses, hierarchical clustering, gene set enrichment, and pathway analysis. ATP6AP2, LNPEP, PREP, IGF2R, CTSA, and THOP1 genes were found to be related to the renin-angiotensin system (RAS) family, while DPP3, GLRA3, CRCP, CHRNA5, CHRNE, and CHRNB1 genes were associated with the neurotransmitter pathways. The determined genes are expressed within different patterns in the AML and healthy groups. The relevant molecular pathways and clusters of genes were identified, as well. The cross-talks of NK-cell dysfunction in relation to the RAS and neurotransmitters seem to be important in the genesis of AML.

Effects of boric acid and potassium metaborate on cytokine levels and redox stress parameters in a wound model infected with methicillin­resistant Staphylococcus aureus.

Methicillin­resistant Staphylococcus aureus (MRSA) infections are usually found in hospital settings and, frequently, in patients with open wounds. One of the most critical virulence factors affecting the severity and recurrence of infections is the biofilm; increasing antibiotic resistance due to biofilm formation has led to the search for alternative compounds to antibiotics. The present study aimed to use boric acid and potassium metaborate against MRSA infection in a fibroblast wound model. For this purpose, a two­part experiment was designed: First, MRSA strains were used for the test, and both boric acid and potassium metaborate were prepared in microdilution. In the second step, an MRSA wound model was prepared using a fibroblast culture, and treatments with boric acid and potassium metaborate were applied for 24 h. For the evaluation of the effects of treatment, cell viability assay (MTT assay), analysis of redox stress parameters, including total oxidant status and total antioxidant capacity analyses, lactate dehydrogenase analysis and immunohistochemical staining were performed. In addition, IL­1ß and IL­10 gene expression levels were assayed. According to the results, potassium metaborate was more effective and exhibited a lower toxicity to fibroblast cells compared to boric acid; moreover, potassium metaborate decreased the level of prooxidant species and increased the antioxidant status more effectively than boric acid. The IL­1ß level in the bacteria group was high; however, boric acid and potassium metaborate significantly decreased the expression levels of inflammatory markers, exhibiting the potential to improve the resolution of the lesion. On the whole, the findings of the present study suggest that boric acid and potassium metaborate may be effective on the tested microorganisms.

Technical note: A novel 3D scan-based optical method for analyzing lines drawn at different pen pressure.

Pen pressure is one of the important elements of handwriting and questioned document analysis which is also crucial to recognize forgery. In this paper, we present a new, non-contact, non-destructive, and relatively inexpensive technique to measure the width of the grooves made by the writing. Results demonstrate a clear difference in measured groove widths for varying pen pressure. The effect of passing a written or signed paper in different types of printers has also been studied. A clear decrease of the groove depth was noted when passing the document through a laser printer. An ink jet printer only resulted in a small decrease of the groove depth, while no effect could be detected from a dot matrix printer.

Ulipristal-temozolomide-hydroxyurea combination for glioblastoma: in-vitro studies.

BACKGROUND: Glioblastoma multiforme (GBM) is a brain malignancy with worst survival. Low dose progesterone stimulates GBM growth, while progesterone receptor (PR)-antagonist mifepristone was shown to reduce growth and to enhance temozolomide sensitivity in GBM cells. Mifepristone is not available in all countries due to ethical reasons and may cause adrenal insufficiency and pelvic infections. Ulipristal is also a PR-antagonist used in treatment of uterine leiomyomas with higher biosafety. Ulipristal is demonstrated to suppress growth of breast cancer, yet it is not tested as yet whether it can also block growth and sensitize to temozolomide in glioblastoma as it was previously shown with mifepristone. Our first aim was to detect whether ulipristal exerts antiproliferative and chemotherapy-sensitizing effects in glioblastoma. Hydroxyurea inhibits DNA replication via blocking ribonucleotide reductase (RR) and it was demonstrated to increase temozolomide antineoplasticity in GBM. Progesterone receptor-activation in the uterus enhances RR transcription. Hence, we have hypothesized that PR-inactivation with ulipristal would further enhance hydroxyurea antineoplasticity by shutting down DNA synthesis mechanisms through further suppression of RR. Lastly, there exists no study as yet whether ulipristal, hydroxyurea and temozolomide could exert ternary antineoplastic efficacy, which was our last aim to define. METHODS: To reveal interactions between ulipristal, hydroxyurea and temozolomide, we treated human U251 GBM cell line with these agents alone and in combination and measured cell proliferation, total antioxidant capacity (TAC) and total oxidant status (TOS) in conditioned medium and cellular cytokine gene expressions. RESULTS: All agents significantly reduced cell proliferation significantly, yet the most significant decrease of GBM cells occured with the triple drug combination at the 96th hour. All agents significantly decreased TAC and increased TOS in culture media, which was mostly relevant for the triple combination at the 96th hour. All these 3 agents tend to reduce the expression of immunosuppressive and/or GBM-growth stimulating cytokines TGFß, IL-10 and IL-17 while increasing the expression of GBM-growth suppressing cytokine IL-23. CONCLUSIONS: Repurposal of these agents in treatment of GBM would be a plausible approach if future studies prove their efficacy.

Professional and psychological perceptions of emergency nurses during the COVID-19 pandemic: A qualitative study.

AIM: To explore the changing roles and responsibilities, difficulties, feelings, and coping strategies of emergency nurses during the COVID-19 pandemic. METHODS: This study was conducted as a qualitative study using a phenomenological approach. A total of 12 emergency nurses were recruited using purposive sampling from a COVID-19-designated hospital in Konya, Turkey for qualitative study. Data were collected through semi-structured individual interviews in January 2021. The data were analyzed using the content analysis method with the MAXQDA 2020 software program. The study conforms to the consolidated criteria for reporting qualitative research checklist. RESULTS: Four theme categories emerged from the data analysis: (a) "Increasing roles and responsibilities as an emergency nurse"; (b) "Difficulties of working in pandemic conditions"; (c) "Emotional responses in the pandemic"; and (d) "Strategies for coping with the effects of the pandemic". In this study, it was determined that emergency nurses had increased roles and responsibilities due to physicians being in the background, fulfilled their roles and responsibilities in a chaotic working environment, experienced many positive and negative feelings together or gradually, and applied individual coping strategies. CONCLUSIONS: This study indicated that emergency nurses fulfilled their increasing roles and responsibilities on the frontlines in a chaotic working environment during the pandemic. Despite many negative feelings, it was determined that they tried to show psychological adjustment and resilience with a strong professional commitment and social support.

UVC-LED-based face mask design and efficacy against common germs.

During the Covid-19 pandemic, one of the best means of personal protection was using face masks. In this context, the World Health Organization has declared the attempts to produce masks inactivating airborne virus species a welcome initiative. This preliminary study aimed to prove that airborne germs passing through a mask filter cartridge can be destroyed by the rays emitted from UVC LEDs placed in such cartridge. We therefore designed such a face mask and tested the efficiency of UVC LEDs placed in its cartridge against common contaminants, gram-positive Staphylococcus aureus, gram-negative Pseudomonas aeruginosa, and the influenza A/Puerto Rico/8/1934 virus because of its similarity with SARS CoV-2. Eight UVC LEDs with a total power of 75 mW provided sufficient germicidal effect for all three germs. In terms of safety, ozone production released during UVC LED emission was negligible. Our findings are promising, as they show that well-designed UVC-based face masks can be effective against airborne germs, but further research on a greater sample may help us learn more and optimise such face masks.

Neuroprotective effect of bromelain in 6-hydroxydopamine induced in vitro model of Parkinson's disease.

BACKGROUND: This study was designed to investigate the neuroprotective effects of bromelain, which is known to have anti-oxidant and anti-inflammatory properties, against the neurotoxicity (induced by 6-OHDA) in SH-SY5Y cells. METHODS AND RESULTS: To establish Parkinson's Disease (PD) model in cell culture conditions, SH-SY5Y cells were exposed to 200 µM 6-OHDA for 1 day. Prior to 6-OHDA treatment, SH-SY5Y cells had been pre-treated with bromelain (25 µg/mL, 50 µg/mL, 75 µg/mL and 100 µg/mL). After 1 day, cell viability was determined with the 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) and lactate dehydrogenase (LDH) assays. Oxidative stress was assessed with total antioxidant capacity (TAC), total oxidant status (TOS), glutathione reductase (GR) and malondialdehyde (MDA) analyses. The effect of the bromelain in SH-SY5Ycells was also examined by 4',6-diamidino-2-phenylindole (DAPI) staining. We found that 6-OHDA increased LDH leakage, and cellular apoptosis in SH-SY5Y cells. 6-OHDA aggravated oxidative stress by increasing TOS, MDA and GR and eventually promoted apoptosis in SH-SY5Y cells, while pretreatment with bromelain attenuated these toxic effects of 6-OHDA. CONCLUSIONS: These findings indicated that bromelain, with its neuroprotective features can be useful for neuroprotection in PD.

Assessment of seroprevalence of Toxoplasma gondii in blood donors applied to the blood center of Gazi university hospital.

BACKGROUND AND OBJECTIVES: Toxoplasmosis is a life-threatening zoonotic infection in immunosuppressive individuals. Determining the prevalence and seropositivity rates of toxoplasmosis in asymptomatic blood donors is crucial in terms of the risk status of the transmission of this infection to the blood recipients. MATERIALS AND METHODS: In this study, the presence and level of the specific Toxoplasma IgG and IgM antibodies in blood donors was investigated by electrochemiluminescence immunoassay (ECLIA). The statistical significance levels between Toxoplasma seropositivity and demographic characteristics of the donors such as age, educational status, raw meat consumption, drinking water supply were examined. RESULTS: Toxoplasma IgG seropositivity was found among the 225 (25.6%) of the donors present in the study group, while IgM seropositivity was detected in 20 donors (2.3%). The number of donors with only IgM (+) was 8 (0.9%). Both IgG and IgM seropositivities were found in 12 donors (1.4%). CONCLUSION: Our study provides information about Toxoplasma seropositivity based on the samples collected from the donors who were admitted to the blood center of a university hospital in Ankara, Turkey. This study demonstrates that Toxoplasma seropositivity is high in the rural areas and the regions where the education level is low.

Effectiveness of Canakinumab Treatment in Colchicine Resistant Familial Mediterranean Fever Cases.

Anti-interleukin 1 agents are used successfully in colchicine-resistant or intolerant Familial Mediterranean Fever (FMF) patients. Sixty-five patients with FMF who received canakinumab treatment for at least 6 months due to colchicine resistance or intolerance between 2016 and 2020 in our department were retrospectively analyzed. Canakinumab treatment was given subcutaneously every 4 weeks. After completing monthly canakinumab therapy over 12 months, in patients with complete remission, the dosing interval was extended to every 1.5 months for 6 months, then every 2 months for 6 months, and finally every 3 months for a year. In patients without disease activation, canakinumab treatment was discontinued at the end of 3 years and followed up with colchicine treatment. Patients who had a flare switched to the previous dosing interval. In patients with renal amyloidosis, monthly canakinumab treatment was continued without extending the dose intervals. The mean duration of canakinumab use in our patients was 31.4 ± 10.57 months (6-52 months). The mean age at onset of symptoms was 4.65 ± 3.84 (range, 1-18) years, and the mean age at diagnosis was 5.59 ± 3.9 (range, 4-19) years. Complete remission was achieved in 57 (87.6%) and partial remission in seven (10.7%) patients. One patient was unresponsive to treatment. Canakinumab treatment was discontinued in three patients with complete remission and one patient with drug resistance. Erythrocyte sedimentation rate (ESR) (51.85 ± 15.7 vs. 27.80 ± 13.73 mm/h) and C-reactive protein (CRP) [26 (3-73) vs. 5 (1-48) mg/L] values were compared before and after canakinumab treatment in attack-free periods, a significant decrease was found after canakinumab treatment (p < 0.001, p < 0.001, respectively). Bodyweight Z-scores (respectively -0.80 ± 0.86 vs. -0.49 ± 0.92) were compared, similarly, a statistically significant increase after canakinumab treatment (p < 0.001), but no significant increase in height Z scores (-1.00 ± 0.88 vs. -0.96 ± 0.94) (p = 0.445) was detected. Four patients had FMF-related renal amyloidosis. The decrease in proteinuria with canakinumab treatment was not statistically significant (p = 0.068). Cervical lymphadenitis developed in one and local reactions in two patients. No severe adverse effects requiring discontinuation of canakinumab treatment were observed. Our study showed that canakinumab treatment was highly effective, well-tolerated in pediatric FMF patients, and controlled extension of the canakinumab dose interval was safe.

Novel MTTP Gene Mutation in a Case of Abetalipoproteinemia with Central Hypothyroidism

Abetalipoproteinaemia (ABL) is an autosomal recessive disorder characterized by very low plasma concentrations of total cholesterol and triglyceride (TG). It results from mutations in the gene encoding microsomal TG transfer protein (MTTP). A nine-month-old girl was admitted to hospital because of fever, cough, diarrhea and failure to thrive. She had low cholesterol and TG levels according to her age. The peripheral blood smear revealed acanthocytosis. Thyroid function test showed central hypothyroidism. Cranial magnetic resonance imaging revealed the retardation of myelination and pituitary gland height was 1.7 mm. A homozygous novel mutation [c.506A>T (p.D169V)] was detected in the MTTP gene. Vitamins A, D, E, and K and levothyroxine were started. The coexistence of ABL and central hypothyroidism has not previously been reported. A homozygous novel mutation [c.506A>T (p.D169V)] was detected in the MTTP gene.

A Skeptical Approach to the Management of Persistent Oral Ulceration in a Child.

The diagnosis of oral lesions is sometimes difficult due to both the clinician's limited experience with the conditions that may cause the lesions and their similar appearances, especially in children. Correctly establishing a definitive diagnosis is of major importance to clinicians who manage patients with oral mucosal diseases. In patients with Fanconi anaemia (FA), oral ulcers occur frequently, which are quite variable, and may lead to a misdiagnosis or failure to diagnose. Here, we report the case of a 15-year-old boy who was examined for squamous cell cancer of the tongue and diagnosed as having FA without any haematological manifestations. While surgery could not be done, both radiotherapy and chemotherapy had to be decreased. He died of progressive disease 6 months after the diagnosis. Unexplained ulcers in a child with a duration longer than 2 weeks should be further evaluated, especially for FA, even without the presence of anaemia.