Experimental measurements and mathematical modeling towards quantification of brain swelling stress

Traumatic brain injury results in brain tissue swelling which can be a life threatening condition due to skull confinement. While previous efforts successfully measured the exhibited volume change in brain tissue swelling, no data exist to provide information about the exhibited stresses. In this study, confined compression mechanical testing was employed to measure swelling stress in murine brain tissue samples by varying the ionic concentration of the bathing solutions. Subsequently, computer simulations of the experimental protocol were employed to confirm a triphasic mathematical model describing the effect and provide insights into the experimental data. We measured the swelling stress to be in the range of 1.2–6.7 kPa (9.0–50.2 mmHg) depending on the ionic strength of the bathing solution, while a good correspondence was demonstrated among the experimentally measured and simulated responses. Furthermore, the mathematical model featured the osmotic pressure as the primary contributor to the swelling stress, while a parametric analysis showed that the densities of the intracellular fixed charges and of the non-permeable solutes significantly affect the swelling stress.     

Magnetic particle translation as a surrogate measure for synovial fluid mechanics

The mechanics of synovial fluid vary with disease progression, but are difficult to quantify quickly in a clinical setting due to small sample volumes. In this study, a novel technique to measure synovial fluid mechanics using magnetic nanoparticles is introduced. Briefly, microspheres embedded with superparamagnetic iron oxide nanoparticles, termed magnetic particles, are distributed through a 100 μL synovial fluid sample. Then, a permanent magnet inside a protective sheath is inserted into the synovial fluid sample. Magnetic particles translate toward the permanent magnet and the percentage of magnetic particles collected by the magnet in a given time can be related to synovial fluid viscosity. To validate this relationship, magnetic particle translation was demonstrated in three phases. First, magnetic particle translation was assessed in glycerol solutions with known viscosities, demonstrating that as fluid viscosity increased, magnetic particle translation decreased. Next, the relationship between magnetic particle translation and synovial fluid viscosity was assessed using bovine synovial fluid that was progressively degenerated via ultrasonication. Here, particle collection in a given amount of time increased as fluid degenerated, demonstrating that the relationship between particle collection and fluid mechanics holds in non-Newtonian synovial fluid. Finally, magnetic particle translation was used to assess differences between healthy and OA affected joints in equine synovial fluid. Here, particle collection in a given time was higher in OA joints relative to healthy horses (p < 0.001). Combined, these data demonstrate potential viability of magnetic particle translation in a clinical setting to evaluate synovial fluid mechanics in limited volumes of synovial fluid sample.     

Male‐induced costs of mating for females compensated by offspring viability benefits in an insect

Sexual conflict facilitates the evolution of traits that increase the reproductive success of males at the expense of components of female fitness. Theory suggests that indirect benefits are unlikely to offset the direct costs to females from antagonistic male adaptations, but empirical studies examining the net fitness pay‐offs of the interaction between the sexes are scarce. Here, we investigate whether matings with males that invest intrinsically more into accessory gland tissue undermine female lifetime reproductive success (LRS) in the cricket Teleogryllus oceanicus. We found that females incur a longevity cost of mating that is proportional to the partner’s absolute investment into the production of accessory gland products. However, male accessory gland weight positively influences embryo survival, and harmful ejaculate‐induced effects are cancelled out when these are put in the context of female LRS. The direct costs of mating with males that sire offspring with higher viability are thus compensated by direct and possibly indirect genetic benefits in this species.     

Relationships between sex hormones assessed in amniotic fluid, and maternal and umbilical cord serum: what is the best source of information to investigate the effects of fetal hormonal exposure?

Levels of testosterone (T) (total and free), androstenedione (A4), dehydroepiandrosterone sulphate (DHEAS), sex hormone-binding globulin (SHBG), and estradiol (E2) were measured by radioimmunoassay (RIA) in 156 normal pregnancies (77 male and 79 female fetuses). Samples were obtained from amniotic fluid, 2nd and 3rd trimester maternal serum, and umbilical cord serum at birth. During the critical period of brain differentiation, at the beginning of the second trimester of pregnancy, sex differences in T and A4 were found in amniotic fluid and not in maternal serum. This finding adds to the fact that mostly low and nonsignificant correlations were found for the different androgenic hormones between levels assessed in amniotic fluid and maternal plasma at this particular and very sensitive period of fetal brain development. On the other hand, high correlations were found for the same hormones between the samples of maternal serum in the 2nd and the 3rd trimester. Our data show that, of all available sources, amniotic fluid seems to be the best candidate to investigate the effects of early fetal androgen exposure.     

Podocalyxin is crucial for the growth of oral squamous cell carcinoma cell line HSC-2

Oral cancers constitute approximately 2% of all cancers, with the most common histological type being oral squamous cell carcinoma (OSCC), representing 90% of oral cancers. Although diagnostic technologies and therapeutic techniques have progressed, the survival rate of patients with OSCC is still 60%, whereas the incidence rate has increased. Podocalyxin (PODXL) is a highly glycosylated type I transmembrane protein that is detected in normal tissues such as heart, breast, and pancreas as well as in many cancers, including lung, renal, breast, colorectal, and oral cancers. This glycoprotein is associated with the progression, metastasis, and poor outcomes of oral cancers. PODXL overexpression was strongly detected using our previously established anti-PODXL monoclonal antibody (mAb), PcMab-47, and its mouse IgG_2a-type, 47-mG_2a. In previous studies, we also generated PODXL-knock out (PODXL-KO) cell lines using SAS OSCC cell lines, in order to investigate the function of PODXL in the proliferation of oral cancer cells. The growth of SAS/PODXL-KO cell lines was observed to be lower than that of parental SAS cells. For this study, PODXL-KO OSCC cell lines were generated using HSC-2 cells, and the role of PODXL in the growth of OSCC cell lines in vitro was assessed. Decreased growth was observed for HSC-2/PODXL-KO cells compared with HSC-2 parental cells. The influence of PODXL on tumor growth of OSCC was also investigated in vivo, and both the tumor volume and the tumor weight were observed to be significantly lower for HSC-2/PODXL-KO than that for HSC-2 parental cells. These results, taken together, indicate that PODXL plays an important role in tumor growth, both in vitro and in vivo.     

口腔鳞状细胞癌患者外周血Naa10及淋巴细胞免疫分型的特点及临床意义

目的探讨口腔鳞状细胞癌（OSCC）患者外周血N-α-乙酰基转移酶10 （Naa10）及淋巴细胞免疫分型的特点,并分析其临床意义。 方法选取97例OSCC患者及50名健康体检者,分别纳入患者组、对照组。检测两组受试者外周血Naa10、淋巴细胞免疫分型,并比较不同TNM分期、不同淋巴结转移状态患者外周血Naa10、淋巴细胞免疫分型的差异,总结其特点与临床意义。不同性别人数采用χ²检验,计量资料行正态性检验,满足正态性且组间方差相等则采用t检验,不满足正态性则采用非参数Wilcoxon秩和检验,相关性分析采用Pearson法。 结果患者组血清Naa10为（62.91±17.15）pg/ml,高于对照组的（38.82±9.04）pg/ml,差异有统计学意义（t?= 9.280,P?< 0.05）。患者组CD3⁺、CD4⁺、CD4⁺/CD8⁺、NK细胞百分比分别为（71.63±9.11）﹪、（34.34±4.26）﹪、（1.03±0.28）、（14.23±4.61）﹪,低于对照组的（76.25±2.87）﹪、（45.41±7.08）﹪、（1.77± 0.39）、（19.96±5.13）﹪,CD8⁺、B淋巴细胞百分比分别为（14.23±4.61）﹪、（14.91±3.29）﹪,高于后者的（19.96±5.13）﹪、（9.11±2.60）﹪,差异有统计学意义（P?< 0.05）。TNM分期Ⅰ~Ⅱ期患者42例,其血清Naa10为（64.08±15.26）?pg/?ml,与Ⅲ~Ⅳ期患者的（61.71±13.15）pg/ml比较,差异无统计学意义（t?= 0.820,P?> 0.05）。淋巴结转移者34例,其血清Naa10为（65.15±14.07）pg/ml,与无淋巴结转移者的（61.45±12.66）?pg/?ml比较,差异无统计学意义（t?= 1.321,P?> 0.05）。Ⅰ~Ⅱ期患者CD3⁺、CD4⁺、CD4⁺/CD8⁺、NK细胞百分比低于Ⅲ~Ⅳ期患者,其CD8⁺、B淋巴细胞百分比高于后者,差异有统计学意义（P?< 0.05）。Pearson相关性分析示,外周血Naa10与CD3⁺ （-0.631）、CD4⁺ （-0.529）、CD4⁺/CD8⁺ （-0.587）、NK细胞百分比（-0.603）呈负相关,与CD8⁺ （0.558）、B淋巴细胞百分比（0.670）呈正相关（P?< 0.05）。 结论OSCC患者外周血Naa10明显升高但与TNM分期、淋巴结转移无关;其淋巴细胞免疫分型存在明显改变,且TNM分期的上升、淋巴结转移的发生伴随着CD3⁺、CD4⁺、CD4⁺/?CD8⁺、NK细胞百分比的下降,以及CD8⁺、B淋巴细胞百分比的上升。     

Ovulatory follicular fluid induces sperm phagocytosis by neutrophils,but oviductal fluid around oestrus suppresses its inflammatory effect in the buffalo oviduct in vitro

We have recently shown that the conditioned media from bovine oviductal epithelial cell culture suppress sperm phagocytosis by neutrophils, suggesting that the oviduct around oestrus supplies the anti‐inflammatory microenvironment. To investigate the immune response of neutrophils toward the sperm at ovulation in the buffalo oviduct, we examined (a) a detailed distribution of neutrophils in the oviduct in buffaloes, (b) the effect of ovulatory follicular fluid (FF) and oviductal fluid (OF) on sperm phagocytosis by neutrophils, and (c) the interaction of the ovulatory FF with OF on sperm phagocytosis by neutrophils in vitro. Buffalo oviducts were collected from healthy reproductive tracts at a local slaughterhouse. A detailed observation by histological examination and transmission electron microscopy revealed that neutrophils exist in the oviduct epithelium and lumen throughout the oestrous cycle in buffaloes. The number of neutrophils at the oestrus stage was higher in ampulla compared with those in isthmus, whereas they remained relatively constant at the dioestrus stage. Two hours of preincubation of neutrophils with FF enhanced sperm phagocytosis through the formation of neutrophil extracellular traps (NETs) together with H₂O₂ production, whereas OF around oestrus (eOF) suppressed sperm phagocytosis, NETs formation, and H₂O₂ production and relieved the above FF‐induced inflammatory response. Our findings show that neutrophils exist in the healthy cyclic oviduct across bovine species, and the OF supplies a strong anti‐inflammatory environment that could minimize the inflammatory effect of the FF that flows into the oviduct lumen after ovulation and supports the occurrence of fertilization.     

p21活化激酶1在口腔癌细胞侵袭和迁移中的作用

p21活化激酶1(PAK1)与多种癌症类型的进展有关,然而,其在口腔癌中的作用仍不明确。本研究以人舌鳞状细胞癌(oral squamous cell carcinoma,OSCC)HSC4细胞系为研究材料,考察了PAK1在细胞系中的定位及血清生长因子对PAK1定位的影响。通过转染PAK1 siRNA来敲低OSCC细胞中的PAK1,并分析PAK1敲低对细胞侵袭和迁移性的影响。研究发现PAK1在人舌鳞状细胞癌细胞系HSC4中主要定位于细胞核,而血清生长因子可调节PAK1在不同亚细胞区域中的易位或积累,并且还可能影响OSCC细胞的细胞骨架结构。此外,敲低PAK1可显著抑制OSCC细胞的迁移和侵袭能力,表明PAK1在OSCC发生发展过程中起着至关重要的作用。     

Increase in the Content of Quinolinic Acid in Cerebrospinal Fluid and Frontal Cortex of Patients with Hepatic Failure

Abstract: Quinolinic acid (QUIN), an excitotoxic tryptophan metabolite, has been identified and measured in human cerebrospinal fluid (CSF) using a mass-fragmentographic method. Furthermore, its content has been evaluated in frontal cortex obtained at autopsy from the cadavers of patients who died after hepatic coma. During the coma, the concentration of QUIN in the CSF was 152 ± 38 pmol ml^-1. In contrast, the concentration in control patients affected by different pathologies was 22 ± 7 pmol ml^-1. In the frontal cortex of patients who died after episodes of hepatic encephalopathy, the content of QUIN was three times higher than in controls (2.6 ± 0.6 versus 0.80 ± 0.08 nmol/g wet weight). As a result of these investigations we are now able to extend our previous observations on the increase of QUIN in the brains of rats used as experimental models of hepatic encephalopathy to man. QUIN should therefore be added to the list of compounds possibly involved in the pathogenesis and symptomatology of brain disorders associated with liver failure.     

Parámetros de control glucémico en pacientes con diabetes tipo 2 no insulinizados derivados a consulta de Endocrinología,y grado de implementación del consenso nacional sobre el tratamiento de la hiperglucemia

ObjectiveTo assess blood glucose in patients with uncontrolled type 2 diabetes mellitus treated with oral antidiabetic drugs in primary care at the time of referral to specialized endocrinologists, and the degree of implementation of the national consensus guidelines of the Spanish Society of Diabetes by evaluating steps one (S1), two (S2), and three (S3) of the escalating therapy.Material and methodsRetrospective, observational study where 81 endocrinologists evaluated patients ≥40 years of age referred from primary care between July 2012 and July 2013, treated with 1 to 2 oral antidiabetic drugs but no insulin therapy, and with glycosylated hemoglobin (HbA_1c) levels ≥6.5%. Patients also had to have HbA_1c levels and both fasting and postprandial plasma glucose measurements from the previous three months.ResultsA total of 285 patients (57.6% males) were assessed. Mean (SD) age was 63.1 (9.7) years, mean HbA_1c was 8.5 (1.2) %, mean FPG was 171.7 (43) mg/dL, and mean postprandial plasma glucose was 206.8 (50) mg/dL. In primary care, 26.0% of patients were at S1 and 74.0% were at S2. After referral to the endocrinologist, 9.8% of patients moved onto S1, 42.8% onto S2, and 47.4% onto S3. Oral antidiabetic drugs most commonly prescribed in primary care were metformin (90.2%), DPP-4 inhibitors (34.4%), and sulfonylureas (30.5%), while drugs most commonly used in the specialized endocrinology setting were metformin (86%), insulin (56.8%), and DPP-4 inhibitors (49.8%). The most commonly followed guidelines were those of the American Diabetes Association and the consensus guidelines of the Spanish Society of Diabetes, in 77% and 45% of cases respectively.ConclusionsApproximately half the patients treated with oral antidiabetic drugs in primary care are prescribed insulin after referral to an endocrinology specialist. The most commonly followed guidelines in specialized care are the American Diabetes Association guidelines.