Iatrogenic atrial septal defects after transseptal puncture for percutaneous left atrial appendage occlusion and their hemodynamic effects

Background Percutaneous left atrial appendage occlusion(LAAO)requires puncture of the interatrial septum.The immediate hemodynamic effects of iatrogenic atrial septal defects(iASD)after LAAO have not been examined so far.We aimed at evaluat-ing these effects through invasive measurements of pressure and oxygen saturation.Moreover,we assessed the incidence of per-sistent iASD at three months.METHODS Forty-eight patients scheduled for percutaneous LAAO were prospectively included in the study.Pressure and oxygen saturation were measured(1)in the right atrium(RA)before transseptal puncture,(2)in the left atrium(LA)through the transseptal sheath after transseptal puncture,(3)in the LA after removal of introducer sheath,and(4)in the RA after removal of introducer sheath.Transesophageal echocardiography was performed at three months to detect iASD.RESULTS Pressure in the RA increased significantly after removing the introducer sheath(P=0.034),whereas no difference was found in oxygen saturation in the RA(P=0.623).Pressure measurement in the LA showed no significant difference after re-moving the introducer sheath(P=0.718).Oxygen saturation in the LA also showed no significant difference(P=0.129).Follow-up transesophageal echocardiogram at 3 months revealed a persistent iASD in 4 patients(8.5%).CONCLUSIONS Our study suggests that iASD after percutaneous LAAO does not result in significant shunts directly after the procedure,although a significant increase of mean right atrial pressure can be observed.Persistent iASDs after percutaneous LAAO seem to be relatively rare at three months.

About the structure of posturography: Sampling duration, parametrization, focus of attention (part II)

There exists a great variety of posturographic parameters which complicates the evaluation of center of pressure (COP) data. Hence, recommendations were given to use a set of complementary parameters to explain most of the variance. However, it is unknown whether a dual task paradigm leads to different parametrization sets. On account of this problem an exploratory factor analysis approach was conducted in a dual task experiment. 16 healthy subjects stood on a force plate performing a posture-cognition dual task (DT, focus of attention on a secondary task) with respect to different sampling durations. The subjects were not aware of being measured in contrast to a baseline task condition (BT, internal focus of attention) in the previously published part I. In compareson to BT a different factor loading pattern appears. In addition, factor loadings are strongly affected by different sampling durations. DT reveals a change of factor loading structure with longer sampling durations compared to BT. Specific recommendations concerning a framework of posturographic parametrization are given.

About the structure of posturography: Sampling duration, parametrization, focus of attention (part I)

This study investigates the choice of posturographic parameter sets with respect to the influence of different sampling durations (30 s, 60 s, 300 s). Center of pressure (COP) data are derived from 16 healthy subjects standing quietly on a force plate. They were advised to focus on the postural control process ( i.e. internal focus of attention). 33 common linear and 10 nonlinear parameters are calculated and grouped into five classes. Component structure in each group is obtained via exploratory factor analysis. We demonstrate that COP evaluation—irrespective of sampling duration—necessitates a set of diverse parameters to explain more variance of the data. Further more, parameter sets are uniformly invariant towards sampling durations and display a consistent factor loading pattern. These findings pose a structure for COP parametrization. Hence, specific recommendations are preserved in order to avoid redundancy or misleading basis for inter-study comparisons. The choice of 11 parameters from the groups is recommended as a framework for future research in posturography.

Erratum to “About the Structure of Posturography: Sampling Duration, Parametrization, Focus of Attention (Part II)” [Journal of Biomedical Science and Engineering 5 (2012) 508-516]

After reading the above mentioned article of [1], we identified a mistake considering the results of the paragraph “3.6. Nonlinear Parameters AP” and the related Table 5 (both on p. 512). Unfortunately, published Table 5 is a duplicate of Table 4, and therefore it is not possible for the reader to comprehend any underlying interrelations. To correct this mistake, we would like to offer the corrected table (Table 5) as follows.

Participation as Input-Legitimacy： The Ambivalent Effects of Multi-Stakeholder Govemance

What legitimacy problems do NGOs experience, when they participate extensively in global governance processes？ What do these problems mean for the input-legitimacy of the governance process？ In this paper the author seeks to answer these questions by looking closely at the UN World Summit on the Information Society （WSIS）, focusing specifically on one of its multi-stakeholder working groups, the Working Group on Internet Governance （WGIG）. This working group provided NGOs with some outstanding possibilities for participation to enable them to contribute to the formulation of the WSIS policy outcomes. Yet, the wide participation of NGOs had ambiguous effects for their internal legitimacy. The author will argue that these legitimacy problems in turn challenged the input-legitimacy of the governance process, particularly because they reduced the variety of issues that NGOs brought into the governance process. The most deeply included NGO actors were inclined to adapt their demands to the necessities of the governance process. The empirical findings from the WSIS thus suggest that the democratizing reforms international organizations currently undertake reduce the legitimizing power that NGOs are often assigned with.

话题和焦点在分裂句中的韵律编码方式及其对感知的影响

前置是突显信息一种语法方式,如:"书,我买了三本。"这种分裂句对应两种语用功能:前置名词是话题或是焦点。对7个人在这两种语境下朗读的280个分裂句进行声学分析,结果表明:(1)两种条件下,前置名词后都有明显停顿。前置名词本身的音高和时长没有差别;(2)两种信息结构对基干部分有不同的韵律调节作用。前置名词为焦点时压低了基干部分的音高,而前置名词为话题时基干部分的音高为渐降。由此可见,话题的语调调节范围是自身,而焦点是全句;(3)前置名词和基干部分间的停顿在焦点条件下长于话题条件。22人对分裂句问答匹配度的判断结果表明,两种信息结构的不同韵律编码方式是有感知意义的。

Chronic intestinal failure and short bowel syndrome in Crohn’s disease

Chronic intestinal failure(CIF)is a rare but feared complication of Crohn’s disease.Depending on the remaining length of the small intestine,the affected intestinal segment,and the residual bowel function,CIF can result in a wide spectrum of symptoms,from single micronutrient malabsorption to complete intestinal failure.Management of CIF has improved significantly in recent years.Advances in home-based parenteral nutrition,in particular,have translated into increased survival and improved quality of life.Nevertheless,60%of patients are permanently reliant on parenteral nutrition.Encouraging results with new drugs such as teduglutide have added a new dimension to CIF therapy.The outcomes of patients with CIF could be greatly improved by more effective prevention,understanding,and treatment.In complex cases,the care of patients with CIF requires a multidisciplinary approach involving not only physicians but also dietitians and nurses to provide optimal intestinal rehabilitation,nutritional support,and an improved quality of life.Here,we summarize current literature on CIF and short bowel syndrome,encompassing epidemiology,pathophysiology,and advances in surgical and medical management,and elucidate advances in the understanding and therapy of CIF-related complications such as catheter-related bloodstream infections and intestinal failure-associated liver disease.

肾细胞癌肝转移的多次经动脉化疗栓塞术后局部控制及生存疗效的评价

本研究的目的是评价经动脉化疗栓塞（TACE）对肾细胞癌（RCC）肝脏转移灶的局部治疗及生存的效果。采用前瞻洼的研究方法，评价1999--2005年22例病人经TACE治疗的效果。45％的病人仅用丝裂霉素作为化疔药物，55％的病人同时使用丝裂霉索与吉西他滨（gemcitabine）。所有病例的栓塞材料均为碘化油和可降解淀粉微球。采用MRI评价局部治疗反应，并参照实体肿瘤治疗效果评价标准（RECIST）做出判断。用KM法计算平均和中位生存时间、

川酒文化传播的新视角:基于文化认知结构的研究

丰富的川酒资源为川酒文化的传播提供了坚实的物质基础。许多专家学者对川酒文化在新媒体时代如何走向世界进行了广泛的理论与实践研究,但这些研究大多集中在对川酒文化自身的挖掘及新媒体时代的传播策略研究上,忽略了对川酒文化传播过程中文化受众的认知、接受、认同的心理过程的研究。因此,本文试图从文化受众的角度、以认知结构作为研究工具,对川酒文化受众的文化认同与心理过程进行研究,为川酒文化传播提供一个新的研究视角。

Histomorphometry of brain tumours

In this review, the results of previous histomorphometric studies of brain tumours are summarized and discussed with respect to their potential value for diagnostic purposes and for tumour research. In the majority of these studies, human gliomas were investigated. In a few studies,

Linking the lab to the patient: Tools for optimizing oral drug delivery

In the development of new drugs as well as new formulations of existing products(including generic products),it is of great interest to be able to predict to what extent the drug can be absorbed from the gastrointestinal(GI)tract and how the formulation and dosing conditions may affect the absorption profile.The hypothesis behind Biorelevant release testing is that“the closer the test conditions can simulate the gastrointestinal environment,the better the prediction will be.”Typical aspects of GI physiology,which can influence drug bioavailability,are the composition of the GI fluids(which affects various processes including release from the dosage form and stability of the drug),GI motility and hydrodynamics(transit characteristics of the dosage form,release from the dosage form etc.).

Surgical Treatment of Penile Deformity Due to Curvature Using a Subcutaneous Soft Silicone Implant: Case Report

Introduction: Congenital and acquired penile curvature has a negative impact on penile aesthetics, sexual capabilities, and male psychology. Surgical procedures yield satisfactory correction of curvature, but are usually associated with penile shortening and palpable suture material and nodules under the skin, resulting in patient dissatisfaction. Aims: To present a novel technique using a subcutaneous soft silicone implant for surgical treatment of penile soft tissue deformities with curvature, with prevention of surgery-associated penile shortening and subcutaneous “bumps”, and with additional gains in overall penile length and girth. Method: 3 patients who complained about congenital, post-traumatic, and post-penile surgery associated penile curvature, with concerns about their penile aesthetics and associated negative psychosocial effects, were treated with the insertion of a subcutaneous soft silicone penile implant. Results: During a follow up period of 2 - 12 months (mean: 6.7 ± 3.6 months) all three patients expressed objective and subjective satisfaction regarding the corrective results of the surgery. Penile length and girth measurements during follow-up showed a mean increase in length of 4.3 cm (±1.4 cm) and a mean increase in girth of 3.0 cm (±1.0 cm). Conclusion: The insertion of the subcutaneous soft silicone implant in addition to corporeal fibrotic tissue removal in patients with congenital or acquired penile curvature is an effective option that provides the patient with aesthetic improvements by correcting penile deviation, preventing post-surgical subcutaneous nodule formation that results from the technique and suture material used, and adding penile length and girth. Further prospective studies are required to validate our initial experience.

Inhibition of the Na⁺/Ca²⁺Exchanger NCX₁Expressed in <i>Xenopus</i>Oocyte by Glycyrrhizic Acid and Cyclophylin A

The Na+/Ca2+ exchanger plays an important role in regulation of airway smooth muscle contraction by regulating intracellular calcium, and is a potential target for treatment of asthma. To test modulation of exchanger activity, we used Xenopus oocytes as model system. Na+/Ca2+ exchanger was expressed in the cells by microinjection of cRNA of the exchanger isoform NCX1. The activity of NCX1 was determined as Ni2+-sensitive current under voltage clamp in low Cl– medium and in the presence of the Cl–-channel inhibitor niflumic acid. Only this composition of solution allowed determining NCX1-mediated current with sufficient accuracy. Among a few tested Chinese herbal drugs, glycyrrhizic acid turned out to be a potent inhibitor of NCX1 with an apparent IC50 value of 40 μM. Previous work had revealed elevated cyclophylin A concentration in serum of asthmatic rats after receiving acupuncture treatment. Extracellular incubation of the oocytes in cyclophylin A for one day led to significant inhibition with an apparent IC50 value of about 1 μM. We suggest that effects of acupuncture and application of glycyrrhizic acid as an active constituent of Chinese medicine for treatment of asthma symptoms may partially be attributed to inhibition of the reversed mode of NCX1 and that these compounds may stimulate the search for new anti-asthmatic drugs.

五粮液酒文化传播的新视角:基于文化认知结构重构的研究

众多专家学者对五粮液酒文化的弘扬与传播进行了广泛的理论与实证研究,但这些研究大多集中在对五粮液酒文化自身的挖掘及传播策略等方面,忽略了对五粮液酒文化传播过程中文化受众的认知心理过程的研究。现试图从文化受众的角度、以认知结构为研究工具,对五粮液酒文化受众的文化认知心理过程进行研究,为五粮液酒文化传播提供一个新的研究视角。

Rescue of p53 functions by in vitro-transcribed mRNA impedes the growth of high-grade serous ovarian cancer

Background:The cellular tumor protein p53(TP53)is a tumor suppressor gene that is frequently mutated in human cancers.Among various cancer types,the very aggressive high-grade serous ovarian carcinoma(HGSOC)exhibits the high-est prevalence of TP53 mutations,present in>96%of cases.Despite intensive efforts to reactivate p53,no clinical drug has been approved to rescue p53 func-tion.In this study,our primary objective was to administer in vitro-transcribed(IVT)wild-type(WT)p53-mRNA to HGSOC cell lines,primary cells,and ortho-topic mouse models,with the aim of exploring its impact on inhibiting tumor growth and dissemination,both in vitro and in vivo.Methods:To restore the activity of p53,WT p53 was exogenously expressed in HGSOC cell lines using a mammalian vector system.Moreover,IVT WT p53 mRNA was delivered into different HGSOC model systems(primary cells and patient-derived organoids)using liposomes and studied for proliferation,cell cycle progression,apoptosis,colony formation,and chromosomal instabil-ity.Transcriptomic alterations induced by p53 mRNA were analyzed using RNA sequencing in OVCAR-8 and primary HGSOC cells,followed by ingenuity path-way analysis.In vivo effects on tumor growth and metastasis were studied using orthotopic xenografts and metastatic intraperitoneal mouse models.Results:Reactivation of the TP53 tumor suppressor gene was explored in differ-ent HGSOC model systems using newly designed IVT mRNA-based methods.The introduction of WT p53 mRNA triggered dose-dependent apoptosis,cell cycle arrest,and potent long-lasting inhibition of HGSOC cell proliferation.Transcriptome analysis of OVCAR-8 cells upon mRNA-based p53 reactivation revealed significant alterations in gene expression related to p53 signaling,such as apoptosis,cell cycle regulation,and DNA damage.Restoring p53 function concurrently reduces chromosomal instability within the HGSOC cells,under-scoring its crucial contribution in safeguarding genomic integrity by moderating the baseline occurrence of double-strand breaks arising from replication stress.Furthermore,in various mouse models,treatment with p53 mRNA reduced tumor growth and inhibited tumor cell dissemination in the peritoneal cavity in a dose-dependent manner.Conclusions:The IVT mRNA-based reactivation of p53 holds promise as a potential therapeutic strategy for HGSOC,providing valuable insights into the molecular mechanisms underlying p53 function and its relevance in ovarian cancer treatment.

Covalent linkage of sulfated hyaluronan to the collagen scaffold Mucograft® enhances scaffold stability and reduces proinflammatory macrophage activation in vivo

Sulfated glycosaminoglycans(sGAG)show interaction with biological mediator proteins.Although collagen-based biomaterials are widely used in clinics,their combination with high-sulfated hyaluronan(sHA3)is unexplored.This study aims to functionalize a collagen-based scaffold(Mucograft®)with sHA3 via electrostatic(sHA3/PBS)or covalent binding to collagen fibrils(sHA3+EDC/NHS).Crosslinking without sHA3 was used as a control(EDC/NHS Ctrl).The properties of the sHA3-functionalized materials were characterized.In vitro growth factor and cytokine release after culturing with liquid platelet-rich fibrin was performed by means of ELISA.The cellular reaction to the biomaterials was analyzed in a subcutaneous rat model.The study revealed that covalent linking of sHA3 to collagen allowed only a marginal release of sHA3 over 28 days in contrast to electrostatically bound sHA3.sHA3+EDC/NHS scaffolds showed reduced vascular endothelial growth factor(VEGF),transforming growth factor beta 1(TGF-β1)and enhanced interleukin-8(IL-8)and epithelial growth factor(EGF)release in vitro compared to the other scaffolds.Both sHA3/PBS and EDC/NHS Ctrl scaffolds showed a high proinflammatory reaction(M1:CD-68+/CCR7+)and induced multinucleated giant cell(MNGC)formation in vivo.Only sHA3+EDC/NHS scaffolds reduced the proinflammatory macrophage M1 response and did not induce MNGC formation during the 30 days.SHA3+EDC/NHS scaffolds had a stable structure in vivo and showed sufficient integration into the implantation region after 30 days,whereas EDC/NHS Ctrl scaffolds underwent marked disintegration and lost their initial structure.In summary,functionalized collagen(sHA3+EDC/NHS)modulates the inflammatory response and is a promising biomaterial as a stable scaffold for full-thickness skin regeneration in the future.

Natural variation in social conditions affects male mate choosiness in the amphipod Gammarus roeselii

The extent of male mate choosiness is driven by a trade-off between various environmental factors associated with the costs of mate acquisition,quality assessment and opportunity costs.Our knowledge about natural variation in male mate choosiness across different populations of the same species,however,remains limited.In this study,we compared male mate choosiness across 10 natural populations of the freshwater amphipod Gammarus roeselii(Gervais 1835),a species with overall high male mating investments,and evaluated the relative influence of population density and sex ratio(both affecting mate availability)on male mate choosiness.We investigated amplexus establishment after separating mating pairs and presenting focal males with a novel,size-matched female from the same population.Our analysis revealed considerable effects of sex ratio and(to a lesser extent)population density on time until amplexus establishment(choosiness).Male amphipods are able to perceive variable social conditions(e.g.,sex ratio)and modify their mating strategy accordingly:We found choosiness to be reduced in increasingly male-biased populations,whereas selectivity increases when sex ratio becomes female biased.With this,our study expands our limited knowledge on natural variations in male mate choosiness and illustrates the importance of sex ratio(i.e.,level of competition)for male mating decisions in natural environments.Accounting for variation in sex ratios,therefore,allows envisioning a distinctive variation of choosiness in natural populations and highlights the importance of considering social background information in future behavioral studies.

Comparison of survival outcomes between laparoscopic versus open radical nephroureterectomy in upper tract urothelial cancer patients:Experiences of a tertiary care single center

Objectives:To test for differences in overall and recurrence-free survival between laparoscopic and open surgical approaches in patients undergoing radical nephroureterectomy(RNU)for upper tract urothelial carcinoma(UTUC).Materials and methods:We retrospectively identified patients treated for UTUC from 2010 to 2020 from our institutional database.Patients undergoing laparoscopic or open RNU with no suspicion of metastasis(cM0)were for the current study population.Patients with suspected metastases at diagnosis(cM1)or those undergoing other surgical treatments were excluded.Tabulation was performed according to the laparoscopic versus open surgical approach.Kaplan-Meier plots were used to test for differences in overall and recurrence-free survival with regard to the surgical approach.Furthermore,separate Kaplan-Meier plots were used to test the effect of preoperative ureterorenoscopy on overall and recurrence-free survival within the overall study cohort.Results:Of the 59 patients who underwent nephroureterectomy,29%(n=17)underwent laparoscopic nephroureterectomy,whereas 71%(n=42)underwent open nephroureterectomy.Patient and tumor characteristics were comparable between groups(p≥0.2).The median overall survival was 93 and 73 months in the laparoscopic nephroureterectomy group compared to the open nephroureterectomy group(p=0.5),respectively.The median recurrence-free survival did not differ between open and laparoscopic nephroureterectomies(73 months for both groups;p=0.9).Furthermore,the median overall and recurrence-free survival rates did not differ between patients treated with and without preoperative ureterorenoscopy.Conclusions:The results of this retrospective,single-center institution showed that overall and recurrence-free survival rates did not differ between patients with UTUC treated with laparoscopic and open RNU.Furthermore,preoperative ureterorenoscopy before RNU was not associated with higher overall or recurrence-free survival rates.

Long noncoding RNA in cardiac aging and disease

Cardiovascular diseases(CVDs)are the main cause of morbidity and mortality in Western society and present an important agerelated risk.With the constant rise in life expectancy,prevalence ofCVD in the population will likely increase further.New therapies,especially in the elderly,are needed to combat CVD.This review is focused on the role of long noncoding RNA(IncRNA)in CVD.RNA sequencing experiments in the past decade showed that most RNA does not code for protein,but many RNAs function as ncRNA.Here,we summarize the recent findings of IncRNA regulation in the diseased heart.The potential use of these RNAs as biomarkers of cardiac disease prediction is also discussed.

Metabolism pathways of arachidonic acids:mechanisms and potential therapeutic targets

The arachidonic acid(AA)pathway plays a key role in cardiovascular biology,carcinogenesis,and many inflammatory diseases,such as asthma,arthritis,etc.Esterified AA on the inner surface of the cell membrane is hydrolyzed to its free form by phospholipase A2 (PLA2),which is in turn further metabolized by cyclooxygenases(COXs)and lipoxygenases(LOXs)and cytochrome P450(CYP)enzymes to a spectrum of bioactive mediators that includes prostanoids,leukotrienes(LTs),epoxyeicosatrienoic acids(EETs),dihydroxyeicosatetraenoic acid(diHETEs),eicosatetraenoic acids(ETEs),and lipoxins(LXs).Many of the latter mediators are considered to be novel preventive and therapeutic targets for cardiovascular diseases(CVD),cancers,and inflammatory diseases.This review sets out to summarize the physiological and pathophysiological importance of the AA metabolizing pathways and outline the molecular mechanisms underlying the actions of AA related to its three main metabolic pathways in CVD and cancer.progression will provide valuable insight for developing new therapeutic drugs for CVD and anti-cancer agents such as inhibitors of EETs or 2J2.Thus,we herein present a synopsis of AA metabolism in human health,cardiovascular and cancer biology,and the signaling pathways involved in these processes.To explore the role of the AA metabolism and potential therapies,we also introduce the current newly clinical studies targeting AA metabolisms in the different disease conditions.