Mejiavestergaard3860
Background Human leukocyte antigen G (HLA-G) belongs to non-classical MHC class I molecules that is involved in the suppression of immune response. As HLA-G plays important role in the maintenance of fetal tolerance, its overexpression has been associated with tumor progression. For the regulation of HLA-G levels, genetic variants within the 5' upstream regulatory region (5'URR) are of crucial importance. Our study aimed to analyze the association between 16 HLA-G 5'URR variants, sHLA-G level and clinical variables in glioma patients.Methods We investigated 59 patients with gliomas (mean age 54.70 ± 15.10 years) and 131 healthy controls (mean age 41.45 ± 9.75 years). Patient's blood was obtained on the day of surgical treatment. The HLA-G 5'URR polymorphisms were typed by direct sequencing and the plasma level of sHLA-G assessed by ELISA.Results Haploblock within HLA-G 5'URR consisting of -762 T, -716 G, -689 G, -666 T, -633 A, followed by -486 C and -201 A alleles were significantly more frequent in patients with gliomas than in the controls (p less then 0.05). No correlation of HLA-G 5'URR variants with sHLA-G plasma level was found. Analysis of HLA-G 5'URR variants with main clinical variables in patients with grade IV gliomas revealed that haploblock carriers of -762CT, -716TG, -689AG, - 666GT, -633GA, -486AC, -477GC, -201GA followed by -369AC carriers tend to have lower age at onset as compared to other genotype carriers (p = 0.04).Conclusion Our results suggest genetic association of HLA-G 5'URR variants with risk of developing gliomas and possible contribution of HLA-G to disease pathology.
Placenta accreta spectrum (PAS) is a group of placental invasion pathologies associated with significant morbidity to both mother and fetus. The majority of patients with PAS will require a blood transfusion at time of delivery and subsequent cesarean hysterectomy. PK11007 The optimal approach to maternal acute blood loss resuscitation is currently unknown.
Here, we present a cohort analysis of 34 patients with pathology-confirmed PAS treated with either whole blood (
= 16) or component therapy (
= 18) for initial intraoperative resuscitation.
We observed comparable results in post-operative outcomes with fewer overall transfusions and subsequently, lower volumes of resuscitation (
=.03) with whole blood initial resuscitation.
Whole blood transfusion may represent a viable option for initial resuscitation with lower resuscitation volumes and transfusion-associated complications without directly effecting post-operative outcomes in cases of PAS.
Whole blood transfusion may represent a viable option for initial resuscitation with lower resuscitation volumes and transfusion-associated complications without directly effecting post-operative outcomes in cases of PAS.The literature suggests that ethnicity affects live birth rate (LBR) and preterm birth (PTB) rate after fresh but not frozen embryo transfer (FET). We analysed 64,530 FET cycles from 2000 to 2016 using the Human Fertilisation and Embryology Authority (HFEA) database. Ethnicity was recorded for 43,735 as White British, 3,034 as Indian, 1,946 as Pakistani, 1,400 as Black African, 1,090 as White Irish, 520 as Chinese, 319 as Bangladeshi and 277 as Black Caribbean women. The LBR per FET when compared with White British women (26.1%) was significantly reduced in women of White Irish (23.4%; adjusted Odds Ratio (aOR) 0.85, 95% CI 0.73 to 1.00), Indian (25.2%; aOR 0.95, 95% CI 0.91 to 0.99), Bangladeshi (21.1%; aOR 0.87, 95% CI 0.79 to 0.95) and Pakistani (25.7%; aOR 0.97, 95% CI 0.94 to 0.99) ethnicities. The PTB rate, when compared with White British women (8.4%) was significantly higher for women of Indian (11.1%; aOR 1.38, 95% CI 1.06 to 1.79), Pakistani (11.8%; aOR 1.49, 95% CI 1.09 to 2.03) and White Irish (12.3%; aOR 1.55, 95% CI 1.01 to 2.38) ethnicities. This study suggests that FET outcomes are influenced by ethnicity.The ratio of T helper (Th) 17 and T regulatory (Treg) cells in patients with polycystic ovary syndrome complicated with autoimmune thyroiditis (PCOS-AIT) remains unreported. The study aimed to determine the Th17/Treg cell paradigm in PCOS-AIT patients. In peripheral blood mononuclear cells from PCOS patients and controls, the percentages of Th17 and Treg cells were measured by flow cytometry, the mRNA levels of a Th17-related transcription factor (ROR-γt) and a Treg-specific transcription factor (Foxp3) were determined by qRT-PCR, and the levels of Th17-related cytokines and Treg-related cytokines were measured by ELISA. Additionally, to examine the effect of testosterone on the Th17/Treg cell balance in vitro, cultured PCOS-AIT CD4+ T cells were treated with 10 μM testosterone for 24 h, and the Th17/Treg cell proportions and expression of Th17/Treg cell-associated transcription factors and cytokines were analyzed by flow cytometry, qRT-PCR, and ELISA. The Th17 cell percentage, Th17/Treg cell ratio, and expression of Th17-related ROR-γt and IL-17 were significantly higher in peripheral blood mononuclear cells from PCOS-AIT patients than in those from controls. In CD4+ T cells derived from PCOS-AIT patients, testosterone significantly decreased the Th17 cell percentage, Th17/Treg ratio, mRNA level of ROR-γt, and production of Th17-related cytokines and increased the Treg cell percentage, mRNA level of Foxp3, and secretion of Treg-related cytokines. The Th17/Treg cell imbalance favoring proinflammatory Th17 cells is involved in the pathogenesis of PCOS-AIT. Targeting the Th17/Treg cell axis may have therapeutic potential in the treatment of PCOS-AIT.Melanoma is the cause of most deaths from skin cancer. The extracellular signal-regulated kinase 1/2 (ERK1/2) pathway has been reported to participate in progression of melanoma in fair skinned populations. ERK1/2 is found in both the cytoplasm and nucleus of cells, and phosphorylated ERK1/2 has been implicated in tumor progression. We investigated the relation between melanoma progression and expression of cytoplasmic and nuclear phosphorylated ERK1/2. We examined 34 surgically resected melanomas and investigated their clinicopathologic characteristics. We found immunostaining of phosphorylated ERK1/2 in all melanomas and faint staining in benign nevi. We found expression of cytoplasmic phosphorylated ERK1/2 in most melanomas; however, nuclear phosphorylated ERK1/2 expression was found in only five melanomas. Expression of cytoplasmic phosphorylated ERK1/2 was related to the tumor stage in melanoma. Nine of 10 cases of distant metastasis were positive for cytoplasmic phosphorylated ERK1/2. Our findings suggest that phosphorylated ERK1/2 expression is relevant to clinical pathology and that in melanoma patients, phosphorylated ERK1/2 expression is found in both the cytoplasm and nucleus.