Clinical and pathological impact of an optimal assessment of brain invasion for grade 2 meningioma diagnosis: lessons from a series of 291 cases

Brain invasion has not been recognized as a standalone criterion for atypical meningioma by the WHO classification until 2016. Since the 2007 edition suggested that meningiomas harboring brain invasion could be classified as grade 2, brain invasion study was progressively strengthened in our center, based on a strong collaboration between neurosurgeons and neuropathologists regarding sample orientation and examination. Practice changes were considered homogeneous enough in 2011. The aim of the present study was to evaluate the impact of gross practice change on the clinical and pathological characteristics of intracranial meningiomas classified as grade 2.

The characteristics of consecutive patients with a grade 2 meningioma surgically managed before (1998–2005, n?=?125, group A) and after (2011–2014, n?=?166, group B) practices changed were retrospectively reviewed.

Sociodemographical and clinical parameters were comparable in groups A and B, and the median age was 62 years in both groups (p?=?0.18). The 5-year recurrence rates (23.2% vs 29.5%, p?=?0.23) were similar. In group A, brain invasion was present in 48/125 (38.4%) cases and was more frequent than in group B (14/166, 8.4%, p?<?0.001). In group A, 33 (26.4%) meningiomas were classified as grade 2 solely based on brain invasion (group A_SBI), and 92 harbored other grade 2 criteria (group A_OCA). Group A_SBI meningiomas had a similar median progression-free survival compared to groups A_OCA (68 vs 80 months, p?=?0.24) and to A_OCA and B pooled together (n?=?258, 68 vs 90 months, p?=?0.42).

An accurate assessment of brain invasion is mandatory as brain invasion is a strong predictor of meningioma progression.

     

Bradykinin induces NO and PGF2α production via B2 receptor activation from cultured porcine basilar arterial endothelial cells

Our previous in vitro study demonstrated that bradykinin (BK) induced relaxation and contraction of porcine basilar artery (PBA) mediated via activation of endothelial B₂ receptors. The main relaxing and contracting factors appeared to be nitric oxide (NO) and prostaglandin (PG) H₂, respectively, but not thromboxane A₂. After obtaining these findings, we succeeded in cultivating endothelial cells isolated from the PBA. Although PGH₂ has different functionally active isoforms, including PGD₂, PGE₂, and PGF_2α, we have not yet clarified which of them is responsible for BK-induced contraction. Therefore, we attempted to quantify NO and PG production from cultured porcine basilar arterial endothelial cells (PBAECs) and to identify which of the PGs was involved in this contraction. The cultured PBAECs produced NO spontaneously, and BK enhanced this production in a concentration-dependent manner. The NO synthase inhibitor Nω-nitro-l-arginine (L-NNA) and the B₂ receptor antagonist HOE-140, but not the B₁ receptor antagonist des-Arg⁹, [Leu⁸]-BK, completely abolished it. In a functional study, PGD₂, PGE₂, and PGF_2α induced concentration-dependent contractions in isolated porcine basilar arterial rings, the order of maximum contraction being PGF_2α?>?PGE₂?>?PGD₂. The cultured PBAECs produced PGD₂, PGE₂, and PGF_2α spontaneously, and BK significantly enhanced the production of PGF_2α, but not that of PGD₂ and PGE₂. The B₂, but not B₁, antagonist completely abolished the BK-enhanced production of PGF_2α. These results suggest that BK induces production of NO and PGF_2α simultaneously from PBAECs via B₂ receptor activation.     

广州市荔湾区青少年脊柱侧凸患病率的调查研究

目的了解广州市荔湾区青少年脊柱侧凸的患病率。方法 2011年7月~2012年1月对荔湾区8351名7~15岁在校中小学生进行了脊柱侧凸普查,应用脊柱侧凸两检法（体检、X线照片）,体检阳性或可疑阳性者到医院照脊柱全长正侧位X片,采用Cobb法测量,Cobb角≥10°诊断为脊柱侧凸。结果一检阳性结果 175名（2.1%）,二检阳性为85名（1.02%）,男性31名,女性54名,男∶女患病率比为1∶1.76,其中特发性脊柱侧凸81名,占95.3%,先天性侧凸3名,神经肌肉源性1名。结论荔湾区中小学生脊柱侧凸发病率为1.02%,通过普查,可以早发现、早诊断青少年脊柱侧凸,及时选择适当方法进行治疗。     

Assessment of bronchial obstruction and its reversibility by shape indexes of the flow‐volume loop in asthmatic children

Asthma assessment by spirometry is challenging in children as forced expiratory volume in 1 s (FEV1) is frequently normal at baseline. Bronchodilator (BD) reversibility testing may reinforce asthma diagnosis but FEV1 sensitivity in children is controversial. Ventilation inhomogeneity, an early sign of airway obstruction, is described by the upward concavity of the descending limb of the forced expiratory flow‐volume loop (FVL), not detected by FEV1. The aim was to test the sensitivity and specificity of FVL shape indexes as β‐angle and forced expiratory flow at 50% of the forced vital capacity (FEF50)/peak expiratory flow (PEF) ratio, to identify asthmatics from healthy children in comparison to “usual” spirometric parameters. Seventy‐two school‐aged asthmatic children and 29 controls were prospectively included. Children performed forced spirometry at baseline and after BD inhalation. Parameters were expressed at baseline as z‐scores and BD reversibility as percentage of change reported to baseline value (Δ%). Receiver operating characteristic curves were generated and sensitivity and specificity at respective thresholds reported. Asthmatics presented significantly smaller zβ‐angle, zFEF50/PEF and zFEV1 (p ≤ .04) and higher BD reversibility, significant for Δ%FEF50/PEF (p = .02) with no difference for Δ%FEV1. zβ‐angle and zFEF50/PEF exhibited better sensitivity (0.58, respectively 0.60) than zFEV1 (0.50), and similar specificity (0.72). Δ%β‐angle showed higher sensitivity compared to Δ%FEV1 (0.72 vs. 0.42), but low specificity (0.52 vs. 0.86). Quantitative and qualitative assessment of FVL by adding shape indexes to spirometry interpretation may improve the ability to detect an airway obstruction, FEV1 reflecting more proximal while shape indexes peripheral bronchial obstruction.     

Development of a portable electrochemical loop mediated isothermal amplification (LAMP) device for detection of hepatitis B virus

The objective of this study was to develop a simple, inexpensive prototype device for rapid detection of hepatitis B virus (HBV). The device was able to simultaneously amplify, detect and quantify the target HBV DNA. The system was fabricated from a custom-made electrochemical set-up of which the temperature was thermostatically controlled by a water bath. Real-time monitoring of HBV DNA was accomplished by measuring the response of redox indicator in the reaction mixture. Concentration of HBV DNA in the samples was determined from the peak high ratio (PHR) and threshold time relationship. The signal was processed by sigmoidal model fitting to enhance the accuracy of the results. Key parameters including concentrations of redox indicator and reaction temperatures were optimized. Sensitivity and specificity of the method toward HBV DNA were evaluated. The prototype was capable of real-time amplification and detection of HBV DNA with concentration as low as 6.18 fg μl⁻¹. The test showed high specificity against HBV DNA. The system was also able to detect HBV positive serum directly with simple thermal pretreatment instead of tedious DNA extraction. The electrochemical set-up was compatible with microfluidic platforms and can be readily adapted for efficient and high throughput point-of-care (POC) diagnosis of HBV.

A novel prototype device using LAMP and electrochemical drop cell set-up for rapid detection of hepatitis B virus.     

Synthesis of benzo[4,5]imidazo[1,2-a]pyrimidines and 2,3-dihydroquinazolin-4(1H)-ones under metal-free and solvent-free conditions for minimizing waste generation

Brønsted acidic ionic liquid was found to be an efficient and recyclable catalyst for the synthesis of benzo[4,5]imidazo[1,2-a]pyrimidines and 2,3-dihydroquinazolin-4(1H)-ones. The reactions proceeded smoothly with a broad scope of substrates providing the expected products in good to excellent yields under an atom-economical pathway. The low-cost recyclable catalyst, metal- and solvent-free conditions, and the ease of product isolation are the highlighted advantages in solving the issue of trace metal contamination in synthesized pharmaceuticals.

A facile, efficient, and atom-economic method for preparing benzo[4,5]imidazo[1,2-a]pyrimidines and 2,3-dihydroquinazolin-4(1H)-ones under metal- and solvent-free condition has been developed.     

Tryptophan and Kynurenine Enhances the Stemness and Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stromal Cells In Vitro and In Vivo

Aging tissues present a progressive decline in homeostasis and regenerative capacities, which has been associated with degenerative changes in tissue-specific stem cells and stem cell niches. We hypothesized that amino acids could regulate the stem cell phenotype and differentiation ability of human bone marrow-derived mesenchymal stromal cells (hBMSCs). Thus, we performed a screening of 22 standard amino acids and found that D-tryptophan (10 μM) increased the number of cells positive for the early stem cell marker SSEA-4, and the gene expression levels of OCT-4, NANOG, and SOX-2 in hBMSCs. Comparison between D- and L-tryptophan isomers showed that the latter presents a stronger effect in inducing the mRNA levels of Oct-4 and Nanog, and in increasing the osteogenic differentiation of hBMSCs. On the other hand, L-tryptophan suppressed adipogenesis. The migration and colony-forming ability of hBMSCs were also enhanced by L-tryptophan treatment. In vivo experiments delivering L-tryptophan (50 mg/kg/day) by intraperitoneal injections for three weeks confirmed that L-tryptophan significantly increased the percentage of cells positive for SSEA-4, mRNA levels of Nanog and Oct-4, and the migration and colony-forming ability of mouse BMSCs. L-kynurenine, a major metabolite of L-tryptophan, also induced similar effects of L-tryptophan in enhancing stemness and osteogenic differentiation of BMSCs in vitro and in vivo, possibly indicating the involvement of the kynurenine pathway as the downstream signaling of L-tryptophan. Finally, since BMSCs migrate to the wound healing site to promote bone healing, surgical defects of 1 mm in diameter were created in mouse femur to evaluate bone formation after two weeks of L-tryptophan or L-kynurenine injection. Both L-tryptophan and L-kynurenine accelerated bone healing compared to the PBS-injected control group. In summary, L-tryptophan enhanced the stemness and osteoblastic differentiation of BMSCs and may be used as an essential factor to maintain the stem cell properties and accelerate bone healing and/or prevent bone loss.     

von Willebrand factor released from Weibel-Palade bodies binds more avidly to extracellular matrix than that secreted constitutively

Large multimers of von Willebrand factor (vWf) are released from the Weibel-Palade bodies of cultured endothelial cells following treatment with a secretagogue (Sporn et al, Cell 46:185, 1986). These multimers were shown by immunofluorescent staining to bind more extensively to the extracellular matrix of human foreskin fibroblasts than constitutively secreted vWf, which is composed predominantly of dimeric molecules. Increased binding of A23187-released vWf was not due to another component present in the releasate, since releasate from which vWf was adsorbed, when added together with constitutively secreted vWf, did not promote binding. When iodinated plasma vWf was overlaid onto the fibroblasts, the large forms bound preferentially to the matrix. These results indicated that the enhanced binding of the vWf released from the Weibel-Palade bodies was likely due to its large multimeric size. It appears that multivalency is an important component of vWf interaction with the extracellular matrix, just as has been shown for vWf interaction with platelets. The pool of vWf contained within the Weibel-Palade bodies, therefore, is not only especially suited for platelet binding, but also for interaction with the extracellular matrix.     

Arterial manifestations of Beh?et's disease. 12 cases

Out of 196 patients with Beh?et's disease, 12 (10 men and 2 women, mean age 34 +/- 7 years) had non-coronary arterial lesions. Beh?et's disease was complete in 4 patients. The arterial lesions had appeared 8.6 +/- 8 years on average (20 years at most) after the first sign of the disease. Three patients showed evidence of stenosis or occlusion involving one or several arteries. Eight patients had both stenotic and aneurysmal lesions. One patient had an arteriovenous fistula. Another developed a false aneurysm at the site of introduction of a femoral catheter. Yet another patient developed an anastomotic aneurysm one year after implantation of an abdominal aortic graft. In 2 cases histology showed fragmentation of the media associated with vasculitis of the vasa vasorum. Two patients with pulmonary aneurysm died of massive haemoptysis. In 2 patients combined corticosteroid and cyclophosphamide therapy failed to prevent the development of aneurysmal lesions. Phlebitis was associated with arterial involvement in 7 patients. Comparison between patients with or without arterial lesions showed no significant difference in time of onset of Beh?et's disease, sex, main clinical features and presence of HLA B5. Aneurysmal lesions respond poorly to medical treatment, and surgery is mandatory. Since recurrence at the site of anastomosis is possible, prolonged monitoring is required.