The maternal 14 bp Ins/Del polymorphism in HLA‐G is not associated with preeclampsia risk

The effect of HLA‐G 14 bp Ins/Del polymorphism (rs371194629) on the risk of preeclampsia has been assessed in several populations, yet the results are still conflicting. Lack of power due to small sample sizes is a common cause of inconsistencies in genetic association studies. We aimed to test whether the maternal polymorphism is associated with preeclampsia, eclampsia or HELLP syndrome (acronym for Hemolysis, Elevation of Liver enzymes, Low Platelets). To achieve a statistical power greater than 0.90, a total of 741 women (332 controls, 246 preeclampsia, 57 eclampsia and 106 HELLP) were genotyped for the 14‐bp Ins/Del polymorphism. The genetic association with disease status was assessed by Fisher's exact test and odds ratio (OR) estimates using logistic regression model adjusted for maternal age and parity status. Allele and genotype distributions were the same between control and case groups (p > .05). The polymorphism was not associated with the risk of developing preeclampsia [OR = 0.93 (0.72–1.19); p = .541], or eclampsia [OR = 0.90 (0.60–1.38); p = .628] nor HELLP syndrome [OR = 0.92 (0.66–1.28); p = .628]. This well‐powered study clearly demonstrates that the maternal HLA‐G 14‐bp Ins/Del polymorphism is not associated with preeclampsia risk. However, as the offspring genotypes were not evaluated here, we could not rule out the effect of the foetal genotype on the preeclampsia pathogenesis.     

Podoplanin,ezrin, and Rho-A proteins may have joint participation in tumor invasion of lip cancer

Introduction

Podoplanin and ezrin connection through Rho-A phosphorylation have been suggested as part of the activation pathway, in the process of tumor invasion and cell movement in oral squamous cell carcinomas.

Objective

The aim of this study was to evaluate the correlation among podoplanin, ezrin, and Rho-A immunoexpressions in 91 squamous cells carcinomas of the lower lip and their influence in patient’s prognosis.

Material and methods

The immunoexpressions of podoplanin, ezrin, and Rho-A were evaluated through a semi-quantitative score method, based on the capture of 10 microscopic fields at the front of tumor invasion. The association and correlation of these proteins with the clinicopathological features were verified by Fischer’s exact test and Spearman’s test. The prognostic values were analyzed by Kaplan-Meier method and log-rank test.

Results

A statistically significant association between strong cytoplasmic podoplanin expression and alcohol (p = 0.024), loco-regional recurrences (p = 0.028), and lymph node metastasis (pN+) (p = 0.010) was found. The membranous (p = 0.000 and r = 0.384) and cytoplasmic (p = 0.000 and r = 0.344) podoplanin expression was statistically correlated with ezrin expression. Also, membranous podoplanin was significantly correlated with Rho-A expression (p = 0.006 and r = 0.282). The expressions of podoplanin, ezrin, and Rho-A were not significant prognostic factors for patients with squamous cell carcinomas of the lower lip.

Conclusions

Therefore, our results confirm a correlation among podoplanin, ezrin, and Rho-A expressions in squamous cell carcinoma of the lip suggesting a cooperative participation of these proteins in cell movement and invasion.

Clinical relevance

Furthermore, strong cytoplasmic podoplanin expression could be helpful to identify patients with squamous cell carcinoma of the lip and lower risk of loco-regional recurrences.

     

A good manufacturing practice method to ex vivo expand natural killer cells for clinical use

BackgroundGreat interest has been raised recently by the design of new adoptive immunotherapeutic strategies based on the in vivo infusion of ex vivo-expanded and activated natural killer (NK) cells. The development of good manufacturing practice (GMP) methods for the efficient production of fully functional NK cells is mandatory for clinical application.ResultsNK-cell populations expanded on average 15.7±4.7 fold by day 14, with a viability of 96% ±0.5. At the end of the incubation period, 97% ±1.1 of the expanded population was CD56⁺ NK cells; these effector cells showed significant up-regulation of the activating receptors NKG2D and DNAM-1. Functional tests demonstrated that expanded NK cells are fully functional with no difference whether tested before cryopreservation or after thawing.DiscussionThese data provide the basis for developing new NK-cell-based immunotherapeutic strategies for the treatment of patients with cancer.     

B‐1 cells produce insulin and abrogate experimental streptozotocin‐induced diabetes

The participation of B‐1 cells in a murine model of spontaneous diabetes has been recently reported. Here, we describe the role of B‐1 cells in streptozotocin (STZ) induced diabetes in mice. We demonstrated that XID (B‐1 cell‐deficient) mice are more susceptible to STZ treatment than WT mice, as evidenced by their higher blood glucose level in response to STZ. Unexpectedly, the XID mice that were i.p. transferred with purified B‐1 cells, either before or after the STZ treatment, did not develop diabetes. These cell transfers provided long‐lasting protection for the XID mice against STZ‐induced diabetes, suggesting that B‐1 cells play an important role in the experimental diabetes pathobiology. We also showed that B‐1 cell culture supernatants were able to regulate the blood glucose level of the diabetic XID mice, and we identified insulin‐producing cells when B‐1 cells were differentiated in B‐1 cell‐derived phagocyte in vitro. These findings provide a novel role for B‐1 cells in metabolic processes, presenting a new mechanism to explain the pathogenesis of diabetes and a possible therapeutical target.     

Grey-Scale Analysis Improves the Ultrasonographic Evaluation of Thyroid Nodules

Ultrasonography is the main imaging method for the workup of thyroid nodules. However, interobserver agreement reported for echogenicity and echotexture is quite low. The aim of this study was to perform quantitative measurements of the degree of echogenicity and heterogeneity of thyroid nodules, to develop an objective and reproducible method to stratify these features to predict malignancy.A retrospective study of patients undergoing ultrasonography-guided fine-needle aspiration was performed in an University hospital thyroid center. From January 2010 to October 2012, 839 consecutive patients (908 nodules) underwent US-guided fine-needle aspiration. In a single ultrasound image, 3 regions of interest (ROIs) were drawn: the first including the nodule; the second including a portion of the adjacent thyroid parenchyma; the third, the strap muscle. Histogram analysis was performed, expressing the median, mean, and SD of the gray levels of the pixels comprising each region. Echogenicity was expressed as a ratio: the nodule/parenchyma, the nodule/muscle, and parenchyma/muscle median gray ratios were calculated. The heterogeneity index (HI) was calculated as the coefficient of variation of gray histogram for each of the 3 ROIs. Cytology and histology reports were recorded.Nodule/parenchyma median gray ratio was significantly lower (more hypoechoic) in nodules found to be malignant (0.45 vs 0.61; P = 0.002) and can be used as a continuous measure of hypoechogenicity (odds ratio [OR] 0.12; 95% confidence interval [CI] 0.03–0.49). Using a cutoff derived from ROC curve analysis (<0.46), it showed a substantial inter-rater agreement (k = 0.74), sensitivity of 56.7% (95% CI 37.4–74.5%), specificity of 72.0% (67.8–75.9%), positive likelihood ratio (LR) of 2.023 (1.434–2.852), and negative LR of 0.602 (0.398–0.910) in predicting malignancy (diagnostic odds ratio 3.36; 1.59–7.10). Parenchymal HI was associated with anti-thyroperoxidase positivity (OR 19.69; 3.69–105.23). The nodule HI was significantly higher in malignant nodules (0.73 vs 0.63; P = 0.03) and, if above the 0.60 cutoff, showed sensitivity of 76.7% (57.7–90.1%), specificity of 46.8% (42.3–51.4%), positive LR of 1.442 (1.164–1.786), and negative LR of 0.498 (0.259–0.960).Evaluation of nodule echogenicity and echotexture according to a numerical estimate (nodule/parenchyma median gray ratio and nodule HI) allows for an objective stratification of nodule echogenicity and internal structure.     

Lower limb muscle strength is associated with functional performance and quality of life in patients with systemic sclerosis

Background:

Complaints of peripheral muscle weakness are quite common in patients with systemic sclerosis (SSc). It is likely that the muscle impairments may reduce the patients'' exercise performance, which in turn may decrease their functional capacity and exert a direct impact on their quality of life.

Objectives:

To assess the peripheral and respiratory muscle strength in individuals with SSc and to investigate their correlation with the 6-min walk distance (6MWD) and quality of life measurements. Moreover, we aimed to characterize their nutritional status, pulmonary function, functional capacity, and quality of life compared to the controls.

Method:

The present cross-sectional study included 20 patients with SSc and 20 control subjects. All of the participants were subjected to isometric dynamometry, surface electromyography, bioelectrical impedance analysis, pulmonary function testing, and the 6-min walk test. Patients with SSc also responded to the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the Health Assessment Questionnaire Disability Index (HAQ-DI).

Results:

The individuals with SSc exhibited a reduction in quadriceps strength (p=0.0001), increased quadriceps fatigability (p=0.034), impaired pulmonary function, and a reduced 6MWD (p=0.0001) compared to the controls. Quadriceps strength was significantly correlated with the 6MWD (Rho=0.719; p=0.0004) and the HAQ-DI (Rho=-0.622; p=0.003). We also found significant correlations between quadriceps fatigability and maximal inspiratory (Rho=0.684; p=0.0009) and maximal expiratory (Rho=0.472; p=0.035) pressure.

Conclusions:

Patients with SSc exhibited reduced respiratory muscle and quadriceps strength and an increase in its fatigability. In these individuals, there was a relationship between quadriceps strength, functional capacity, and quality of life.