The efficacy of oral versus intravenous tranexamic acid in reducing blood loss after primary total knee and hip arthroplasty: A meta-analysis.
Blood management after arthroplasties has become a serious problem. The objective is to perform a meta-analysis to compare the efficacy and safety between oral tranexamic acid (TXA) and intravenous TXA for blood management in total knee and hip arthroplasty. We systematically searched randomized controlled trials (RCTs) from Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science and Google scholar. Eligibility criteria: Patients: adult patients with end-stage joint osteoarthritis, rheumatoid arthritis, and osteonecrosis of the femoral head, who prepared for TJA; Interventions: The experiential group received the intravenous form of TXA; Comparisons: Oral form of TXA; Outcomes: Total blood loss, hemoglobin reduction, transfusion requirements, duration of hospitalization, and thrombotic complications including deep vein thrombosis (DVT) and pulmonary embolism (PE); Study design: Randomized control trials (RCTs) and non-RCT. Meta-analysis results were collected and analyzed by the software STATA 11.0. After testing for heterogeneity between studies, data were aggregated for random-effects models when necessary. Four RCTs and 2 non-RCTs were included in the meta-analysis. The present meta-analysis revealed that there were no significant differences regarding total blood loss (WMD = -25.013, 95% CI: -51.002 to 0.977, P = .059), postoperative hemoglobin decline (WMD = -0.090, 95% CI: -0.205 to 0.024, P = .122), or transfusion rate (RD = -0.039, 95% CI: -0.080 to 0.002, P = .062) between the 2 groups. Oral TXA shows comparable efficacy to that of the intravenous forms after total knee and hip arthroplasty. Due to the limited quality of evidence currently available, higher quality RCTs is necessary.


The role of detectability in the evolution of avian-dispersed fruit color.
If the primary function of avian-dispersed fruit coloration were the maximization of detectability, then the commonest avian-dispersed fruit colors should be the ones most detectable to birds. We tested this prediction by photographing 63 fruit species primarily dispersed by birds, in situ in Sweden and Australia, with a multispectral camera closely mimicking the predominant spectral sensitivities of birds, including both UVS and VS (peak ultraviolet sensitivity ∼370 and 409 nm respectively) visual systems. Fruits were classified into nine distinct color categories based on different patterns of cone excitations, and were named by combining human color names with fruits' UV reflective properties. For example, a bluish-UV fruit would be a fruit that excited the avian UV cone the most, but that also strongly excited the blue cone. Color and achromatic contrasts were calculated between each fruit color and common background objects, and compared to the relative abundance of the different fruit colors. Although red was highly detectable and the commonest color, the second and third commonest colors, purplish-UV and bluish-UV (often termed "black" by humans), were the least detectable. Although these latter two colors were more detectable to UVS than to VS birds, they were the least detectable to both visual systems. Rare fruit colors, such as UVish-purple, pink, and orange, were highly detectable to both visual systems. The lack of correlation between fruit color abundance and detectability suggests that the maximization of detectability has not been the primary driving force behind the evolution of fruit color.


Search for microbial insect growth regulators. II. Allosamidin, a novel insect chitinase inhibitor.
Allosamidin, a novel insect chitinase inhibitor, was isolated from the mycelium of Streptomyces sp. It showed strong inhibitory activity against the chitinases of the silkworm, Bombyx mori, in vitro, and also insecticidal activity by preventing its ecdysis in vivo.


Characteristics of the patellofemoral joint of patients with DDH and the effects of Bernese periacetabular osteotomy on the patellofemoral joint.
Some patients with developmental dysplasia of the hip (DDH) complained of anterior knee pain (AKP) before and after Bernese periacetabular osteotomy (PAO) surgery. The purpose of this study was to (1) identify the characteristics of patellofemoral joint (PFJ) deformities in patients with DDH and (2) to determine the effects of PAO on the PFJ. Seventy patients (86 hips) were included in the DDH group. Thirty-three patients (33 knees) without AKP and hip pain were included in the control group. All patients underwent simultaneous CT scans of the hip and knee joints before PAO and after hardware removal surgery. The distance from the anterior inferior iliac spine to the ilioischial line (DAI), was measured in DDH patients. Imaging parameters of knees, including the sulcus angle (SA), femoral trochlear depth (FTD), patellar width (PW), tibial tuberosity-trochlear groove (TT-TG), patellar tilt angle (PTA) and lateral shift of the patella (LSP) were measured in patients in both the DDH and control group. TT-TG, PTA, and LSP of DDH patients were measured before PAO and after hardware removal. The DAI, PTA, LSP and TT-TG of all DDH patients before and after Bernese PAO were compared using paired t-tests. The FTD, PW, and SA of the DDH patients and the control group were analyzed using independent t-tests. PTA, TT-TG, and LSP between the control group and preoperative DDH patients, between the control group and post PAO patients were compared using independent t-tests. The DAI changed from 4.04 ± 0.61 mm before PAO surgery to 5.44 ± 0.63 mm after PAO surgery. The SA of the DDH group (140.69 ± 11.30 degree) was greater than that of the control group (130.82 ± 6.43 degree). The FTD and the PW of the DDH group (5.45 ± 1.59 mm, 4.16 ± 0.36 mm) were smaller than that of the control group (7.39 ± 1.20 mm, 4.24 ± 0.38 mm). The changes in LSP, PTA, and TT-TG before and after surgery were not statistically significant. Both before and after PAO, there was no statistically significant difference in the parameters of LSP, PTA, and TT-TG compared with the control group. The knee joints of DDH patients presented a certain degree of femur trochlear groove dysplasia and patellofemoral instability. PAO surgery did not change PFJ stability, although the origination point of the rectus femoris muscle moved laterally during PAO surgery.


Fibrous hyaluronic acid hydrogels that direct MSC chondrogenesis through mechanical and adhesive cues.
Electrospinning has recently gained much interest due to its ability to form scaffolds that mimic the nanofibrous nature of the extracellular matrix, such as the size and depth-dependent alignment of collagen fibers within hyaline cartilage. While much progress has been made in developing bulk, isotropic hydrogels for tissue engineering and understanding how the microenvironment of such scaffolds affects cell response, these effects have not been extensively studied in a nanofibrous system. Here, we show that the mechanics (through intrafiber crosslink density) and adhesivity (through RGD density) of electrospun hyaluronic acid (HA) fibers significantly affect human mesenchymal stem cell (hMSC) interactions and gene expression. Specifically, hMSC spreading, proliferation, and focal adhesion formation were dependent on RGD density, but not on the range of fiber mechanics investigated. Moreover, traction-mediated fiber displacements generally increased with more adhesive fibers. The expression of chondrogenic markers, unlike trends in cell spreading and cytoskeletal organization, was influenced by both fiber mechanics and adhesivity, in which softer fibers and lower RGD densities generally enhanced chondrogenesis. This work not only reveals concurrent effects of mechanics and adhesivity in a fibrous context, but also highlights fibrous HA hydrogels as a promising scaffold for future cartilage repair strategies.


Serum Alkaline Phosphatase, Phosphate, and In-Hospital Mortality in Acute Ischemic Stroke Patients.
The clinical impacts of serum alkaline phosphatase (ALP) and phosphate on early death are not fully understood in patients with acute ischemic stroke. We examined the associations between serum ALP, phosphate, and in-hospital mortality after ischemic stroke. Serum ALP and phosphate were measured in 2944 ischemic stroke patients from 22 hospitals in Suzhou City from December 2013 to May 2014. Cox proportional hazard models and restricted cubic splines were used to estimate the relationships between serum ALP and phosphate (both as categorical and continuous variables) and risk of in-hospital mortality. During hospitalization, 111 patients (3.7%) died from all causes. After multivariable adjustment, the hazard ratio (HR) of the highest quartile compared with the lowest quartile of ALP was 2.19 (95% confidence interval [CI], 1.20-4.00) for early death. Restricted cubic spline analysis indicated a significant linear association between ALP and death (P-linearity = .017). A U-shaped association of phosphate with in-hospital mortality was observed (P-nonlinearity = .011). Compared with the third quartile of phosphate (1.08-1.21 mmol/L), HRs of the lowest and highest quartiles for early death were 2.17 (1.15-4.08) and 1.70 (.88-3.30), respectively. Sensitivity analyses further confirmed our findings. We observed a graded relationship between serum ALP levels and risk of early death in patients with acute ischemic stroke. There was a U-shaped association between phosphate and all-cause mortality with significantly increased risk among patients with lower phosphate levels.


Indirect costs of absenteeism due to rheumatoid arthritis, psoriasis, multiple sclerosis, insulin-dependent diabetes mellitus, and ulcerative colitis in 2012: a study based on real-life data from the Social Insurance Institution in Poland.
The aim of this study is to assess the indirect costs of six major autoimmune diseases including seropositive rheumatoid arthritis, other types of rheumatoid arthritis, psoriasis, multiple sclerosis, Type 1 diabetes, and ulcerative colitis. Relevant data for 2012 on sick leave and short- and long-term work disabilities were obtained from the Social Insurance Institution in Poland. Indirect costs were estimated using the human capital approach based on gross domestic product per capita, gross value added per worker, and gross income per worker in Poland in 2012 and expressed in euro. We recorded data on the total number of 45,500 patients. The total indirect costs were EUR 146,862,569; 353,683,508; and 108,154,271, calculated using gross domestic product, gross value added, and gross income, respectively. Considering only data on absenteeism collected by the Social Insurance Institution in Poland, we can conclude that the selected autoimmune diseases are associated with great indirect costs.


The mode of action of CY216 and CY222 in plasma.
Three fractions of the low molecular weight heparin CY216 (fraxiparin, mean molecular weight [MMW] 5,090), with MMWs of respectively, 3,090, 4,400 and 7,910 were prepared by gel permeation chromatography. From CY222 (MMW 3,770) as well as from CY216 and its three fractions the material with high affinity to antithrombin III (AT III) was obtained by chromatography on immobilised AT III. The molecular weight distribution of each of the ten preparations thus obtained was determined by high performance liquid chromatography, while the content of AT III binding material was determined by stoichiometric titration of AT III, monitored by intrinsic fluorescence enhancement. We measured the effect of all heparins on the decay of endogenous thrombin in plasma and on the overall generation of thrombin in plasma, triggered via the extrinsic or via the intrinsic pathway. From these data we calculated the time course of prothrombin conversion, i.e. the course of factor Xa activity as expressed by prothrombinase activity. It was found that in platelet-poor plasma the anticoagulant properties of the heparins are largely dependent on their antithrombin action, which is determined by their content of high affinity material with a MW of 5,400 or higher. The specific antithrombin activity of all heparins, when expressed in terms of material with high affinity to antithrombin III (HAM) with a MW greater than 5,400 is 13.0 min-1/(microgram/ml) (range 10.5-15.9).(ABSTRACT TRUNCATED AT 250 WORDS)


Operative management of adrenal metastases from lung carcinoma.
Most surgeons consider patients with solitary adrenal metastasis from a primary lung carcinoma incurable and avoid excision of both the adrenal and primary lung tumors. However, several cases of successful surgical management of these patients recently have been reported. We reviewed 12 surgically treated patients with isolated adrenal and lung disease and identified 2 survivors of greater than fifteen years (17%) and 4 additional patients who are still alive following combined resection (34%). This survival rate, albeit in a selected population, represents an improvement over the natural history of nine months' survival. We suggest that if after six to twelve months of following patients with lung cancer and isolated adrenal metastasis no other evidence of spread of disease is evident, the tumor biology may be favorable and resection of both adrenal and lung lesions is reasonable.


Powered mobility and preschoolers with complex developmental delays.
The purpose of this study was to explore the effects of a powered mobility riding toy on the participation behaviors of young children with complex developmental delays. A single-subject withdrawal design was used to study the effects of powered mobility on child-initiated movement occurrences, initiation of contact with others, and affect. The participants were two young children with complex developmental delays, including spastic quadriplegia. The intervention consisted of having the children use a powered mobility riding toy in their school settings during gym class and outdoor recess. Primary findings were that use of the powered mobility riding toy (a) increased the number of self-initiated movement occurrences; (b) appeared to have some effect on initiation of contacts with adults and, for one child, negative adult initiations and positive peer initiations; and (c) did not have a clear impact on the amount of positive affect. For some young children with severe motor impairments and developmental delay, use of a powered mobility device may increase self-initiated movement occurrences during free play.


Sexuality after total abdominal hysterectomy in Srinagarind Hospital.
To determine the effects on sexuality after Total Abdominal Hysterectomy (TAH) in north-eastern Thai women. Prospective descriptive study. Srinagarind Hospital, Faculty of Medicine, Khon Kaen University from December 2004 to May 2006. 80 married women, equal or less than 45 years old, which indicated for TAH with or without unilateral salpingo-oophorectomy. All patients had to attend the first questionnaire before surgery. The second and third questionnaires would be collected by mail in 3 and 6 months after surgery. Frequency of dyspareunia, sexual desire, coitus, masturbation, and the quality of sexuality after TAH. The frequency of dyspareunia was decreased from 91.25% before TAH to 5% in 6 months after TAH (95% CI 1.19-1.61, p < 0.05). The frequency of sexual desire was increased from 55% before TAH to 88.75% in 6 months (95% CI 0.22-0.61, p < 0.05). The frequency of coitus was increased from 38.75% before TAH to 96.25% in 6 months after TAH (95% CI 0.54-0.98, p < 0.05). Normal sexual relations were increased from 53.8% before TAH to 85% in 6 months after TAH (95% CI 0.20-0.47, p < 0.05). Sexuality was significantly improved overall after TAH and these might be the strong positive effects of TAH on sexual function.


[HLA-DRB and -DQB allele contribution to narcolepsy susceptibility in Chinese patients with narcolepsy].
To study the association of narcolepsy with HLA class II alleles in Chinese narcoleptic patients. 31 patients with narcolepsy underwent brain computed tomography (CT) scan and magnetic resonance imaging (MRI) testing. All patients received a MSLT test following a routine night's sleep, and serological HLA typing for HLA DR(2). 21 patients received PCR-SSP HLA DR and DQ typing. All patients had sleepiness and cataplexy. There was no evidence for other functional or structural diseases. Sleep paralysis was elicited in 45%; hypnagogic hallucinations, in 61%. Mean sleep latency on MSLT was 2.1 min +/- 1.3 min; sleep-onset rapid eye movement (SOREM) occurred during 2/5 naps in 30 of 31 patients. The average number and latency of SOREM episodes were 4.2 +/- 1.0 episodes and 4.0 min +/- 1.8 min, respectively. All patients but one were HLA DR(2) positive and 86% were HLADRB(1) * 1501-HLADQB(1)*0602 positive. HLA DR(2) and HLADQw6 are markers for narcolepsy-cataplexy in Chinese.


Enhancing isobutyric acid production from engineered Acidithiobacillus ferrooxidans cells via media optimization.
The chemolithoautotrophic bacterium Acidithiobacillus ferrooxidans has previously been genetically modified to produce isobutyric acid (IBA) from carbon dioxide while obtaining energy from the oxidation of ferrous iron. Here, a combinatorial approach was used to explore the influence of medium composition in both batch and chemostat cultures in order to improve IBA yields (g IBA/mol Fe(2+)) and productivities (g IBA/L/d). Medium pH, ferrous concentration (Fe(2+)), and inclusion of iron chelators all had positive impact on the IBA yield. In batch experiments, gluconate was found to be a superior iron chelator because its use resulted in smaller excursions in pH. In batch cultures, IBA yields decreased linearly with increases in the final effective Fe(3+) concentrations. Chemostat cultures followed similar trends as observed in batch cultures. Specific cellular productivities were found to be a function of the steady state ORP (Oxidation-reduction potential) of the growth medium, which is primarily determined by the Fe(3+) to Fe(2+) ratio. By operating at low ORP, chemostat cultures were able to achieve volumetric productivities as high as 3.8 ± 0.2 mg IBA/L/d which is a 14-fold increase over the previously reported value.


Cricopharyngeal electromyography: patterns of injury based on etiology.
Although cricopharyngeal electromyography (CP-EMG) is recognized as a diagnostic tool for dysphagia assessment, few reports in the literature characterize CP-EMG abnormalities in relation to clinical presentation. The aim of this study was to review a large series of CP-EMG studies, and compare the CP-EMG results with the patients' diagnoses. A retrospective review of all CP-EMG performed at our institution over a 10-year period was executed. CP-EMG findings were then compared with the patients' clinical history, focusing on potential etiologies of neurogenic injury. Seventy CP-EMGs were reviewed, with 47 (67%) demonstrating neural injury. Of those cases with neural injury on EMG, 29 (60%) had known vagal injuries, 13 (28%) had idiopathic nerve palsies, and 5 (11%) had central etiologies, such as stroke. Each of these three neurogenic subgroups revealed a distinct pattern of EMG abnormalities. This study suggests there is an association between patterns of CP-EMG abnormalities and underlying etiology based on clinical history.


The effect of ethanol on the ability of guinea-pigs to survive severe cold.
Some parameters related to withstanding severe cold (-20 degrees C) after administration of increasing doses of ethanol were investigated using guinea-pigs. The animals had been reared either at 22-23 degrees C or at 17-18 degrees C. They received ethanol in doses of 0.8 g, 1.2 g, 1.4 g or 1.6 g per kg of body weight. The fall of rectal temperature and its level at death were registered. The survival time, ethanol concentration in the blood and the brain, serum glucose and serum FFA at death were determined. In the animals reared at 22-23 degrees C the ethanol doses of 1.2-1.6 g/kg caused a significant shortening of the survival time and accelerated the fall of the rectal temperature. In addition the rectal temperature at death after ethanol was lower than in the controls. In the animals reared at 17-18 degrees C the ethanol doses used did not have any significant effect on the survival time and the rectal temperature. In both groups, ethanol concentration in the brain was lower (about 20-40%) than in the blood, the difference being greater in the group reared at 22-23 degrees C. Ethanol had no effect on the glucose concentrations. Serum FFA levels were slightly lower in animals reared at 22-23 degrees C than in those grown in the cooler temperature. It became evident that ethanol has a dose dependent deleterious effect on the thermoregulation of animals reared in warm (22-23 degrees C). The effect was seen at and above the dose of 1.2 g/kg. The results indicate further even a slight acclimation to cold was able to abolish the effect of these rather great doses of ethanol in severe cold exposure.


Prevalence of left ventricular hypertrophy in children and young people with primary hypertension: Meta-analysis and meta-regression.
Left ventricular hypertrophy (LVH) is the main marker of HMOD in children and young people (CYP). We aimed to assess the prevalence of LVH and its determinants in CYP with primary hypertension (PH). A meta-analysis of prevalence was performed. A literature search of articles reporting LVH in CYP with PH was conducted in Medline, Embase, and Cochrane databases. Studies with a primary focus on CYP (up to 21 years) with PH were included. Meta-regression was used to analyze factors explaining observed heterogeneity. The search yielded a total of 2,200 articles, 153 of those underwent full-text review, and 47 reports were included. The reports evaluated 51 study cohorts including 5,622 individuals, 73% male subjects, and a mean age of 13.6 years. LVH was defined as left ventricle mass index (LVMI) ≥ 95th percentile in 22 (47%), fixed cut-off ≥38.6 g/m2.7 in eight (17%), sex-specific fixed cut-off values in six (13%), and miscellaneously in others. The overall prevalence of LVH was 30.5% (95% CI 27.2-33.9), while heterogeneity was high (I 2 = 84%). Subgroup analysis including 1,393 individuals (76% male subjects, mean age 14.7 years) from pediatric hypertension specialty clinics and LVH defined as LVMI ≥95th percentile only (19 study cohorts from 18 studies), reported prevalence of LVH at 29.9% (95% CI 23.9 to 36.3), and high heterogeneity (I 2 = 84%). Two studies involving patients identified through community screening (n = 1,234) reported lower LVH prevalence (21.5%). In the meta-regression, only body mass index (BMI) z-score was significantly associated with LVH prevalence (estimate 0.23, 95% CI 0.08-0.39, p = 0.004) and accounted for 41% of observed heterogeneity, but not age, male percentage, BMI, or waist circumference z-score. The predominant LVH phenotype was eccentric LVH in patients from specialty clinics (prevalence of 22% in seven studies with 779 participants) and one community screening study reported the predominance of concentric LVH (12%). Left ventricular hypertrophy is evident in at least one-fifth of children and young adults with PH and in nearly a third of those referred to specialty clinics with a predominant eccentric LVH pattern in the latter. Increased BMI is the most significant risk association for LVH in hypertensive youth.


Crosstalk between the liver and kidney in diabetic nephropathy.
Diabetic nephropathy (DN) is a serious complication of diabetes, and its pathogenesis has not been fully elucidated. Recently, communication between organs has gradually become a new focus in the study of diseases pathogenesis, and abnormal interorgan communication has been proven to be involved in the occurrence and progression of many diseases. As an important metabolic organ in the human body, the liver plays an important role in maintaining homeostasis in humans. The liver secretes a series of proteins called hepatokines that affect adjacent and distal organs through paracrine or endocrine signaling pathways. In this review, we summarize some of the hepatokines identified to date and describe their roles in DN to discuss the possibility that the liver-renal axis is potentially useful as a therapeutic target for DN. We summarize the important hepatokines identified thus far and discuss their relationship with DN. We propose for the first time that the "liver-renal axis" is a potential therapeutic target in individuals with DN.


Reliable Pain Relief But Variable Return to Play After Arthroscopic Elbow Debridement in Baseball Players.
We sought to determine the rate of return to play (RTP) in baseball players following arthroscopic elbow debridement for the management of the symptomatic elbow. A retrospective case series with prospectively collected data via questionnaire was conducted on all baseball players who underwent an arthroscopic elbow debridement, from July, 15, 2004 to November 1, 2017. A postoperative questionnaire was released at an average 7.25 year follow-up. Data collected included age, gender, laterality, preoperative diagnosis, range of motion, duration and characterization of symptoms, visual analog scale (VAS) pain score, complications, level of play, and RTP. Follow-up data were available on 18 baseball players. Average age was 19.7 years (range 16-24). Seventeen were pitchers, and 1 was a catcher. Level of play included 12 collegiate athletes, 2 high school athletes, 2 recreational athletes, 1 minor league athletes, and 1 major league athlete. Rate of RTP was 61% (11/18) with 6 returning to a greater level and 5 to an equal level. The length of time to RTP following surgery was most commonly within 6-8 months (44.4%, 8/18). Mean VAS pain score improved from 6.9 to 0.75 (P = <.001). 27.8% (5/18) had repeat surgery secondary to recurrent/persistent stiffness or heterotopic ossification. 77.8% (14/18) of patients rated their final outcome as either "very satisfied" (9/18), or "satisfied" (5/18). Pain can reliably be relieved following arthroscopic elbow debridement in baseball players. Although patient satisfaction may be high, patients do not always return to their previous level of play. Patients must be counseled on the risk of limited postoperative athletic capacity before the time of surgery. Level IV, therapeutic case series.


The NRF2/Keap1 pathway as a therapeutic target in inflammatory bowel disease.
Oxidative stress (OS) is an important pathophysiological mechanism in inflammatory bowel disease (IBD). However, clinical trials investigating compounds directly targeting OS in IBD yielded mixed results. The NRF2 (nuclear factor erythroid 2-related factor 2)/Keap1 (Kelch-like ECH-associated protein 1) pathway orchestrates cellular responses to OS, and dysregulation of this pathway has been implicated in IBD. Activation of the NRF2/Keap1 pathway may enhance antioxidant responses. Although this approach could help to attenuate OS and potentially improve clinical outcomes, an overview of human evidence for modulating the NRF2/Keap1 axis and more recent developments in IBD is lacking. This review explores the NRF2/Keap1 pathway as potential therapeutic target in IBD and presents compounds activating this pathway for future clinical applications.


Cytotoxic and mutagenic effects of emodin on cultured mouse carcinoma FM3A cells.
Employing a suspension culture of a mouse mammary carcinoma cell line, FM3A cells, the cytotoxicity and induced mutagenicity of emodin (EM) were examined and compared with those of 2-hydroxy-emodin (2-OH-EM), which was identified as an active form of EM in the Ames/microsomes assay. EM was cytotoxic to FM3A cells in concentrations of 1-10 micrograms/ml, and induced 6-thioguanine-resistant (6TGr) mutation. 2-OH-EM was a little more toxic than EM, but induced little mutation.


Comparative Mitochondrial Genome Analyses of Sesarmid and Other Brachyuran Crabs Reveal Gene Rearrangements and Phylogeny.
Mitochondrial genomes (mitogenomes) are important for understanding molecular evolution and phylogenetic relationships. The complete mitogenome of Perisesarma bidens was determined, which is 15,641 bp in length. The A + T content of P. bidens mitogenome was 74.81%. The AT skew was slightly negative (-0.021). The 22 tRNAs ranged from 65 to 73 bp and were highly A + T biased. All tRNA genes had typical cloverleaf structures, except for the trnS1 gene, which lacked a dihydrouridine (DHU) arm. The gene order within the P. bidens mitogenome was identical to the pancrustacean ground pattern, except for the translocation of the trnH. Additionally, the gene order of trnI-trnQ-trnM in pancrustacean ground pattern became trnQ-trnI-trnM in P. bidens. Phylogenetic analyses supported the inclusion of P. bidens in Sesarmidae and the promotion of Sesarminae to Sesarmidae. The results will help us to better understand the status and evolutionary history of Grapsoidea crabs.


Associating brain imaging phenotypes and genetic in Alzheimer's disease via JSCCA approach with autocorrelation constraints.
Imaging genetics research can explore the potential correlation between imaging and genomics. Most association analysis methods cannot effectively use the prior knowledge of the original data. In this respect, we add the prior knowledge of each original data to mine more effective biomarkers. The study of imaging genetics based on the sparse canonical correlation analysis (SCCA) is helpful to mine the potential biomarkers of neurological diseases. To improve the performance and interpretability of SCCA, we proposed a penalty method based on the autocorrelation matrix for discovering the possible biological mechanism between single nucleotide polymorphisms (SNP) variations and brain regions changes of Alzheimer's disease (AD). The addition of the penalty allows the proposed algorithm to analyze the correlation between different modal features. The proposed algorithm obtains more biologically interpretable ROIs and SNPs that are significantly related to AD, which has better anti-noise performance. Compared with other SCCA-based algorithms (JCB-SCCA, JSNMNMF), the proposed algorithm can still maintain a stronger correlation with ground truth even when the noise is larger. Then, we put the regions of interest (ROI) selected by the three algorithms into the SVM classifier. The proposed algorithm has higher classification accuracy. Also, we use ridge regression with SNPs selected by three algorithms and four AD risk ROIs. The proposed algorithm has a smaller root mean square error (RMSE). It shows that proposed algorithm has a good ability in association recognition and feature selection. Furthermore, it selects important features more stably, improving the clinical diagnosis of new potential biomarkers.


Preparatory suppression of the human primary motor cortex induced by repetition of simple and choice reaction time tasks: a transcranial magnetic stimulation study.
Transcranial magnetic stimulation was performed to investigate preparatory suppression of activity in the human primary motor cortex (M1) in relation to trial repetition of simple (SRT) and Go/NoGo choice RT (CRT) tasks. These tasks were performed in such a way that after a warning signal, the subjects (N=16) maintained 5% MVC isometric finger force against the force sensor to secure a facilitated state of M1. A response signal to generate pulsed force came at 2 s after the warning signal. TMS was given 1.5 s after the warning signal, and the amplitudes of motor-evoked potentials (MEPs) in the first dorsal interosseous muscle were evaluated during 30 repetitive trials over 3 sessions for each subject. For the SRT task, the MEP amplitude was significantly decreased from baseline values in all trials of the three sessions. For the CRT task, on the other hand, there was a clear decreasing trend of the MEP amplitude with trial at the first and second sessions. The mean MEP amplitude at the first session was clearly higher than the baseline while it decreased significantly and reached the value below the baseline at the third session. The findings indicate that active suppression of M1 activity is involved in the preparatory state for RT tasks and that the degree of this suppression can relate to trial experience. The effect is thus most likely a consequence of a rapid adaptive change with the central nervous system in optimizing the preparatory state of M1 for the upcoming motor response.


Becoming a father: a review of nursing research on expectant fatherhood.
A review and analysis of nursing research focused on understanding the experiences of men becoming fathers is presented. Designs, sampling, methods, and substantive findings of the research studies are summarized. Implications for nursing are given.


Pharmacokinetics of etoposide in rats with uranyl nitrate (UN)-induced acute renal failure (ARF): optimization of the duration of UN dosing.
A uranyl nitrate-induced model of acute renal failure (UN-ARF) for various time periods was used to study its effect on the disposition of several drugs like chlorzoxazone, clarithromycin, vancomycin, methotrexate etc. An attempt to optimize the duration of UN dosing with respect to the pharmacokinetics of etoposide in rats was carried out after intravenous (i.v.) dosing of UN at 5 mg/kg for 1, 3, 5 and 7 days. Irrespective of the duration of UN dosing apart from day 1, ARF was observed, with significantly increased serum levels of creatinine (0.36 +/- 0.11 for controls vs 2.44 +/- 0.72 [day 7] for UN-ARF rats) and urea (33.71 +/- 9.46 for controls vs. 169.2 +/- 9.71 [day 5] for UN-ARF rats) in all the UN-treated groups. It has been reported that ARF may alter the pharmacokinetics (PK) and the exposure of renally eliminated drugs. Further, as exposure to etoposide has a correlation with toxicity, the need to investigate the possible alterations in etoposide pharmacokinetics in the UN-ARF model could be of significance. The PK of etoposide was therefore investigated in control and UN-ARF rats after a single i.v. dose of 25 mg/kg. The concentrations of etoposide in the plasma were determined by high- performance liquid chromatography (HPLC) method with fluorescence detector set at excitation and emission wavelengths of 380 and 520 nm respectively. The metabolic stability of etoposide was investigated in rat liver microsomes prepared from control and UN-ARF treated rats. The PK results showed increased plasma levels and systemic exposure to etoposide (19.97 +/- 2.12 for control vs 29.03 +/- 2.32, 34.45 +/- 3.37, 34.19 +/- 2.98 for 3, 5 and 7day UN-treated groups respectively), i.e. for all UN-ARF groups except for 1-day UN-ARF rats (20.06 +/- 1.53). Incubation with liver microsomes from UN-ARF rats treated for up to 5 days and control rats showed no significant difference in etoposide metabolism suggesting that the CYP3A4 isoenzyme responsible for the metabolism of etoposide was not considerably expressed thereby leading to the conclusion that 3 days UN dosing was sufficient to induce ARF in rats, and that the dose of etoposide required needs to be monitored due to altered PK.


Marginal zone cell lymphoma--an update on recent advances.
The marginal zone represents one of the distinct compartments of the B-cell area in lymphoid tissues. It is especially well developed in the spleen and in Peyer's patches of the gut, but not in lymph nodes, with the exception of the ones in the mesenterium. However, the pronounced proliferation of so-called 'monocytoid B-cells' that may be seen in some inflammatory conditions of the lymph node may be regarded as a nodal reactive marginal zone cell expansion. The cellular compositions of the marginal zone and the monocytoid B-cell proliferation are similar and both show a heterogeneous population of B-cells, of which the functions are being slowly unravelled. Neoplasms originating in the marginal zone have been recognized in the past and are listed in the REAL classification as marginal zone B-cell lymphomas including extranodal MALT-type lymphomas, splenic marginal zone lymphomas and nodal (monocytoid) marginal zone lymphomas. Marginal zone cell lymphomas display a broad morphological spectrum, which is reflected by the heterogeneity of the cellular composition and the variation in the growth pattern of the lymphoma, but is independent of the anatomical site. All three marginal zone cell lymphomas share immunophenotypic, genetic and chromosomal similarities which will be discussed. The morphologic features are dealt with only briefly as they have been extensively discussed elsewhere.


Quality of Life in Sickle Cell Disease: What Matters.
Health-related quality of life (HRQoL) represents the practical effects of an illness in terms of symptoms and impacts, and of consequent treatments, as perceived by the patient. HRQoL is a complex multidimensional phenomenon in sickle cell disease (SCD) involving external stressors, thought patterns, emotional distress, physiological arousal, pain, and other complications of SCD. Social determinants of health comprise food and housing security, employment and education, and experiences of racism and discrimination; these social determinants also potentially affect health, HRQoL, and access to health care. Interventions must be implemented in partnership between individuals with SCD and their health-care providers.


Novel MRI Contrast Agent from Magnetotactic Bacteria Enables In Vivo Tracking of iPSC-derived Cardiomyocytes.
Therapeutic delivery of human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMs) represents a novel clinical approach to regenerate the injured myocardium. However, methods for robust and accurate in vivo monitoring of the iCMs are still lacking. Although superparamagnetic iron oxide nanoparticles (SPIOs) are recognized as a promising tool for in vivo tracking of stem cells using magnetic resonance imaging (MRI), their signal persists in the heart even weeks after the disappearance of the injected cells. This limitation highlights the inability of SPIOs to distinguish stem cell viability. In order to overcome this shortcoming, we demonstrate the use of a living contrast agent, magneto-endosymbionts (MEs) derived from magnetotactic bacteria for the labeling of iCMs. The ME-labeled iCMs were injected into the infarcted area of murine heart and probed by MRI and bioluminescence imaging (BLI). Our findings demonstrate that the MEs are robust and effective biological contrast agents to track iCMs in an in vivo murine model. We show that the MEs clear within one week of cell death whereas the SPIOs remain over 2 weeks after cell death. These findings will accelerate the clinical translation of in vivo MRI monitoring of transplanted stem cell at high spatial resolution and sensitivity.


Forensic veterinary radiology: ballistic-radiological 3D computertomographic reconstruction of an illegal lynx shooting in Switzerland.
The lynx, which was reintroduced to Switzerland after being exterminated at the beginning of the 20th century, is protected by Swiss law. However, poaching occurs from time to time, which makes criminal investigations necessary. In the presented case, an illegally shot lynx was examined by conventional plane radiography and three-dimensional multislice computertomography (3D MSCT), of which the latter yielded superior results with respect to documentation and reconstruction of the inflicted gunshot wounds. We believe that 3D MSCT, already described in human forensic-pathological cases, is also a suitable and promising new technique for veterinary pathology.


Dysfunctional protection against advanced glycation due to thiamine metabolism abnormalities in gestational diabetes.
While the pathogenic role of dicarbonyl stress and accelerated formation of advanced glycation end products (AGEs) to glucose intolerance and to the development of diabetic complications is well established, little is known about these processes in gestational diabetes mellitus (GDM), a condition pathogenically quite similar to type 2 diabetes. The aims of the present study were (i) to determine plasma thiamine and erythrocyte thiamine diphosphate (TDP) and transketolase (TKT) activity in pregnant women with and without GDM, (ii) to assess relationships between thiamine metabolism parameters and selected clinical, biochemical and anthropometric characteristics and, finally, (iii) to analyse relationship between variability in the genes involved in the regulation of transmembrane thiamine transport (i.e. SLC19A2 and SLC19A3) and relevant parameters of thiamine metabolism. We found significantly lower plasma BMI adjusted thiamine in women with GDM (P = 0.002, Mann-Whitney) while levels of erythrocyte TDP (an active TKT cofactor) in mid-trimester were significantly higher in GDM compared to controls (P = 0.04, Mann-Whitney). However, mid-gestational TKT activity - reflecting pentose phosphate pathway activity - did not differ between the two groups (P > 0.05, Mann-Whitney). Furthermore, we ascertained significant associations of postpartum TKT activity with SNPs SLC19A2 rs6656822 and SLC19A3 rs7567984 (P = 0.03 and P = 0.007, resp., Kruskal-Wallis). Our findings of increased thiamine delivery to the cells without concomitant increase of TKT activity in women with GDM therefore indicate possible pathogenic role of thiamine mishandling in GDM. Further studies are needed to determine its contribution to maternal and/or neonatal morbidity.


Investigation of the common intermediates over Fe-ZSM-5 in NH3-SCR reaction at low temperature by in situ DRIFTS.
The surface species formed in the reaction of NO and NO2 with pre-adsorbed NH3 over a Fe-ZSM-5 catalyst (1.27 wt.% Fe, SiO2/Al2O3 = 25) at low temperature (140°C) were studied by in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). Through using a background spectrum of NH3-saturated Fe-ZSM-5, we clearly observed the formation of common intermediates resulting from the reaction of NO2 or NO + O2 with pre-adsorbed NH3. This presents strong evidence that the oxidation of NO to form surface nitrates and nitrites is the key step for standard SCR at low temperature. In addition, the results suggest that in the SCR reaction at low temperature, the NH4+ ions absorbed on Brønsted acid sites are less active than NH3 adsorbed on Lewis acid sites related to Fe species.


Effects of pantetheine on cholesteryl ester synthesis in the arterial wall of rats on high cholesterol diet.
Increase of acyl-CoA synthesis was observed when extracts of rat arterial wall were incubated with pantetheine [D-bis-(N-pantothenyl-beta-aminoethyl)-disulfide]. Cholesteryl ester synthesis from palmitate in the arterial wall extract in vitro was higher with arteries from rats on high cholesterol diet than with those from rats on normal diet, but the synthesis was reduced in the arteries of rats on high cholesterol diet with pantetheine. Triglyceride synthesis was higher with arterial wall extracts of rats on high cholesterol diet than with preparations from rats on normal diet and was not reduced with those of rats on high cholesterol diet plus pantetheine. The value of the effects of pantetheine on lipid metabolism in the prevention of atherosclerosis is pointed out.


Peak early diastolic strain rate improves prediction of adverse cardiovascular outcomes in patients with ST-elevation myocardial infarction.
The prognostic role of diastolic dysfunction measured by the circumferential peak early diastolic strain rate (PEDSR) on ST-elevation myocardial infarction (STEMI) is not completely established. We aimed to investigate the prognostic value of diastolic function by measuring PEDSR within 1 week after STEMI. The cardiac magnetic resonance (CMR) pictures of 420 subjects from a clinical registry study (NCT03768453) were analyzed and the composite major adverse cardiac events (MACEs) were followed up. The PEDSR of patients was significantly lower compared with that of control subjects (P < 0.001). Within the median follow-up period of 52 months, PEDSR of patients who experienced MACEs deceased more significantly than that of patients without MACEs (P < 0.001). After adjusting with clinical or CMR indexes, per 0.1/s reduction of PEDSR increased the risks of MACEs to 1.402 or 1.376 fold and the risk of left ventricular (LV) remodeling to 1.503 or 1.369 fold. When PEDSR divided by best cutoff point, significantly higher risk of MACEs (P < 0.001) and more remarkable LV remodeling (P < 0.001) occurred in patients with PEDSR ≤ 0.485/s. Moreover, when adding the PEDSR to the conventional prognostic factors such as LV ejection fraction and infarction size, better prognostic risk classification models were created. Finally, aging, tobacco use, remarkable LV remodeling, and a low LV ejection fraction were factors related with the reduction of PEDSR. Diastolic dysfunction has an important prognostic effect on patients with STEMI. Measurement of the PEDSR in the acute phase could serve as an effective index to predict the long-term risk of MACEs and cardiac remodeling.


Differential induction of type I interferons in macaques by wild-type measles virus alone or with the hemagglutinin protein of the Edmonston vaccine strain.
Measles vaccines are highly effective and safe; however, the mechanism(s) underlying their attenuation has not been well understood. In this study, type I IFNs (IFN-α and IFN-β) induction in macaques infected with measles virus (MV) strains was examined. Type I IFNs were not induced in macaques infected with wild-type MV. However, IFN-α was sharply induced in most macaques infected with recombinant wild-type MV bearing the hemagglutinin (H) protein of the Edmonston vaccine strain. These results indicate that the H protein of MV vaccine strains may have a role in MV attenuation.


Bioinspired Polysaccharide-Derived Zwitterionic Brush-like Copolymer as an Injectable Biolubricant for Arthritis Treatment.
Developing highly efficient and biocompatible biolubricants for arthritis treatment is extraordinarily demanded. Herein, inspired by the efficient lubrication of synovial joints, a paradigm that combines natural polysaccharide (chitosan) with zwitterionic poly[2-(methacryloyloxy) ethyl phosphorylcholine] (PMPC), to design a series of brush-like Chitosan-g-PMPC copolymers with highly efficient biological lubrication and good biocompatibility is presented. The Chitosan-g-PMPC copolymers are prepared via facile one-step graft polymerization in aqueous medium without using any toxic catalysts and organic solvents. The as-prepared Chitosan-g-PMPC copolymers exhibit very low coefficient of friction (μ < 0.01) on Ti6 Al4 V alloy substrate in both pure water and biological fluids. The superior lubrication is attributed primarily to the hydrated feature of PMPC side chains, interface adsorption of copolymer as well as to the hydrodynamic effect. In vivo experiments confirm that Chitosan-g-PMPC can alleviate the swelling symptom of arthritis and protect the bone and cartilage from destruction. Due to their facile preparation, distinctive lubrication properties, and good biocompatibility, Chitosan-g-PMPC copolymers represent a new type of biomimetic lubricants derived from natural biopolymer for promising arthritis treatment and artificial joint lubrication.


Suicidal behavior in problematic substance uses in South Gondar zone, Northwest Ethiopia: a cross-sectional survey.
Suicidal behavior has a significant contribution to the global burden of disease that affects individuals, families and communities at different age groups. Sadly, up to 75% of suicides in the world occur in low-and- middle income countries which have no adequate resource to prevent it. The aim of this study was to assess suicidal behavior and associated factors among community residents with problematic substance use in South Gondar zone, northwest Ethiopia. Community based cross-sectional survey was conducted by using a suicidal behavior revised questionnaire from January 15 to March 15, 2019. A total of 4035 participants were screened for problematic substance use by using multi stage cluster sampling and 846 participants were positive for problematic substance use then asked for suicidal behavior. Multiple logistic regression analyses used to see adjusted odd rations (AOR). Multilevel binary logistic regression was used to account for the hierarchical structure of the two-level data within individual and districts level. The prevalence of suicidal behavior over the last 12 months in problematic substance uses was found to be 41.4% with 95% of confidence interval (CI) (38.2-44.9). Perceived stigma, [AOR = 1.605, 95% CI (1.16-2.23)], family history of suicide [AOR = 3.22, 95% CI (1.46-7.10)], physical illness [AOR = 2.45 95% CI (1.157-3.84)], rural resident [AOR = 1.74, 95% CI (1.16-2.62)], depression [AOR = 4.44, 95% CI (3.15-6.27)] and living alone (AOR = 1.61, 95% CI (1.16-2.24) were risks factors for suicidal behavior. Suicidal behavior in problematic substance uses found to be high. Health workers should pay attention to decrease suicidal behavior and to control amendable factors.


Electrophysiological measures of visual and auditory function as indices of neurotoxicity.
The application of auditory and visual evoked potentials (VEP) to neurotoxicity testing of humans and animals is reviewed. VEPs elicited by flash, reversing-checkerboard patterns, and sine wave grating are described. The flask evoked potential in rats is altered by exposure to many heavy metals, pesticides and solvents. The brainstem auditory evoked potential also appears to be sensitive to neurotoxic chemicals, but the evidence available is limited. The homology of auditory and visual evoked potentials in rats and humans is useful for cross-species extrapolation in neurotoxicology research.


Sleeve Fistulectomy: A Novel Hybrid Technique to Manage the Degenerative Arteriovenous Fistula.
Aneurysmal degeneration following long-term access is an important problem associated with an arteriovenous fistula (AVF) and can result in rupture, thrombosis, or the need for ligation. We describe five patients receiving hemodialysis through large degenerative brachiocephalic AVFs who underwent successful revision and avoided the need for a temporary dialysis catheter. A hybrid approach using an open surgical technique with both endovascular and laparoscopic tools provides an opportunity to maintain patency and restore function by combining modern surgical tools.


Awake craniotomy for trapping a giant fusiform aneurysm of the middle cerebral artery.
Giant fusiform aneurysms of the distal middle cerebral artery (MCA) are rare lesions that, because of the absence of an aneurysm neck and the presence of calcified walls and partial thrombosis, can be difficult to clip without sacrificing the parent vessel. Moreover, when the aneurysm is located in the dominant hemisphere, it is not possible to test language and cognitive functions during surgical intervention, making the closure of the parent vessel extremely dangerous. A 46-year-old woman presented with a one-year history of frontal headache without neurological deficit. A magnetic resonance imaging and an angiography showed a giant fusiform aneurysm of the left M2 tract. Because of the location and the absence of a neck, the aneurysm was considered difficult to coil and not amenable to preoperative balloon occlusion; thus, the patient was a candidate for surgical treatment. After a preoperative psychological evaluation, patient underwent awake craniotomy with the asleep-awake-asleep technique. A standard left pterional approach was performed to expose the internal carotid artery, the MCA and the aneurysm originating from the frontal branch of the MCA. Neurological examination responses remained unchanged during temporary parent artery occlusion, and trapping was successfully performed. Awake craniotomy is a useful option in intracranial aneurysm surgery because it permits neurological testing before vessels are permanently clipped or sacrificed. With the asleep-awake-asleep technique, it is possible to perform a standard pterional craniotomy, which allows good exposure of the vascular structures without cerebral retraction.


Endothelin mediated nitric oxide effects in ischemia--reperfusion associated with pancreas transplantation.
Formation of nitric oxide (NO) in ischemia-reperfusion (I-R) associated with pancreas transplantation could modulate the inflammatory response. In this sense, previous studies have demonstrated the action of NO on vasoactive substances like prostacyclin or endothelin. The present study was designed to evaluate the contribution of endothelin to the inflammatory events induced by NO in the I-R process associated with pancreas transplantation. For this purpose, pancreatic levels of endothelin, neutrophil infiltration, and prostacyclin were evaluated in an experimental model of pancreas transplantation after inhibition of NO synthesis or after NO inhibition plus addition of endothelin. Results show significant posttransplantation increases in endothelin, neutrophil infiltration, and prostacyclin production. These increases were prevented by NO inhibition. Endothelin administration plus nitric oxide inhibition reversed this effect, resulting in an increase in myeloperoxidase and 6-keto-prostaglandin F1alpha. These results suggest that the proinflammatory effects of NO in I-R associated with pancreas transplantation are mediated by the induction of endothelin generation.


Measurement of glucose and 2-deoxy-2-[18F]fluoro-D-glucose transport and phosphorylation rates in myocardium using dual-tracer kinetic experiments.
To examine the use of 2-deoxy-2-[18F]fluoro-D-glucose (2-FDG) as a glucose analog for measuring glucose utilization rate in myocardium, dual-tracer kinetic experiments with 2-FDG and 2-[3H]glucose were performed in the perfused, isolated rabbit interventricular septum to measure simultaneously the transport and phosphorylation rates of glucose and 2-FDG. Results of the present study indicated that, in the septum, the transport rate constants of 2-FDG and glucose were similar in magnitude, the phosphorylation rate constant for 2-FDG was about 60% of that of glucose, hypoxia caused an increase in phosphorylation rates of glucose and 2-FDG without affecting transport.


Comprehensive insight into the neurotoxic mechanisms of low dose Pb exposure in Wistar rats: Benchmark dose analysis.
Lead (Pb) is a toxic metal that affects almost all human's system and organs, with the nervous system as the most sensitive. Better understanding of the Pb neurobehavioral effects and neurotoxicity requires realistic study scenarios based on low level exposure. The aim of this study was to determine neurotoxic effects and mechanisms of Pb in six low doses and to establish dose-response relationship for these effects and related Benchmark dose (BMD). Forty-two, male albino Wistar rats were randomized into seven groups, control and Pb-exposed: 0.1, 0.5, 1, 3, 7 and 15 mg Pb/kg body weight/day (oral gavage) for 28 days. Behavioural tests (Elevated plus maze test, Spontaneous locomotor activity test and Novel object recognition test) were conducted in the last week of experiment, in the control, lower (0.5 mg Pb/kg), middle (3 mg Pb/kg) and higher (15 mg Pb/kg) dose groups. The acetylcholinesterase activity, oxidative status and essential elements levels (Cu, Zn, Mn and Fe) were measured in brain tissue along with histological analyses. External and internal dose-response analyses were performed using PROASTweb 70.1 software. The results have shown that subacute exposure to very low doses of Pb resulted in memory deficits in rats that was accompanied with acetylcholinesterase enzyme activity decrease. The observed hyperactive behaviour was accompanied by dose-dependent induction of brain oxidative stress and Zn elevation. The histological alterations in Purkinje cells were only detected in the group treated with the highest Pb dose. The lowest BMD considering entire oxidative status was calculated based on total oxidative status (4.5e-06 mg Pb/kg b.w./day). The findings reported in our study may be beneficial in further evaluating the health consequences and human health risk assessment of low-level Pb exposure.


Ultrasound characterization of acoustic properties of acute intracardiac thrombi: studies in a new experimental model.
Echocardiographic differentiation among intracavitary thrombus, cavity noise, and adjacent myocardium can be difficult. As an initial step toward quantitative thrombus characterization with ultrasound, 11 dogs were studied with an in vivo intracardiac thrombus model to delineate the acoustic properties of acute thrombi. The apical coronary arteries were ligated, and subsequently injections of 5% sodium rescinoleate and 1000 units of thrombin at the endocardium-blood interface created left ventricular mural thrombi. Echocardiographic images were obtained in long- and short-axis views with a digital acquisition system, and a statistical analysis of echo intensities was performed in regions of interest in the thrombus, surrounding ventricular cavity and adjacent myocardium. Statistical measurements used to evaluate echo intensities in each region of interest included mean gray level, standard deviation, skewness, and kurtosis. The results showed that thrombus could be distinguished from myocardium (by mean gray level and standard deviation) only in short-axis views, where regions of interest could be placed at similar depths of field. Mean gray level, standard deviation, and skewness all distinguished thrombus from intracavitary blood regardless of the region of interest placement. The phase of the cardiac cycle at which data were acquired did not alter the results. We conclude that acute intracardiac thrombi can be distinguished from surrounding blood and myocardium with ultrasound tissue characterization techniques that may have the potential for clinical application.


Nicotinic-dopaminergic relationships and radial-arm maze performance in rats.
Accurate performance on the radial-arm maze is dependent upon the integrity of nicotinic-cholinergic, muscarinic-cholinergic, and dopaminergic systems. Pharmacological blockade of these systems with mecamylamine, scopolamine, or haloperidol impairs choice accuracy in the maze. We have previously demonstrated that the performance deficit caused by muscarinic blockade is enhanced by coadministration of the nicotinic antagonist, mecamylamine, and is diminished by coadministration of the dopamine antagonist, haloperidol. In the present study, it was found that the choice accuracy deficit produced by nicotinic blockade is enhanced, not antagonized, by coadministration of haloperidol. Thus, although both nicotinic and muscarinic cholinergic systems are involved in radial-arm maze performance and antagonists of these receptors are additive in the deficits they cause, nicotinic and muscarinic interactions with dopaminergic systems are opposite in nature.


Cloning and expression of a Bacillus coagulans amylase gene in Escherichia coli.
A partial EcoRI fragment of Bacillus coagulans DNA cloned in an Escherichia coli K12 bacteriophage lambda host-vector system was shown to direct the synthesis of a thermostable alpha-amylase whose activity could be detected in situ on petri plates using the iodine staining method. A 3.31 kb EcoRI fragment containing the active gene with its own promoter was subcloned in pBR322; in the new clone, called pAMY2, the amylase was shown to accumulate in the periplasmic space. The molecular weight of the enzyme, confirmed by in vivo labelling of plasmid products in minicells, was estimated to be 60000. The restriction map of the plasmid was determined for five restriction enzymes and two new plasmids with smaller DNA inserts were constructed, both directing the synthesis of amylase; one of them with a 2.2 kb PstI insert was shown to be responsible for the synthesis of a fused beta-lactamase-alpha-amylase protein with amylase activity.


The primary structure of rat ribosomal protein S19.
The covalent structure of rat ribosomal protein S19 was deduced from the sequence of nucleotides in a recombinant cDNA and confirmed from the NH2-terminal amino acid sequence of the protein. Ribosomal protein S19 contains 144 amino acids (the NH2-terminal methionine is removed after translation of the mRNA) and has a molecular weight of 15,944. Hybridization of the cDNA to digests of nuclear DNA suggests that there are 15-18 copies of the S19 gene. The mRNA for the protein is about 640 nucleotides in length. Rat S19 is related to Saccharomyces cerevisiae S16A and to Halobacterium marismortui S12.


Hemodynamic effects of fluid restriction in preterm infants with significant patent ductus arteriosus.
To determine the hemodynamic impact of fluid restriction in preterm newborns with significant patent ductus arteriosus. Newborns ≥24 and <32 weeks' gestational age with significant patent ductus arteriosus were eligible for this prospective multicenter observational study. We recorded hemodynamic and Doppler echocardiographic variables before and 24 hours after fluid restriction. Eighteen newborns were included (gestational age 24.8 ± 1.1 weeks, birth weight 850 ± 180 g). Fluid intake was decreased from 145 ± 15 to 108 ± 10 mL/kg/d. Respiratory variables, fraction of inspired oxygen, blood gas values, ductus arteriosus diameter, blood flow-velocities in ductus arteriosus, in the left pulmonary artery and in the ascending aorta, and the left atrial/aortic root ratio were unchanged after fluid restriction. Although systemic blood pressure did not change, blood flow in the superior vena cava decreased from 105 ± 40 to 61 ± 25 mL/kg/min (P < .001). The mean blood flow-velocity in the superior mesenteric artery was lower 24 hours after starting fluid restriction. Our results do not support the hypothesis that fluid restriction has beneficial effects on pulmonary or systemic hemodynamics in preterm newborns.


Investigation of ascorbate-mediated iron release from ferric phytosiderophores in the presence of nicotianamine.
Phytosiderophores (PS) are strong iron chelators, produced by graminaceous plants under iron deficiency. The ability of released PS to chelate iron(III), and subsequent uptake of this chelate into roots by YS1-type transport proteins, are well-known. The mechanism of iron release from the stable chelate inside the plant cell, however, is unclear. One possibility involves the reduction of ferric PS in the presence of an iron(II) chelator via ternary complex formation. Here, the conversion of ferric PS species by ascorbate in the presence of the intracellular ligand nicotianamine (NA) has been investigated at cytosolic pH (pH 7.3), leading to the formation of a ferrous NA chelate. This reaction takes place when supplying Fe(III) as a chelate with 2'-deoxymugineic acid (DMA), mugineic acid (MA), and 3-epi-hydroxymugineic acid (epi-HMA), with the reaction rate decreasing in this order. The progress of the conversion of ferric DMA to ferrous NA was monitored in real-time by high resolution mass spectrometry (FTICR-MS), and the results are complemented by electrochemical measurements (cyclic voltammetry), which allows detecting reactive intermediates and their change with time at high sensitivity. Hence, the combined results of electrochemistry and mass spectrometry indicate an ascorbate-mediated mechanism for the iron release from ferric PS, which highlights the role of ascorbate as a simple, but effective plant reductant.


The mean and noise of stochastic gene transcription.
Gene transcription in single cells is inherently a probabilistic process. Even in a hypothetically homogeneous intracellular environment, the stochasticity of transcription would produce fluctuations in the number of transcripts, constituting the phenotypic heterogeneity in cell population. Noise, the variance normalized by the square of the mean, has typically been utilized to quantify the heterogeneity of transcript distribution. The noise has been thought to arise from random switching between gene on and gene off states, but what underlies the stochastic transition between the on state and the off state remains largely unknown. To examine how the environmental signals contribute to the gene transcription regulation, we employ a three states model to evaluate the dynamical and stationary mean transcript level, and the noise of transcript distribution. Our findings reinforce the assertion of Raser and O'Shea [2004. Control of stochasticity in eukaryotic gene expression. Science 304, 1811-1814] that two cells can produce the same mean mRNA population but display different noise characteristics. The theoretical analysis also brings new characteristics to the subtle correlations between the mean and the noise, which extends beyond the categorization of Raser and O'Shea.


Reversible diffusion-weighted imaging changes in the splenium of the corpus callosum and internal capsule associated with hypoglycemia - case report - .
A 63-year-old man presented with hypoglycemia-induced hemiparesis manifesting as diffusion-weighted magnetic resonance (MR) imaging changes in the splenium of the corpus callosum and internal capsule which disappeared after glucose administration. Clinicians should be aware that hypoglycemia can cause reversible splenium abnormalities on MR imaging, although the underlying mechanism still remains unclear, as this may be helpful in the differential diagnosis of hypoglycemia-induced hemiparesis and stroke.


Over-expression of the yeast multifunctional arom protein.
The pentafunctional arom protein of Saccharomyces cerevisiae is encoded by the ARO1 gene. Substantial elevation of the levels of the arom protein (25-fold) was achieved in yeast using a vector that exploited the ubiquitin-fusion cleavage system of yeast. However, attempts to express the N-terminal 3-dehydroquinate synthase domain (E1) or the internal 3-dehydroquinase domain (E2) using the same system did not succeed. The yeast arom protein was successfully purified from the over-expressing transformant, and was found to possess all five enzymatic activities in a ratio similar to that observed in crude cell extracts. The purified material consisted mainly of a polypeptide that co-migrated in SDS-PAGE with intact arom proteins from other species.


Cerebral cavernomas in the adult. Review of the literature and analysis of 72 surgically treated patients.
The authors review the pertinent literature dealing with all aspects of cerebral cavernous malformations in the adult. Clinical, neuroradiological, pathological, and epidemiological aspects are presented. The clinical significance of bleeding from cavernous malformations and various hemorrhage patterns are discussed in relation to the factors that influence hemorrhage rates. Recent reports describing the genetic mechanisms of inheritance, de novo formation, and angiogenesis of cavernomas are reviewed as well. Brainstem cavernomas have received special attention, since their clinical management is controversial in the literature. Presently, microsurgical removal is favored by the majority of authors and stereotactic radiosurgery appears to be inappropriate for prevention of bleeding from a cavernoma. Our own case material consists of data of 72 patients operated upon during the past 5 years. Twenty-four patients harbored the lesion within the brainstem, 18 within the deep white matter of the hemispheres, 12 in the basal ganglia or thalamus, 11 in superficial areas of the hemisphere, and seven within the cerebellum. The perioperative morbidity rate was 29.2% (21/72) while the rate of long-term morbidity was 5.5% (4/72), with no mortality in this series. It is concluded that cerebral cavernous malformations, including lesions in critical regions of the brain, can be treated microsurgically with excellent results and an acceptable morbidity.


Population structure within lineages of Wheat streak mosaic virus derived from a common founding event exhibits stochastic variation inconsistent with the deterministic quasi-species model.
Structure of Wheat streak mosaic virus (WSMV) populations derived from a common founding event and subjected to serial passage at high multiplicity of infection (MOI) was evaluated. The founding population was generated by limiting dilution inoculation. Lineages of known pedigree were sampled at passage 9 (two populations) and at passage 15, with (three populations) or without mixing (four populations) of lineages at passage 10. Polymorphism within each population was assessed by sequencing 17-21 clones containing a 1371 nt region (WSMV-Sidney 81 nts 8001-9371) encompassing the entire coat protein cistron and flanking regions. Mutation frequency averaged approximately 5.0 x 10(-4)/nt across all populations and ranged from 2.4 to 11.6 x 10(-4)/nt within populations, but did not consistently increase or decrease with the number of passages removed from the founding population. Shared substitutions (19 nonsynonymous, 10 synonymous, and 3 noncoding) occurred at 32 sites among 44 haplotypes. Only four substitutions became fixed (frequency = 100%) within a population and nearly one third (10/32) never achieved a frequency of 10% or greater in any sampled population. Shared substitutions were randomly distributed with respect to genome position, with transitions outnumbering transversions 5.4:1 and a clear bias for A to G and U to C substitutions. Haplotype composition of each population was unique with complexity of each population varying unpredictably, in that the number and frequency of haplotypes within a lineage were not correlated with number of passages removed from the founding population or whether the population was derived from a single or mixed lineage. The simplest explanation is that plant virus lineages, even those propagated at high MOI, are subject to frequent, narrow genetic bottlenecks during systemic movement that result in low effective population size and stochastic changes in population structure upon serial passage.


[Botryoid odontogenic cyst].
The botryoid odontogenic cyst (BOC) is a developmental cyst of odontogenic epithelial origin considered as a rare multilocular variety of lateral periodontal cyst (WHO 1992). This cystic lesion site is in the periodontal space of vital teeth. A 21-year-old woman consulted for a swelling of the anterior maxillary region. The clinical examination revealed bucal swelling extending from the left central incisor to the first left premolar. The mucosa was normal. The adjacent teeth were vital. X-ray revealed a bilocular radiolucency extending between the roots of teeth 21 and 24. The lesion was enucleated, under local anaesthesia via a vestibular approach. Histology was typical of a BOC with cystic spaces lined by squamous epithelium with thickening and clear cells. Forty-eight months after surgery, there was sign of recurrence. BOC is known to be a recurrent odontogenic cyst. Several cases of multiple recurrences have been reported up to nine years after the initial surgery. Long-term follow-up is thus mandatory.


The site of origin of cardiac preganglionic fibers of the vagus nerve: an HRP study in the cat.
After injection of horseradish peroxidase (HRP) into the right cardiac branches of the vagus nerve in the cat, the majority of HRP-labeled neurons were located ipsilaterally in the reticular formation ventrolateral to the nucleus ambiguus. Additionally, HRP-labeled neurons were also observed within the nucleus ambiguus (Am) and the dorsal motor nucleus of the vagus nerve (DM).


Preferred provider organization claims showed high predictive value but missed substantial proportion of adults with high-risk conditions.
We assessed the validity and utility of a claims-based ICD-9-CM algorithm for identifying preferred provider organization (PPO) enrollees ages 18-64 years at high risk for influenza complications. PPO enrollees with >/= 2 encounters in an ambulatory setting or >/= 1 encounters in an inpatient or emergency room setting with ICD-9-CM diagnosis codes for the high-risk conditions were considered algorithm positive. Stratified random sampling was used to select 1,001 algorithm-positive and 330 algorithm-negative enrollees for medical chart abstractions. The prevalence of high-risk conditions using claims data was 2.5% compared to 18.2% according to medical records. The algorithm had a sensitivity of 12% and a specificity of 99%. Positive and negative predictive values were 87 and 84%, respectively. Sensitivity was twofold higher among adults aged 50-64 years than among younger adults (17 vs. 9%). Applying an algorithm definition of >/= 1 encounters in any setting resulted in an increased sensitivity, but captured a higher proportion of false positives. A claims-positive record was highly indicative of the presence of high-risk conditions, but such claims missed a large proportion of PPO enrollees with high-risk conditions. It is important to assess the validity of administrative data in different age groups.


Efficacy and safety of immune checkpoint inhibitors in elderly patients with metastatic renal cell carcinoma.
To clarify the efficacy and safety profile of immune checkpoint inhibitors (ICIs) for elderly patients with metastatic renal cell carcinoma (mRCC). We retrospectively evaluated 149 mRCC patients treated with nivolumab monotherapy as subsequent therapy (n = 89) and nivolumab plus ipilimumab as first-line therapy (n = 60) at 5 affiliated institutions. The patients were divided according to age: > 70 (elderly) vs. ≤ 70 years (young). Efficacy was analyzed by comparing progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR) between elderly and young patients. Safety was assessed by comparing the incidence rates of immune-related adverse events (irAEs). In the nivolumab monotherapy group, 34/89 patients (38%) were classified as elderly. There was no significant difference in PFS (p = 0.607), OS (p = 0.383), ORR (p = 0.0699), or DCR (p = 0.881) between elderly and young patients. In the nivolumab plus ipilimumab group, 20/60 patients (33%) were classified as elderly. There was no significant difference in PFS (p = 0.995), OS (p = 0.714), ORR (p = 0.763), or DCR (p = 1.000) between the two groups. The incidence rate of irAEs was not significantly different in the nivolumab (any grade: p = 0.121; grade ≥ 3: p = 0.542) or in the nivolumab plus ipilimumab (any grade: p = 0.666; grade ≥ 3: p = 0.576) group; a higher rate of gastrointestinal irAEs was observed in elderly than in young patients (any grade 15% vs. 3%). The efficacy and safety of nivolumab monotherapy and nivolumab plus ipilimumab were comparable between elderly and young patients. Thus, chronological age alone should not be a contraindication in the use of ICIs for mRCC.


Correlation of thermal analysis and pyrolysis coupled to GC-MS in the characterization of tacrolimus.
In recent years, thermal analysis has assumed major role in the pharmaceutical industry because it can be used to evaluate the stability both in the control of raw materials and the finished product, having employment potential in the development and characterization of new products and assessment processes. Tacrolimus (TCR) is a macrolide lactone with potent immunosuppressive activity. The purpose of this study was to characterize tacrolimus raw material using Thermal analysis and Pyrolysis coupled to Gas chromatography-Mass spectrometry (Pyr-GC-MS). It was analyzed four samples of tacrolimus named TCR A, B, C and D. Thermal analysis experiments was performed in Shimadzu equipment, under nitrogen and synthetic air atmosphere in different heating rate. Pyrolysis analysis was conducted in isothermal conditions of 300°C and 400°C coupled to GC-MS, in which the mass spectrometer was operated in scan mode to detect ions in the range of mass of m/z 25-900. The thermal studies by DSC, DTA and DSC-Photovisual showed desolvation process for all tacrolimus raw materials and TG-dynamical demonstrated two pseudo-polymorphic forms (monohydrate and sesquihydrate) of tacrolimus. It was observed good correlation between the stoichiometric mass losses of the TG-dynamical and identification of product ion in Pyr-GC/MS technique. It was possible to correlate the five pyrolytic product ions with the Ozawa kinetic analysis from the thermal decomposition of TG-dynamical. The thermal studies (DSC, DSC-Photovisual, DTA and TG-dynamical) were applied in the thermal characterization of the raw materials of tacrolimus which showed pseudo-polymorphic forms, which must be monitored by pharmaceutical industry, avoiding future problems in pharmaceutical process, chemical stability and bioavailability of the tacrolimus product.


The effects of mazindol on local cerebral glucose utilization in rats.
The effects of mazindol (1 mg or 10 mg/animal, p.o.) on local cerebral utilization of glucose were studied by the quantitative autoradiographic [14C]2-deoxyglucose method in conscious adult male rats. Significant increases in local cerebral utilization of glucose were observed 2 hr after administration of 10 mg of mazindol in 10 out of 37 anatomically discrete regions examined. These 10 areas included regions rich in dopaminergic receptors (substantia nigra, globus pallidus), and also regions with few dopaminergic receptors (cerebral cortex, thalamus, cerebellum). Only the habenular nucleus showed a significant decrease in utilization of glucose induced by the administration of 10 mg of mazindol. No significant changes in local cerebral utilization of glucose were observed following the administration of 1 mg of mazindol. The fact that the pattern of utilization of glucose observed in this study resembled that produced by apomorphine, a putative dopaminergic agonist, indicates that the pharmacological effects of mazindol are related to the dopaminergic system.


Segmental resection of splenic flexure colon cancers provides an adequate lymph node harvest and is a safe operative approach - an analysis of the ACS-NSQIP database.
Fewer than 10% of colon cancers are found at the splenic flexure. A standard surgical approach to these cancers has not been defined. The goal of this study was to compare lymph node harvest and post-operative morbidity between segmental resection and formal left hemicolectomy for splenic flexure colon cancers. Patients diagnosed with a splenic flexure cancer were identified from the 2012-2018 ACS-NSQIP colectomy-targeted database. Patients were categorized based on type of surgical resection - left hemicolectomy with colorectal anastomosis or segmental colectomy with colocolonic anastomosis. Demographic, clinicopathologic, and post-operative outcomes were compared between groups. Factors independently associated with lymph node harvest, operative time, and post-operative morbidity were investigated by linear and binomial logistic regression models. A total of 3,049 patients underwent colectomy for a splenic flexure cancer. Of these, 83.6% had a segmental colectomy and 73% were performed by a minimally invasive approach. T- and N-stage did not differ between segmental and left hemicolectomy groups (p = 0.703 and p = 0.429, respectively). Inadequate nodal harvest (< 12 nodes) was infrequent and similar between the two procedures (7.4% vs. 9.1%, p = 0.13). Operative time was significantly shorter for segmental colectomy (213 ± 83.5 min vs. 193 ± 84.1 min, p < 0.0001) and major morbidity was similar between the two surgical techniques (8.4% vs. 8.9%, p = 0.75). After accounting for demographic, clinicopathologic, and operative factors, binomial logistic regression showed that type of procedure was not significantly associated with LN harvest (OR 0.80, 95%CI 0.54-1.17) or major morbidity (OR 1.17, 95%CI 0.36-3.81). However, on linear regression, segmental splenic flexure resection was associated with shorter operative time (estimate 20.29, 95%CI 12.61-27.97, p < 0.0001). Splenic flexure resection for colon cancer is associated with an adequate lymph node harvest. Compared to a formal left hemicolectomy, a segmental resection also has a shorter operative time with equivalent post-operative morbidity.


Natural occurrence of mycotoxins and mycoflora of argentinien popcorn.
Argentina is the first popcorn exporting country worldwide. In 1997-1998 harvest season, 40,000 ha were sown with a production of 125,000 tons; 120,000 tons of this production were exported to more than 40 countries. The objectives of this study were to isolate and to identify the fungi present in this cereal and to assess the occurrence of mycotoxins in freshly harvested popcorn in Buenos Aires province, Argentina, in 1999. All popcorn samples showed fungal contamination. A total of 4,211 isolates were recovered from popcorn kernel samples. The prevalent species isolated wasFusarium verticillioides followed byPenicillium funiculosum, F. graminearum andAlternaria alternata. No aflatoxins, zearalenone, deoxynivalenol or ochratoxin A were detected in the 42 popcorn simples. All samples but one were contaminated with fumonisins (FB) in a range in ug/kg of (not detected-529) for FB1; (not detected-216) for FB2 and (not detected-103) for FB3. Fumonisin contamination levels in Argentinean popcorn were lower than observed in flint corn. No significant differences in fungal and fumonisins contamination levels were observed in the different tested hybrids.


Insulin enhances the expression of the endothelial nitric oxide synthase in native endothelial cells: a dual role for Akt and AP-1.
Insulin-induced vasodilatation in vivo has been attributed to the activation of the endothelial nitric oxide (NO) synthase (eNOS). The present study addressed the effects of insulin on the activity and expression of eNOS in native and cultured endothelial cells. Insulin applied to native porcine aortic endothelial cells elicited the tyrosine phosphorylation of the insulin receptor and receptor substrate, the subsequent activation of phosphatidylinositol 3-kinase (PI 3-K), Akt (protein kinase B), and ERK1/2. Insulin did not activate eNOS in cultured endothelial cells nor relax endothelium-intact arterial segments. However, 4h after application of insulin to native endothelial cells eNOS mRNA was increased 2-fold. A comparable increase in eNOS protein was detected after 18-24h and associated with an increase in intracellular cyclic GMP. In native endothelial cells, insulin enhanced the DNA-binding activity of Sp1 and AP-1, but not that of NF-kappaB. The insulin-induced increase in eNOS expression was prevented by wortmannin as well as by AP-1 decoy oligonucleotides. The MEK1 inhibitor, PD 98059, also enhanced eNOS expression in native and cultured endothelial cells, an effect which was independent of ERK1/2 and associated with an increase in the DNA-binding activity of AP-1 and Sp1. These results demonstrate that insulin activates multiple signalling pathways in endothelial cells but does not acutely activate eNOS. Insulin however enhances eNOS mRNA and protein by a mechanism involving the combined activation of a PI 3-K- and AP-1-dependent pathway.


TT2013 meeting report: the Transgenic Technology meeting visits Asia for the first time.
The 11th Transgenic Technology meeting was held in Guangzhou, China on 25th-27th February 2013. Over 300 scientists and students from round the world gathered to hear the latest developments in the technologies underpinning the creation of transgenic and knockout animals and their application to biological sciences in areas such as the modeling human diseases and biotechnology. As well as informative presentations from leading researchers in the field, an excellent selection of short talks selected from abstracts and posters, attendees were also treated to an inspiring talk from Allan Bradley who was awarded the 9th International Society of Transgenic Technologies Prize for outstanding contributions to the field of transgenic technologies.


Perspectives of adult patients with lysosomal storage diseases on the transition from pediatric to adult healthcare in Turkey.
In many countries, adult clinics specifically dedicated to adult patients with lysosomal storage diseases (LSDs) do not exist. In Turkey, these patients are managed either by pediatric metabolic specialists or adult physicians who do not specifically specialize in LSDs. In this study, we aimed to identify the unmet clinical needs of these adult patients and their suggestions. The focus group participants were 24 adult LSD patients. Interviews were conducted in person. A total of 23 LSD patients and parents of a patient with mucopolysaccharidosis type-3b with intellectual deficit were interviewed, with 84.6% of patients diagnosed after the age of 18 years and 18% of patients diagnosed before the age of 18 years desiring management by adult physicians. Patients with particular physical characteristics or severe intellectual deficit declined the transition. Patients reported structural problems in the hospital and social problems associated with pediatric clinics. They made suggestions to facilitate the possible transition. With improved care, more patients with LSDs survive into adulthood or receive the diagnosis in adulthood. Children with chronic diseases need to transition to the care of adult physicians when they reach adulthood. Thus, there is an increasing need for adult physicians to manage these patients. In this study, most LSD patients accepted a well-planned and organized transition. Problems were related to stigmatization and social isolation in the pediatric clinic or adult issues with which pediatricians are not familiar. There is a need for adult metabolic physicians. Thus, health authorities should adopt necessary regulations for training of physicians in this field.


Workshop report on the evaluation of the updated and expanded carcinogen database to support derivation of threshold of toxicological concern values for DNA-reactive carcinogens


Assimilable organic carbon removal strategy for aquifer storage and recovery applications.
Aquifer storage and recovery (ASR) technology has been adopted as a strategic water management tool. However, during the injection of oxic and organic carbon-containing water to the underground aquifers, severe phenomena such as clogging and groundwater deterioration have been reported. To prevent these severe phenomena, assimilable organic carbon (AOC) concentration has been controlled in the ASR applications by supporting bacteria growth potential. In this study, the AOC removal strategy was investigated in a simulated ASR system using an indigenous bacterium, Pseudomonas jinjuensis. AOC removal was evaluated under three different experimental conditions: (i) 30 °C and aerobic, (ii) 15 °C and aerobic, and (iii) 15 °C and anoxic. The effects of contact media such as sand and granular activated carbon on AOC removal efficiency were also investigated. Results show that under the 30 °C aerobic condition, P. jinjuensis could remove 99.8% (13 μg L-1) of AOC with soil. The variations in the organic fractions determined by liquid chromatography with organic carbon detector analysis were observed and showed trends similar to those of AOC determined by the flow cytometry method. The indirect injection method in ASR application was recommended due to the AOC removal benefit by soil indigenous bacterium.


A minicomputer system for display and rate analysis in vectorcardiography.
A system has been constructed for recording vectorcardiographic signal with a FM taperecorder. Off-line AD-conversion and analysis of rates and magnitudes of partial vectors are made with a minicomputer. The reason for studying particularly initial vectorrates is that according to our hypothesis these contain valuable information for classification of certain cardiac arrythmias according to supraventricular or ventricular impulse focus. Preliminary results confirm the hypothesis. In vectorcardiography one difficulty is to give an easily comprehensible presentation of the vectorloop. In this study a method for '3-dimensional' display has been developed, using a graphic display processor and varying intensities of the beam. The system is to a high degree man-machine interactive.


[Adenomas of Vater's ampulla and of the duodenum. Presentation of diagnosis and therapy by endoscopic interventional and surgical methods].
Adenoma of the ampulla of Vater and the duodenum are rare tumors. The leading symptoms are unspecific; sometimes they are due to the disturbances of the passage or erosion of the tumor. Early and correct diagnosis and the appropriate therapy are of decisive importance because these tumors are precancerous. We report the cases of seven patients with periampullary adenoma of the duodenum, in one case with incorporation of the the distal bile duct. The diagnostic steps and the surgical treatment are reported and discussed. In achieving a definitive diagnosis, endoscopic retrograde cholangiopancreatography is of paramount importance. Three patients subsequently underwent partial pancreatoduodenectomy (Whipple's procedure); in three patients transduodenal local tumor excision was performed. Postoperative course was without complications in each case and no operative mortality occurred. One patient was treated by argon-coagulation. The histopathological examination showed a tubular villous adenoma in six cases and in one case a villous adenoma (ranging from low to high grade dysplasia). Because there is evidence of an adenoma-carcinoma-sequence, radical surgical treatment is recommended, even in adenoma with low grade dysplasia, in spite of the absence of malignancy.


Measurement of the fluorescence lifetime in scattering media by frequency-domain photon migration.
A method is presented to determine fluorescence decay lifetimes within tissuelike scattering media. Fluorescence lifetimes are determined for micromolar concentrations of the dyes 3,3'-Diethylthiatricarbocyanine Iodide and Indocyanine Green by frequency-domain investigations of light propagating in turbid media. Dual-wavelength photon-migration measurements that use intensity-modulated sources at excitation and emission wavelengths of the fluorophores provide optical parameters of the media as well as fluorescence properties of the dyes. The deduction of fluorescence lifetimes requires no calibration with reference fluorophores, and the results are shown to be independent of dye concentration.


ATM immunohistochemistry as a potential marker for the differential diagnosis of no specific molecular profile subtype and POLE-mutation subtype endometrioid carcinoma.
Ancillary immunohistochemical tools can facilitate an integrated diagnosis of endometrial pathology. According to The Cancer Genome Atlas classification, endometrial cancers are of four molecular subtypes: mismatch repair (MMR)-deficient (MMR-d), p53 mutation (p53mut), DNA polymerase epsilon (POLE) mutation (POLEmut), and no specific molecular profile (NSMP). As the specific histological and immunohistochemical features of POLEmut and NSMP subtypes are unknown, these cancers are categorized based on molecular analysis. In this study, we analyzed POLEmut-subtype endometrioid carcinoma (EC) using a custom-made cancer gene panel and the Catalog of Somatic Mutations in Cancer (COSMIC) database, extracted a characteristic genome profile, and identified an immunohistochemical marker that could be used as a diagnostic tool. The results indicated that the POLEmut-subtype EC exhibited nonsense mutations in the ataxia telangiectasia mutated (ATM) gene and a subsequent loss of ATM expression, which was monitored through immunohistochemical analysis. Moreover, analyses using the COSMIC database indicated that POLEmut-subtype EC cases often harbored similar ATM nonsense mutations. These results suggest that ATM expression is a potential immunohistochemical marker for the differential diagnosis of POLEmut- and NSMP-subtype EC. DATA AVAILABILITY: The data supporting the findings of this study are available upon request from the corresponding author. The data are not publicly available because of privacy or ethical restrictions.


Cyclic Naphthalene Diimide with a Ferrocene Moiety as a Redox-Active Tetraplex-DNA Ligand.
Cyclic naphthalene diimides (cNDIs), with a ferrocene moiety (cFNDs) and different linker lengths between the ferrocene and cNDI moieties, were designed and synthesized as redox-active, tetraplex-DNA ligands. Intramolecular stacking was observed between ferrocene and the NDI planes, which could affect the binding properties for G-quadruplexes. Interestingly, the circular dichroism spectrum of one of these compounds clearly shows new Cotton effects around 320-380 and 240 nm, which can be considered a direct evidence of intramolecular stacking of ferrocene and the NDI. Regarding recognition of hybrid G-quadruplexes, the less rigid structures (longer linkers) show higher binding affinity (106 m-1 order of magnitude). All new compounds show higher selectivity for G4 during electrochemical detection than noncyclic FND derivatives, which further identifies the redox-active potentiality of the cFNDs. Two of the three compounds tested even show preferential inhibition of cell growth in cancer cells over normal cells in a low concentration range, highlighting the potential for bioapplications of these cFNDs.


Prognostic Implications of Prestent Pullback Pressure Gradient and Poststent Quantitative Flow Ratio in Patients Undergoing Percutaneous Coronary Intervention.
Background Coronary diffuse disease associates with poor outcomes, but little is known about its role after percutaneous coronary intervention (PCI). We aimed to investigate the prognostic implication of pre-PCI focal or diffuse disease patterns combined with post-PCI quantitative flow ratio (QFR). Methods and Results Pre-PCI QFR derived pullback pressure gradient (PPG) (QFR-PPG) was measured to assess physiological disease patterns for 1685 included vessels; the vessels were classified according to dichotomous pre-PCI QFR-PPG and post-PCI QFR. Vessel-oriented composite outcome, a composite of vessel-related ischemia-driven revascularization, vessel-related myocardial infarction, or cardiac death at 2 years was compared among these groups. Vessels with low pre-PCI PPG (3.9% versus 2.0%, hazard ratio [HR], 1.93; 95% CI, 1.08-3.44; P=0.02) or low post-PCI QFR (9.8% versus 2.7%, HR, 3.78; 95% CI, 1.61-8.87; P=0.001) demonstrated higher vessel-oriented composite outcome risk after stent implantation. Of note, despite high post-PCI QFR achieved, vessels with low pre-PCI QFR-PPG presented higher risk of vessel-oriented composite outcome than those with high pre-PCI QFR-PPG (3.7% versus 1.8%, HR, 2.03; 95% CI, 1.09-3.76; P=0.03) and pre-PCI QFR-PPG demonstrated direct prognostic effect not mediated by post-PCI QFR. Integration of groups classified by pre-PCI QFR-PPG and post-PCI QFR showed significantly higher discriminant and reclassification abilities than clinical factors (C-index 0.77 versus 0.72, P=0.03; integrated discrimination improvement 0.93%, P=0.04; net reclassification index 0.33, P=0.02). Conclusions Prognostic value of pre-PCI focal or diffuse disease patterns assessed by QFR-PPG index was retained even after successful PCI, which is mostly explained by its direct effect that was not mediated by post-PCI QFR. Integration of both pre-PCI and post-PCI physiological information can provide better risk stratification in vessels with stent implantation. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT05104580.


Fatal nosocomial Legionella pneumophila infection due to exposure to contaminated water from a washbasin in a hematology unit.
A fatal nosocomial infection with Legionella pneumophila serogroup 5 occurred in a patient with leukemia. Isolates recovered from both the potable water supply and the patient showed an identical genomic profile. With no other exposure identified, the water from the washbasin was evidently the source of infection.


Cutaneous vasculitis.
Vasculitis is defined as inflammation of blood vessels and can affect multiple organs. Several classification systems exist to categorize vasculitis such as vessel size, presence of anti-neutrophil cytoplasmic antibody, pathogenesis of the inflammation, and type of inflammatory cell infiltrate. Cutaneous vasculitis occurs as a manifestation of many diseases including rheumatologic diseases, hypersensitivity syndromes, infections, and malignancies. The diagnosis of the cutaneous vasculitis and the underlying cause requires a complete history and physical exam and usually a biopsy or angiogram. The treatment depends on the etiology of the inflammation and includes immunosuppression, withdrawal of the offending agent, antibacterial/antiviral agents, and chemotherapies. A clear understanding and approach to this condition will improve the physician's ability to provide optimal patient care.


Acute effects of a very low nicotine content cigarette on laboratory smoking lapse: Impacts of nicotine metabolism and nicotine dependence.
Reducing cigarette nicotine content to nonaddictive levels facilitates smoking cessation; however, very low nicotine content cigarettes (VLNCs) may not be equally effective across heterogeneous smokers. We evaluated the impact of acute VLNC smoking versus control (sham puffs) on craving, withdrawal and smoking lapse behaviour and whether genetically influenced differences in nicotine metabolism and individual differences in nicotine dependence moderate observed effects. Thirty-three overnight-abstinent smokers (15 slow vs. 17 normal nicotine metabolizers; 17 low vs. 16 high nicotine dependence) smoked a 0.05-mg nicotine VLNC during one session and took sham VLNC puffs during another session, in a counterbalanced order. Craving and withdrawal were assessed before and after smoking and sham puffing. Next, participants completed the McKee Smoking Lapse Task, which measures ability to resist smoking and quantity of ad libitum smoking. VLNC (vs. sham) reduced craving and withdrawal, increased ability to resist smoking and reduced ad libitum smoking. VLNC-induced reduction in craving for positive reinforcement was greater in slow (vs. normal) metabolizers. Nicotine metabolism did not moderate any other VLNC responses. High-dependence (vs. low-dependence) participants engaged in greater ad lib smoking across VLNC and sham conditions. Nicotine dependence did not moderate VLNC responses. VLNC reduced craving, withdrawal and smoking lapse behaviour. Individual differences in nicotine metabolism and dependence had a minimal impact on VLNC responses; however, VLNCs were less effective at reducing craving for positive reinforcement among normal (vs. slow) metabolizers. These findings suggest that desirable VLNC effects may extend across heterogeneous groups of smokers.