Artemis deficiency: A large cohort including a novel variant with increased radiosensitivity.

BACKGROUND: Artemis deficiency is an autosomal recessive disorder characterized by a combined immunodeficiency with increased cellular radiosensitivity. In this review, the clinical and genetic characteristics of 15 patients with DCLRE1C variants are presented. METHODS: The demographic, clinical, immunologic, and genetic characteristics of patients with confirmed DCLRE1C variants diagnosed between 2013 and 2023 were collected retrospectively. Three patients were evaluated for radiosensitivity by the Comet assay, compared with age- and sex-matched healthy control. RESULTS: Seven patients who had severe infections in the first 6 months of life were diagnosed with T-B-NK+ SCID (severe combined immunodeficiency). Among them, four individuals underwent transplantation, and one of those died due to post-transplant complications in early life. Eight patients had hypomorphic variants. Half of them were awaiting a suitable donor, while the other half had already undergone transplantation. The majority of patients were born into a consanguineous family (93.3%). Most patients had recurrent sinopulmonary infections (73.3%), and one patient had no other infection than an acute respiratory infection before diagnosis. Two patients (13.3%) had autoimmunity in the form of autoimmune hemolytic anemia. Growth retardation was observed in only one patient (6.6%), and no malignancy was detected in the surviving 11 patients during the median (IQR) of 21.5 (12-45) months of follow-up. Three patients who had novel variants exhibited increased radiosensitivity and compromised DNA repair, providing a potential vulnerability to malignant transformation. CONCLUSION: Early diagnosis, radiation avoidance, and careful preparation for transplantation contribute to minimizing complications, enhancing life expectancy, and improving the patient's quality of life.

Minipuberty period of children with atopic dermatitis compared to healthy children.

Background/aim: Atopic dermatitis (AD) is an inflammatory, pruritic, noncontagious, chronic relapsing skin disease. Skin barrier abnormalities, excessive T helper 2 activity, and immune dysregulation are held responsible. Androgens have a negative effect on the integrity of the epidermal skin barrier, while estrogen has a positive effect. We aimed to investigate whether hormones make a difference between healthy children and children with AD during minipuberty. Materials and methods: A total of 96 infants (postnatal 4-13 weeks), 48 diagnosed with AD and 48 controls, were included. Each group consisted of 23 girls (47.9%) and 25 boys (52.1%). Anthropometric examinations and hormone measurements were compared. Results: The two groups, having similar age, sex, body mass index, and weight-for-length standard deviation scores, were compared. Serum free thyroxine (FT4) levels were found to be lower and insulin-like growth factor binding protein-3 (IGFBP3) levels were found to be higher in children with AD (p < 0.001 and p = 0.038, respectively). In girls with AD, estradiol, FT4, and insulin-like growth factor-1 (IGF-1) levels were found to be lower, but thyroid-stimulating hormone (TSH) levels were found to be higher (p = 0.023, p < 0.001, p = 0.038, and p = 0.034, respectively). In boys with AD, the FT4 level was found to be lower (p = 0.023). Serum FT4 and TSH levels were within normal reference ranges in all comparisons. Conclusion: Especially in girls with AD, decreased estradiol and IGF-1 levels were observed compared to the controls during minipuberty. In the logistic regression model, decreased levels of serum estradiol, dehydroepiandrosterone sulfate, FT4, and IGF-1, and increased levels of IGFBP3 were associated with an increased likelihood of exhibiting atopic dermatitis.

Expanding the clinical and immunological phenotypes of PAX1-deficient SCID and CID patients.

Paired box 1 (PAX1) deficiency has been reported in a small number of patients diagnosed with otofaciocervical syndrome type 2 (OFCS2). We described six new patients who demonstrated variable clinical penetrance. Reduced transcriptional activity of pathogenic variants confirmed partial or complete PAX1 deficiency. Thymic aplasia and hypoplasia were associated with impaired T cell immunity. Corrective treatment was required in 4/6 patients. Hematopoietic stem cell transplantation resulted in poor immune reconstitution with absent naïve T cells, contrasting with the superior recovery of T cell immunity after thymus transplantation. Normal ex vivo differentiation of PAX1-deficient CD34+ cells into mature T cells demonstrated the absence of a hematopoietic cell-intrinsic defect. New overlapping features with DiGeorge syndrome included primary hypoparathyroidism (n = 5) and congenital heart defects (n = 2), in line with PAX1 expression during early embryogenesis. Our results highlight new features of PAX1 deficiency, which are relevant to improving early diagnosis and identifying patients requiring corrective treatment.

Genetic, Immunological, and Clinical Features of 32 Patients with Autosomal Recessive STAT1 Deficiency.

Autosomal recessive (AR) STAT1 deficiency is a severe inborn error of immunity disrupting cellular responses to type I, II, and III IFNs, and IL-27, and conferring a predisposition to both viral and mycobacterial infections. We report the genetic, immunological, and clinical features of an international cohort of 32 patients from 20 kindreds: 24 patients with complete deficiency, and 8 patients with partial deficiency. Twenty-four patients suffered from mycobacterial disease (bacillus Calmette-Guérin = 13, environmental mycobacteria = 10, or both in 1 patient). Fifty-four severe viral episodes occurred in sixteen patients, mainly caused by Herpesviridae viruses. Attenuated live measles, mumps, and rubella and/or varicella zoster virus vaccines triggered severe reactions in the five patients with complete deficiency who were vaccinated. Seven patients developed features of hemophagocytic syndrome. Twenty-one patients died, and death was almost twice as likely in patients with complete STAT1 deficiency than in those with partial STAT1 deficiency. All but one of the eight survivors with AR complete deficiency underwent hematopoietic stem cell transplantation. Overall survival after hematopoietic stem cell transplantation was 64%. A diagnosis of AR STAT1 deficiency should be considered in children with mycobacterial and/or viral infectious diseases. It is important to distinguish between complete and partial forms of AR STAT1 deficiency, as their clinical outcome and management differ significantly.

Serum sRAGE levels in children with atopic dermatitis: a prospective study.

Introduction: Atopic dermatitis (AD) is chronic inflammatory skin disorder. The receptor for advanced glycation end products (RAGE) plays a role in inflammatory reactions. The soluble form of RAGE (sRAGE) acts as a decoy to inhibit interactions of RAGE. Aim: To determine serum sRAGE levels in children with AD. Material and methods: AD diagnosis was made according to Hanifin and Rajka criteria. Disease severity was scored by the scoring atopic dermatitis (SCORAD) index. Skin prick testing (SPT), total immunoglobulin E (Ig E) and eosinophil counts were analysed. The sRAGE levels were determined using ELISA technique. Results: The children, aged 0.4 to 2.0 years with AD (n = 65) were investigated in two groups according to the presence (AD+/Atopy+ [n = 40]) or absence (AD+/Atopy- [n = 25]) of SPT positivity. The comparisons were made with a healthy control group matched for age and sex. The medians (interquartile range) of sRAGE levels in patient and control groups were 8.43 (1.04-18.37) and 14.09 (6.35-28.64), respectively (p < 0.001). The medians (interquartile range) of sRAGE levels in AD+/Atopy+, AD+/Atopy- and control groups were 8.5 (3.1-17.27), 7.75 (1.04-18.37) and 14.09 (6.35-28.64), respectively (p = 0.004). Correlation analysis failed to reach significance with the disease severity sRAGE levels, total IgE levels and eosinophil counts. Conclusions: To our knowledge, this is the first study investigating the association of sRAGE levels with AD and disease severity in childhood. Serum sRAGE levels are decreased in AD but not correlated with disease severity. sRAGE levels may be important in the AD disease process.

A Novel Intronic Mutation Reduces HAX1 Level and is Associated With Severe Congenital Neutropenia.

Severe congenital neutropenia (SCN) is a rare disease. Autosomal recessive forms of SCN are more frequent in countries where consanguineous marriages are common. In this report, we describe a 54-day-old female with neutropenia who presented with ecthyma gangrenosum. Clinical exome sequencing was used to identify the mutation. HAX1 messenger RNA and isoforms were examined by real-time quantitative and conventional polymerase chain reaction. Bone marrow aspiration was stained by hematoxylin and eosin. Granulocytes were tested for apoptosis upon H2O2 exposure. T-cell proliferation was tested by flow cytometry. Clinical exome sequencing revealed a novel homozygous acceptor splice site mutation in intron 3 of HAX1 (c.505-1G>C), which reduced both isoforms A and B of HAX1 messenger RNA. The Western blot studies showed a complete absence of HAX1 protein. The purified neutrophils from the patient showed increased apoptosis upon H2O2 exposure, whereas T-cell proliferative responses to various stimuli were intact. The patient was treated with combined antibiotics, filgrastim, and placed on antibiotics prophylaxis. To the best of our knowledge, our data provide the first experimental evidence for HAX1 deficiency because of a splice site mutation. Although 3 other splice site variants have been deposited in databases, functional studies were missing. This novel variant of HAX1 may explain the SCN and secondary infections in our patients.

Spirometry in children with asthma and/or allergic rhinitis: comparison of FEF25-75% with the standard measures.

BACKGROUND: Forced expiratory flow between 25% and 75% of vital capacity (FEF25-75%), a spirometric measure of small airways, may predict the presence of airway responsiveness both in asthmatics and in allergic rhinitis (AR). We aimed to search the correlation between FEF25-75% and standard measures of spirometry (forced expiratory volume in the first second [FEV1%] and FEV1/FVC [forced vital capacity]) in different clinical conditions, that is in children with asthma, in children with asthma and AR, in children with AR and in healthy children. METHODS: Children with asthma (N.=116), asthma plus AR (N.=25), AR (N.=75) and healthy controls (N.=52) were evaluated. Clinical examinations, spirometry and bronchodilation tests were performed. RESULTS: In asthmatics there was a strong correlation between FEF25-75% and FEV1% (r=0.596, P<0.001); and between FEF25-75% and FEV1/FVC (r=0.740, P<0.001). In AR patients correlation between FEF25-75% and FEV1% (r=0.367, P=0.001); and between FEF25-75% and FEV1/FVC (r=0.534, P<0.001) were less prominent compared to asthmatics but they were still significant and strong. In children with both AR and asthma correlation between FEF25-75% and FEV1% (r=0.633, P=0.001) and between FEF25-75% and FEV1/FVC (r=0.539, P=0.005) were again significant. Pre-test FEV1% and FEF25-75% in AR patients were lower than that of the control subjects. After the bronchodilation, percentage change in the FEV1 in AR patients were significantly higher than the control subjects (P=0.010). AR patients showed significant increases in FEV1%, (P<0.001), FEF25-75%, (P<0.001) and (P=0.001) after the bronchodilation test. Within the AR patients, only 12/75 (16.0%) showed bronchodilation with salbutamol. Among the ones with a FEF25-75% <65%, FEV1% was normal in 6/43 (14%) patients in asthmatics, and FEV1% was normal in 3/9 (33%) patients in asthma +AR patients. CONCLUSIONS: Besides the FEV1% and FEV1/FVC, the FEF25-75% may be a useful and early spirometric parameter to evaluate the children with asthma and or AR.

Factors that predict disease severity in atopic dermatitis: The role of serum basal tryptase.

BACKGROUND: Increased numbers of mast cells that contain tryptase are found in lesional atopic dermatitis (AD) skin. The association of serum basal tryptase (sBT) with anaphylactic reactions and mast cell diseases has recently been shown in children with venom and food allergy. OBJECTIVE: We aimed to identify the risk factors that predict the severity of AD and the association of sBT levels with AD and disease severity. METHOD: AD diagnosis was made according to Hanifin and Rajka criteria. Disease severity was scored by the objective scoring atopic dermatitis (SCORAD) index. The sBT levels were measured. Skin-prick testing, total immunoglobulin E, eosinophil percentages and counts, and a questionnaire concerning the history of atopic diseases and the risk factors of AD were applied. RESULTS: The children, ages 0.5 to 3.0 years, with AD (n = 85) were analyzed in two groups according to the presence (AD+/atopy+ [n = 55]) or absence (AD+/atopy- [n = 30]) of skin-prick test positivity. The comparisons were made with an age- and sex-matched control group (n = 82). The median (interquartile range) sBT in the AD+/atopy+, AD+/atopy-, and control groups were 5.01 ng/mL (2.75-6.79 ng/mL), 3.02 ng/mL (1.67-4.44 ng/mL), and 2.63 ng/mL (1.31-4.49 ng/mL), respectively (p = 0.003). The median (interquartile range) sBT levels were higher in patients with moderate-severe objective SCORAD index scores compared with the those with mild disease (3.85 ng/mL [2.04-5.91 ng/mL] versus 2.80 ng/mL [1.83-3.48 ng/mL]; p = 0.038). Multivariate logistic regression analysis showed that an sBT level of ≥3.9 ng/mL (odds ratio 8.77 [95% confidence interval, 1.87-41.18]; p = 0.006) was independently associated with an increased risk of moderate-severe AD (objective SCORAD index). CONCLUSION: To our knowledge, this was the first study that indicated that sBT levels may be important in the AD disease process and associated with the disease severity and atopy.

Increased plasma soluble human leukocyte antigen-G in persistent wheezy infants.

BACKGROUND: Human leukocyte antigen (HLA)-G is a non-classical major histocompatibility complex class I antigen characterized by limited polymorphism in its coding region, unique tissue expression pattern in physiologic conditions and immunomodulatory properties. Recently, the level of soluble (s)HLA-G was found to be higher in atopic asthma and allergic rhinitis, but this remains to be clarified in wheezy infants. The aim of the present study was therefore to investigate sHLA-G in wheezy infants. METHODS: The subjects consisted of infants with persistent wheezing and positive modified asthma predictive index (mAPI; n = 30; persistent group) and those with transient wheezing and negative mAPI (n = 17; transient group). sHLA-G was measured in plasma using enzyme-linked immunosorbent assay. Total immunoglobulin E (IgE) and eosinophil count were measured, and skin testing was performed with a battery of 13 antigens with appropriate positive and negative controls. RESULTS: sHLA-G was significantly higher in the persistent wheezing (positive mAPI) group compared with the transient wheezing (negative mAPI) group (P = 0.008). There was no significant difference in peripheral blood eosinophil count and total IgE between the groups. CONCLUSIONS: The increased sHLA-G in infants with persistent wheeze suggests that sHLA-G may be able to be used to distinguish persistent from transient wheeze. Further comprehensive studies are needed on this topic.

The plasma gelsolin levels in atopic dermatitis: Effect of atopy and disease severity.

BACKGROUND: Gelsolin is an actin-binding protein with several cellular functions including anti-apoptosis and is reported to have an anti-inflammatory effect. Apoptosis of keratinocytes has been implicated as a key mechanism of atopic dermatitis (AD). OBJECTIVE: We aimed to determine plasma gelsolin (pGSN) levels in children with atopic dermatitis (AD). METHOD: The diagnosis of AD was made according to Hanifin and Rajka criteria. The disease severity was scored by objective SCORAD index by the same allergist. Skin prick testing (SPT), total IgE levels, and eosinophil counts were analyzed. The pGSN levels were determined using ELISA technique. RESULTS: Children aged between 0.5 and 3.0 years were included in the study. The children with AD (AD; n=84) were analyzed in two groups according to the presence (AD+/Atopy+; n=54) or absence of SPT positivity (AD+/Atopy-; n=30). The comparisons were made with a healthy control group matched for age and sex (n=81). The median (interquartile range) of pGSN levels in AD+/A+, AD+/A- and control groups were 267µg/ml (236-368), 293 (240-498) and 547 (361-695), respectively (p<0.001). The difference between the control group and AD sub-groups remained significant after Bonferroni correction (p<0.001). Correlation analysis failed to reach significance with the disease severity total IgE levels and eosinophil counts. CONCLUSION: This is the first study investigating the association of pGSN levels with AD and disease severity. pGSN levels decreased in AD. These findings suggest that gelsolin may have a role in the disease process in AD patients.

Effect of montelukast on clinical score and cytokine levels of infants for clinically diagnosed acute bronchiolitis.

BACKGROUND: Acute bronchiolitis comprises a major cause for morbidity in infants with viral infection which induces an immune inflammatory response that may produce long lasting harmful effects. Currently, there is no effective therapy for bronchiolitis. OBJECTIVE: Our aim was to investigate the efficacy of five-day montelukast therapy in acute bronchiolitis management. METHODS: The study included 50 infants with acute bronchiolitis. The infants with first episode of acute bronchiolitis were randomly assigned to receive daily montelukast dose of 4mg over five days after admission or no treatment. Plasma eotaxin, IL-4, IL-8 and IFN-gamma levels were evaluated before and after treatment by ELISA method. In the present study, the primary outcome measure was change in clinical severity score, whilst secondary outcome measures were changes in plasma eotaxin, IL-4, IL-8, IFN-gamma levels. RESULTS: No significant differences was found in clinical severity score with five-day montelukast treatment (p>0.05, Mann-Whitney U test). There were no significant differences in plasma eotaxin, IL-4, IL-8, IFN-gamma levels between the groups (p>0.05 Mann-Whitney U test). There was significant decrease in plasma IFN-gamma levels following five-day montelukast treatment (p=0.027, Wilcoxon). There were no significant differences in plasma IL-4, IL-8, IFN-gamma levels between the groups after five-day montelukast treatment (p>0.05, Wilcoxon). There was significant increase in eotaxin levels after five-day montelukast treatment (p=0.009, Wilcoxon). CONCLUSION: Our study showed that montelukast affected plasma IFN-gamma and eotaxin levels after five days of treatment. Further studies are needed to demonstrate effects of montelukast on chemokine levels in bronchiolitis.

Hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) impair immunity and increase serum IgE levels.

BACKGROUND: Recurrent bacterial and fungal infections, eczema, and increased serum IgE levels characterize patients with the hyper-IgE syndrome (HIES). Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. However, glycosylation defects have not been described in patients with HIES. One crucial enzyme in the glycosylation pathway is phosphoglucomutase 3 (PGM3), which catalyzes a key step in the synthesis of uridine diphosphate N-acetylglucosamine, which is required for the biosynthesis of N-glycans. OBJECTIVE: We sought to elucidate the genetic cause in patients with HIES who do not carry mutations in STAT3 or DOCK8. METHODS: After establishing a linkage interval by means of SNPchip genotyping and homozygosity mapping in 2 families with HIES from Tunisia, mutational analysis was performed with selector-based, high-throughput sequencing. Protein expression was analyzed by means of Western blotting, and glycosylation was profiled by using mass spectrometry. RESULTS: Mutational analysis of candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families identified 2 homozygous mutations in PGM3 that segregated with disease status and followed recessive inheritance. The mutations predict amino acid changes in PGM3 (p.Glu340del and p.Leu83Ser). A third homozygous mutation (p.Asp502Tyr) and the p.Leu83Ser variant were identified in 2 other affected families, respectively. These hypomorphic mutations have an effect on the biosynthetic reactions involving uridine diphosphate N-acetylglucosamine. Glycomic analysis revealed an aberrant glycosylation pattern in leukocytes demonstrated by a reduced level of tri-antennary and tetra-antennary N-glycans. T-cell proliferation and differentiation were impaired in patients. Most patients had developmental delay, and many had psychomotor retardation. CONCLUSION: Impairment of PGM3 function leads to a novel primary (inborn) error of development and immunity because biallelic hypomorphic mutations are associated with impaired glycosylation and a hyper-IgE-like phenotype.

Decreased levels of lipoxin A4 and annexin A1 in wheezy infants.

OBJECTIVE: Wheezing is a common and challenging health issue in infancy and early childhood. Asthma diagnosis is frequent in patients with a history of recurrent wheezing. A relationship has been reported between asthma and anti-inflammatory mediators such as lipoxin A4 and annexin A1. However, this remains uncertain in wheezy infants. The aim of the present study was to determine lipoxin A4 and annexin A1 levels in wheezy infants. MATERIALS AND METHODS: Eighty-seven patients aged 6-36 months were included in this study. Demographic characteristics, clinical features, laboratory data, clinical diagnoses, and treatments, if present, were recorded. Patients were divided into 2 groups: patients with wheezing (n = 59) and healthy controls (n = 28). Blood samples were taken and lipoxin A4 and annexin A1 levels were evaluated by ELISA. RESULTS: Lipoxin A4 and annexin A1 levels were significantly lower in the wheezing group than in the control group (p < 0.05). A significant correlation was found between the serum total immunoglobulin E (IgE) level and the percentage and absolute number of eosinophils (p < 0.05). No significant correlation was found in terms of lipoxin A4 and annexin A1 levels, the serum total IgE level, and the percentage and absolute number of eosinophils among groups (p > 0.05). CONCLUSION: This is the first study to assess lipoxin A4 and annexin A1 levels in wheezy infants. The levels of lipoxin A4 and annexin A1 were found to be low in wheezy infants. We hope that these results will lead to novel therapeutic options for asthma in cases where an optimal treatment modality is lacking.

Is yoga training beneficial for exercise-induced bronchoconstriction?

BACKGROUND: Some studies have shown the beneficial effects of yoga for individuals with bronchial hyperreactivity with regard to (1) a reduction in the use of rescue medication, (2) an increase in exercise capacity, and (3) an improvement in lung function. Despite the fact that yoga is promising as a new treatment for pediatric patients, further studies are needed to assess the use of this training for asthma management. OBJECTIVE: This study was performed to assess the beneficial effects of yoga in exercise-induced bronchoconstriction (EIB) in children. DESIGN: The study was prospective, with no control group. Participants were randomly chosen among the new patients at the unit. SETTING: This study was conducted in the Erciyes University School of Medicine, Pediatric Allergy Unit, in Kayseri, Turkey. PARTICIPANTS: Two groups of asthmatic children aged 6-17 y were enrolled in the study: (1) children with positive responses to an exercise challenge (n = 10), and (2) those with negative responses (n = 10). INTERVENTION: Both groups attended 1-h sessions of yoga training 2 ×/wk for 3 mo. OUTCOME MEASURES: Researchers administered spirometric measurement to all children before and immediately after participating in an exercise challenge. This process was performed at baseline and at the study's end. Age, gender, IgE levels, eosinophil numbers, and spirometric measurement parameters including forced expiratory volume in 1 sec (FEV1), forced expiratory flow 25%-75% (FEF25%-75%), forced vital capacity (FVC), peak expiratory flow percentage (PEF%), and peak expiratory flow rate (PEFR) were compared using the Mann-Whitney U test and the Wilcoxon test. A P value < .05 was considered significant. RESULTS: At baseline, no significant differences were observed between the groups regarding demographics or pre-exercise spirometric measurements (P > .05, Mann-Whitney U test). Likewise, no significant differences in spirometric measurements existed between the groups regarding the change in responses to an exercise challenge after yoga training (P > .05, Wilcoxon test). For the exercise-response-positive group, the research team observed a significant improvement in maximum forced expiratory volume 1% (FEV1%) fall following the exercise challenge after yoga training (P > .05, Wilcoxon test). All exercise-response-positive asthmatics became exerciseresponse-negative asthmatics after yoga training. CONCLUSION: This study showed that training children in the practice of yoga had beneficial effects on EIB. It is the research team's opinion that yoga training can supplement drug therapy to achieve better control of asthma.

Gastric signet ring carcinoma in a patient with ataxia-telangiectasia: a case report and review of the literature.

Ataxia-telangiectasia (A-T) is an autosomal recessive primary immunodeficiency disease characterized by progressive cerebellar ataxia, telangiectasia, sinopulmoner recurrent infections, and cancer susceptibility. Individuals with A-T are known to be at increased risk of certain malignancies including leukemia, lymphoma, and breast and gastric cancer. We present an 18-year-old case of A-T with Hashimoto thyroiditis who admitted with complaints of nausea, vomiting, anorexia, and weight loss. An upper endoscopic biopsy revealed gastric signet ring cell carcinoma. To the best of our knowledge, we report the first case of signet ring cell carcinoma in the patient with A-T. Our experience with occurrence of Hashimoto thyroiditis and gastric signet ring cell carcinoma in the same case of A-T underlines that the clinicians handling A-T must be vigilant about both malignancy and autoimmune disorders.

cERBB-2/Her-2 Neu Overexpression and Prognostic Significance in Uterine Carcinosarcoma.

OBJECTIVE: There is not enough data in the literature regarding Her-2 overexpression in uterine carcinosarcomas or its association with the prognosis. The aim of this study was to determine the Her-2 overexpression rate in uterine carcinosarcoma and to evaluate its relationship with the prognosis. MATERIAL AND METHOD: Her-2 protein and gene status were evaluated by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), respectively, in hysterectomy specimens from 51 patients with uterine carcinosarcoma. RESULTS: Her-2 protein expression in the epithelial component was negative in 42 patients (score 0 in 33 cases, score (+1) in 9 cases), score (+2) in 7 patients and score (+3) in 2 patients. None of the patients had Her-2 protein expression within the sarcomatous component of the tumors. Her-2 gene was not amplified in epithelial or mesenchymal tumor areas according to the FISH method. There was no difference between the Her-2 overexpression negative and positive groups in terms of disease-free survival (DFS) and overall survival (OS). Her-2 overexpression was significantly higher in tumors of patients diagnosed at 65 years or older (p=0.046). CONCLUSION: In our study, no relationship could be shown between Her-2 overexpression and prognosis in uterine carcinosarcoma. More comprehensive studies are needed to illustrate the relationship between Her-2 overexpression and carcinosarcoma prognosis.

Cobalt-Free Layered LiNi0.8Mn0.15Al0.05O2/Graphene Aerogel Composite Electrode for Next-Generation Li-Ion Batteries.

In this work, we introduce LiNi0.8Mn0.15Al0.05O2 (NMA), which is cobalt-free and has a high nickel content, and a conductive composite material to NMA by supporting it with a three-dimensional (3D) graphene aerogel (GA). With an easy freeze-drying approach, NMA nanoparticles are properly dispersed on graphene sheets, and GA creates a strong and conductive framework, significantly improving the structure and conductivity. The structure of the pure NMA and NMA/graphene aerogel (NMA/GA) composite was investigated by X-ray diffraction (XRD) and field emission scanning electron microscopy (FE-SEM). XRD and FE-SEM analyses clearly indicated that ultrapure NMA structures are homogeneously dispersed among the GAs. In addition, the composite structure was examined using transmission electron microscopy (TEM) to determine the dispersion mechanisms. The electrochemical cycling performance of the pure NMA and NMA/GA composite was evaluated by rate capacitance, cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). The synthesized NMA/GA was able to provide 89.81% specific capacity retention after the 500th cycle at C/2. The average charge/discharge rates of the obtained cathode show good electrochemical results and exhibit capacities of 190.2,186.3, 185.2, 176.2, 161.2,142.6, and 188.5 mAh g-1 at C/20, C/10, C/5, C, 3C, 5C, and C/20, respectively. EIS data showed an improvement in the impedance of the composite containing GA. According to the results of the electrochemical tests, NMA nanoparticles formed a conductive network with its porous structure thanks to GA, formed a protective layer on the surface, prevented the side reactions between the cathode and the electrolyte, decreased the impedance of the cathode, and increased the redox kinetics. In addition, the changes in the structure were investigated in the NMA/GA composite cathode by XRD, FE-SEM, and Raman analyses at the end of the 50th, 250th, and 500th cycles. In summary, the NMA/GA cathode is expected to play an important role in lithium-ion batteries (LIBs) by taking advantage of its easy synthesis and excellent cycle stability.

Hashimoto thyroiditis associated with ataxia telangiectasia.

Ataxia telangiectasia is a rare genetic disease characterized by neurological manifestations, infections, and cancers. In addition to these cardinal features, different autoimmune diseases can be seen in patients with ataxia telangiectasia. Although there were reports of positive autoimmune thyroid antibodies associated with ataxia telangiectasia, to our knowledge, we report the first cases of nodular Hashimoto thyroiditis in two patients with ataxia telangiectasia in the English medical literature. These cases illustrate that despite the rarity of nodular Hashimoto thyroiditis associated with ataxia telangiectasia, physicians should be aware of this possibility. Furthermore, thyroid examination of patient with ataxia telangiectasia is recommended for early diagnosis.