[Bmim]FeCl4 mediated inhibition and toxicity during anaerobic digestion: Dose-response kinetics, biochar-dependent detoxification and microbial resistance.
[Bmim]FeCl4, or 1‑butyl‑3-methylimidazolium tetrachloroferrate, is a typical ionic liquid (IL). Its recyclable, magnetic, multicomponent, and solvent-free nature makes it a particularly attractive ionic liquid for use in industrial processes. Despite its widespread use, the potential hazards that [Bmim]FeCl4 might pose to the environment, including productive microorganisms, have not been explored. In this study, the dose-response of [Bmim]FeCl4 in anaerobic digestion (AD) was investigated to assess the potential toxification and biochar-dependent detoxification in microbial communities, including enzymatic activity and molecule docking dynamics. Our results showed that methane production (31.52 mLmax/gVS) was sharply inhibited following [Bmim]FeCl4 treatment. Moreover, increasing the dosage of [Bmim]FeCl4 caused more dissolved organic matter (DOM) to be generated. Interestingly, 0.4 g/L of [Bmim]FeCl4 could stimulate the high activity of microbial hydrolase and ATPase. However, a higher concentration of 2.65 g/L prevented these enzymatic processes from continuing. At the cellular level, higher concentration of [Bmim]FeCl4 (>0.4 g/L) increased malondialdehyde (MDA) levels, leading to a higher cell lethal rate and weakening of the secondary structures of protein (especially, the amide I region). At the molecular level, the competitive H-bonding in the active sites caused low activity and consummated more energy. At the community level, structural equation modeling (SEM) revealed that [Bmim]FeCl4 and biochar were the main drivers for microbial community succession. For instance, high [Bmim]FeCl4 (8 g/L) benefited the growth of Clostridium sensu_stricto (from ≤1% to 27%). It is worth mentioning that biochar reversed the inhibition with high α-diversity, which caused a resurgence in the activity of previously inhibited ATPase and hydrolase. H2-trophic methanogens (Methanolinea and Methaofastidisoum) were sensitive to [Bmim]FeCl4 and decreased linearly while acetoclastic methanogens (Methanosaeta) were unchanged. These findings were consistent with the short-term activity tests and further verified by functional analysis.


"I feel reassured, but there is no guarantee." How do women with a future childbearing desire respond to active surveillance of cervical intraepithelial neoplasia grade 2? A qualitative study.
In Denmark, women with a future childbearing desire diagnosed with cervical intraepithelial neoplasia grade 2 (CIN2) are recommended active surveillance instead of excisional treatment. However, we have limited and contradictory knowledge about how active surveillance of CIN2 may affect women emotionally. The aim of this study was to explore thoughts and emotional responses in women undergoing active surveillance of CIN2 and to explore how active surveillance may affect women's future childbearing desire. This qualitative study was conducted in the gynecological outpatient clinic, the Department of Obstetrics and Gynecology, Gødstrup Hospital, Denmark. Women of childbearing age undergoing active surveillance with colposcopy, biopsy and smear every 6 months due to CIN2 were eligible for enrollment. In-depth semi-structured interviews were conducted. The interviews were audiotaped and transcribed verbatim. A thematic analysis was performed using a phenomenological approach. A total of 20 women were included. All women experienced nervousness and anxiety when they were diagnosed with CIN2 initially. Their main concern was whether they had cancer. Most women carried on with their everyday lives with only minor occasional worries about CIN2, often prompted just before check-up. However, some women were particularly nervous and found the period between check-ups frustrating and challenging. Women did not want to postpone their plans for pregnancy because of CIN2, but experienced the worries and check-ups associated with active surveillance as disruptive elements in their family planning. Women preparing for fertility treatment had their startup unnecessarily delayed due to active surveillance of CIN2, as clinical guidelines were inconsistent across subspecialties. Various factors influenced women's emotional well-being: life circumstances, information needs, and mental and physical discomfort during colposcopic examination. Women felt that worries and check-ups due to active surveillance of CIN2 were disrupting elements in their family planning, although they did not affect their every-day life. Some women, however, were particularly anxious, demonstrating the importance of including women's experiences and preferences in clinical counseling. The fact that fertility treatment was delayed due inconsistent guidelines across subspecialties, suggests a need for a revision of current guidelines.


Conditioned preference and avoidance induced in mice by the rare sugars isomaltulose and allulose.
Isomaltulose, a slowly digested isocaloric analog of sucrose, and allulose, a noncaloric fructose analog, are promoted as "healthful" sugar alternatives in human food products. Here we investigated the appetite and preference conditioning actions of these sugar analogs in inbred mouse strains. In brief-access lick tests (Experiment 1), C57BL/6 (B6) mice showed similar concentration dependent increases in licking for allulose and fructose, but less pronounced concentration-dependent increases in licking for isomaltulose than sucrose. In Experiment 2, B6 mice were given one-bottle training with a CS+ flavor (e.g., grape) mixed with 8% isomaltulose or allulose and a CS- flavor (e.g., cherry) mixed in water followed by two-bottle CS flavor tests. The isomaltulose mice showed only a weak CS+ flavor preference but a strong preference for the sugar over water. The allulose mice strongly preferred the CS- flavor and water over the sugar. The allulose avoidance may be due to gut discomfort as reported in humans consuming high amounts of the sugar. Experiment 3 found that the preference for 8% sucrose over 8% isomaltulose could be reversed or blocked by adding different concentrations of a noncaloric sweetener mixture (sucralose + saccharin, SS) to the isomaltulose. Experiment 4 revealed that the preference of B6 or FVB/N mice for isomaltulose+0.01%SS or sucrose over 0.1%SS increased after separate experience with the sugars and SS. This indicates that isomaltulose, like sucrose, has postoral appetition effects that enhances the appetite for the sugar. In Experiments 5 and 6, the appetition actions of the two sugars were directly compared by giving mice isomaltulose+0.05%SS vs. sucrose choice tests before and after separate experience with the two sugars. In general, the initial preference the mice displayed for isomaltulose+0.05%SS was reduced or reversed after separate experience with the two sugars although some strain and sex differences were obtained. This indicates that isomaltulose has weaker postoral appetition effects than sucrose.


[Immunoblastic lymphosarcomas. Clinicopathological aspects and course. Retrospective analysis of a series of 50 patients (author's transl)].
The immunoblastosarcoma (IB) was preceeded by another pathological state in almost one third of patients. The clinical picture was often very typical, with large inflammatory node involvement. In one third of cases, the initial site of the tumor was not nodal, but in Waldeyer's ring or a non-lymphoid organ. Analysis of topographic extension indicates a weak propensity to dissemination. The tissues which are the more frequent site of secondary invasion were the lung parenchyma and the subcutaneous tissue. The course was rapid, almost always fatal. Only a combination of radiotherapy and chemotherapy would seem capable of eradicating the tumour. On the basis of all these characteristics, the IB has a special place alongside other non-Hodgkin lymphomas and they may be individualised histologically. These cases are in general in agreement with the little data published in the literature.


The presenilin 2 M239I mutation associated with familial Alzheimer's disease reduces Ca2+ release from intracellular stores.
Mutations in presenilin (PS) genes account for the majority of the cases of the familial form of Alzheimer's disease (FAD). PS mutations have been correlated with both over-production of the amyloid-beta-42 (Abeta42) peptide and alterations of cellular Ca(2+) homeostasis. We here show, for the first time, the effect of the recently described PS2 FAD-associated M239I mutation on two major parameters of intracellular Ca(2+) homeostasis: the Ca(2+) storing capacity of the endoplasmic reticulum (ER) and the activation level of capacitative Ca(2+) entry (CCE), the Ca(2+) influx pathway activated by depletion of intracellular stores. Ca(2+) release from intracellular stores was significantly reduced in fibroblasts from FAD patients, compared to that found in cells from healthy individuals or patients affected by sporadic forms of Alzheimer's Disease (AD). No significant difference was however found in CCE between FAD and control fibroblasts. Similar results were obtained in two cell lines (HEK293 and HeLa) stably or transiently expressing the PS2 M239I mutation.


Preoperative clinical and radiographic predictors of major vascular surgery in patients with testicular cancer undergoing post-chemotherapy residual tumor resection (PC-RPLND).
To evaluate the probability to correctly predict major vascular surgery (MVS) in patients undergoing postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for testicular cancer. From a database of 504 RPLNDs performed in 434 patients (2008-2018), 78 patients submitted to PC-RPLND for non-seminoma germ-cell cancer after cisplatin-based chemotherapy with available preoperative CT scans were identified. Second PC-PLNDs (Re-Dos), salvage RPLNDs, or RPLNDs for late-relapse were excluded as well as thoraco-abdominal approaches. Preoperative imaging was reviewed by a urologist and a radiologist blinded to operative details. Of 78 patients, 16 (20.5%) underwent MVS (caval and/or aortic replacement or reconstruction). On univariable analyses, transversal diameter, sagittal diameter, tumor volume, aorta- and cava-tumor contact angle, poor IGCCCG score, clinical stage III and preoperative positive markers were predictors of MVS (all p values ≤ 0.01). At multivariable analyses aorta- (cut-off 64°) and cava-tumor contact angle (cut-off 98°) and poor IGCCCG score represented the three most important predictors of MVS (all p values ≤ 0.05). The model constructed has a PPV 100%, NPV 87% and an accuracy of 88%. Presence of aorta-tumor contact angle ≥ 64°, cava-tumor contact angle ≥ 98° and poor IGCCCG score identify correctly 9 out of 10 patients requiring MVS at the time of first PC-RPLND.


The cytoplasmic fraction of the histone lysine methyltransferase Setdb1 is essential for embryonic stem cells.
The major lysine methyltransferase (KMT) Setdb1 is essential for self-renewal and viability of mouse embryonic stem cells (mESCs). Setdb1 was primarily known to methylate the lysine 9 of histone 3 (H3K9) in the nucleus, where it regulates chromatin functions. However, Setdb1 is also massively localized in the cytoplasm, including in mESCs, where its role remains elusive. Here, we show that the cytoplasmic Setdb1 (cSetdb1) is essential for the survival of mESCs. Yeast two-hybrid analysis revealed that cSetdb1 interacts with several regulators of mRNA stability and protein translation machinery, such as the ESCs-specific E3 ubiquitin ligase and mRNA silencer Trim71/Lin41. We found that cSetdb1 is required for the integrity of Trim71 complex(es) involved in mRNA metabolism and translation. cSetdb1 modulates the abundance of mRNAs and the rate of newly synthesized proteins. Altogether, our data uncovered the cytoplasmic post-transcriptional regulation of gene expression mediated by a key epigenetic regulator.


Colonic histopathology in untreated celiac sprue or refractory sprue: is it lymphocytic colitis or colonic lymphocytosis?
Colonic histopathology in some patients with untreated celiac sprue and refractory sprue has been said to be indistinguishable from lymphocytic colitis, but there have been no objective comparisons on which this is based. The purpose of this study was to determine the prevalence and to characterize the nature of colonic histopathology at the time of diagnosis in patients with celiac or refractory sprue. Colonoscopic biopsy specimens obtained at the time of diagnosis from 16 patients with celiac sprue, six patients with refractory sprue, nine patients with lymphocytic colitis, and five normal controls were analyzed blindly by histological and morphometric methods, quantitating the number and specific subtypes of inflammatory cells within the lamina propria and epithelium. Immunoperoxidase staining of intraepithelial lymphocytes with a monoclonal antibody to CD8 also was performed. Three of 16 patients with untreated celiac sprue (19%) were thought to have colonic histological abnormalities, which by morphometry consisted of slightly increased numbers of lymphocytes in the surface epithelium and lamina propria, many of which were CD8-positive. These abnormalities were distinguishable from lymphocytic colitis by the lack of increased overall lamina propria cellularity and surface epithelial abnormalities, and by fewer intraepithelial lymphocytes. In refractory sprue, colonic histological abnormalities were more frequent than in celiac sprue, occurring in four of six patients (67%), more pronounced, and identical to those in the lymphocytic colitis syndrome. However, colonic intraepithelial lymphocytes in lymphocytic colitis were mostly CD8-positive, whereas those in the colitis of refractory sprue rarely were. Mild colonic lymphocytosis in patients with untreated celiac sprue should be distinguished from lymphocytic colitis by the lack of surface epithelial abnormalities, the lack of increased cellularity of the lamina propria, and the lack of ongoing watery diarrhea after treatment with a gluten-free diet. In contrast, colonic histopathology in refractory sprue is indistinguishable from lymphocytic colitis, although immunohistochemical differences do exist.


Concurrent Chemoradiotherapy With or Without Induction Chemotherapy for Patients with Stage II Nasopharyngeal Carcinoma: An Update.
In contrast to other studies, our previous study showed that adding induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) significantly worsened the prognosis of patients with stage II nasopharyngeal carcinoma (NPC). However, the population used was small; therefore, there is an urgent need to confirm the result in a larger population because IC is still widely used in certain sections of china for stage II NPC. We retrospectively analyzed an additional 272 patients. Therefore, in total, we report the results for 445 patients with stage II NPC treated with IC + CCRT or CCRT between June 2003 to June 2016 at the Zhejiang Cancer Hospital and Sun Yat-Sen University Cancer Center. This study included 445 patients treated with IC + CCRT (n = 195) or CCRT (n = 250). By last analysis, 22 (11.3%) patients in the IC + CCRT group developed local-regional recurrence and 23 (11.8%) patients developed distant metastases. Twenty-four (9.6%) patients in the CCRT group developed local-regional recurrence and 12 (4.8%) patients developed distant metastases. Univariate analyses showed that adding IC to CCRT significantly decreased the 5-year disease-free survival (DFS) (80.6% vs. 88.5%, P = .043); however, there was no statistically significant difference in 5-year overall survival (OS) (90.5% vs. 95.0%, P = .375). Using a larger population, the present study showed that adding IC to CCRT had a negative effect on patients with stage II NPC, which warrants further investigation.


Fungal arthritis with adjacent osteomyelitis caused by Candida pelliculosa: a case report.
Candida sp. osteoarticular infection is rare and most often due to hematogenous seeding during an episode of candidemia in immunocompromised patients. However, the diagnosis can be delayed in patients with subtle symptoms and signs of joint infection without a concurrent episode of candidemia. A 75-year-old woman presented with a three-year history of pain and swelling of the left knee. Candida pelliculosa was detected from the intraoperative tissue when the patient had undergone left total knee arthroplasty 32 months ago, but no antifungal treatment was performed. One year after the total knee arthroplasty, C. pelliculosa was repeatedly isolated from the left knee synovial fluid and antifungal treatment comprising amphotericin B deoxycholate and fluconazole was administered. However, joint infection had extended to the adjacent bone and led to progressive joint destruction. The patient underwent surgery for prosthesis removal and received prolonged antifungal treatment with micafungin and fluconazole. This case shows that C. pelliculosa, an extremely rare non-Candida albicans sp., can cause fungal arthritis and lead to irreversible joint destruction owing to delayed diagnosis and treatment.


The effect of pre-injection of mice with pristane on ascites tumour formation and monoclonal antibody production.
Experiments were performed to determine whether for mice pre-injected with pristane (2,6,10,14-tetramethylpentadecane) there is an optimum interval before injection of hybridomas in order to maximize ascites fluid formation and yield of monoclonal antibodies. With injections of 0.5 ml of pristane followed by injections of 5 x 10(5) hybridoma cells making monoclonal antibodies against mammalian carbamyl phosphate synthetase, a pre-injection time of 10 days was optimum with respect to (a) the time taken for the ascites tumours to appear; (b) the percentage of mice developing ascites tumours (all mice developed tumours over a span of 2 days); and (c) the concentration of monoclonal antibodies in ascites fluid: 11 mg/ml compared with 7 mg/ml for the next highest group.


Molecular cloning and expression analysis of the aryl hydrocarbon receptor of Xenopus laevis.
The aryl hydrocarbon receptor (AHR) is a member of the basic helix-loop-helix/Per-Arnt-Sim (bHLH/PAS) family of transcription factors. Although this receptor has been known to mediate the toxic effects of environmental pollutants, its physiological functions remain elusive. Here, we describe the isolation and expression pattern of the Xenopus AHR gene. The predicted amino acid sequence contained regions characteristic of other vertebrate AHRs. However, in line with previously described fish AHR genes, no distinct Q-rich domain was found. Phylogenetic analysis demonstrated that Xenopus AHR was clustered within the AHR1 clade. As in the case of mammalian AHR genes, the Xenopus AHR gene was expressed in all the adult tissues tested. Xenopus AHR was also expressed during early development, in parallel with expression of the CYP1A7 gene, which is thought to be regulated by AHR. These results suggest that while frogs are relatively tolerant to TCDD toxicity, the AHR of frogs has characteristics similar to those of other vertebrate AHRs.


Stereochemical determination of NMR chemical shifts in marine terpenoids, antheliol and sangiangol B, using DFT calculations.
Stereochemical determination of the flexible trinor-guaiane sesquiterpenoid, antheliol (1a) and the flexible diterpenoid, sangiangol B (2a), isolated from a marine soft coral, Anthelia sp., was supported by quantum chemical calculations of NMR chemical shifts at DFT levels. The relative configuration of antheliol is now revealed, as 1S*, 4S*, 7S*, 10R* as in 1b, whereas sangiangol B (2c) has complete stereochemistry as 1S*, 7R*, 8R*, 10R*, 11R*, 12S*.


An in vitro model to study suction events by a ventricular assist device: validation with clinical data.
Introduction: Ventricular assist devices (LVADs) are a valuable therapy for end-stage heart failure patients. However, some adverse events still persist, such as suction that can trigger thrombus formation and cardiac rhythm disorders. The aim of this study is to validate a suction module (SM) as a test bench for LVAD suction detection and speed control algorithms. Methods: The SM consists of a latex tube, mimicking the ventricular apex, connected to a LVAD. The SM was implemented into a hybrid in vitro-in silico cardiovascular simulator. Suction was induced simulating hypovolemia in a profile of a dilated cardiomyopathy and of a restrictive cardiomyopathy for pump speeds ranging between 2,500 and 3,200 rpm. Clinical data collected in 38 LVAD patients were used for the validation. Clinical and simulated LVAD flow waveforms were visually compared. For a more quantitative validation, a binary classifier was used to classify simulated suction and non-suction beats. The obtained classification was then compared to that generated by the simulator to evaluate the specificity and sensitivity of the simulator. Finally, a statistical analysis was run on specific suction features (e.g., minimum impeller speed pulsatility, minimum slope of the estimated flow, and timing of the maximum slope of the estimated flow). Results: The simulator could reproduce most of the pump waveforms observed in vivo. The simulator showed a sensitivity and specificity and of 90.0% and 97.5%, respectively. Simulated suction features were in the interquartile range of clinical ones. Conclusions: The SM can be used to investigate suction in different pathophysiological conditions and to support the development of LVAD physiological controllers.


Machine learning slice-wise whole-lung CT emphysema score correlates with airway obstruction.
Quantitative CT imaging is an important emphysema biomarker, especially in smoking cohorts, but does not always correlate to radiologists' visual CT assessments. The objectives were to develop and validate a neural network-based slice-wise whole-lung emphysema score (SWES) for chest CT, to validate SWES on unseen CT data, and to compare SWES with a conventional quantitative CT method. Separate cohorts were used for algorithm development and validation. For validation, thin-slice CT stacks from 474 participants in the prospective cross-sectional Swedish CArdioPulmonary bioImage Study (SCAPIS) were included, 395 randomly selected and 79 from an emphysema cohort. Spirometry (FEV1/FVC) and radiologists' visual emphysema scores (sum-visual) obtained at inclusion in SCAPIS were used as reference tests. SWES was compared with a commercially available quantitative emphysema scoring method (LAV950) using Pearson's correlation coefficients and receiver operating characteristics (ROC) analysis. SWES correlated more strongly with the visual scores than LAV950 (r = 0.78 vs. r = 0.41, p < 0.001). The area under the ROC curve for the prediction of airway obstruction was larger for SWES than for LAV950 (0.76 vs. 0.61, p = 0.007). SWES correlated more strongly with FEV1/FVC than either LAV950 or sum-visual in the full cohort (r = - 0.69 vs. r = - 0.49/r = - 0.64, p < 0.001/p = 0.007), in the emphysema cohort (r = - 0.77 vs. r = - 0.69/r = - 0.65, p = 0.03/p = 0.002), and in the random sample (r = - 0.39 vs. r = - 0.26/r = - 0.25, p = 0.001/p = 0.007). The slice-wise whole-lung emphysema score (SWES) correlates better than LAV950 with radiologists' visual emphysema scores and correlates better with airway obstruction than do LAV950 and radiologists' visual scores. The slice-wise whole-lung emphysema score provides quantitative emphysema information for CT imaging that avoids the disadvantages of threshold-based scores and is correlated more strongly with reference tests than LAV950 and reader visual scores. • A slice-wise whole-lung emphysema score (SWES) was developed to quantify emphysema in chest CT images. • SWES identified visual emphysema and spirometric airflow limitation significantly better than threshold-based score (LAV950). • SWES improved emphysema quantification in CT images, which is especially useful in large-scale research.


Activation of proteases in an anaerobic sulphidogenic bioreactor.
Activities of proteases were stimulated by specific sulphur metabolites during the enhanced hydrolysis of complex polymeric organic carbon in an anaerobic sulphidogenic environment. While sulphate at 1000 mg l(-1) inhibited proteases by 50%, there was a 2.5-fold increase in activity of proteases by added sulphite and a 3.6-fold increase from added sulphide. Two hypothetical models are proposed. First the sulphur species, sulphite (HSO3-) and sulphide (HS-), liberated at different times during the sulphate reduction process, directly activate the proteases, which are associated with the organic particulate matter, leading to a subsequent enhancement of hydrolysis of polymeric material. Second, they indirectly activate the proteases by neutralising the cations on the floc surface disrupting the integrity of the organic particulate floc therebye releasing further entrapped enzymes from the organic particulate matter.


Hidden problems in geological heritage sites: The microplastic issue on Saint Mary's Island, India, Southeast Arabian Sea.
Microplastics (MPs) have become a dominant constituent of several oceanic islands. This study focuses on the occurrence and distribution of MPs present in the beach sediments of Saint Mary's Island (SMI), a geological heritage site located in the south-eastern part of the Arabian Sea. The average (standard deviation) abundance of MPs on this island was 97.18 (80.49) particles/kg. Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy revealed that MPs are composed of high-density polyethylene (HDPE), low-density polyethylene (LDPE), polyethylene (PE), polypropylene (PP), polystyrene (PS), and polyamide (PA). Scanning Electron Microscopy (SEM) and Energy-Dispersive X-ray Spectroscopy (EDS) highlighted the presence of Cr, As, Pb, and Cd (harmful pollutants) on MP surfaces. The MPs in the SMI are largely contributed by the nearby fishing harbour, touristic beaches and estuaries. The results of this study, act as a starting point for continuous environmental monitoring in this unique region of the world.


Factors associated with syndemic anemia and stunting among children in Myanmar: A cross-sectional study from a positive deviance approach.
Anemia and stunting in children are detrimental to the prospects of a normal, healthy upbringing. Having similar risk factors and serious consequences, the syndemic aspect of these two ailments is mostly underrated, and positive deviant (PD) factors that ensure non-anemic status in stunted children have not been studied to date. This study aimed to identify PD factors that have potential to prevent syndemic anemia among stunted children aged 6-59 months in Myanmar. This was a cross-sectional secondary analysis of the Myanmar Demographic and Health Survey (DHS) data conducted in 2016, applying the PD concept, where children who were stunted without anemia were considered as PDs. Among 1248 stunted children, those who had the syndemic condition were compared with their PD peers in terms of maternal characteristics as well as socioeconomic and health-related factors. Multivariable logistic regression analyses were used to identify the determinants of syndemic state. The results showed that three out of every five stunted children were anemic. The syndemic risk was decreased among children of maternal age groups 20-34 years and 35-44 years: [aOR] = 0.19, 95% CI = 0.05-0.69; p = 0.012, and aOR = 0.19, 95% CI = 0.05-0.75; p = 0.018, respectively. Moderately stunted children (aOR = 0.53, 95% CI = 0.34-0.81; p = 0.004) and children who were not currently breastfed (aOR = 1.56, 95% CI = 1.01-2.41; p = 0.044) were less likely to develop the syndemic condition. Maternal age, stunting severity, breastfeeding duration, and maternal anemic status are strong predictors in determining hemoglobin concentrations among stunted children. This study suggests that nutritional interventions targeting PD factors could represent syndemic action in improving child health.


Surfactants and complexing agents: new tasks for specimen banking?
Surfactants and complexing agents are chemical products that are released into the environment in large amounts after being used in cleaning processes, mineral flotation, pesticide formulations, etc. Although these compounds are largely degraded during sewage treatment in industrialized countries, significant amounts will be found in sediments or sewage sludges. Furthermore, large concentrations of these compounds can be found in small rivers and brooks in the vicinity of outfalls of sewage treatment plants. Since these compounds can be expected to alter the organic matrix of the soil (surfactants) or to remobilize heavy metals from soils or sediments (complexing agents), their occurrence in the environment and their effects have to be investigated to estimate their long-term risk potential. This could be a new task for specimen banking. To this end, (a) sensitive and specific detection methods for surfactants and complexing agents have to be developed at concentrations relevant to environmental occurrence, and (b) the effect of surfactants and complexing agents on the distribution of organic and inorganic pollutants in environmental compartments has to be investigated. Preliminary investigations show significant synergistic or antagonistic effects of various surfactants on the adsorption of pollutants at clay minerals.


Task difficulty determines the differential memory-impairing effects of EAA antagonists in gerbils.
Excitatory amino acid antagonists (EAAAs) have been shown to disrupt learning and memory in a variety of cognitive tasks. EAAAs have been reported to produce differential effects on working memory (WM) and reference memory (RM) or to have no effect at all. Apparent selective effects of EAAAs on WM and/or RM may have been due to differences between the effects of competitive and noncompetitive EAAAs, dose selection, or to different task requirements for the WM and RM components. In the present experiments, we assessed the effects of a noncompetitive EAAA (MK-801), a competitive EAAA (CPP), and the muscarinic antagonist scopolamine in two cognitive tasks, the split-stem T-maze and the eight-arm radial maze. In these two tasks, the WM and the RM components differed in their relative degree of difficulty. Gerbils were trained on either the T-maze, where WM was more difficult than RM, or on the radial arm maze, where RM was more difficult than WM. In the T-maze, MK-801 (0.1 mg/kg, IP, 30 min prior), CPP (30.0 mg/kg, IP, 2 h prior) and scopolamine (0.3 mg/kg, IP, 30 min prior) impaired both WM and RM, but the magnitude of the impairing effect was statistically greater for the WM component, the more difficult of the two components. Lower doses of these three compounds produced either selective effects on WM or no effect at all. In the radial arm maze all three drugs impaired both components, but the magnitude of the impairing effect was statistically greater for the RM component, the more difficult of the two components.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of educational intervention based on theory of planned behaviour on promoting preventive behaviours of oral cancer in rural women.
Oral cancer has created an alarming situation around the world, and being the 16th most common cancer worldwide, it has become a global concern. The present study aimed to investigate the effect of educational intervention based on a theory of planned behavior (TPB) on promoting preventive behaviors of oral cancer in rural women. This quasi-experimental study was conducted on 120 female hookah users referring to rural health centers in Fasa and Shiraz city, Fars province, Iran. The subjects were divided into experimental and control groups by simple random sampling. The educational intervention for the experimental group consisted of 8 training sessions of 50 min. Both groups completed a questionnaire including demographic characteristics and constructs of TPB before and four months after the educational intervention. Data were analyzed using SPSS 22 software through independent t-test, chi-square, and paired t-test (p = 0.05). The mean age of the experimental and control group subjects were 41.12 ± 8.86 and 40.63 ± 9.62 years, respectively (p = 0.185). The mean age of onset of hookah use in the experimental and control group was 24.16 ± 9.50 and 23.35 ± 9.44 years, respectively (p = 0.182). Also, before the educational intervention, there was a significant difference between the experimental and control groups in terms of knowledge (p < 0.189), attitude (p < 0.122), perceived behavioral control (p < 0.142), subjective norms (p < 0.236), behavioral intention (p < 0.126), oral cancer prevention behaviors (p < 0.108) and nicotine dependence (p < 0.218); however, four months after the educational intervention, there was a significant increase in the experimental group in all variables except nicotine dependence (p < 0.005). Due to the alarming situation of oral cancer and the prevalence of hookah use among women, educational programs based on TPB could effectively prevent hookah use and oral cancer.


Familial congenital saccade initiation failure and isolated cerebellar vermis hypoplasia.
The underlying lesion in congenital saccade initiation failure (c-SIF) ('congenital ocular motor apraxia', 'Cogan's apraxia') is uncertain. Often no abnormality can be found, yet in others a midline cerebellar abnormality has often been reported. We examined this cerebellar association in a brother and sister. In addition to standard ophthalmological and neurological examinations, both siblings underwent ocular motor testing and neuroradiological investigations including CT and MRI. Both siblings exhibited the typical signs of c-SIF, including headthrusting, synkinetic blinking, missed-nystagmus quick phases, mild developmental delay, and speech difficulties. CT and MRI revealed cerebellar vermis hypoplasia in the brother, but appeared normal in the sister. No other neuroradiological abnormalities were detected. These cases highlight the wide variability in the association of vermis abnormalities with c-SIF, despite the inheritance and similar clinical manifestations. They show that either: (1) the vermis is causal in saccade triggering, but that c-SIF may result from very subtle damage that is beyond MRI resolution in some cases; or (2) that a vermis abnormality per se is not causative but only a marker of another subtle abnormality, either structural or possibly biochemical.


B-cell response to a standardized breakfast in end-stage renal failure.
Twelve uremic patients (U) on regular hemodialysis were submitted to a standardized test meal. In comparison with normal controls (C), U patients demonstrated a slight increase of HbA1 level and a definite elevation of fasting plasma C-peptide immunoreactivity. They showed glucose intolerance at 60 and 120 min. This was associated with an inappropriate insulin response as evidenced by a significantly lower insulin/glucose index at 60 min. U patients were tested again during a hemodialysis session in order to reduce the 60-min glucose intolerance. Six patients (U1) were selected because they exhibited mean fasting and 60-min glucose values similar to those of the controls. In these conditions, the insulin response at 60 min was significantly decreased in comparison to basal conditions and this could not be accounted for by a concomitant decrease of plasma alpha-aminonitrogen values. It is concluded that, in uremic patients, glucose intolerance is associated with an inappropriately low B-cell response.


A rapid preparation of plasmid DNA from Saccharomyces cerevisiae.
A procedure for extraction of plasmid DNA from Saccharomyces cerevisiae is described. The plasmid DNA of interest is extracted together with 2-micron circular DNA naturally occurring in many yeast strains. Spheroplasts are lyzed at alkaline pH which denatures linear but not covalently closed circular (CCC) DNA. The CCC DNA is recovered by ethanol precipitation and can be detected by gel electrophoresis or used for routine bacterial transformation.


Pediatric inguinal hernia repair with a single-incision approach using an Endo Close™ suturing device.
Diverse techniques have been described for pediatric inguinal hernia repair, based on extraperitoneal [1-4] and intraperitoneal [5-8] methodologies. In this video, we describe a novel technique to repair pediatric inguinal hernia using an Endo Close™ suturing device by percutaneous puncture with a single incision. With a transumbilical approach, a 5-mm trocar is inserted for a 30° laparoscope. A 3-mm incision is made, and the Endo Close™ suturing device (Covidien, Minneapolis, MN, USA), with a 2-0 polypropylene suture retained by the stylet, is inserted perpendicularly to the skin. An extraperitoneal dissection is made on a side the inguinal ring and the needle of the device penetrates the peritoneum through the inferior border. Then, the stylet mechanism is pushed to free the lasso inside the cavity. At the same incision site, the needle of the Endo Close™ is inserted again, but an extraperitoneal dissection is made on the other side of the ring, ensuring that the needle penetrates at the same exit orifice. Now, the suture lasso is recovered and retracted to close the ring. Finally, the suture is extracted and knots are tied extracorporeally at the level of the skin. A total of 34 patients (20 females and 14 males) underwent surgery with this procedure. Operative time for unilateral repair was 10-15 and 25-30 min for the bilateral repair (29 unilateral/5 bilateral). The patients experienced minimal postoperative pain. The follow-up period was 12 months with no complications, no recurrence and without cases of postoperative hydrocele. There were no injuries to the structures as vessels or vas deferens, and the esthetic outcome was excellent. The technique presents a simple, safe and reliable method to repair inguinal hernias in children. The long-term results of this novel technique will be evaluated in future studies.


Agonist-selected T cell development requires strong T cell receptor signaling and store-operated calcium entry.
T cell receptor (TCR) signaling driven by interaction of the TCR with specific complexes of self-peptide and the major histocompatibility complex determines T cell fate in thymic development. However, the signaling pathway through which TCR signal strength regulates distinct T cell lineages remains unknown. Here we have used mice lacking the endoplasmic reticulum Ca2+ sensors stromal interaction molecule 1 (STIM1) and STIM2 to show that STIM-induced store-operated Ca2+ entry is not essential for thymic development of conventional TCRαβ+ T cells but is specifically required for the development of agonist-selected T cells (regulatory T cells, invariant natural killer T cells, and TCRαβ+ CD8αα+ intestinal intraepithelial lymphocytes). The severe impairment of agonist-selected T cell development is mainly due to a defect in interleukin-2 (IL-2) or IL-15 signaling. Thus, STIM1 and STIM2-mediated store-operated Ca2+ influx, leading to efficient activation of NFAT (nuclear factor of activated T cells), is critical for the postselection maturation of agonist-selected T cells.


Epidemic dynamics with time-varying transmission risk reveal the role of disease stage-dependent infectiousness.
A key characteristic of acute communicable diseases is the infectiousness that varies over time as the infection dynamics evolve within a host, which influences the risk of transmission in different stages of the disease. Despite the evidence of time-varying transmission risk, most dynamic models of epidemics assume a constant transmission rate during the infectious period. Recent work has shown the difference in epidemic dynamics when this assumption is relaxed and different transmission rates are used by discretizing the infectious period into multiple sub-periods. Here, we develop an age-structured model to integrate a continuous time-varying transmission risk, based on an established correlation between the viral dynamics and infectiousness profile. Taking into account the natural history and parameter estimates of COVID-19 caused by the original strain of SARS-CoV-2, we demonstrate the difference in temporal epidemic dynamics when a continuous time-varying transmission probability is used as compared to multiple constant transmission probabilities. Our results show a significant difference between the incidence curves in terms of the magnitude and peak time, even when the reproduction number and total number of infections are the same for continuous and discrete transmission probabilities. Finally, we demonstrate the spurious outcome of preventing an epidemic through the isolation of infectious individuals when constant transmission probabilities are used, highlighting the importance of integrating a continuous time-dependent transmission parameter in dynamic models. These findings suggest a more cautious interpretation of model outcomes, especially those that are intended to evaluate the effectiveness of interventions and inform policy decisions for disease mitigation strategies.


Label-free, High-Resolution Optical Metabolic Imaging of Human Cervical Precancers Reveals Potential for Intraepithelial Neoplasia Diagnosis.
While metabolic changes are considered a cancer hallmark, their assessment has not been incorporated in the detection of early or precancers, when treatment is most effective. Here, we demonstrate that metabolic changes are detected in freshly excised human cervical precancerous tissues using label-free, non-destructive imaging of the entire epithelium. The images rely on two-photon excited fluorescence from two metabolic co-enzymes, NAD(P)H and FAD, and have micron-level resolution, enabling sensitive assessments of the redox ratio and mitochondrial fragmentation, which yield metrics of metabolic function and heterogeneity. Simultaneous characterization of morphological features, such as the depth-dependent variation of the nuclear:cytoplasmic ratio, is demonstrated. Multi-parametric analysis combining several metabolic metrics with morphological ones enhances significantly the diagnostic accuracy of identifying high-grade squamous intraepithelial lesions. Our results motivate the translation of such functional metabolic imaging to in vivo studies, which may enable improved identification of cervical lesions, and other precancers, at the bedside.


Childhood Experiences of Physical, Emotional and Sexual Abuse among College Students in South India.
To document the prevalence of physical, emotional and sexual abuse during childhood among college students. The study was conducted among college students of Puducherry, South India. Stratified random sampling was done to select colleges. Data were gathered using the adapted 'Ministry of Women and Child Development Questionnaire on Child Abuse for Young adults'. A total of 936 college students completed the questionnaire. Mean ± SD age of the participants was 19.2 ± 1.1 years. Half (48%) of the participants reported being mocked because of their physical appearance. In all, 56% (524/936) of the participants reported that they were beaten during their childhood, of which 13.4% (70/524) required medical treatment. Around 10% reported someone exposing his/her private parts to them, while in 6.4% of the cases, the perpetrator forced the study participants to expose their private parts. Emotional, physical and sexual abuse is common in childhood and demands prompt interventions at the familial, community and political levels.


[The biological activity of platinum and methionine complexes: the antitumor action and inhibition of root growth by complexes of differing compositions and structures].
The effect of 21 methionine-platinum(II) and (IV) complexes on growth and division of cells in maize seedling roots has been studied. The studied complexes did not possess properties inherent in typical cytostatic compounds, e.g. cis-dichlorodiammineplatinum (DDP). They inhibited root growth at higher concentrations as compared to DDP. In contrast to DDP, the studied complexes inhibited cell elongation to a similar or greater extent than cell division, did not prevent lateral root formation, and their inhibitory effect did not change with time. No correlation between the level of tumor growth inhibition and the pattern of root growth was observed.


Immunoelectron microscopic localization of dystrophin in myofibres.
Duchenne muscular dystrophy, a common X-linked recessive human disease, has recently been shown to be caused by the deficiency of a large, low abundance protein called 'dystrophin'. Biochemical techniques have shown dystrophin to be membrane-associated in skeletal muscle, with enrichment of dystrophin in the t-tubules of 'triads'. Other studies using immunohistochemistry on thick (10 micron) sections have shown dystrophin to be located at the periphery of muscle fibres, possibly at the plasma membrane. These results have been interpreted as being either consistent and complementary, or contradictory. To localize dystrophin more precisely relative to these membrane systems we have employed highly sensitive and spatially accurate immuno-gold electron microscopy of ultra-thin (70-100 nm) cryosections. The major distribution of dystrophin was on the cytoplasmic face of the plasma membrane of muscle fibres, and possibly on the contiguous t-tubule membranes. The presented data, taken together with recently accumulated information regarding the primary structure of dystrophin, suggests that dystrophin is a component of the membrane cytoskeleton in myogenic cells. Thus, myofibre necrosis in patients affected with Duchenne muscular dystrophy is likely the result of plasma membrane instability.


Morphological characteristics, anatomical structure, and dynamic change of ascorbic acid under different storage conditions of celery.
Ascorbic acid (AsA) is a crucial antioxidant in vegetables. Celery (Apium graveolens L.) is a vegetable of Apiaceae and is rich in AsA. Till now, the effects of different storage conditions on celery morphological characteristics, anatomical features, and antioxidant accumulation are unclear. Here, the celery cvs. 'Sijixiaoxiangqin' and 'Liuhehuangxinqin' were selected as experimental materials, and the two celery plants grown for 65 days were harvested from soils and stored in light at room temperature (25 °C), darkness at low temperature (4 °C), and darkness at room temperature (25 °C) for 0, 6, 24, 30, 48, and 54 h, respectively. The results showed that celery in darkness had better water retention capacity than celery in light. Morphological changes in celery mesophyll, leaf veins, and petioles were the least in darkness at low temperature (4 °C). The weight loss rate and wilting degree in darkness at low temperature (4 °C) were the lowest, and the AsA content remained at a high level. The expression patterns of GDP-D-mannose pyrophosphorylase (AgGMP) and L-galactose dehydrogenase (AgGalDH) were similar to the change of AsA content. The results indicated that low temperature and dark was the optimized storage condition for 'Sijixiaoxiangqin' and 'Liuhehuangxinqin' celery. AgGMP and AgGalDH genes may play an important role in the accumulation of AsA in celery. This paper will provide potential references for prolonging the shelf life of celery and other horticultural crops.


Venous Evaluation.
The vascular lab (VL) provides unequalled information regarding venous disease especially in the depiction and characterization of venous waveforms. This article provides the indications, protocol, and diagnostic criteria for peripheral and central venous disease and venous mapping. Venous evaluation is one of the most common studies performed at vascular labs (VL). Patient may present with swelling for evaluation of thrombosis, central obstruction, or venous insufficiency, or may need preoperative planning prior to a bypass or dialysis access creation. It is my hope that the added value a VL brings to the sonographic evaluation of veins, beyond the compressibility of the veins, is the utmost respect and attention to the depiction and characterization of the venous waveform.


Implementation of multidimensional knowledge translation strategies to improve procedural pain in hospitalized children.
Despite extensive research, institutional policies, and practice guidelines, procedural pain remains undertreated in hospitalized children. Knowledge translation (KT) strategies have been employed to bridge the research to practice gap with varying success. The most effective single or combination of KT strategies has not been found. A multifaceted KT intervention, Evidence-based Practice for Improving Quality (EPIQ), that included tailored KT strategies was effective in improving pain practices and clinical outcomes at the unit level in a prospective comparative cohort study in 32 hospital units (16 EPIQ intervention and 16 Standard Care), in eight pediatric hospitals in Canada. In a study of the 16 EPIQ units (two at each hospital) only, the objectives were to: determine the effectiveness of evidence-based KT strategies implemented to achieve unit aims; describe the KT strategies implemented and their influence on pain assessment and management across unit types; and identify facilitators and barriers to their implementation. Data were collected from each EPIQ intervention unit on targeted pain practices and KT strategies implemented, through chart review and a process evaluation checklist, following four intervention cycles over a 15-month period. Following the completion of the four cycle intervention, 78% of 23 targeted pain practice aims across units were achieved within 80% of the stated aims. A statistically significant improvement was found in the proportion of children receiving pain assessment and management, regardless of pre-determined aims (p < 0.001). The median number of KT strategies implemented was 35 and included reminders, educational outreach and materials, and audit and feedback. Units successful in achieving their aims implemented more KT strategies than units that did not. No specific type of single or combination of KT strategies was more effective in improving pain assessment and management outcomes. Tailoring KT strategies to unit context, support from unit leadership, staff engagement, and dedicated time and resources were identified as facilitating effective implementation of the strategies. Further research is required to better understand implementation outcomes, such as feasibility and fidelity, how context influences the effectiveness of multifaceted KT strategies, and the sustainability of improved pain practices and outcomes over time.


The N-linked carbohydrate moiety of male reproductive tract CD52 (mrt-CD52) interferes with the complement system via binding to C1q.
Antisperm antibody detected in infertile female patients' sera has been shown to correlate with reduced fertility. The antibody showed strong complement-dependent cytotoxicity as determined by the sperm immobilization test (SIT). CD52 is a human glycosylphosphatidylinositol (GPI)-anchored antigen present in lymphocytes and male reproductive tracts (mrt), including mature sperm and seminal plasma. Recently, purified mrt-CD52 from human seminal plasma has been reported to interfere with the classical complement pathway, but not lectin binding or alternative pathways of the complement system. The purpose of this study is to determine which stage of the classical pathway mrt-CD52 regulates. mrt-CD52 was purified from human seminal plasma or intact sperm membrane. Immunoprecipitation assay was performed with the reaction of mrt-CD52, human complement and mAb H6-3C4. Immunoprecipitate was formed by the carbohydrate moiety of mrt-CD52, but not by the GPI-anchor peptide. The C1q molecule (29 kDa) was detected in the immunoprecipitates by Western blotting analysis probed with anti C1q antibody, indicating that the carbohydrate moiety of mrt-CD52 binds to C1q. Also, the complement-dependent SIT revealed that purified CD52 inhibited sperm immobilization activity by antisperm antibody. These results suggest that mrt-CD52 protects sperm function from complement attack if antisperm antibody is generated in the female reproductive tracts.


Evidence for the involvement of lutropin-independent RNA synthesis in Leydig cell steroidogenesis.
The effect of incubating purified Leydig cells in Eagle's medium and the subsequent effect of the RNA synthesis inhibitors, actinomycin D and cordycepin, on lutropin-stimulated testosterone synthesis have been investigated. The inhibiting effect was found to be inversely related to the time of preincubation; with cells preincubated for 0, 1, 2 and 3 h with Eagle's medium only, followed by 2-h incubation with lutropin with and without actinomycin D, testosterone synthesis was inhibited by 37 +/- 4, 31 +/- 3, 18 +/- 4 and 14 +/- 3% respectively (means +/- s.e.m., n = 5). In cells that had been preincubated for 3 h there was no significant effect of actinomycin D on testosterone synthesis during the first hour of incubation with lutropin. Thereafter the inhibition increased with time reaching a maximum of 30% after 5 h. The effects of preincubation were not due to endogenous lutropin in the Leydig cells because cells isolated from hypophysectomized rats gave similar results. The inhibition of [3H]uridine incorporation into the Leydig cell RNA was 80 +/- 1% with 8 microgram/ml actinomycin D. Increasing the concentration of this inhibitor to 80 microgram/ml did not significantly increase the inhibition of [3H]uridine incorporation or lutropin-stimulated steroidogenesis in preincubated and non-preincubated cells. With cordycepin the inhibition of both RNA synthesis and lutropin-stimulated testosterone synthesis in non-preincubated cells were the same; with 25.1--251 microgram/ml approx. 30--70% resp. With preincubated cells (3 h), 0--50% inhibition of testosterone synthesis was obtained respectively. The inhibitory effect of actinomycin D oimilar to that obtained with lutropin. These observations suggest that during preincubation and independently of lutropin, synthesis of intermediates, including RNAs required for stimulation of steroidogenesis, takes place and that subsequent stimulation of steroidogenesis by lutropin occurs without further de novo RNA synthesis. These results provide evidence for a permissive role of specific RNA and protein synthesis in the action of lutropin on testosterone synthesis in the Leydig cell.


Selective degradation of antibiotic in a novel Cu7S4/peroxydisulfate system via heterogeneous Cu(III) formation: Performance, mechanism and toxicity evaluation.
Efficient degradation of antibiotic by peroxydisulfate (PDS)-based advanced oxidation processes in complex water environment is challenging due to the interference of impurities and the low activation efficiency of PDS caused by its symmetric structure. Herein, a novel Cu7S4/PDS system was developed, which can selectively remove tetracycline hydrochloride (TC) without interference of inorganic ions (e.g., Cl- and HCO3-) and natural organic matter (e.g., humic acid). The results of quenching and probe experiments demonstrated that surface high-valent copper species (Cu(III)), rather than radicals and 1O2, are main active species for TC degradation. Cu(III) can be generated via Cu(I)/O2 and Cu(II)/Cu(I)/PDS systems and the S species on the surface of Cu7S4 promotes the cycle of Cu(II)/Cu(I) and Cu(III)/Cu(II), resulting in continuous generation of Cu(III). In addition, the degradation pathways of TC were proposed based on product analysis and DFT theory calculations. The acute toxicity, developmental toxicity and mutagenicity of treated TC were significantly reduced according to the results of toxicity estimation software tool. This study shows a promising Cu7S4/PDS system for the degradation and detoxication of antibiotic in complex water environment, while also providing a comprehensive understanding of PDS activation by Cu7S4 to generate active Cu(III) species.


Risk factors associated with left atrial appendage thrombosis in patients with non-valvular atrial fibrillation by transesophageal echocardiography.
This study investigated possible mechanism of left atrial appendage (LAA) thrombosis and constructed a model to evaluate the future risk of LAA thrombosis and spontaneous echo contrast (SEC) in non-valvular atrial fibrillation (NVAF) patients. This retrospective study included 2591 patients diagnosed with NVAF. Patients were divided based on the presence of transesophageal echocardiography (TEE) into a thrombus group, SEC group, and control group. General, biochemical, and echocardiography data of the three groups were analyzed. The variables independently associated with LAA thrombosis and SEC were determined by the logistic regression analysis. A nomogram was constituted based on the regression analysis and the discriminatory ability was analyzed by receiver operating characteristic (ROC) curve. LAA thrombosis and SEC were present in 110 (4.2%) patients and 103 (3.9%) patients, respectively. AF type (OR = 1.857), previous stroke (OR = 1.924), fibrinogen (OR = 1.636), diameters of the left atria (OR = 1.094), left ventricular ejection fraction (OR = 0.938), and LAA maximum caliber (OR = 1.238) resulted as independent risk factors for LAA thrombosis and SEC. The area under curve of the nomogram established by multivariate logistic regression was 0.824. Conclusions; Through the study, 6 independent risk factors related to the LAA thrombosis and SEC were found, and an effective nomogram was constructed to predict the LAA thrombosis and SEC in NVAF patients.


Detection of siRNA-mediated target mRNA cleavage activities in human cells by a novel stem-loop array RT-PCR analysis.
The small interfering RNA (siRNA)-mediated target mRNA cleavage activity generates cleaved mRNA fragments with varied termini, which creates major technical challenges for the accurate and efficient detection and verification of cleavage sites on target mRNAs. Here we used a sensitive stem-loop array reverse transcription polymerase chain reaction (SLA-RT-PCR) approach to detect and verify the siRNA-mediated target mRNA cleavage sites by determining precise sequences at the 3'-termini of cleaved mRNA fragments in human cells under physiological conditions. Our results demonstrated the great potential and broad applications of using the SLA-RT-PCR as a sensitive, cost-efficient, and high-throughput tool to systematically detect siRNA-targeted mRNA cleavage sites and fragments in human cells.


Spiritual and religious dimensions of mental illness recovery narratives.
Key themes in narratives of recovery from mental illness illustrate some of the functions of religion and spirituality in consumers' self-understanding and coping.


CD34 selected alloPBSCT and adoptive immunotherapy.
To circumvent aGVHD in the early phase after allogeneic stem cell transplantation but to provide GVL activity later on, we performed alloPBSCT with CD34+ selected grafts followed by delayed add-back of CD3+ T cells. Ten consecutive patients having an HLA-identical sibling donor were enrolled on to this trial. Four patients were in first CR of high-risk ALL, another four in first CR of AML, one was in second myeloid blast crisis of CML, and one was in PR of relapsed NHL. Conditioning consisted of 2 x 60 mg/kg CY plus 12 Gy TBI. G-CSF (Filgrastim) mobilized peripheral cells were CD34+ selected using the Isolex 300i system in nine patients and the CliniMacs system in one. Median CD34+ purity was 86%. A median of 2.8 x 10(6)/kg CD34+ cells were transplanted. The number of CD3+ cells in the allografts was 5.7 x 10(4)/kg (median) after Isolex 300i, and 0.2 x 10(4)/kg after CliniMacs. All patients received G-CSF (Filgrastim) and engrafted rapidly. Standard-dose CsA was administered, and until day +60 no aGVHD occurred. At that time point, seven patients received 2 x 10(6)/kg CD3+ cells while CsA had been tapered to 50% of the starting dose. One of these patients died after a second T cell boost given on day +90 without concomitant immunosuppression due to grade IV intestinal aGVHD. Three others developed cutaneous cGVHD. Taken together, T cell depletion by CD34+ selection does not impair rapid engraftment in the HLA-identical sibling donor setting. Using standard-dose CsA the risk for acute GVHD seems to be minimized. Add-back of 2 x 10(6)/kg CD3+ cells on day +60 with CsA protection is feasible. However, whether this is the optimal time point and number of T cells remain to be further elucidated.


Optic nerve microangioarchitecture in the aging eye.
We investigated the various segments of optic nerve microangioarchitecture in the aging eye. Some clinical results were obtained.


Enhancement of 2,3-butanediol production from Jerusalem artichoke tuber extract by a recombinant Bacillus sp. strain BRC1 with increased inulinase activity.
A Bacillus sp. strain named BRC1 is capable of producing 2,3-butanediol (2,3-BD) using hydrolysates of the Jerusalem artichoke tuber (JAT), a rich source of the fructose polymer inulin. To enhance 2,3-BD production, we undertook an extensive analysis of the Bacillus sp. BRC1 genome, identifying a putative gene (sacC) encoding a fructan hydrolysis enzyme and characterizing the activity of the resulting recombinant protein expressed in and purified from Escherichia coli. Introduction of the sacC gene into Bacillus sp. BRC1 using an expression vector increased enzymatic activity more than twofold. Consistent with this increased enzyme expression, 2,3-BD production from JAT was also increased from 3.98 to 8.10 g L-1. Fed-batch fermentation of the recombinant strain produced a maximal level of 2,3-BD production of 28.6 g L-1, showing a high theoretical yield of 92.3%.


Vitamin e-loaded membrane dialyzers reduce hemodialysis inflammaging.
Inflammaging is a persistent, low-grade, sterile, nonresolving inflammatory state, associated with the senescence of the immune system. Such condition downregulates both innate and adaptive immune responses during chronic disorders as type II diabetes, cancer and hemodialysis, accounting for their susceptibility to infections, malignancy and resistance to vaccination. Aim of this study was to investigate hemodialysis inflammaging, by evaluating changes of several hemodialysis treatments on indoleamine 2,3-dioxygenase-1 activity and nitric oxide formation. We conducted a randomized controlled observational crossover trial. Eighteen hemodialysis patients were treated with 3 different hemodialysis procedures respectively: 1) Low-flux bicarbonate hemodialysis, 2) Low-flux bicarbonate hemodialysis with vitamin E - loaded dialyzers, and 3) Hemodialfitration. The control group consisted of 14 hospital staff healthy volunteers. Blood samples were collected from all 18 hemodialysis patients just after the long interdialytic interval, at the end of each hemodialysis treatment period. Hemodialysis kynurenine and kynurenine/L - tryptophan blood ratio levels were significantly higher, when compared to the control group, indicating an increased indoleamine 2,3-dioxygenase-1 activity in hemodialysis patients. At the end of the low-flux bicarbonate hemodialysis with vitamin E - loaded dialyzers period, L - tryptophan serum levels remained unchanged vs both low-flux bicarbonate hemodialysis and hemodialfitration. Kynurenine levels instead decreased, resulting in a significant reduction of kynurenine/L - tryptophan blood ratio and indoleamine 2,3-dioxygenase-1 activity, when matched to both low-flux bicarbonate hemodialysis and HDF respectively. Serum nitric oxide control group levels, were significantly lower when compared to all hemodialysis patient groups. Interestingly, low-flux bicarbonate hemodialysis with vitamin E - loaded dialyzers nitric oxide serum levels from venous line blood samples taken 60 min after starting the hemodialysis session were significantly lower vs serum taken simultaneously from the arterial blood line. The treatment with more biocompatible hemodialysis procedure as low-flux bicarbonate hemodialysis with vitamin E - loaded dialyzers, reduced indoleamine 2,3-dioxygenase-1 activity and nitric oxide formation when compared to both low-flux bicarbonate hemodialysis and hemodialfitration. These data suggest that low-flux bicarbonate hemodialysis with vitamin E - loaded dialyzers lowering hemodialysis inflammaging, could be associated to changes of proinflammatory signalling a regulated molecular level. NCT Number: NCT02981992; Other Study ID Numbers: 20100014090. First submitted: November 26, 2016. First posted: December 5, 2016. Last Update Posted: December 5, 2016.


Nuclear translocation of MRP1 contributes to multidrug resistance of mucoepidermoid carcinoma.
Multidrug resistance-related protein 1 (MRP1 or ABCC1), a membrane-bound energy-dependent efflux transporter, is overexpressed in several kinds of multidrug-resistant cell lines and related to multidrug-resistance (MDR) of various cancers. In this study, we investigated whether MRP1 was involved in the chemoresistance of mucoepidermoid carcinoma (MEC). We demonstrated that down-regulation of MRP1 in MC3/5FU, a drug-resistant MEC cell line, by RNA interference increased the drug sensitivity of the cells to 5-fluorouracil, doxorubicin, pharmorubicin, bleomycin-A5, cis-platinum and taxol. However, no significant quantitative difference of MRP1 mRNA and protein expression was found between MC3/5FU cells and its parental cell line (MC3) as determined by RT-PCR and Western blot. Interestingly, MRP1 was translocated from the cytoplasmic membrane of the MC3 cells to the nuclei of MC3/5FU cells as revealed by indirect immunofluorescence staining. Furthermore, MRP1 down-regulation mainly decreased the nuclear expression of MRP1 rather than the cytoplasmic membrane expression. Our results suggested that MRP1 was involved in the chemoresistance of MEC and MRP1 may confer drug-resistance by a mechanism associated with its nuclear translocation.


Multidetector computed tomography in the evaluation of cirsoid aneurysm of the scalp--a manifestation of trauma.
Cirsoid aneurysms of the scalp are a rare abnormality with severe cosmetic deformity and possibly of severe hemorrhage. They present as a diagnostic and management challenge, but evaluation with multidetector computed tomography is useful in the diagnosis and treatment planning of these clinically complex disorders of the extracranial circulation. We present a case report of a 38-year-old New Caledonian male who had a large pulsatile mass in his scalp, which had progressively increased in size since the age of 17 years. The clinical and imaging features are outlined, in addition to treatment and prognosis.


Improving body image and sexual life among postpartum women: a single-blind-randomized controlled trial to evaluate a social network-based cognitive-behavioral intervention.
To determine the effect of a social network-based cognitive-behavioral intervention on postpartum body image and sexual life of primiparous women. In this single-blind randomized controlled trial, 82 postpartum women were allocated into two intervention and control groups (allocation ratio, 1:1) using permuted block randomization. Primary outcome was change in body image scores between the groups over time. Secondary outcomes were genital self-image, sexual quality of life, and sexual satisfaction. The intervention group participated in eight (2 weeks) 60-minute sessions through WhatsApp (WhatsApp Inc., Mountain View, CA, USA). Data were collected at recruitment, post-intervention, and 1-month of follow-up. Cognitive-behavioral intervention had a medium effect on improving body image in postpartum women (partial eta squared, 0.33; P<0.001). The results showed significant differences between the two groups regarding sexual quality of life and sexual satisfaction at 1-month follow-up. The results of this study can be used to develop psychological interventions targeting body image in postpartum women.


Relationships between physical characteristics and biomechanics of lower extremity during the squat.
There is a lack of information about relationship between physical characteristics and biomechanics of the lower extremity during the squat. Additionally, studies did not examine sex-related differences. The purpose of this study was to investigate relationships between physical characteristics and biomechanics of the lower extremity during the squat, and to determine if any sex differences are present. Fifty three participants recruited (21.82 ± 2.3 years; 75.56 ± 14.98 kg; 171.57 ± 8.38 cm) performed three squats with 75% of one repetition maximum. Femur to tibia length ratio, hip and ankle joints' flexibilities, and relative muscular strength were measured and used as physical characteristics. Net joint torques (NJT) and flexion angles of the lower extremity were extracted as dependent variables. Multiple regression (stepwise) analysis was conducted to examine the relationships with physical characteristics being factors. Pearson correlation coefficients were calculated to determine intercorrelations among the dependent variables. Relative muscular strength was related to hip NJT and knee flexion angle, and hip flexibility was related to ankle dorsiflexion. Hip and knee NJT showed moderate correlations with the corresponding flexion angles (r = 0.48-0.53; p < .01). Ankle dorsiflexion angle showed weak to moderate correlations with hip NJT and hip flexion angle (r = -0.36-0.50; p < .01) and a moderate correlation with knee NJT. No significant sex difference was observed (r = 0.52; p < .05). Biomechanics of the lower extremity has been shown to correlate more with relative muscular strength and joint flexibility than with leg length ratio.


Effects of substitution of threonine 654 of the epidermal growth factor receptor on epidermal growth factor-mediated activation of phospholipase C.
Addition of epidermal growth factor (EGF) to many cell types activates phospholipase C resulting in increased levels of diacylglycerol and intracellular Ca2+ which may lead to activation of protein kinase C. EGF treatment of cells can also lead to phosphorylation of the EGF receptor at threonine 654 (a protein kinase C phosphorylation site) which appears to attenuate some aspects of receptor signaling. Thus, a feedback loop involving the EGF receptor, phospholipase C, and protein kinase C may regulate EGF receptor function. In this report, the role of phosphorylation of threonine 654 of the EGF receptor in regulation of EGF-stimulated activation of phospholipase C was investigated. NIH-3T3 cells expressing the normal human EGF receptor or expressing EGF receptor in which an alanine residue had been substituted at residue 654 of the receptor were used. Addition of EGF to cells expressing wild-type receptor induced a rapid, but transient, increase in phosphorylation of threonine 654. EGF addition also caused the rapid accumulation of inositol phosphates in these cells. EGF-stimulated accumulation of inositol phosphates was significantly higher in cells expressing Ala-654 receptors compared to control cells. Treatment of cells with 12-O-tetradecanoylphorbol 13-acetate (TPA), which stimulated phosphorylation of threonine 654 to a greater degree than EGF, completely inhibited EGF-dependent inositol phosphate accumulation in cells expressing wild-type receptor, but caused only a 20-30% inhibition in Ala-654 expressing cells. EGF stimulated phosphorylation of phospholipase C-gamma on serine and tyrosine residues in cells expressing wild-type of Ala-654 receptors. However, TPA treatment of cells inhibited EGF-induced tyrosine phosphorylation of phospholipase C-gamma only in cells expressing wild-type receptors. Similarly, TPA inhibited tyrosine-specific autophosphorylation of the EGF receptor and tyrosine phosphorylation of several other proteins in wild-type receptor cells, but not in Ala-654 cells. TPA treatment abolished high affinity binding of EGF to cells expressing wild-type receptors, while decreasing the number of high affinity binding sites 20-30% in Ala-654 cells. These data suggest that phosphorylation of threonine 654 can regulate early events in EGF receptor signal transduction such as phosphoinositide turnover, probably through a feedback mechanism involving protein kinase C. Subsequent dephosphorylation of threonine 654 could reactivate the EGF receptor for participation in later signaling events.


Multilevel information storage using magnetoelastic layer stacks.
The use of voltages to control magnetisation via the inverse magnetostriction effect in piezoelectric/ferromagnet heterostructures holds promise for ultra-low energy information storage technologies. Epitaxial galfenol, an alloy of iron and gallium, has been shown to be a highly suitable material for such devices because it possesses biaxial anisotropy and large magnetostriction. Here we experimentally investigate the properties of galfenol/spacer/galfenol structures in which the compositions of the galfenol layers are varied in order to produce different strengths of the magnetic anisotropy and magnetostriction constants. Based upon these layers, we propose and simulate the operation of an information storage device that can operate as an energy efficient multilevel memory cell.


Operant novelty seeking predicts cue-induced reinstatement following cocaine but not water reinforcement in male rats.
An important facet of cocaine addiction is a high propensity to relapse, with increasing research investigating factors that predispose individuals toward uncontrolled drug use and relapse. A personality trait linked to drug addiction is high sensation seeking, i.e., a preference for novel sensations/experiences. In an animal model of sensation seeking, operant novelty seeking predicts the acquisition of drug self-administration. The primary goal of this research was to evaluate the hypothesis that sensitivity to the reinforcing effects of novel sensory stimuli predicts more intensive aspects of drug-taking behaviors, such as relapse. Rats were first tested for Operant Novelty Seeking, during which responses resulted in complex visual/auditory stimuli. Next, rats were trained to respond to water/cocaine reinforcers signaled by a cue light. Finally, rats were exposed to extinction in the absence of discrete cues and subsequently tested in a single session of cue-induced reinstatement, during which active responses resulted in cues previously paired with water/cocaine delivery. The present study showed operant responses to produce novel sensory stimuli positively correlate with responding for cocaine during self-administration and during discrete cue-induced reinstatement, but no association with performance during extinction. A different pattern of associations was observed for a natural reward, in this case, water reinforcement. Here, the degree of novelty seeking also correlated with responding to water reinforcement and extinction responding; however, operant novelty seeking did not correlate with responding to water cues during testing of cue-induced reinstatement. Taken together, the incongruence of relationships indicates an underlying difference between natural and drug reinforcers. In summary, we found a reinforcer-dependent relationship between operant novelty seeking (i.e., sensation seeking) and responsivity to extinction and discrete cues signaling availability for cocaine (i.e., craving), demonstrating the validity of the operant novelty seeking model to investigate drug seeking and relapse.


Synthesis and metabotropic glutamate receptor antagonist activity of N1-substituted analogs of 2R,4R-4-aminopyrrolidine-2,4-dicarboxylic acid.
A series of N1-substituted derivatives of (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC) has been prepared as constrained analogs of gamma-substituted glutamic acids and examined for their effects at recombinant metabotropic glutamate receptor (mGluR) subtypes in vitro. Appropriate substitution of the N1 position of 2R,4R-APDC resulted in the identification of a number of selective group II mGluR antagonists.


Ventriculoarterial coupling with intra-aortic balloon pump in acute ischemic heart failure.
We analyzed the mechanism of effects of intra-aortic balloon pumping using the pressure-volume relationship and ventriculoarterial coupling in the normal and failing hearts. In 12 anesthetized Holstein calves (weight, 94 +/- 8 kg), the ventricular end-systolic and arterial elastances, pressure-volume area, and external work were analyzed during steady-state contractions with traditional hemodynamic parameters with intra-aortic balloon pumping-off and -on (1:1 synchronous ratio). An acute ischemic heart failure was induced by injecting 10 microm microspheres (4.2 +/- 1.8 x 10(7). 100g left ventricular weight-1) into the left main coronary artery; all measurements were repeated. Intra-aortic balloon pumping did not change hemodynamic parameters in the control. However, during heart failure, intra-aortic balloon pumping decreased the arterial elastance from 3.6 +/- 1.3 mm Hg to 2.9 +/- 1.2 mm Hg. mL-1 while not affecting the ventricular end-systolic elastance, this resulted in an improvement of the ventriculoarterial coupling ratio from 3.1 +/- 0.8 to 2.3 +/- 0.8. Intra-aortic balloon pumping decreased not only end-systolic pressure (from 69 +/- 16 mm Hg to 64 +/- 19 mm Hg) but end-diastolic volume and pressure (from 139 +/- 38 mL to 137 +/- 37 mL and from 13. 9 mm Hg to 12.8 mm Hg, respectively) with the leftward shift of the pressure-volume loop. Pressure-volume area decreased (from 914 +/- 284 mm Hg to 849 +/- 278 mm Hg. mL) although stroke volume increased (from 21 +/- 6 mL to 24 +/- 6 mL). Reduction of the arterial elastance with intra-aortic balloon pumping improved the ventriculoarterial coupling ratio and increased stroke volume. Leftward shift of the pressure-volume loop resulted in the reduction of pressure-volume area, which suggests the conservation of the myocardial oxygen consumption.


Denaturation of RNA and DNA in situ induced by acridine orange.
The products of interaction of acridine orange (AO) with single-stranded (ss) nucleic acids are precipitates which exhibit red luminescence. Titration of rRNA or thymus DNA with AO results in formation of such products suggesting that the dye, per se, denatures double-stranded (ds) sections of these biopolymers. This transition, measured as the increase of red luminescence, a concomitant decrease of green fluorescence, and followed by an increase of light scatter of the AO-nucleic acid complexes, is cooperative and at 0.15 N NaCl occurs at 4-20 and 10-50 microM range of AO concentration for rRNA and DNA, respectively. The changes in stainability of nucleic acids in situ, in permealized cells, occur at higher AO concentration. Thus, the transition of RNA in situ is biphasic and seen at 20-120 microM AO. In the presence of EDTA, however, the change is monophasic and shifted to the 10-30 microM range of AO concentration. The change in stainability of DNA also shows two phases: one at 30-60 microM and another at 70-120 microM of AO. Extraction of basic proteins with 0.08 N HCl shifts the transition of DNA to the 30-60 microM AO concentration and makes it monophasic. The observed differences in denaturability of RNA vs DNA explain the specificity of AO in differential staining of these bipolymers in histochemical reactions. In living cells the products of interaction of AO with nucleic acids are detected by electron microscopy. In the cytoplasm of interphase cells the formation of dense precipitates within ribosomes and polysomes, simultaneous with a specific retraction of ribosome-polysome complexes from the periphery of the cell to the nucleus is evident. The latter suggests higher order organization of these particles involving their association with each other or with the nucleus via polyanionic macromolecules which collapse upon binding with AO. The DNA in heterochromatin is more sensitive to AO-induced denaturation, as evidenced by the fact that the dense complexes are formed preferentially in the regions of condensed chromatin of the interphase nucleus, or in metaphase chromosomes.


Parallel epigenetic and genetic changes in the pathogenesis of hepatitis virus-associated hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is one of the most frequent tumor types in the world, with short survival times and few treatment options. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are major etiologic agents of HCC, although the associated mechanisms are incompletely understood. The available evidence suggests that both viruses promote tumorigenesis by up-regulating genes that promote hepatocellular growth and survival, and by down-regulating other genes that act as tumor suppressors and negative growth regulatory molecules. Significantly, a number of the pathways that are altered by these viruses are the same ones that accumulate genetic alterations during tumor progression. This suggests that the pathways that promote virus persistence and replication may also promote cell growth and survival. From the perspective of the virus, this promotes chronic infection, while from the perspective of the host, this promotes tumorigenesis.


Isorhamnetin represses adipogenesis in 3T3-L1 cells.
Adipocyte dysfunction is strongly associated with the development of obesity, which is a major risk factor for many disorders including diabetes, hypertension, and heart disease. It is generally accepted that the regulation of adipogenesis or adipokines expression prevents obesity. In this study, we show that isorhamnetin inhibits adipocyte differentiation, as evidenced by reduced triglyceride (TG) accumulation and glycerol-3-phosphate dehydrogenase (GPDH) activity. At the molecular level, the mRNA expression levels of peroxidase proliferator-activated receptor-gamma (PPAR-gamma) and CCAAT/enhancer-binding protein-alpha (C/EBP-alpha), which are the major adipogenic transcription factors, were markedly reduced by isorhamnetin. However, the mRNA levels of C/EBP-beta and -delta, the upstream regulators of PPAR-gamma and C/EBP-alpha, were not reduced by isorhamnetin. Moreover, the mRNA levels of PPAR-gamma target genes such as lipoprotein lipase (LPL), CD36, aP2, and liver X receptor-alpha (LXR-alpha) were downregulated by isorhamnetin. We also showed that isorhamnetin inhibits the expression and secretion of adiponectin, and the results of adiponectin promoter assays suggest the inhibition of PPAR-gamma expression as a possible mechanism underlying the isorhamnetin-mediated effects. Taken together, these results indicate that isorhamnetin inhibits adipogenesis through downregulation of PPAR-gamma and C/EBP-alpha.


Analysis of the variation in learning curves for achieving competency in convex EUS training: a prospective cohort study using a standardized assessment tool.
The need for mastering standard imaging techniques for convex EUS in the biliopancreatic regions has been increasing; however, large variations in the aptitude for achieving EUS competency hinder expert development. Therefore, we investigated the factors influencing the achievement of expert competency in EUS using a new assessment tool for multiple imaging items. Between January 2018 and February 2022, 3277 consecutive EUS procedures conducted by 5 beginners (EUS procedures <250), 7 intermediate trainees (250-749), and 2 experts (≥750) were prospectively evaluated. Immediately after each EUS procedure, the success or failure of imaging for each item was recorded using a newly developed EUS assessment tool that requires 17 items to be photographed. After correcting for missing values using multiple imputation, learning curves of EUS scores were created, and a competency was set based on expert scores. Finally, a comparative analysis between high and low performers was performed to extract factors influencing EUS scores. Although 3 of 7 intermediates (43%; mean, 317 cases) achieved competency, none of the beginners achieved competency. During a comparative analysis, although no significant difference in the number of EUS procedures performed was observed between the high and low performers, the former had significantly higher scores in the written test (theoretical knowledge). Our results showed that theoretical knowledge, rather than the number of EUS cases, may be a possible influencing factor for distinguishing high and low performers after treating 250 cases. (Clinical trial registration number: UMIN 000043271.).


Tensor hypercontraction equation-of-motion second-order approximate coupled cluster: electronic excitation energies in O(N4) time.
The tensor hypercontraction (THC) formalism is applied to equation-of-motion second-order approximate coupled cluster singles and doubles (EOM-CC2). The resulting method, THC-EOM-CC2, is shown to scale as O(N4), a reduction of one order from the formal O(N5) scaling of conventional EOM-CC2. Numerical tests for a variety of molecules show that errors of less than 0.02 eV are introduced into the excitation energies.


In vivo molecular imaging of vascular stress.
Noninvasive in vivo imaging is an emerging specialty in experimental radiology aiming at developing hardware and appropriate contrast agents to visualize the molecular basis and pathophysiological processes of many pathological conditions, including atherosclerosis. The list of potentially useful tracers and targets for in vivo molecular imaging in the cascade of early atherosclerotic events has been narrowed down to some very promising endothelial factors, i.e., cell adhesion molecules, macrophages, apoptosis, lipoproteins, heat shock proteins, and others. In this review, we will update on the progress of recent developments in the field of noninvasive molecular imaging in experimental atherosclerosis.


Pelvic movements during walking throughout gestation - the relationship between morphology and kinematic parameters.
Many researchers emphasize adaptations following pregnancy. Our purpose was to get more insight into how morphology interacts with the pelvic walking pattern - the segment most prone to the adaptation following altered body demands. Thirty women were enrolled. Three experimental sessions were arranged according to the same protocol in the first, second and third trimesters of pregnancy. First, the anthropometric measures were taken, then walking trials at a self-selected speed were registered. At the end of the experimental session the subjects were asked to fill out a questionnaire on pain. The sagittal plane pelvic range of motion (RoM) significantly increased throughout pregnancy. There were significant positive correlations between pelvic anthropometric dimensions and pelvic tilt and rotation primarily in the third trimester of pregnancy. Significant positive correlations were found between pelvic RoM and thigh circumference. Indicators associated with body mass increase were positively correlated with pelvic obliquity in the second trimester and pelvic tilt and rotation in late pregnancy. It is also worth noting that the individual differences were not related to back pain and that the reported correlations were observed in some but not in all trimesters. Morphological changes following the fetus growth induced increased pelvic tilt and rotation, however, pelvis movements were not associated with back pain. Overall, the results highlight correlations between morphology and pelvis kinematic patterns in some but not in all trimesters.


Hypoplastic anaemia complicating myxoedema coma.
The case of a 68 year old women presenting in myxoedema coma is described. She was found to be anaemic with a haemoglobin of 8.2 g/dl. Further investigations showed a pancytopenia and a hypoplastic anaemia confirmed by bone marrow. The patient recovered and became euthyroid following initial treatment with intravenous tri-iodothyronine (T3) and later oral thyroxine (T4) replacement with resolution of pancytopenia and return of bone marrow to normal.


Inferring design: evidence of a preference for teleological explanations in patients with Alzheimer's disease.
Unlike educated adults, young children demonstrate a "promiscuous" tendency to explain objects and phenomena by reference to functions, endorsing what are called teleological explanations. This tendency becomes more selective as children acquire increasingly coherent beliefs about causal mechanisms, but it is unknown whether a widespread preference for teleology is ever truly outgrown. The study reported here investigated this question by examining explanatory judgments in patients with Alzheimer's disease (AD), whose dementia affects the rich causal beliefs adults typically consult in evaluating explanations. The results indicate that unlike healthy adults, AD patients systematically and promiscuously prefer teleological explanations, suggesting that an underlying tendency to construe the world in terms of functions persists throughout life. This finding has broad relevance not only to understanding conceptual impairments in AD, but also to theories of development, learning, and conceptual change. Moreover, this finding sheds light on the intuitive appeal of creationism.


Assignment of the stereochemistry and anomeric configuration of sugars within oligosaccharides via overlapping disaccharide ladders using MS(n).
A systematic approach is described that can pinpoint the stereo-structures (sugar identity, anomeric configuration, and location) of individual sugar units within linear oligosaccharides. Using a highly modified mass spectrometer, dissociation of linear oligosaccharides in the gas phase was optimized along multiple-stage tandem dissociation pathways (MS(n), n = 4 or 5). The instrument was a hybrid triple quadrupole/linear ion trap mass spectrometer capable of high-efficiency bidirectional ion transfer between quadrupole arrays. Different types of collision-induced dissociation (CID), either on-resonance ion trap or beam-type CID could be utilized at any given stage of dissociation, enabling either glycosidic bond cleavages or cross-ring cleavages to be maximized when wanted. The approach first involves optimizing the isolation of disaccharide units as an ordered set of overlapping substructures via glycosidic bond cleavages during early stages of MS(n), with explicit intent to minimize cross-ring cleavages. Subsequently, cross-ring cleavages were optimized for individual disaccharides to yield key diagnostic product ions (m/z 221). Finally, fingerprint patterns that establish stereochemistry and anomeric configuration were obtained from the diagnostic ions via CID. Model linear oligosaccharides were derivatized at the reducing end, allowing overlapping ladders of disaccharides to be isolated from MS(n). High confidence stereo-structural determination was achieved by matching MS(n) CID of the diagnostic ions to synthetic standards via a spectral matching algorithm. Using this MS(n) (n = 4 or 5) approach, the stereo-structures, anomeric configurations, and locations of three individual sugar units within two pentasaccharides were successfully determined.


A comprehensive overview of hepatoprotective natural compounds: mechanism of action and clinical perspectives.
Hepatoprotective effects of natural compounds have been frequently attributed to their antioxidant properties and the ability to mobilize endogenous antioxidant defense system. Because of involvement of oxidative stress in virtually all mechanisms of liver injury, it is a reasonable presumption that antioxidant properties of these compounds may play a key role in the mechanism of their hepatoprotective activity. Nevertheless, growing evidence suggests that other pharmacological activities of natural compounds distinct from antioxidant are responsible for their therapeutic effects. In this review, we discussed currently known molecular mechanisms of the hepatoprotective activity of 27 most intensively studied phytochemicals. These compounds have been shown to possess anti-inflammatory, antisteatotic, antiapoptotic, cell survival and antiviral activity through interference with multiple molecular targets and signaling pathways. Additionally, antifibrotic properties of phytochemicals have been closely associated with apoptosis of hepatic stellate cells and stimulation of extracellular matrix degradation. However, although these compounds exhibit a pronounced hepatoprotective effects in animal and cell culture models, the lack of clinical studies remains a bottleneck for their official acceptance by medical experts and physicians. Therefore, controlled clinical trials have an imperative in confirmation of the therapeutic activity of potentially hepatoprotective compounds. Understanding the principles of the hepatoprotective activity of phytochemicals could guide future drug development and help prevention of clinical trial failure. Also, the use of new delivery systems that enhances bioavailability of poorly water soluble compounds may improve the results already obtained. Most importantly, available data suggest that phytochemicals possess a various degree of modulation of specific signaling pathways, pointing out a need for usage of combinations of several hepatoprotective compounds in both experimental studies and clinical trials.


Ternary borate-nucleoside complex stabilization by ribonuclease A demonstrates phosphate mimicry.
Phosphate esters play a central role in cellular energetics, biochemical activation, signal transduction and conformational switching. The structural homology of the borate anion with phosphate, combined with its ability to spontaneously esterify hydroxyl groups, suggested that phosphate ester recognition sites on proteins might exhibit significant affinity for nonenzymatically formed borate esters. (11)B NMR studies and activity measurements on ribonuclease A (RNase A) in the presence of borate and several cytidine analogs demonstrate the formation of a stable ternary RNase A.3'-deoxycytidine-2'-borate ternary complex that mimics the complex formed between RNase A and a 2'-cytidine monophosphate (2'-CMP) inhibitor. Alternatively, no slowly exchanging borate resonance is observed for a ternary RNase A, borate, 2'-deoxycytidine mixture, demonstrating the critical importance of the 2'-hydroxyl group for complex formation. Titration of the ternary complex with 2'-CMP shows that it can displace the bound borate ester with a binding constant that is close to the reported inhibition constant of RNase A by 2'-CMP. RNase A binding of a cyclic cytidine-2',3'-borate ester, which is a structural homolog of the cytidine-2',3'-cyclic phosphate substrate, could also be demonstrated. The apparent dissociation constant for the cytidine-2',3'-borate.RNase A complex is 0.8 mM, which compares with a Michaelis constant of 11 mM for cytidine-2',3'-cyclic phosphate at pH 7, indicating considerably stronger binding. However, the value is 1,000-fold larger than the reported dissociation constant of the RNase A complex with uridine-vanadate. These results are consistent with recent reports suggesting that in situ formation of borate esters that mimic the corresponding phosphate esters supports enzyme catalysis.


Translocations involving chromosomes 2 and 13 in benign and malignant cartilaginous neoplasms.
Cytogenetic analysis of a chrondromyxoid fibroma of bone and an extraskeletal myxoid chondrosarcoma revealed clonal chromosomal rearrangements involving chromosomes 2 and 13. The significance of these findings in these neoplasms of cartilaginous origin, one benign and one malignant, is discussed.


The family history: the first genetic test, and still useful after all those years?
The family history has its origins in genealogy and over the past century has become embedded in clinical practice. Its importance in specialized circumstances is unquestioned but largely untested. Moreover, the relevance of the family history to common diseases, especially in an era of genomic markers that convey risk and the emphasis on "personalized medicine," must be given careful scrutiny. Given the time and expertise needed to obtain and interpret the family history, without a clearer sense of clinical validity and utility, its role will likely diminish. The time to perform the requisite investigations is now.


Preliminary investigation of brown adipose tissue assessed by PET/CT and cancer activity.
To determine the role of brown adipose tissue (BAT) in cancer activity. The study group comprised 142 patients (121 female, 21 male; mean age, 49 ± 16 years) who underwent F18-FDG PET/CT (PET/CT) for staging or surveillance of cancer and who were BAT-positive on PET/CT. BAT volume by PET/CT, abdominal (visceral and subcutaneous) fat and paraspinous muscle cross-sectional areas (CSA) were assessed. Groups with and without active cancer on PET/CT were compared using a two-sided paired t test. Linear regression analyses between BAT and body composition parameters were performed. There were 62 patients (54 female, eight male) who had active cancer on PET/CT and 80 patients (67 female, 13 male) without active cancer. Groups were similar in age and BMI (p ≥ 0.4), abdominal fat and muscle CSA, fasting glucose, and outside temperature at time of scan (p ≥ 0.2). Patients who had active cancer on PET/CT had higher BAT volume compared to patients without active cancer (p = 0.009). In patients without active cancer, BAT was positively associated with BMI and abdominal fat depots (r = 0.46 to r = 0.59, p < 0.0001) while there were no such associations in patients with active cancer (p ≥ 0.1). No associations between BAT and age or muscle CSA were found (p ≥ 0.1). BAT activity is greater in patients with active cancer compared to age-, sex-, and BMI-matched BAT-positive patients without active cancer, suggesting a possible role of BAT in cancer activity.


New approaches to NAD(P)H regeneration in the biosynthesis systems.
Nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH), as two kinds of well-known cofactor, are widely used in the most of enzymatic redox reactions, playing an important role in industrial catalysis. In general, supply of NAD(P)H is a major challenged factor in redox fermentation systems due to its high cost and low stability, which have stimulated the development of NADH regeneration systems in recent years. Until now, a series of NAD(P)H regeneration systems have been developed. This review focuses primarily on new approaches of NAD(P)H cofactor regeneration in the biosynthesis systems, such as single cell in vivo NADH regeneration system, double cell coupling NADH regeneration system, in vitro enzyme-coupled NADH regeneration system, microbial cell surface display NADH regeneration system. Finally, the prospect and tendency of NADH regeneration are discussed.