Effects of differentially expressed microRNAs induced by rootstocks and silicon on improving chilling tolerance of cucumber seedlings (Cucumis sativus L.).
Rootstocks can improve the chilling tolerance of grafted cucumbers, but their effectiveness varies. Rootstocks with strong de-blooming capacity may result in lower chilling tolerance of grafted cucumbers compared to those with weak de-blooming capacity, while also reducing the silicon absorption. However, it remains unclear whether this reduction in chilling tolerance is due to differences in rootstock genotypes or the reduction in silicon absorption. The chilling tolerance of cucumber seedlings was improved by using rootstocks and silicon nutrition. Rootstocks had a more significant effect than silicon nutrition, and the weak de-blooming rootstock 'Yunnan figleaf gourd' was superior to the strong de-blooming rootstock 'Huangchenggen No. 2'. Compared to self-rooted cucumber, twelve miRNAs were regulated by two rootstocks, including seven identical miRNAs (novel-mir23, novel-mir26, novel-mir30, novel-mir37, novel-mir46, miR395a and miR398a-3p) and five different miRNAs (novel-mir32, novel-mir38, novel-mir65, novel-mir78 and miR397a). Notably, four of these miRNAs (novel-mir38, novel-mir65, novel-mir78 and miR397a) were only identified in 'Yunnan figleaf gourd'-grafted cucumbers. Furthermore, six miRNAs (miR168a-5p, miR390a-5p, novel-mir26, novel-mir55, novel-mir67 and novel-mir70) were found to be responsive to exogenous silicon. Target gene prediction for 20 miRNAs resulted in 520 genes. Functional analysis of these target genes showed that 'Yunnan figleaf gourd' improves the chilling tolerance of cucumber by regulating laccase synthesis and sulfate metabolism, while 'Huangchenggen No. 2' and exogenous silicon reduced chilling stress damage to cucumber by regulating ROS scavenging and protein protection, respectively. Among the identified miRNAs, novel-mir46 and miR398a-3p were found in cucumbers in response to chilling stress and two types of rootstocks. However, no identical miRNAs were identified in response to chilling stress and silicon. In addition, the differential expression of novel-mir38, novel-mir65, novel-mir78 and miR397a may be one of the important reasons for the differences in chilling tolerance of grafted cucumbers caused by two types of rootstocks.


The relationship between sleep disturbance and pulmonary function in stable pediatric cystic fibrosis patients.
Cystic fibrosis (CF) is the most common inherited disease affecting northern European populations. It is characterized by a progressive clinical course that causes diurnal and nocturnal pulmonary and gastrointestinal symptoms. To determine whether clinically stable pediatric patients with CF have lower sleep efficiency than healthy control subjects, and to examine the relationship between sleep efficiency and pulmonary function. Forty-four CF patients and 40 control subjects completed 5 days of actigraphy recordings. Additionally, sleep questionnaires were independently completed by all study participants and their parents. Pulmonary function testing was performed in all patients with CF. Multiple regression analysis was used to measure the independent correlation between sleep variables and pulmonary function. CF patients had significantly lower sleep efficiency than control subjects. The FEV1 of these patients correlated positively with sleep duration and efficiency, and negatively with the number and duration of nocturnal awakenings, age, and body mass index (BMI). The independent effect of FEV1 on sleep was first examined. Age and FEV1 were the only variables that predicted sleep duration (R2 = 0.3; p = 0.0007), while FEV1 was the only variable predicting sleep efficiency (R2 = 0.28; p = 0.0002). When the independent effect of sleep on FEV1 was analyzed, sleep efficiency, BMI percentile, and gender predicted FEV1 (R2 = 0.46; p < or = 0.0001). The frequency of nocturnal cough reported by patients and their parents was an independent predictor of FEV1. Pediatric patients with CF and stable pulmonary function have lower sleep efficiency and more frequent nocturnal awakenings than do healthy control subjects. After adjustment for demographic characteristics, there was an independent and significant correlation between sleep parameters and FEV1, when either sleep variables or FEV1 were used as dependent variables. These findings suggest a bidirectional relationship between sleep disturbance and CF lung disease.


Haematology, physiological parameters, morphometry and parasitological status of rescued bearded capuchin monkeys (Sapajus libidinosus).
There are few studies on the physiology and haematology of rescued bearded capuchin monkeys. These are necessary to better understand the health and welfare status of the animals, including when performing reintroductions, and to avoid zoonoses. We aimed to obtain physiological and haematological values, morphometry and parasitological status of 26 bearded capuchins in two rescue centres in Northeast Brazil. We found sex- and age-related differences in respiratory rate, body weight and body mass index, but not haematology. The haematological values obtained were significantly different from published data but within the reference intervals for the species. Animals infected with Ancylostoma spp. had significantly lower values in the parameters: haemoglobin concentration, mean corpuscular volume and mean corpuscular haemoglobin concentration than non-infected individuals. Physiological and haematological values of rescued capuchins were similar to those found in previous studies. Ancylostomiasis appears to cause alterations to haematological values of this species.


Sensitive determination of polychlorinated biphenyls in environmental water samples by headspace solid-phase microextraction with bamboo charcoal@iron oxide black fibers prior to gas chromatography with tandem mass spectrometry.
We have investigated the feasibility of bamboo charcoal@iron oxide black for the headspace solid-phase microextraction of polychlorinated biphenyls in environmental water samples. Bamboo charcoal@iron oxide black was prepared and used as a solid-phase microextraction coating material, and gas chromatography with tandem mass spectrometry was used for detection. Several important factors affecting the extraction efficiency were systematically investigated and optimized. Under the optimum conditions, the experimental data exhibited wide linear range over the range 0.2-1000 ng/L and low limits of detection in the range of 4.7-22.2 pg/L. The novel coating was successfully used for the enrichment and determination of polychlorinated biphenyls in real environmental water samples. All these results indicated that bamboo charcoal@iron oxide black-based headspace solid-phase microextraction coupled to gas chromatography with tandem mass spectrometry was an excellent alternative for the sensitive analysis of polychlorinated biphenyls at ultratrace levels in the environment.


Cerebral cavernous malformation remnants after surgery: a single-center series with long-term bleeding risk analysis.
The aim of this work is to investigate the long-term bleeding risk of cerebral cavernous malformation (CCM) remnants. A review of clinical, radiological, operative, and post-operative data of a cerebral cavernous malformation (CCMs) prospective database was performed. Fisher's exact test and Mann-Whitney U-test were used to assess differences between non-hemorrhagic and hemorrhagic CCM remnants for 14 variables. Recursive partitioning analysis was performed to assess the order of variables most associated with CCM remnant bleeding. Twenty-four patients out of 126 had a CCM post-surgical remnant. Of these, 7 had at least one post-operative hemorrhagic event. The mean follow-up was 80.7 months (range 12-144). CCM post-surgical remnant bleeding presented mostly with acute headache (50%) and focal neurological deficit (25%); in the remaining cases, the hemorrhage was asymptomatic. Retreatment was performed in two patients, with surgery and radiosurgery, respectively; no treatment was performed in the majority of cases. All patients ranked as non-II, according to Zabramski classification, did not show any post-surgical bleeding. The presence of a pre-operative perilesional hemosiderin ring was highly significant in predicting post-surgical bleeding (sensitivity = 0.94, specificity = 0.88) and incorrectly predicted bleeding in only two of the 24 patients. This study provides an evaluation of clinical and radiological factors influencing the bleeding risk of a CCM post-surgical remnant in a homogeneous population. Perilesional hemosiderin ring and Zabramski Type II appear to strongly condition the bleeding risk of a CCM post-surgical remnant.


A possible mechanism of action for azelaic acid in the human epidermis.
Azelaic acid, and other saturated dicarboxylic acids (C9-C12), are shown to be competitive inhibitors of tyrosinase (KI azelaic acid = 2.73 X 10(-3) M) and of membrane-associated thioredoxin reductase (KI azelaic acid = 1.25 X 10(-5) M). The monomethyl ester of azelaic acid does not inhibit thioredoxin reductase, but it does inhibit tyrosinase, although double the concentration is necessary compared with azelaic acid (KI azelaic acid monomethyl ester = 5.24 X 10(-3) M). Neither azelaic acid nor its monomethyl ester inhibit tyrosinase when catechol is used as a substrate instead of L-tyrosine. Therefore, the weak inhibitory action of azelaic acid on tyrosinase appears to be due to the competition of a single carboxylate group on this inhibitor for the alpha-carboxylate binding site of the L-tyrosine substrate on the enzyme active site. Based on the inhibitor constant on tyrosinase, at least cytotoxic levels of azelaic acid would be required for the direct inhibition of melanin biosynthesis in melanosomes if this mechanism is responsible for depigmentation in the hyperpigmentation disorders lentigo maligna and melasma. Alternatively only 10(-5) M azelaic acid is required to inhibit thioredoxin reductase. This enzyme is shown to regulate tyrosinase through a feedback mechanism involving electron transfer to intracellular thioredoxin, followed by a specific interaction between reduced thioredoxin and tyrosinase. Furthermore, the thioredoxin reductase/thioredoxin system is shown to be a principal electron donor for the ribonucleotide reductases which regulates DNA synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)


Urchin-like fluorinated covalent organic frameworks decorated fabric for effective self-cleaning and versatile oil/water separation.
Oil contamination and industrial organic pollutants emission have been a serious problem affecting the ecological and residential environment. Membrane-based separation shows great application prospect due to its low-cost, environmental-friendly and easy operation. Therefore, the development of efficient oil-water separation membranes is highly desirable. Herein, a fabric filter with superwettability was prepared by coating urchin-like fluorinated covalent organic frameworks (COFs) on fabric, which was well utilized in filtering immiscible oil-water mixture and surfactant-stabilized water-in-oil emulsion driven only by gravity for the first time. The as-prepared COF fabric filter (defined as fabric@u-FCOF) possessed many outstanding properties, including superhydrophobicity with the water contact angle of approximately 151.6°, satisfactory resistance for alkaline, acidic and saline environments, as well as superior mechanical durability under harsh conditions. Because of the super-micropore of fabric@u-FCOF and the nanopore in the COF coating, the obtained fabric@u-FCOF exhibited excellent performances in terms of separation efficiency and permeability, in which the oil flux was up to 16964 L·m-1·h-2 and separation efficiency for the mixed o-dichlorobenzene/water was higher than 99.4%. In addition, the fabric@u-FCOF also showed excellent self-cleaning performance due to the micro/nano hierarchical structure of its surface. These excellent properties make it an ideal candidate for applications of oil/water separation and water purification.


Involvement of VEGFR-2 (kdr/flk-1) but not VEGFR-1 (flt-1) in VEGF-A and VEGF-C-induced tube formation by human microvascular endothelial cells in fibrin matrices in vitro.
Different forms of vascular endothelial growth factor (VEGF) and their cellular receptors (VEGFR) are associated with angiogenesis, as demonstrated by the lethality of VEGF-A, VEGFR-1 or VEGFR-2 knockout mice. Here we have used an in vitro angiogenesis model, consisting of human microvascular endothelial cells (hMVEC) cultured on three-dimensional (3D) fibrin matrices to investigate the roles of VEGFR-1 and VEGFR-2 in the process of VEGF-A and VEGF-C-induced tube formation. Soluble VEGFR-1 completely inhibited the tube formation induced by the combination of VEGF-A and TNF alpha (VEGF-A/TNF alpha). This inhibition was not observed when tube formation was induced by VEGF-C/TNF alpha or bFGF/TNF alpha. Blocking monoclonal antibodies specific for VEGFR-2, but not antibodies specifically blocking VEGFR-1, were able to inhibit the VEGF-A/TNF alpha-induced as well as the VEGF-C/TNF alpha-induced tube formation in vitro. P1GF-2, which interacts only with VEGFR-1, neither induced tube formation in combination with TNF alpha, nor inhibited or stimulated by itself the VEGF-A/TNF alpha-induced tube formation in vitro. These data indicate that VEGF-A or VEGF-C activation of the VEGFR-2, and not of VEGFR-1, is involved in the formation of capillary-like tubular structures of hMVEC in 3D fibrin matrices used as a model of repair-associated or pathological angiogenesis in vitro.


Production of a recombinant capsid protein VP1 from a newly described polyomavirus (RacPyV) for downstream use in virus characterization.
Here we describe the methods for production of a recombinant viral capsid protein and subsequent use in an indirect enzyme linked immunosorbent assay (ELISA), and for use in production of a rabbit polyclonal antibody. These reagents were utilized in development and optimization of an ELISA, which established the extent of exposure of free ranging raccoons to a newly described polyomavirus (RacPyV) [1]. Production of a polyclonal antibody has allowed for further characterization of RacPyV, including immunohistochemistry and immunocytochemistry techniques, in order to answer questions about pathogenesis of this virus.


Public-private partnership in care provision for ageing-in-place: A comparative study in Guangdong, China.
This paper investigates how the public-private partnership (PPP) functions in the care provision for older people in Guangdong, China, particularly for ageing-in-place programs. Three cities with diversified PPP forms of care provision for older people were chosen as case studies. Focus groups were conducted in these cities for the local authorities and care homes involved in the partnerships. Three forms of PPP, including private sector involvement for the ownership, construction, and operation of the facilities delivering care services, were identified. The public-private co-constructed and privately run model with greater private sector involvement may lead to higher quality care in one specific program. The publicly constructed and privately run program is widely used in many cities, advancing the expansion of ageing-in-place programs in more communities. These PPPs reflect flexible and practical collaboration between the public and private sectors at the local level in the Chinese context. PPP have accelerated the development of a better care system for older people, mainly in terms of more affordable and higher-quality care options for the public. They are also a feasible solution for the local government due to more cost-effective and sustainable care provisions than previous publicly provided programs. The specific forms adopted are primarily associated with the scale of home care provision for ageing-in-place and the local government's financial capacity. Despite increasing private sector involvement, the public sector retains its crucial role in delivering care services targeting ageing in China.


Industry Bias in Randomized Controlled Trials in General and Abdominal Surgery: An Empirical Study.
Industry sponsorship has been identified as a source of bias in several fields of medical science. To date, the influence of industry sponsorship in the field of general and abdominal surgery has not been evaluated. A systematic literature search (1985-2014) was performed in the Cochrane Library, MEDLINE, and EMBASE to identify randomized controlled trials in general and abdominal surgery. Information on funding source, outcome, and methodological quality was extracted. Association of industry sponsorship and positive outcome was expressed as odds ratio (OR) with 95% confidence interval (CI). A χ test and a multivariate logistic regression analysis with study characteristics and known sources of bias were performed. A total of 7934 articles were screened and 165 randomized controlled trials were included. No difference in methodological quality was found. Industry-funded trials more often presented statistically significant results for the primary endpoint (OR, 2.44; CI, 1.04-5.71; P = 0.04). Eighty-eight of 115 (76.5%) industry-funded trials and 19 of 50 (38.0%) non-industry-funded trials reported a positive outcome (OR, 5.32; CI, 2.60-10.88; P < 0.001). Industry-funded trials more often reported a positive outcome without statistical justification (OR, 5.79; CI, 2.13-15.68; P < 0.001). In a multivariate analysis, funding source remained significantly associated with reporting of positive outcome (P < 0.001). Industry funding of surgical trials leads to exaggerated positive reporting of outcomes. This study emphasizes the necessity for declaration of funding source. Industry involvement in surgical research has to ensure scientific integrity and independence and has to be based on full transparency.


Detection, isolation, and identification of cadmium-resistant bacteria based on PCR-DGGE.
This study focused on the screening of cadmium-resistant bacterial strains from Pb-Zn tailing. We investigated the diversity of microbial community inhabiting Dong-san-cha Pb-Zn tailing in Beijing, China, by polymerase chain reaction-denaturing gradient gel electrophoresis (DGGE) of 16S rRNA gene of bacterial strain, and found two dominant strains in the DGGE profile. Using special culture media, we isolated two strong cadmium-resistant bacterial strains. On the basis of morphological, physiological, and biochemical characteristics, BIOLOG, and 16S rDNA sequencing, the two strains were identified as Bacillus cereus and Enterobacter cloacae. Minimal inhibitory concentrations (MICs) of heavy metals for the bacteria were determined. E. cloacae showed higher MIC values for heavy metals and a larger range of antibiotic resistance than B. cereus.


Topographical brain electrical activity mapping on an IBM-compatible personal computer.
A new system for computing brain electrical activity maps on a standard IBM-compatible computer has been developed. The EEG is recorded using a CED1401 intelligent laboratory interface and stored in the computer; colour coded maps are generated using software developed in Turbo PASCAL and displayed on the EGA graphics screen. An acceptable computation time of 1.2 s for a 64 x 64 map displayed as a 128 x 128 pixel image has been achieved by incorporating assembly language routines and a maths coprocessor. The system may be readily upgraded as improved hardware becomes available and further software can be added. In addition to triggering auditory, visual and somatosensory stimulators, it provides the potential for the generation of complex stimuli for cognitive experiments by means of mass RAM and digital-to-analogue converters.


[Clinical features and managements of breast cancer patients with pulmonary metastasis].
One hundred-thirty-nine patients with advanced breast cancer were treated during five years since 1977 in our Department. Treatments consisted of chemotherapy (ACF and ACFM), hormone therapy (tamoxifen) and their combination (ACFT). Seventy patients had lung metastases at the initiation of these therapies. An overall response rate was 41%, whereas a response rate for metastatic lung lesions was 26% (18/69). Breast cancer is known as a systemic disease, thus other therapies such as pulmonary resection or irradiation had a limited indication to control the lung metastasis. Our result indicates that favorable responses to advanced breast cancer with systemic therapies will improve the prognosis of breast cancer patients with lung metastasis.


Serotonergic mediation of the brain-wide neurogenesis: Region-dependent and receptor-type specific roles on neurogenic cellular transformation.
Brain serotonin (5-hydroxytryptamine, 5-HT) is a key molecule for the mediation of depression-related brain states, but the neural mechanisms underlying 5-HT mediation need further investigation. A possible mechanism of the therapeutic antidepressant effects is neurogenic cell production, as stimulated by 5-HT signaling. Neurogenesis, the proliferation of neural stem cells (NSCs), and cell differentiation and maturation occur across brain regions, particularly the hippocampal dentate gyrus and the subventricular zone, throughout one's lifespan. 5-HT plays a major role in the mediation of neurogenic processes, which in turn leads to the therapeutic effect on depression-related states. In this review article, we aim to identify how the neuronal 5-HT system mediates the process of neurogenesis, including cell proliferation, cell-type differentiation and maturation. First, we will provide an overview of the neurogenic cell transformation that occurs in brain regions containing or lacking NSCs. Second, we will review brain region-specific mechanisms of 5-HT-mediated neurogenesis by comparing regions localized to NSCs, i.e., the hippocampus and subventricular zone, with those not containing NSCs. Highlighting these 5-HT mechanisms that mediate neurogenic cell production processes in a brain-region-specific manner would provide unique insights into the role of 5-HT in neurogenesis and its associated effects on depression.


Integrated survey on the heavy metal distribution, sources and risk assessment of soil in a commonly developed industrial area.
The Jiangzhe Area was relatively common area that rely on industrial process for rapid development with serious heavy metals contamination. This study investigated the spatial, vertical and speciation distribution, correlation of heavy metals, as well as assessed pollution and health risks in three representative contamination industries at Jingjiang (electroplating site), Taizhou (e-waste recycling site) and Wenzhou (leather production site) in the Jiangzhe Area. The results indicated that the Cr(VI) pollution was serious in all three sites and there was a tendency to gradually decrease with depth. As for other heavy metals, not only the total concentration, but also the addition of acid soluble and reducible speciation generally decreased with soil depth at Jingjiang and Taizhou sites. Significantly positive correlations supported by correlation analysis were detected between the following elements: Cu-Ni (p < 0.01), Cr(VI)-Ni (p < 0.05) and Cr(VI)-Cu (p < 0.05) at Jingjiang site, Cu-Ni (p < 0.01), Cu-Cd (p < 0.01) and Ni-Cd (p < 0.05) at Taizhou site indicating possibly the same sources and pathways of origin, while the significantly negative correlation of Cd-Ni (p < 0.05) at Wenzhou site meaning the different sources. As regards the pollution assessment of topsoil, the mean PI value indicated that Cr(VI) contaminated severe in all three sites. In general, Jingjiang site was severe pollution (4.06), while Taizhou and Wenzhou (2.27 and 2.66) were moderate pollution, as NIPI value shown. In terms of health risk assessment that received much attention, non-carcinogenic risks caused by Pb contamination were significant for children at Jingjiang and Taizhou sites, with the HI values of 3.42E+ 00 and 2.03E+ 00, respectively. Ni caused unacceptable carcinogenic risk for both adults and children at all three sites. The present study can help to better understand the contamination characteristics of heavy metals in the commonly developed industrial area, and thus to control the environmental quality, so as to truly achieve the goal of "Green Deal objectives ".


Restoring Dystrophin Expression by Skipping Exons 6 and 8 in Neonatal Dystrophic Dogs.
Duchenne muscular dystrophy (DMD) is caused by the mutations in the DMD gene resulting in no dystrophin production. Skipping DMD exons using phosphorodiamidate morpholino oligomers (PMOs) is an emerging treatment strategy that can restore the reading frame of the mutated gene and produce truncated but functional dystrophin protein. To date, four PMOs, including eteplirsen, casimersen, viltolarsen, and golodirsen, have been conditionally approved by the FDA for the treatment of DMD. Since degeneration of muscle fibers and irreversible fibrosis occur from childhood, the earlier treatment is preferred. The canine X-linked muscular dystrophy in Japan (CXMDj), a dog model of DMD, produces no dystrophin and exhibits a severe phenotype similar to human patients from early childhood. As such, CXMDj, which harbors a splice site mutation in intron 6, is a useful model for examining the long-term effects of early PMO treatment. In this chapter, we describe the systemic delivery of a cocktail of four PMOs that can successfully induce multiple exon skipping (exons 6-9) in neonatal dystrophic dogs. We also describe the procedures to evaluate the efficacy and toxicity, including clinical grading of dystrophic dogs, ELISA-based quantification of PMOs, histology, RT-PCR, and western blotting.


Erectile dysfunction and silent coronary artery disease: abnormal computed tomography coronary angiogram in the presence of normal exercise ECGs.
Erectile dysfunction (ED) and coronary artery disease (CAD) frequently coexist. ED may be present in the absence of cardiac symptoms 3-5 years before a coronary event. Exercise electrocardiography may identify flow-limiting CAD but cardiac computed tomography (CT) may identify early non-calcified plaque disease potentially vulnerable to rupture precipitating an acute event. Twenty men aged 39-69 years with ED and no cardiac symptoms underwent screening for cardiovascular risk including maximal treadmill exercise testing and CT coronary angiography. ED was confirmed using the Sexual Health Inventory for Men questionnaire. Eighteen had a low-density lipoprotein cholesterol > 3 mmol/l, none were diabetic and seven were hypertensive controlled on medical therapy. Coronary calcium scores were > 50 in 11 men (range: 54-1234) all of whom had angiographic CAD on CT. Nine of these had normal exercise ECGs. Four men had calcium scores of 6-17 and single plaque disease on CT. Five had normal cardiac CT studies. Erectile dysfunction may be a predictor of subclinical non-flow limiting CAD not detectable on exercise electrocardiography. Men with organic ED and no cardiac symptoms should be considered as 'cardiac equivalents' and aggressive risk reduction therapy initiated.


Enhancement of trypsin-induced contraction by in vivo treatment with 17beta-estradiol and progesterone in rat myometrium.
We have previously reported that the contractile response to thrombin and trypsin was enhanced in the pregnant rat myometrium. We herein determined whether or not sex hormones contribute to this enhancement and the expression of protease-activated receptors (PARs). The nonpregnant rats received daily injections of either 17beta-estradiol or progesterone, and then the contractile response of the myometrium was examined ex vivo. Treatment with either 17beta-estradiol or progesterone had almost no significant enhancing effect on the high K(+)- or oxytocin-induced contraction. On the other hand, both 17beta-estradiol and progesterone dose-dependently enhanced the contractile response to trypsin. A maximal enhancement was obtained at 25 and 40 mg kg weight(-1) day(-1) for 17beta-estradiol and progesterone, respectively. The extent of the enhancement of the trypsin-induced contraction seen in the sex hormone-treated rats in the present study was comparable to that reported in the pregnant rats. However, the contractile response to thrombin and PAR1/PAR2-AP, SFLLRNP was not enhanced either by progesterone or 17beta-estradiol. PAR2-AP and PAR4-AP failed to induce contraction under any conditions. PAR1 mRNA was scarcely detected in the control myometrium by an RT-PCR analysis, while it slightly increased only in the progesterone-treated rats. Neither PAR2 nor PAR4 mRNA was detected. We thus conclude that the responsiveness to trypsin, but not thrombin, is controlled by sex hormones. A novel type of receptor, other than PAR1, PAR2 or PAR4, is suggested to mediate the trypsin-induced contraction as in the case of the pregnant rat myometrium.


Laparoscopic Discoid Excision of Bowel Endometriosis Using Sutures for Closure.
To demonstrate the technique of discoid excision of bowel endometriosis followed by closure of the bowel defect using sutures, without the application of the transanal stapler device. Stepwise demonstration of the technique with narrated video footage. Bowel endometriosis is a common pattern of deep endometriosis [1]. Discoid excision is 1 of the 3 surgical interventions applied to manage this pathologic entity, with shaving and segmental resection being the other 2 [2]. When discoid excision is performed, a transanal stapler device is used for bowel closure in most cases [3,4]. Only a few studies so far have reported the application of sutures for this purpose [5]. This video highlights the technique of bowel suturing after discoid excision. This video presents the technique of bowel discoid excision with the application of sutures to close the bowel defect (Supplemental Video 1). The key surgical steps are as follows: 1. Dissection of both ureters and development of pararectal spaces. 2. Recognition and preservation of the inferior hypogastric plexus and the hypogastric nerve. 3. Detachment of the nodule from the cervix. 4. Detachment of the nodule from the bowel, beginning with deep shaving and followed by discoid excision. 5. Thorough description of the bowel closure using 2 layers of Vicryl 3-0 sutures, the first being interrupted and the second continuous. The described technique of bowel closure using sutures may be a safe and effective alternative to the transanal stapler. Its advantage is that it can be performed when the pathology is located higher than 15 cm from the anal verge or the diameter of the nodule is more than 30 mm.


Sharp Sobolev Inequalities via Projection Averages.
A family of sharp L p Sobolev inequalities is established by averaging the length of i-dimensional projections of the gradient of a function. Moreover, it is shown that each of these new inequalities directly implies the classical L p Sobolev inequality of Aubin and Talenti and that the strongest member of this family is the only affine invariant one among them-the affine L p Sobolev inequality of Lutwak, Yang, and Zhang. When p = 1 , the entire family of new Sobolev inequalities is extended to functions of bounded variation to also allow for a complete classification of all extremal functions in this case.


Regulation of cell surface protease receptor S100A10 by retinoic acid therapy in acute promyelocytic leukemia (APL)☆.
S100A10 (p11), a member of the S100 family of small dimeric EF-hand-type Ca2+-binding proteins, plays a role in a variety of both intracellular and extracellular processes. Previous studies have suggested that p11 is intrinsically unstable and requires binding to annexin A2 (p36) to prevent its rapid ubiquitylation and degradation. Our laboratory has shown that p11 levels are stimulated by the expression of the oncoprotein, PML/RARα. Furthermore, treatment of the APL cell line, NB4 with all-trans retinoic acid (ATRA) causes the rapid loss of p36 and p11 protein. However, the mechanism by which ATRA regulates p11 levels has not been established. Here, we show that the proteasomal inhibitor, lactacystin reversed the ATRA-dependent loss of p11, but did not cause an accumulation of ubiquitylated forms of p11, suggesting that ATRA promotes the proteasomal degradation of p11 in an ubiquitin-independent manner. ATRA treatment of MCF-7 breast cancer cells reduced p11 but not p36 transcript and protein levels, thus indicating that ATRA can regulate p11 levels independently of PML/RARα and p36. Overexpression of p36 upregulated p11 protein but not mRNA levels, indicating that p36 affects p11 post translationally. The forced expression of ubiquitin and p11 in 293 T cells resulted in ubiquitylation of p11 that was blocked by mutagenesis of lysine 57. This study highlights the complex regulation of p11 by retinoid signaling and challenges the hypothesis that ubiquitin-mediated proteasomal degradation of p11 represents a universal mechanism of regulation of this protein.


Epidemiological, clinical and viral characteristics of fatal cases of human avian influenza A (H7N9) virus in Zhejiang Province, China.
The high mortality of avian influenza H7N9 in humans is a cause of great concern in China. We compared epidemiological, clinical and viral features of H7N9 influenza of 10 fatal cases and 30 survivors. Increasing age (p = 0.021), smoking (p = 0.04), underlying medical background (p = 0.05) and chronic drug use (p = 0.042) had a strong relationship with death due to H7N9 infection. Serological inflammatory markers were higher in fatal cases compared to survivors. Acute respiratory distress syndrome (100%), respiratory failure (100%), co-infection with bacteria (60%), shock (50%) and congestive heart failure (50%) were the most common complications observed in fatal cases. The median time from onset of symptoms to antiviral therapy was 4.6 and 7.4 days in those who survived and those who died, respectively (p = 0.04). Viral HA, NA and MP nucleotide sequences of isolates from both study groups exhibited high molecular genetic homology. Age along with a history of smoking, chronic lung disease, immuno-suppressive disorders, chronic drug use and delayed Oseltamivir treatment are risk factors which might contribute to fatal outcome in human H7N9 infection.


Effects of intestinal alkaline phosphatase on intestinal barrier function in a cecal ligation and puncture (CLP)-induced mouse model for sepsis.
Sepsis is a severe pathological condition associated with systemic inflammation, intestinal inflammation, and gastrointestinal barrier dysfunction. Intestinal alkaline phosphatase (IAP) has been demonstrated to detoxify lipopolysaccharide, an important mediator in the pathophysiology of sepsis. We investigated the effect of treatment with IAP on intestinal permeability, intestinal inflammation, and bacterial translocation. OF-1 mice were divided into 4 groups (n = 12/group), undergoing either a sham or cecal ligation and puncture (CLP) procedure to induce sepsis. Mice received IAP or a vehicle intraperitoneally 5 minutes prior to the onset of the CLP or sham procedure, which was repeated every 12 hours for two consecutive days. After two days, in vivo intestinal permeability, intestinal inflammation, and bacterial translocation were determined. CLP-induced sepsis resulted in significantly more weight loss, worse clinical disease scores, bacterial translocation, and elevated inflammatory cytokines. Intestinal permeability was increased up to 5-fold (P < .001). IAP activity was significantly increased in septic animals. Treatment with IAP had no effect on clinical outcomes but reduced the increased permeability of the small intestine by 50% (P = .005). This reduction in permeability was accompanied by a modified gene expression of claudin-1 (P = .025), claudin-14 (P = .035), and interleukin 12 (P = .015). A discriminant analysis showed that treatment with IAP is linked to modified mRNA levels of several tight junction proteins and cytokines. Treatment with IAP diminished CLP-induced intestinal barrier disruption, associated with modified expression of several cytokines and claudins. Nevertheless, this effect did not translate into better clinical outcomes in our experimental setup.


Development of myocardial perfusion tracers for positron emission tomography.
Six positron-emitting cations were investigated as possible perfusion tracers: [13N]NH4, 38K, 51Mn, 52mMn, 81Rb, and 82Rb. Aspects of the production of the radionuclides and their separations from the irradiated target materials were addressed. The thick target, saturated yields of several nuclear reactions leading to these radionuclides were studied theoretically and experimentally in the energy range 6-10 MeV. A figure-of-merit describing the production aspects of each tracer was calculated, and tomographic imaging results in normal human subjects were reported.


Misoprostol induces cervical nitric oxide release in pregnant, but not in nonpregnant, women.
The cells of the human uterine cervix synthesize nitric oxide, which may be a factor in cervical ripening. We studied the effect of misoprostol on cervical nitric oxide release in nonpregnant and pregnant women. Seventy-two nonpregnant (n=15) and pregnant (n=57; 26 in early pregnancy, 31 in late pregnancy) women were treated with either vaginal misoprostol (n=54) or vaginal placebo (n=18). The dose of misoprostol was 400 mug in nonpregnant and early pregnancy group, and 25 mug in late pregnancy group. Serial cervical fluid samples, collected before and up to 3 hours after misoprostol/placebo, were assessed for the concentration of nitric oxide metabolites by means of the Griess reaction. Placebo had no effect on cervical fluid nitric oxide metabolite level. In 1 to 3 hours, misoprostol induced 4.3- to 5.2-fold elevations in cervical fluid Nox concentrations in early pregnancy (P < .01), and 4.4- to 18.2-fold elevations in late pregnancy (P < .01), but these responses did not differ significantly from each other. Misoprostol had no effect on cervical fluid nitric oxide metabolites in nonpregnant women. There was a trend towards a relationship between cervical nitric oxide stimulation after misoprostol and cervical ripening. Vaginal misoprostol stimulates cervical nitric oxide release in pregnancy. This suggests a joint action of nitric oxide and prostaglandins in cervical ripening.


Immediate sterility after vasectomy.
Phenyl mercuric nitrate as an injection, in a dilution of 0-02% and buffered to pH 7, is a potent spermicidal agent which has been demonstrated to have no harmful side effects. It produces rapid death of all spermatozoa on contact. The injection of 2-5 ml of the solution into the lumen of each vas at the time of vasectomy is a simple procedure and adds no significant time and no complications to the operation. Studies have shown that no viable spermatozoa were present at seminal counts carried out one or two weeks after operation.


Correction: Rubnawaz et al. Polyphenol Rich Ajuga bracteosa Transgenic Regenerants Display Better Pharmacological Potential. Molecules 2021, 26, 4874.
The authors of this paper [...].


Conservative Management of Cervical Ectopic Pregnancy.
To evaluate the safety and effectiveness of conservative management for cervical ectopic pregnancies. We conducted a retrospective review of all cases of cervical ectopic pregnancy diagnosed at our tertiary care academic centre between January 2002 and July 2014. The diagnosis of cervical ectopic pregnancy was made using transvaginal ultrasound according to published criteria. Management decisions were made by individual clinicians. Cervical ectopic pregnancy was diagnosed in 27 women with a median age of 34 years. Two thirds of them were nulliparous, and 44% (12/27) reported infertility. The mean gestational age at diagnosis was seven weeks. The median serum human chorionic gonadotropin level was 11 300 IU/L (range 610 to 163 700). Fetal cardiac activity was present in 19 pregnancies (70%). Vaginal bleeding was the most common presentation, occurring in 23 cases (85%). Three women presented with acute life-threatening hemorrhage. All cases were successfully managed conservatively, allowing uterine preservation. Systemic methotrexate (single or multi-dose protocol) was the mainstay of therapy. Other minimally invasive interventions included ultrasound-guided injection of potassium chloride into the pregnancy, uterine artery embolization, vaginal ligation of cervical branches of the uterine arteries, and dilatation and curettage, with or without dilute vasopressin cervical infiltration and Foley catheter tamponade. Systemic methotrexate alone or in combination with other minimally invasive techniques can be effective conservative treatment for cervical pregnancies. A fertility-sparing approach is the optimal treatment for this patient population, which has high rates of infertility and nulliparity. We present a management algorithm based on our results to aid in standardizing the management of cervical ectopic pregnancies.


Analysis of weight at birth and at diagnosis of childhood-onset type 2 diabetes mellitus in Japan.
The prevalence of childhood-onset type 2 diabetes mellitus (T2DM) has increased dramatically over the past two to three decades in Japan, but epidemiological and clinical data remain limited. Several epidemiological studies stress the importance of elucidating the pathophysiology of prenatal nutrition and other intra-uterine environmental factors and the risk of T2DM in each of the different populations. We examined the associations of weight at birth, weight at diagnosis of T2DM, and clinical characteristics of childhood-onset T2DM. Clinical data sheets were sent to councillors of the Japanese Society for Pediatric Endocrinology (JSPE) and members of the Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT) in June 2003. Clinical data on 259 children (9-17 yr of age) categorized as T2DM by pediatric endocrinologists, who are members of the JSPE and/or JSGIT, using 1999 Japan Diabetes Society criteria were analyzed. Degree of overweight was assessed by percent overweight and standard deviation score-body mass index. The age (mean +/- SD) of the 259 patients recruited (121 boys and 138 girls) was 11.9 +/- 2.1 yr at diagnosis and 14.4 +/- 2.0 yr at the time of the survey. Sixty-nine percent of all patients were obese (percent overweight >or=20%) at the time of diagnosis. Obese patients were older at the time of diagnosis and had a higher level of hemoglobin A1c (HbA1c) at diagnosis than non-obese patients (p < 0.05), and there were fewer girls than boys. Twenty two (11.3%) of 195 patients had low birth weights (<2500 g) and 19 (9.7%) had high birth weights (>or=4000 g). The frequencies of low and high birth weights were higher among patients with T2DM than among a control group, producing a U-shaped distribution (p < 0.05). The frequency of a family history of diabetes was lower among low-birth weight patients. In contrast, high-birth weight patients had a higher prevalence of diabetic mothers and medication including insulin therapy (p < 0.05). Obesity was shown to be a major risk factor for childhood-onset T2DM in Japan. The frequencies of low and high birth weights were higher among patients with T2DM, and differences in clinical characteristics, such as family history of diabetes, were recognized among patients with T2DM with low, normal, and high birth weights.


Effect of anesthetics on the heart.
In man, high doses of the "group 1" inhalation anesthetics (diethylether, cyclopropane, and fluroxene) produce relatively minor depression of ventricular function, although it is possible to depress the heart if the dose is great enough. The "group 2" drugs (halothane, methoxyflurane, etc.) produce dose-related depression in cardiac function, but reasonable caridac outputs and blood pressure can be maintained at light anethetic levels. Much the same can also be said for the intravenous barbiturates and other hypnotics. If ventilation is supported and hypovolemia avoided, large doses of the narcotic analgesics appear to produce minimal cardiac effects. The only intravenous drug which stimulates the heart is the dissociative anesthetic ketamine, and this is probably an autonomic, reflex phenomenon (as with group 1 inhalation anesthetics). Regional anesthesia and the neuromuscular blocking drugs appear to have relatively little effect on ventricular function. Most of the work in man on the effect of anesthetics has been in healthy patients or volunteers. The effects on patients with severe heart or other systemic disease may well be different. In fact, low concentrations of fluroxene have been shown to produce significant depression of stroke volume in patients with aortic vavular disease in contrast to the effects on healthy volunteers. All potent central nervous system depressant drugs possess the potential for significant cardiac depression. If such depression is undersirable in a particular patient, the only safe way to administer anesthesia is by careful titration of the dose against the best measurement of cardiac function which is available. At the present time, this would mean measuring at least direct arterial pressure, central venous pressure, and a continuous electrocardiogram. The optimal management would prpbably include recording systolic time intervals, pulmonary capillary wedge pressure, and some measure of cardiac output as well. All the skill and pharmacologic knowledge available connot substitute for vigilant monitoring and carful tiration of drug dose in the clinical situation.


77Br-p-bromospiperone: a ligand for in vivo labelling of dopamine receptors.
A high striatum: cerebellum ratio of 77Br-p-bromospiperone (77Br-BrSp) was observed in rat brain following tail vein injection of the drug. Striatal 77Br-BrSp was stereospecifically displaced by the isomers of flupenthixol. After chronic haloperidol administration striatal dopamine receptor supersensitivity was demonstrated both by increased 3H-spiperone binding to striatal membranes in vitro and by increased striatal 77Br-BrSp content. These results confirm and extend previous findings and enhance interest in the use of 77Br-BrSp for the in vivo assessment of central dopamine receptors in man.


Psychological counselling in patients with a peripheral facial palsy: initial experience from an expert centre.
The aims of this pilot study were to evaluate the psychologist's role on the multidisciplinary team during peripheral facial palsy (PFP) patient care and to identify the potential predictors of anxiety and depressive symptoms/disorders in PFP patients. Using the prospective non-controlled study design, PFP patients aged 18-75 years who presented to the Radboud Facial Palsy Expert Centre, the Netherlands, were enrolled during a 1-year interval. The main outcome variables were 1) anxiety and depression in relation to PFP using the Hospital Anxiety and Depression Scale (HADS) and 2) the outcome of psychological counselling in patients with a HADS score ≥ 8. A sample comprised 25 patients (68% females, 56% right-side PFP, 16% House-Brackmann scale I-II) with a mean age of 50 ± 14 years were referred to a psychologist. The proportion of patients with a HADS score ≥8, were 16 (64%) and 13 (52%), respectively. Especially, coping (in general or coping with the disease, 48%) and/or help with the choice of possible surgery (8.0%) were important reasons for counselling. In one case, a patient had chronic fatigue syndrome and was therefore referred to a psychological specialist centre. One patient was treated with acceptance and commitment therapy (ACT) with good results. Despite a small sample size and limited statistical analyses, the results of this study suggest that one-eighth of the PFP patients require psychological evaluation and treatments. This pilot study emphasises the important role of psychological screening and counselling in PFP patient care.


A historical vignette. The imagination and medical nomenclature; Teutonic mythology as a presence in ENT and related fields.
The imagination is one of the sources of inspiration for medical nomenclature, as can be seen when nomenclature reflects mythology. In this paper, we consider Teutonic (Scandinavian, Germanic) mythology as it appears in the field of minerals, in the field of hearing and in the field of respiration. As far as hearing is concerned, the author suggests naming "Heimdall's ear" physiological hyperacusis.


Unaltered innervation of the human cervix uteri in contrast to the corpus during pregnancy and labor as revealed by PGP 9.5 immunohistochemistry.
To examine the occurrence of the general neuronal marker protein gene product 9.5 (PGP 9.5) in the human corpus (isthmus region) and the cervix uteri during pregnancy and parturition Biopsies were taken from the upper edge of the hysterotomy during caesarean section (CS) at term (n=5), in labor (n=5) and from the corresponding area in the non-pregnant uterus after hysterectomy (n=5). Cervical biopsies were obtained transvaginally from the anterior cervical lip. Serial cryostate sections were prepared for immunohistochemistry using polyclonal antibodies to PGP 9.5. Nerve fibers displaying PGP 9.5 immunoreactivity were observed in all sections from the three groups examined. They were identified in muscle tissue, in the stroma, and around blood vessel walls. A 30-fold decline of immunoreactive nerve fibers was observed in the isthmus part of the corpus uteri at term compared to the non-pregnant. There were no significant differences between the immunoreactivity in the cervix uteri of the three groups The innervation of the cervix uteri is dense and unaltered throughout pregnancy and labor. In contrast, the corpus is almost denervated. Further studies are needed to clarify the reason and the impact of these findings.


Quality of Life of Adult Patients with Type 2 Diabetes Mellitus in Kuwait: A Cross-Sectional Study.
The aim of this study was to evaluate the Quality of Life (QoL) of Kuwaiti patients with Type 2 Diabetes Mellitus (T2DM), aged ≥45 years of both genders, and identifying factors associated with poor QoL. This cross-sectional study was conducted on a random sample stratified by gender, consisting of 604 Kuwaiti patients with T2DM, aged ≥45 years, diagnosed as diabetics for ≥6 months. A validated demographic and WHOQOL-BREF questionnaire was used to assess the QoL. Both genders were equally represented; 46% of patients were 56-65 years of age. Only 24% of the participants had intermediate school education, while 57% were retired, and 54% of the study population had incomes of >1,000 Kuwaiti dinars (KD) (USD 3,300)/month. Most patients (76%) were married, and 99% were living with their families. Obesity was reported in 54%, and 16% were smokers. Only oral antidiabetic drugs were used by 50% of patients, while 24% of patients had complications, and 11% of them developed retinopathy. A family history of diabetes was reported in 74% of patients, and 45% of them have a duration of diabetes >10 years. The median score of QoL was 71, and around 77% of the sample has a good QoL. Kuwaiti patients with T2DM aged ≥45 years reported an overall good level of QoL with higher scores in psychological and social relationships than physical and environmental domains of QoL. Health region, type of treatment, educational level, marital status, and BMI level were statistically significant predictors of poor QoL. More public health action is required to control the disease and improve the QoL.


The indolaminergic innervation of the inferior olive. 2. Relation to harmaline induced tremor.
The possible involvement of serotoninergic mechanisms in the induction of harmaline generated tremor in the inferior olive has been investigated electrophysiologically in the cat and rat. Mass recordings of Purkinje cell activity in the cat showed that harmaline induces strong, synchronous and rhythmic activity in those parts of the climbing fibre system originating in the caudal part of the medial accessory olive and the caudolateral parts of the dorsal accessory nucleus. These are the areas of the cat olive shown to receive a dense serotoninergic innervation. In the rat, the selective removal of the serotoninergic innervation--produced by an intraventricular injection of 5,6-dihydroxytryptamine, or 5,7-dihydroxytryptamine in combination with desipramine--caused a significant attenuation of both the tremor and the climbing fibre activity induced by an intravenous harmaline injection. In the 5,6-dihydroxytryptamine-treated animals the reappearance of the harmaline tremor seemed to parallel the regrowth of new serotoninergic axon sprouts in the inferior olive. On the basis of the present results it is proposed that the serotoninergic afferents to the accessory olivary nuclei are of critical importance for the tremor induction of harmaline in the inferior olive. It is suggested that harmaline, rather than acting directly on the olivary neurones, exerts its effect through an interference with a serotoninergic (possibly inhibitory) innervation of these cells.


A second albumin variant in an Irish population.
Three patients with bisalbuminemia of the slow type (relative mobility 0.94) were detected and the properties of the variant albumin investigated. Three additional patients possessing a fast type variant (relative mobility 1.05) have been detected since a previous report of 4 such cases and studies on these patients are also reported.


Cell-secreted matrices perpetuate the bone-forming phenotype of differentiated mesenchymal stem cells.
Prior to transplantation, mesenchymal stem/stromal cells (MSCs) can be induced toward the osteoblastic phenotype using a cocktail of soluble supplements. However, there is little evidence of differentiated MSCs directly participating in bone formation, suggesting that MSCs may either die or revert in phenotype upon transplantation. Cell-secreted decellularized extracellular matrices (DMs) are a promising platform to confer bioactivity and direct cell fate through the presentation of a complex and physiologically relevant milieu. Therefore, we examined the capacity of biomimetic DMs to preserve the mineral-producing phenotype upon withdrawal of the induction stimulus. Regardless of induction duration, ranging up to 6 weeks, MSCs exhibited up to a 5-fold reduction in osteogenic markers within 24 h following stimulus withdrawal. We show that seeding osteogenically induced MSCs on DMs yields up to 2-fold more calcium deposition than tissue culture plastic, and this improvement is at least partially mediated by increasing actin cytoskeletal tension via the ROCK II pathway. MSCs on DMs also secreted 25% more vascular endothelial growth factor (VEGF), a crucial endogenous proangiogenic factor that is abrogated during MSC osteogenic differentiation. The deployment of DMs into a subcutaneous ectopic site enhanced the persistence of MSCs 5-fold, vessel density 3-fold, and bone formation 2-fold more than MSCs delivered without DMs. These results underscore the need for deploying MSCs using biomaterial platforms such as DMs to preserve the in vitro-acquired mineral-producing phenotype and accelerate the process of bone repair.


The role of GABAergic transmission in the dentate gyrus on acquisition, consolidation and retrieval of an inhibitory avoidance learning and memory task in the rat.
The hippocampal GABAergic interneurons are responsible for controlling the input of large principal cell populations, and they thereby determine the oscillatory discharge patterns and synaptic plasticity in the hippocampus. Such oscillations within neuronal systems serve various complex functions, such as perception, cognition, plasticity and memory. The aim of this study is to define the function of GABAergic synaptic transmission in the dentate gyrus (DG) of the hippocampus in the different stages of inhibitory avoidance (IA) learning and memory in the rat. Two cannulae were implanted above the hippocampal DG. Then the rats were trained on a step-through IA learning task. Each rat received intra-DG injection of picrotoxin (PTX) or saline before training, after training or before the retrieval test. The results show that post-training injection of PTX impaired the IA memory. On the other hand, pre-training and pre-retrieval injection of PTX had no significant effect on the IA activity. Therefore, it seems that GABAergic transmission in the DG is involved in the consolidation step (but not in the acquisition and retrieval steps) of the IA task by controlling the input to the principal cells.


EEG evidence that morally relevant autobiographical memories can be suppressed.
Remembering unpleasant events can trigger negative feelings. Fortunately, research indicates that unwanted retrieval can be suppressed to prevent memories from intruding into awareness, improving our mental state. The current scientific understanding of retrieval suppression, however, is based mostly on simpler memories, such as associations between words or pictures, which may not reflect how people control unpleasant memory intrusions in everyday life. Here, we investigated the neural and behavioural dynamics of suppressing personal and emotional autobiographical memories using a modified version of the Think/No-Think task. We asked participants to suppress memories of their own past immoral actions, which were hypothesised to be both highly intrusive and motivating to suppress. We report novel evidence from behavioural, ERP, and EEG oscillation measures that autobiographical memory retrieval can be suppressed and suggest that autobiographical suppression recruits similar neurocognitive mechanisms as suppression of simple laboratory associations. Suppression did fail sometimes, and EEG oscillations indicated that such memory intrusions occurred from lapses in sustained control. Importantly, however, participants improved at limiting intrusions with repeated practice. Furthermore, both behavioural and EEG evidence indicated that intentional suppression may be more difficult for memories of our morally wrong actions than memories of our morally right actions. The findings elucidate the neurocognitive correlates of autobiographical retrieval suppression and have implications for theories of morally motivated memory control.


Sotrovimab Treatment for COVID-19 Effective in a B-Cell-Depleted Patient After Anti-CD20 Treatment.
Patients with hematologic malignancies are well known to have prolonged COVID-19 pneumonia. The cause has been reported to be B cell depletion after administration of anti-CD20 antibodies. Here, we report a case of COVID-19 pneumonia due to prolonged B-cell depletion after anti-CD20 antibody therapy for malignant lymphoma two years before. Sotrovimab, a neutralizing antibody that was designed to prevent the progression of COVID-19, was successful in preventing the progression to severe disease in this B-cell-depleted patient.


Apoptosis in rat jejunal mucosa is regulated partly through the central nervous system, which controls feeding behavior.
The aim of this study was to investigate whether central nervous system-related feeding behavior regulates mucosal apoptosis in rat small intestines. The test solutions used in this study were an H(1) receptor antagonist (chlorpheniramine maleate), 2-deoxy-D-glucose, leptin, and 1-deoxy-D-glucosamine (2-amino-1,5-anhydro-2-deoxy-D-glucitol). Test solutions were injected into the third cerebroventricles of rats. Feeding behavior and jejunal apoptosis were evaluated both with and without truncal vagotomy. Intestinal apoptosis was evaluated by percentage fragmented DNA, electrophoresis, and TUNEL staining. Chlorpheniramine and 2-deoxy-D-glucose elicited feeding, whereas leptin and 1-deoxy-D-glucosamine suppressed feeding. The test solutions, which elicited feeding (0.24 and 24 micromol/rat of chlorpheniramine and 2-deoxy-D-glucose, respectively), suppressed mucosal apoptosis in the rat jejunum 1 h after cerebroventricular infusion. In contrast, the test solutions, which suppressed feeding (8 and 24 micromol/rat of leptin and 1-deoxy-D-glucosamine, respectively), induced jejunal mucosal apoptosis 3 h after infusion. The effects of the test solutions on feeding behavior and changes in apoptosis were not affected by truncal vagotomy. The central nervous system, which regulates feeding behavior, might control intestinal function through the regulation of intestinal apoptosis.


H19 promote calcium oxalate nephrocalcinosis-induced renal tubular epithelial cell injury via a ceRNA pathway.
Intrarenal calcium oxalate (CaOx) crystals induce inflammation and kidney tubular cell injury, which are processes that involve TLR4/NF-κB signalling. A recent genome-wide gene expression profile analysis of Randall's plaques in CaOx stone patients revealed that the expression of the long noncoding RNA H19 was significantly upregulated. However, to date, its role in kidney CaOx stones has not been reported. A Gene Expression Omnibus (GEO) dataset was utilized to analyse gene expression profiles. Luciferase reporter, Western blotting, qRT-PCR, immunofluorescence staining and reactive oxygen species (ROS) assays were employed to study the molecular mechanism of HMGB1/TLR4/NF-κB regulation by H19 and miR-216b. In vitro and in vivo assays were performed to further confirm the proinflammatory and prooxidative stress effects. H19 expression was significantly increased and positively correlated with the expression levels of HMGB1, TLR4 and NF-κB in Randall's plaques and glyoxylate-induced CaOx nephrocalcinosis mouse models. H19 interacted with miR-216b and suppressed its expression. Additionally, miR-216b inhibited HMGB1 expression by directly binding its 3'-untranslated region. Moreover, H19 downregulation inhibited HMGB1, TLR4 and NF-κB expression and suppressed CaOx nephrocalcinosis-induced renal tubular epithelial cell injury, NADPH oxidase, and oxidative stress in vivo and in vitro. Interestingly, miR-216b inhibition partially reversed the inhibitory effect of H19 knockdown on HMGB1 expression. We determined that H19 might serve as a facilitator in the process of CaOx nephrocalcinosis-induced oxidative stress and renal tubular epithelial cell injury, and we revealed that the interaction between H19 and miR-216b could exert its effect via the HMGB1/TLR4/NF-κB pathway. This work was supported by the National Nature Science Foundation of China (Nos. 8196030190, 8190033175, 81370805, 81470935, 81900645, 81500534, and 81602236).


Effect of X-ray beam quality on determination of exposure index.
We investigated the effect of X-ray beam qualities RQA3, 5, 7, and 9 on the exposure index (EI) as defined by International Electrotechnical Commission guideline 62494-1. Half-value layers (HVLs) of RQA5 X-rays passing through anti-scatter grids (grid ratios 6:1, 8:1, 10:1, and 12:1) were also evaluated because grids are frequently used in clinical situations. The maximum percent differences in the EIs for RQA3, 7, and 9 with respect to RQA5 were 35.0, 11.6, and 38.7 %, respectively. The range of HVLs for RQA5-7 beams was 7.10-9.10 mm of aluminum (mm Al). This was wider than the range of HVLs when grids were used (6.94-7.29 mm Al). The effect of variations in X-ray beam qualities in the RQA series on the EI was significantly greater than the effect of grids. This study indicated that, in clinical settings, the EI should be used carefully in X-ray examinations with different X-ray beam qualities.


Thal fundoplication: a simple and safe operative treatment for gastroesophageal reflux.
One hundred patients with complications of severe gastroesophageal reflux were treated surgically by the Thal fundoplication. In all patients the symptoms of reflux were eliminated by the operation, although 4 recurred within 8 months. Two of these were due to disruption of the fundoplication and two were due to hiatus hernia not recognized and repaired at initial operation. There were 8 deaths, none related to gastroesophageal reflux or the operation. Four patients required re-operation for intestinal obstruction. The Thal fundoplication is a simple procedure which fixes the distal esophagus within the abdomen and produces an acute angle of His. It is effective in prevention of reflux and the patient is able to burp and vomit if necessary. It has not been associated with dysphagia or "gas bloat" which may follow the Nissen fundoplication.


Transpelvic urethrostomy in a female dog with congenital vestibulovaginal and urethral stenosis: A case report.
To describe transpelvic urethrostomy (TPU) as a surgical technique for the successful treatment of vestibulovaginal and urethral stenosis in a 7 month old female spayed mixed-breed dog. Case report. Female spayed mixed-breed dog with obstructive vaginal tissue present on vaginal examination. The dog presented with a history of persistent urine dribbling, stranguria, and dysuria since birth. Vaginoscopy and fluoroscopy revealed severe vestibulovaginal and urethral stenosis. An episiotomy and partial vaginectomy were performed to remove stenotic tissue. A perineal urethrostomy was attempted from a blind-ended pouch associated with the stenotic urethral tissue but was unsuccessful. The dog was repositioned in dorsal recumbency and a postpubic urethrostomy was performed. Six days postoperatively, incisional dehiscence occurred at the cranial aspect of the urethrostomy. The site was revised at this location using a TPU to decrease tension at the urethrostomy site. The dog recovered uneventfully with no further complications identified after surgery. Forty-two months after surgical intervention, the dog continued to show no clinical signs. Transpelvic urethrostomy may be a viable surgical alternative for dogs diagnosed with urethral stenosis.


Redistribution and internalisation of anti-AH1e (anti-AHP)- and Concanavalin A-binding sites.
The redistribution and internalisation of two different lectin-binding sites on the same cell was investigated electron microscopically on unfixed rat liver cell cultures. For these purposes an electron microscopic double labeling technique was used for visualisation of the anti-AHel-binding sites by the gold-labeled lectin and for the demonstration of the Concanavalin A-binding sites by the Concanavalin A-peroxidase technique. From the experiments it was evident that the ligand-induced redistribution of the antiAHel-binding sites effects a rearrangement of the Concanavalin A-binding sites. Both markers were found in a clustered distribution on the cell surface. Following the redistribution an internalisation of both lectin-binding sites could be observed on central and peripheral cell parts. In the lateral cell parts an accumulation of the both markers occurred on the plasma membrane.


The development of children's concepts of invisibility.
One of the most striking examples of appearance-reality discrepancy is invisibility - when something has no appearance yet still exists. The issue of invisibility sits at the juncture of two foundational ontological distinctions, that between appearance and reality and that between reality and non-reality. We probed the invisibility concepts of 47 3-7-year-olds using two sets of tasks: (1) an entity task, in which children were queried about the visibility and reality status of a variety of both visible and invisible entities, and (2) two standard appearance-reality tasks. Results showed that children's concepts of visibility and reality status are intertwined, and that an understanding that some entities are impossible to see develops between the ages of 3 and 7.


Management of Ruptured and Rapidly Progressive Mycotic Cerebral Aneurysms in the Setting of Unilateral Carotid Occlusion and Endocarditis with Valve Failure.
Mycotic cerebral aneurysms can present unique neurosurgical challenges. We report a patient with left carotid occlusions, a ruptured left middle cerebral artery mycotic aneurysm, and a rapidly appearing unruptured left anterior cerebral artery/anterior communicating artery (ACA/ACom) mycotic aneurysm in the setting of mitral valve endocarditis with a perivalvular leak and evolving congestive heart failure. Following medical stabilization and antibiotic administration, a combined endovascular (with contralateral access via the ACom) and open surgical approach was used to selectively secure both aneurysms with preservation of distal flow, allowing lifesaving cardiac valve replacement. This case illustrates the therapeutic complexity of mycotic cerebral aneurysms, which we discuss in the context of an increasing reliance on endovascular approaches.


Effect of Nocturnal Oxygen Therapy on Nocturnal Hypoxemia and Sleep Apnea Among Patients With Chronic Obstructive Pulmonary Disease Traveling to 2048 Meters: A Randomized Clinical Trial.
There are no established measures to prevent nocturnal breathing disturbances and other altitude-related adverse health effects (ARAHEs) among lowlanders with chronic obstructive pulmonary disease (COPD) traveling to high altitude. To evaluate whether nocturnal oxygen therapy (NOT) prevents nocturnal hypoxemia and breathing disturbances during the first night of a stay at 2048 m and reduces the incidence of ARAHEs. This randomized, placebo-controlled crossover trial was performed from January to October 2014 with 32 patients with COPD living below 800 m with forced expiratory volume in the first second of expiration (FEV1) between 30% and 80% predicted, pulse oximetry of at least 92%, not requiring oxygen therapy, and without history of sleep apnea. Evaluations were performed at the University Hospital Zurich (490 m, baseline) and during 2 stays of 2 days and nights each in a Swiss Alpine hotel at 2048 m while NOT or placebo treatment was administered in a randomized order. Between altitude sojourns, patients spent at least 2 weeks below 800 m. Data analysis was performed from January 1, 2015, to December 31, 2018. During nights at 2048 m, NOT or placebo (room air) was administered at 3 L/min by nasal cannula. Coprimary outcomes were differences between NOT and placebo intervention in altitude-induced change in mean nocturnal oxygen saturation (SpO2) as measured by pulse oximetry and apnea-hypopnea index (AHI) measured by polysomnography during night 1 at 2048 m and analyzed according to the intention-to-treat principle. Further outcomes were the incidence of predefined ARAHE, other variables from polysomnography results and respiratory sleep studies in the 2 nights at 2048 m, clinical findings, and symptoms. Of the 32 patients included, 17 (53%) were women, with a mean (SD) age of 65.6 (5.6) years and a mean (SD) FEV1 of 53.1% (13.2%) predicted. At 490 m, mean (SD) SpO2 was 92% (2%) and mean (SD) AHI was 21.6/h (22.2/h). At 2048 m with placebo, mean (SD) SpO2 was 86% (3%) and mean (SD) AHI was 34.9/h (20.7/h) (P < .001 for both comparisons). Compared with placebo, NOT increased SpO2 by a mean of 9 percentage points (95% CI, 8-11 percentage points; P < .001), decreased AHI by 19.7/h (95% CI, 11.4/h-27.9/h; P < .001), and improved subjective sleep quality measured on a visual analog scale by 9 percentage points (95% CI, 0-17 percentage points; P = .04). During visits to 2048 m or within 24 hours after descent, 8 patients (26%) using placebo and 1 (4%) using NOT experienced ARAHEs (P < .001). Lowlanders with COPD experienced hypoxemia, sleep apnea, and impaired well-being when staying at 2048 m. Because NOT significantly mitigated these undesirable effects, patients with moderate to severe COPD may benefit from preventive NOT during high altitude travel. ClinicalTrials.gov Identifier: NCT02150590.


Oncology nursing students' views of a modified OSCE.
This paper discusses oncology nursing students' views of an objective structured clinical examination (OSCE). The OSCE has been used as a form of assessment in medical education since the 1970s. It has subsequently been used by nursing faculties as one of a number of approaches to assessment of clinical skills. As a form of assessment it has been lauded as being more objective than traditional clinical examinations. The information in this study was collected through annual evaluations since 1998, when the OSCE was first employed to assess the students on a post-graduate oncology nursing programme. The sample comprised 185 students, and the principle areas addressed were students' perceptions regarding their degree of preparation for the examination, the overall efficacy and relevance of the OSCE in testing clinical skills and their views on stress and anxiety associated with this form of assessment. The results indicate that while students acknowledge the OSCE was stressful, they felt they were well prepared and appreciated the efficacy and relevance of this assessment method.


The metabolic activation and nucleic acid adducts of naturally-occurring carcinogens: recent results with ethyl carbamate and the spice flavors safrole and estragole.
A small (approximately 30) but varied group of organic and inorganic compounds appear to be carcinogenic in both humans and experimental animals. A much larger number and wider variety of chemical carcinogens, primarily synthetic organic compounds, are known for experimental animals. These agents include a small (approximately 30) and varied group of metabolites of green plants and fungi. Many more of these carcinogens must exist in the living world. As with the synthetic carcinogens, the majority of these naturally occurring carcinogens are procarcinogens that require metabolic conversion into reactive electrophilic and mutagenic ultimate carcinogens. These strong electrophiles combine covalently and non-enzymatically with nucleophilic sites in DNAs, RNAs, proteins, and small molecules in target tissues. One or more of the DNA adducts appear to initiate carcinogenesis in an irreversible manner. The subsequent promotion step leading to gross tumours may be completed by further administration of carcinogen or by treatment with non-carcinogenic promoters. Roles for the RNA and protein adducts in the carcinogenic process have not been excluded. Recent data on the metabolic activation and reactivity in vivo of the naturally occurring carcinogens ethyl carbamate and certain of the alkenylbenzene spice flavours are illustrative of these principles. These agents can initiate the carcinogenic process in male mouse liver with small doses given prior to weaning. Subsequent growth of the liver and male hormonal factors appear to function as promoters leading to gross hepatic tumors after one year. Reactive electrophilic metabolites of ethyl carbamate and of safrole and estragole and their nucleic acid adducts formed during initiation in mouse liver have been characterized.


Shadows of artistry: cortical synchrony during perception and imagery of visual art.
Functional and topographical differences between two groups, artists and non-artists, during the performances of visual perception and imagery of paintings were presented by means of EEG phase synchrony analysis. In artists as compared with non-artists, significantly higher phase synchrony was found in the high frequency beta and gamma bands during the perception of the paintings; in the low frequency bands (primarily delta), phase synchrony was mostly enhanced during imagery. Strong decreases in phase synchrony of alpha were found primarily in artists for both tasks. The right hemisphere was found to present higher synchrony than the left in artists, whereas hemispheric asymmetry was less significant in non-artists. In the artists, enhanced synchrony in the high frequency band is most likely due to their enhanced binding capabilities of numerous visual attributes, and enhanced synchrony in the low frequency band seems to be due to the higher involvement of long-term visual memory mostly in imagery. Thus, the analysis of phase synchrony from EEG signals yields new information about the dynamical co-operation between neuronal assemblies during the cognition of visual art.


Antimicrobial activity and mechanism of action of a novel cationic α-helical octadecapeptide derived from heat shock protein 70 of rice.
Hsp70(241-258), an octadecapeptide derived from the heat shock protein 70 (Hsp70) of rice (Oryza sativa L. japonica), is a novel cationic α-helical antimicrobial peptide (AMP) that contains four lysine, two arginine, and two histidine residues. The antimicrobial activity of Hsp70(241-258) against Porphyromonas gingivalis, a periodontal pathogen, and Candida albicans, an opportunistic fungal pathogen, was quantitatively evaluated using a chemiluminescence method that measures ATP derived from viable cells. The 50% growth-inhibitory concentrations of Hsp70(241-258) against P. gingivalis and C. albicans cells were 63 μM and 70 μM, respectively. Hsp70(241-258) had little or no hemolytic activity even at 1mM, and showed negligible cytotoxicity up to 300 μM. The degrees of calcein leakage from large unilamellar vesicles, which mimic the membranes of Gram-negative bacteria, and 3,3'-dipropylthiadicarbocyanine iodide release from P. gingivalis cells induced by the addition of Hsp70(241-258) increased in a concentration-dependent manner. When Hsp70(241-258) was added to calcein-acetoxymethyl ester-loaded C. albicans cells, calcein release from the cells increased in a concentration-dependent manner. Flow cytometric analysis also showed that the percentages of C. albicans cells stained with propidium iodide, a DNA-intercalating dye, increased as the concentration of Hsp70(241-258) added was increased. Therefore, Hsp70(241-258) appears to exhibit antimicrobial activity against P. gingivalis and C. albicans through membrane disruption. These results suggest that Hsp70(241-258) could be useful as a safe and potent AMP against P. gingivalis and C. albicans in many fields of health care, especially in the control of oral infections.


The in vitro response of osteoblasts to bioactive glass.
Osteoblasts from neonate rat calvaria migrated in culture from the endocranial surface of parietal bones onto fragments of bone-bonding 45S5 glass or non-bone-bonding quartz glass. These organ culture units were maintained for up to 4 wk. No significant production of extracellular matrix (ECM) was seen on the quartz glass samples. However, osteoblasts colonized the 45S5 samples in multilayers and produced abundant ECM as seen by light (LM), scanning electron (SEM) and transmission electron (TEM) microscopy. The interface developed on 45S5 glass was designated as either Type I (non-collagen-bonding) or Type II (showing direct interdigitation of collagen with the calcium phosphate-rich glass surface). It was concluded that, since this in vitro method is capable of reproducing some aspects of the known in vivo behaviour of 45S5, such techniques may be developed as a means of batch-testing bioactive biomaterials and investigating bone cell/biomaterial interactions.


MALDI imaging mass spectrometry reveals COX7A2, TAGLN2 and S100-A10 as novel prognostic markers in Barrett's adenocarcinoma.
To characterize proteomic changes found in Barrett's adenocarcinoma and its premalignant stages, the proteomic profiles of histologically defined precursor and invasive carcinoma lesions were analyzed by MALDI imaging MS. For a primary proteomic screening, a discovery cohort of 38 fresh frozen Barrett's adenocarcinoma patient tissue samples was used. The goal was to find proteins that might be used as markers for monitoring cancer development as well as for predicting regional lymph node metastasis and disease outcome. Using mass spectrometry for protein identification and validating the results by immunohistochemistry on an independent validation set, we could identify two of 60 differentially expressed m/z species between Barrett's adenocarcinoma and the precursor lesion: COX7A2 and S100-A10. Furthermore, among 22 m/z species that are differentially expressed in Barrett's adenocarcinoma cases with and without regional lymph node metastasis, one was identified as TAGLN2. In the validation set, we found a correlation of the expression levels of COX7A2 and TAGLN2 with a poor prognosis while S100-A10 was confirmed by multivariate analysis as a novel independent prognostic factor in Barrett's adenocarcinoma. Our results underscore the high potential of MALDI imaging for revealing new biologically significant molecular details from cancer tissues which might have potential for clinical application. This article is part of a Special Issue entitled: Translational Proteomics.


Phosphorylation of focal adhesion kinase tyrosine 397 critically mediates gastrin-releasing peptide's morphogenic properties.
We have proposed that gastrin-releasing peptide (GRP) and its receptor (GRP-R) are morphogens that when aberrantly re-expressed in colon cancer promote tumor cell differentiation and retard metastasis. Because circumstantial evidence suggested that these properties were mediated via focal adhesion kinase (FAK), the purpose of this study was to elucidate the role of GRP-induced activation of this enzyme on properties fundamental to metastasis including cell attachment, motility, and deformability. To do this, we studied 293 cells, a non-malignant epithelial cell line that we show expresses GRP and GRPR. To dissect out the role of FAK, 293 cells were modified to inducibly express the dominant negative enzyme FAK-related non-kinase (FRNK) under control of a Tet-On (i.e., doxycycline-sensitive) promoter. Under serum-free conditions, GRP acting in an autocrine manner caused FAK to be phosphorylated at Y397; and this could be completely inhibited either by incubating with the specific GRP-R antagonist D-Phe(6)(bombesin) methyl ester, or by upregulating FRNK using doxycycline. To measure cell attachment, we designed a cone-plate viscometer that recorded the shear stress required to detach cells from their underlying matrix. To assess motility, confluent cells were wounded and behavior assessed by time-lapse photography. To measure deformability, we recorded the ability of cells to be completely drawn into a micropipette <50% the size of the non-deformed cell. Control 293 cells adhered more avidly to their underlying matrix, rapidly remodeled wounded tissues without any increase in overall proliferation, and were less distensible than cells treated with antagonist or doxycycline. Thus, these findings suggest that expression of GRP/GRPR in cancer inhibits metastasis by enhancing cell attachment to the matrix, regulating motility in the context of remodeling, and decreasing deformability.


A combined activation mechanism for the glucagon receptor.
We report on a combined activation mechanism for a class B G-protein-coupled receptor (GPCR), the glucagon receptor. By computing the conformational free-energy landscape associated with the activation of the receptor-agonist complex and comparing it with that obtained with the ternary complex (receptor-agonist-G protein) we show that the agonist stabilizes the receptor in a preactivated complex, which is then fully activated upon binding of the G protein. The proposed mechanism contrasts with the generally assumed GPCR activation mechanism, which proceeds through an opening of the intracellular region allosterically elicited by the binding of the agonist. The mechanism found here is consistent with electron cryo-microscopy structural data and might be general for class B GPCRs. It also helps us to understand the mode of action of the numerous allosteric antagonists of this important drug target.


Two new compounds from Carthamus tinctorius.
From the dried petals of Carthamus tinctorius, a new flavonoid, (2R)-4',5-dihydroxyl-6,7-di-O-beta-d-glucopyranosyl flavanone (1) and a new aromatic glucoside, methyl-3-(4-O-beta-d-glucopyranosylphenyl) propionate (4) were isolated along with four known compounds (2S)-4',5-dihydroxyl-6,7-di-O-beta-d-glucopyranosyl flavanone (2), 6-hydroxykaempferol-3,6-di-O-beta-d-glucopyranoside (3), 4-O-beta-d-glucosyl-trans-p-coumaric acid (5), and 4-O-beta-d-glucosyl-cis-p-coumaric acid (6). Their structures were identified on the basis of chemical and spectroscopic methods.


Clinical presentation of retinoblastoma in Eastern Nepal.
The purpose of the present study was to determine modes of presentation of retinoblastoma and the association between proptosis with orbital extension and histopathologically detectable optic nerve infiltration by the tumour. Clinical records and histopathological reports of patients with retinoblastoma were studied retrospectively. The work was undertaken at a tertiary care hospital in eastern Nepal during the period from September 1995 to August 2002. A total of 43 patients with retinoblastoma were studied. Among them unilateral involvement was found in 39 patients (90.70%) and bilateral involvement in four patients (9.30%). The mean age of presentation was 3.04 +/- 1.80 years (95% confidence interval = 2.49-3.59). The commonest mode of presentation was proptosis with orbital extension in 19 eyes (40.42%) followed by leucokoria in 14 eyes (29.78%). Histopathological reports of 42 eyes (one patient died shortly after admission and did not have an autopsy) confirmed the diagnosis of retinoblastoma and revealed that the optic nerve cut section had been infiltrated in 18, of which 16 had the clinical finding of proptosis with orbital extension. This was statistically significant (relative risk = 21.33, P < 0.001). The commonest mode of presentation of retinoblastoma in Nepal is proptosis. Presence of proptosis with orbital extension is associated with optic nerve cut end infiltration by the tumour. The diagnosis or presentation of retinoblastoma in Nepal is delayed and there is tremendous scope for improvement in its management.


LIN28B-AS1-IGF2BP1 binding promotes hepatocellular carcinoma cell progression.
IGF2BP1 overexpression promotes hepatocellular carcinoma (HCC) progression. Long non-coding RNA LIN28B-AS1 directly binds to IGF2BP1. In the present study, LIN28B-AS1 and IGF2BP1 expression and their potential functions in HCC cells were tested. Genetic strategies were applied to interfere their expression, and cell survival, proliferation and apoptosis were analyzed. We show that LIN28B-AS1 is expressed in established/primary human HCC cells and HCC tissues. RNA-immunoprecipitation (RIP) and RNA pull-down results confirmed that LIN28B-AS1 directly associated with IGF2BP1 protein in HCC cells. LIN28B-AS1 silencing (by targeted siRNAs) or knockout (KO, by CRISPR-Cas9 method) depleted IGF2BP1-dependent mRNAs (IGF2, Gli1, and Myc), inhibiting HCC cell growth, proliferation, migration, and invasion. Conversely, ectopic overexpression of LIN28B-AS1 upregulated IGF2BP1-dependent mRNAs and promoted HCC cell progression in vitro. Importantly, ectopic IGF2BP1 overexpression failed to rescue LIN28B-AS1-KO HepG2 cells. LIN28B-AS1 siRNA and overexpression were ineffective in IGF2BP1-KO HepG2 cells. In vivo, LIN28B-AS1 KO-HepG2 xenograft tumors grew significantly slower than the control tumors in the nude mice. Taken together, we conclude that LIN28B-AS1 associates with IGF2BP1 to promote human HCC cell progression in vitro and in vivo.


Primary synovial sarcoma of the kidney.
Primary synovial sarcoma arising from the kidney is extremely rare. We report two cases with primary renal synovial sarcoma. Both were initially diagnosed as renal cell carcinoma. The first case was a 30-year-old woman who presented with right flank soreness. Ultrasonography disclosed a multiloculated cystic tumor measuring 9 x 7 cm. She underwent hand-assisted laparoscopic radical nephrectomy; there was no recurrence during 15 months of follow-up. The second case was a 49-year-old woman who presented with a palpable mass in the left upper quadrant of the abdomen of 1 month's duration. Computed tomography showed a heterogeneously enhanced tumor measuring 13 x 11 cm at the left retroperitoneum with displacement of the pancreas and the left kidney. Hand-assisted retroperitoneoscopic radical nephrectomy was performed. She had no evidence of recurrence after 27 months of follow-up. Pathology of the two cases showed histologic and immunochemical features of synovial sarcoma with coexisting spindle and epithelial cells. Physicians should be aware of the possibility of malignancy in cystic renal masses and that synovial sarcoma is one of the possibilities.


Effect of isomazole on the responsiveness to calcium of the contractile elements in skinned cardiac muscle fibres of various species.
We report here that the new cardiotonic agent isomazole increases the Ca2+ responsiveness of skinned myocardial fibres from different species. Isomazole (0.01-1 mM) increased the half-maximal, Ca2+-activated force development in atrial fibres from humans and in ventricular fibres from pigs, monkeys, guinea-pigs and rats in a concentration-dependent manner. The maximal force development was also increased in fibres from all species except pig. Isomazole shifted force-calcium curves to the left and enhanced maximal force as demonstrated for guinea-pig and human fibres, indicating increases in both calcium sensitivity and maximum force-generating capability of the contractile apparatus. In guinea-pig tissue, the concentration dependence for the activation of skinned fibres was similar to that for the positive inotropic effect in papillary muscle. These results suggest a direct effect of isomazole on contractile proteins, but the degree to which this effect contributes to the overall positive inotropic action of isomazole remains to be determined.


Pan-genome analysis of Paenibacillus polymyxa strains reveals the mechanism of plant growth promotion and biocontrol.
Rapid development of gene sequencing technologies has led to an exponential increase in microbial sequencing data. Genome research of a single organism does not capture the changes in the characteristics of genetic information within a species. Pan-genome analysis gives us a broader perspective to study the complete genetic information of a species. Paenibacillus polymyxa is a Gram-positive bacterium and an important plant growth-promoting rhizobacterium with the ability to produce multiple antibiotics, such as fusaricidin, lantibiotic, paenilan, and polymyxin. Our study explores the pan-genome of 14 representative P. polymyxa strains isolated from around the world. Heap's law model and curve fitting confirmed an open pan-genome of P. polymyxa. The phylogenetic and collinearity analyses reflected that the evolutionary classification of P. polymyxa strains are not associated with geographical area and ecological niches. Few genes related to phytohormone synthesis and phosphate solubilization were conserved; however, the nif cluster gene associated with nitrogen fixation exists only in some strains. This finding is indicative of nitrogen fixing ability is not stable in P. polymyxa. Analysis of antibiotic gene clusters in P. polymyxa revealed the presence of these genes in both core and accessory genomes. This observation indicates that the difference in living environment led to loss of ability to synthesize antibiotics in some strains. The current pan-genomic analysis of P. polymyxa will help us understand the mechanisms of biological control and plant growth promotion. It will also promote the use of P. polymyxa in agriculture.


Transcription factor human Skn-1a enhances replication of human papillomavirus DNA through the direct binding to two sites near the viral replication origin.
Human papillomavirus type 16 (HPV16) DNA replication, which requires two viral proteins E1 and E2, occurs only in the differentiating epithelium. Besides the general factors necessary for cellular DNA synthesis, other unidentified cellular factors are assumed to be involved in the regulation of HPV DNA replication. In the present study, we found that the POU-domain transcription factor human Skn-1a, which induces the terminal differentiation of keratinocytes and activates the HPV16 late promoter, enhanced the transient replication of a plasmid containing the HPV16 replication origin in HEK293 cells when co-transfected with a plasmid expressing E1 and E2. An electrophoretic mobility shift assay with a bacterially expressed human Skn-1a or an extract of HeLa cells over-expressing human Skn-1a revealed the presence of two human Skn-1a binding sites that are distinct from the known three sites, near the replication origin. A chromatin immunoprecipitation analysis showed that human Skn-1a bound to these sites in cells. Nucleotide substitutions in the sites abolished the binding of human Skn-1a and the human Skn-1a-mediated replication enhancement. The data strongly suggest that, through the binding to the two sites, human Skn-1a enhances HPV DNA replication.


Pitfalls and Key Features of a Case of Sclerosing Pneumocytoma: A Cytological Challenge?
The aim of the current case report is to re-evaluate the key features and pitfalls of fine-needle aspiration cytology (FNAC) in the diagnosis of sclerosing pneumocytoma (previously named sclerosing hemangioma) and to establish the importance of FNAC in addressing a proper surgical strategy. Herein we documented a case of a 70- year-old man with a lung nodule which showed a hypermetabolic uptake on positron emission tomography. He therefore underwent FNAC under computed tomography scan guidance with a 22-gauge needle. The cytopathological examination allowed a diagnosis of sclerosing pneumocytoma. A wedge surgical excision was performed and the histological examination confirmed the cytological diagnosis. FNAC is a fundamental tool for distinguishing sclerosing pneumocytoma from a malignant lung tumour and together with clinical, radiological and pathological multidisciplinary assessment is indispensable in planning appropriate surgical management. Cytopathologists should be aware of the pitfalls and key features of the cytopathological diagnosis of sclerosing pneumocytoma, which can significantly change the surgical approach to the patient and protect him from aggressive overtreatment.


Adult-onset non-5q proximal spinal muscular atrophy: a comprehensive review.
Adult-onset spinal muscular atrophy (SMA) represents an expanding group of inherited neurodegenerative disorders in clinical practice. This review aims to synthesize the main clinical, genetic, radiological, biochemical, and neurophysiological aspects related to the classical and recently described forms of proximal SMA. The authors performed a non-systematic critical review summarizing adult-onset proximal SMA presentations. Previously limited to cases of SMN1-related SMA type 4 (adult form), this group has now more than 15 different clinical conditions that have in common the symmetrical and progressive compromise of lower motor neurons starting in adulthood or elderly stage. New clinical and genetic subtypes of adult-onset proximal SMA have been recognized and are currently target of wide neuroradiological, pathological, and genetic studies. This new complex group of rare disorders typically present with lower motor neuron disease in association with other neurological or systemic signs of impairment, which are relatively specific and typical for each genetic subtype.


Risk factors of abnormal carbohydrate metabolism after pregnancy complicated by gestational diabetes mellitus.
In gestational diabetes mellitus (GDM) abnormal glucose metabolism normalizes soon after delivery. However, the history of GDM predisposes to carbohydrate intolerance in the future. The aim of the study was to explore risk factors and to evaluate risk of glucose intolerance and diabetes mellitus in women with a history of GDM. 155 patients entered this case-control study. Participants fulfilled the inclusion criteria: a history of GDM, perinatal care in the study center. Medical and family history and laboratory findings were analyzed. Oral glucose tolerance test (OGTT) was performed. 18.1% of patients presented impaired fasting glucose during the study, 20% presented impaired glucose tolerance and 23.2% presented diabetes mellitus. Gestational age at diagnosis of GDM, the results of OGTT during pregnancy, serum HbA1c concentration at 2nd and 3rd trimester, serum fructosamine concentration, symptoms of diabetic fetopathy in the neonate, the need for insulin therapy after delivery, maternal age at diagnosis of GDM and maternal body mass index before pregnancy were the significant risk factors of impaired glucose tolerance or diabetes in the future. GDM increases the risk of diabetes mellitus. Several risk factors of impaired carbohydrate metabolism can be distinguished in patients with a history of GDM.


In vivo-in vitro correlations with a commercial dissolution simulator II: papaverine, phenytoin, and sulfisoxazole.
The dissolution profiles of 11 commercially available papaverine, phenytoin, and sulfisoxazole dosage forms were determined using a dissolution simulator. The products had been the subject of earlier in vivo bioavailability studies with human subjects. The use of an absorption simulator, which is designed to provide an estimate of the optimum sampling scheme for the dissolution simulator, did not provide useful data for this purpose. Good in vivo-in vitro correlations were found for the papaverine dosage forms, which included nine controlled-release products. Less satisfactory correlations were obtained for the phenytoin capsules and the sulfisoxazole tablet products.