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

Volume CXIV, Number 4, November 7, 1996

Objective: Turner syndrome (TS) is a chromosomal disorder caused by complete or partial X chromosome monosomy that manifests various clinical features depending on the karyotype and on the genetic background of affected girls. This study aimed to systematically investigate the key clinical features of TS in relationship to karyotype in a large pediatric Turkish patient population.Methods: Our retrospective study included 842 karyotype-proven TS patients aged 0-18 years who were evaluated in 35 different centers in Turkey in the years 2013-2014.Results: The most common karyotype was 45,X (50.7%), followed by 45,X/46,XX (10.8%), 46,X,i(Xq) (10.1%) and 45,X/46,X,i(Xq) (9.5%). Mean age at diagnosis was 10.2±4.4 years. The most common presenting complaints were short stature and delayed puberty. Among patients diagnosed before age one year, the ratio of karyotype 45,X was significantly higher than that of other karyotype groups. Cardiac defects (bicuspid aortic valve, coarctation of the aorta and aortic stenosis) were the most common congenital anomalies, occurring in 25% of the TS cases. This was followed by urinary system anomalies (horseshoe kidney, double collector duct system and renal rotation) detected in 16.3%. Hashimoto's thyroiditis was found in 11.1% of patients, gastrointestinal abnormalities in 8.9%, ear nose and throat problems in 22.6%, dermatologic problems in 21.8% and osteoporosis in 15.3%. Learning difficulties and/or psychosocial problems were encountered in 39.1%. Insulin resistance and impaired fasting glucose were detected in 3.4% and 2.2%, respectively. Dyslipidemia prevalence was 11.4%.Conclusion: This comprehensive study systematically evaluated the largest group of karyotype-proven TS girls to date. The karyotype distribution, congenital anomaly and comorbidity profile closely parallel that from other countries and support the need for close medical surveillance of these complex patients throughout their lifespa

Tümör mikroçevresinde ve tümörde etkin yolakların glioma seyrindeki rolü

Amaç: Glial hücrelerin farklılaşması sonucu oluşan gliomada bir çok yolak etkilidir. Hücre proliferasyonunda etkili olan Hippo yolağıdır bunlardan biridir. Çalışmamızın amacı HGG ve LGG dokularında ve mikro çevresinde Hippo yolağı üzerinden metastazda etkin LATS2 (Large Tumor Suppressor Kinase 2 ve proliferasyonda etkili olan WWTR1 (WW Domain Containing Transcription Regulator) ve hücre adezyonunda etkili aşağı yöndeki CYR61 (Cysteine-rich angiogenic inducer 61) genlerinin ekspresyonlarını karşılaştırmalı olarak saptamaktır.Gereç ve Yöntem: Çalışmaya Marmara Üniversitesi Eğitim Araştırma Hastanesi Beyin ve Sinir Cerrahisi AD’ de opere olan beş adet LGG (yaş: 47,2±17,9) ve sekiz adet HGG (yaş: 60±10,06) hastası dahil edildi. Dokulardan mRNA izolasyonu ardından cDNA’ya sentezi gerçekleştirildi. RT-qPCR yöntemiyle SYBR green kullanılarak yapılan çalışmada hedef genlerin ekspresyonları BioRad CFX 96 cihazında analiz edildi. İç kontrol olarak ACTB (B Actin) geni kullanıldı. Genlerin HGG’lerde LGG’lere oranla kat artışları 2^–∆∆Ct metoduyla GeneGlobe Software’de analiz edildi. Bulgular: LGG ve HGG örneklerinin gen ekspresyonları birbirlerine göre analiz edildiğinde CYR61’in ekspresyon değerleri HGG örneklerinde 3,09 kat yüksek bulundu. LATS2 ve WWTR1’in ekspresyonlarında anlamlılık saptanmadı. GBM tümörü ve tümör mikroçevresinin ekspresyonları karşılaştırıldığında tümörde LATS2’nin ekspresyonu azalırken CYR61 ve WWTR1’in arttığı saptandı. Yapılan regresyon analizlerinde ve demografik olgularda da istatiksel anlamlı sonuçlar elde edilmedi. Sonuç: CYR61, epitel-mezenkimal dönüşümü sağlayarak olarak glioma gelişimine neden olur. Çalışmamızda HGG hastalarımızda saptanan bu bulgu, tümörün GBM’e dönüşebilme kapasitesi olduğunu göstermektedir. Tümörde olduğu gibi tümör mikroçevresinde de gen ekspresyon analizlerinin yapılması klinik seyir hakkında bilgi verebilecek önemli bir analiz aracı olmalıdır.Objective: Many pathways are effective in glioma formed because of differentiation of glial cells. Proliferation related Hippo pathway is one of them. Objective of our study is to express genes of LATS2(Large Tumor Suppressor Kinase 2), which effects metastasis, WWTR1(WW Domain Containing Transcription Regulator) that changes proliferation, and downstream CYR61(Cysteine-rich angiogenic inducer 61), which alters cell adhesion in HGG&LGG tissues and microenvironment via Hippo pathway.Material and Methods: Five LGG (age: 47.2±17.9) and eight HGG (age: 60±10.06) patients who were operated in Marmara University Training and Research Hospital, Department of Neurosurgery were included. mRNA isolation and cDNA synthesis were performed. SYBR green with RT-qPCR method was used, expressions of genes were analyzed in BioRad CFX 96 device. ACTB (B Actin) gene was used as internal control. Fold increase of genes in HGGs compared to LGGs was analyzed with 2^–∆∆Ct method. Results: When gene expressions of LGG&HGG samples were analyzed, expression values of CYR61 were found 3.09 times higher in HGGs. Expressions of LATS2 and WWTR1 were not significant. When expressions of GBM tumor and tumor microenvironment were compared, it was found that expression of LATS2 in tumor decreased, while CYR61 and WWTR1 increased. No statistically significant results were obtained. Conclusion: CYR61 leads glioma by providing epithelial-mesenchymal transformation. This finding, which was found in our study, shows that tumor has capacity to transform into GBM. Gene expression analyzes in tumor microenvironment as well as in the tumor should be an important analysis tool that can provide information about clinical course

Isotropic Riemannian submersions

WOS:000590703900015In this paper, we present the notion of isotropic submersions between Riemannian manifolds. We first give examples to illustrate this new notion. Then we express a characterization in terms of O'Neill's tensor field T and examine certain relations between sectional curvatures of the total manifold and the base manifold. We also study lambda-isotropic submersions with pointwise planar horizontal sections

The predictive value of halp score and systemic immune inflammation (sii) index in hyperemesis gravidarum

Aim: Hyperemesis gravidarum (HG) is one of the most common serious diseases in early pregnancy. This study aimed to investigate the clinical significance of hemoglobin, albumin, lymphocyte, and platelet (HALP) score and systemic immune inflammation (SII) index in the presence and severity of HG.Methods: This retrospective case-control study was conducted in a training and educational university hospital between January 2019 and July 2022. A total of 521 pregnant women, of whom 360 were diagnosed with HG at 6-14 weeks of gestation and 161 were low-risk pregnancies, were included in the study. Patients' demographic characteristics and laboratory parameters were recorded. Patients with HG were divided into three categories: mild (n = 160), moderate (n = 116), and severe (n = 84), according to disease severity. The modified PUQE scoring was used to determine the severity of HG.Results: The mean age of the patients was 27.6 (16-40) years. We divided the pregnant women into the control group and HG group. The HALP score was significantly lower in the HG group (average, 2.8 +/- 1.3), whereas the SII index was found to be significantly higher (average, 895.8 +/- 458.1). A negative correlation was found between the increase in the severity of HG and HALP score. The HALP score was the lower in severe HG (mean, 2.16 +/- 0.81) and was significantly different from other HG categories (p < 0.01). Moreover, a positive correlation was noted between increased HG severity and SII index levels. The SII index was higher in the severe HG group and was significantly different from the others (1001.2 +/- 437.2) (p < 0.01).Conclusions: The HALP score and SII index can be useful, cost-effective, and easily accessible objective biomarkers to predict the presence and severity of HG

Norden Golden Manifolds with Constant Sectional Curvature and Their Submanifolds

This paper discusses the Norden golden manifold having a constant sectional curvature. First, it is shown that if a Norden golden manifold has a constant real sectional curvature, the manifold is flat. For this reason, the notions of holomorphic-like sectional curvature and holomorphic-like bisectional curvature on the Norden golden manifold are investigated, but it is seen that these notions do not work on the Norden golden manifold. This shows the need for a new concept of sectional curvature. In this direction, a new notion of sectional curvature (Norden golden sectional curvature) is proposed, an example is given, and if this new sectional curvature is constant, the curvature tensor field of the Norden golden manifold is expressed in terms of the metric tensor field. Since the geometry of the submanifolds of manifolds with constant sectional curvature has nice properties, the last section of this paper examines the semi-invariant submanifolds of the Norden golden space form