Indole-3-acetonitrile Is a Critical Molecule with Weed Allopathic Suppression Function in Broccoli (Brassica oleracea var. italica).
Cruciferous plants are frequently used for ecologically benign weed control in agricultural production. Most effective Broccoli varieties were screened using the entropy method-based topsis model at first. Result showed that varieties of Lvwawa and Lvbaoshiwere most effective in allelopathic suppression on radishes. Column and thin-layer chromatography were used to extract the allelopathic compounds from broccoli residues, which contained various herbicidal active substances; among them, purified single-molecule indole-3-acetonitrile has a stronger inhibitory effect than pendimethalin (commercial herbicide). The weed inhibition rate increased with increasing broccoli residue dosage, with a 40 g/m2 broccoli residue dose yielding the highest suppression rate. Its effect was similar to that of indole-3-acetic acid. Too much of this substance leads to the plant's death. Moreover, broccoli residues had effective control effect on weeds in natural soils in greenhouse and field trials. The results demonstrated that broccoli residue could be used for weed management in field for abundant allopathic suppression molecules to weeds, and that Indole-3-acetonitrile is one of the most important allopathic molecule.


The Chinese version of the Functionality Appreciation Scale: Psychometric properties and measurement invariance across gender and age.
Functionality appreciation, as an important aspect of positive image, is associated with fewer body image disturbances, fewer disordered eating behaviors, and improved psychological well-being. However, it has been under-researched in Asian countries. The current work aimed to examine the psychometric properties of the Functionality Appreciation Scale (FAS) among four Chinese samples of different ages, and further examine measurement invariance and differences of the FAS across gender and age groups. Exploratory and confirmatory factor analyses (EFA and CFA) were conducted to examine the factorial structure of the FAS among four Chinese samples of different ages, including middle school adolescents (n = 894, Mage = 12.17 years), high school adolescents (n = 1347, Mage = 15.07 years), young adults (n = 473, Mage = 21.95 years), and older adults (n = 313, Mage = 67.90 years). The measurement invariance of the FAS across gender and age was examined. Internal consistency reliability and construct validity were evaluated. The FAS had a unidimensional structure and was invariant across gender and age groups. The FAS presented sound psychometric properties in all age groups by gender, with good internal consistency reliability [e.g., high Cronbach's α values (.91 ~ .97)] and good construct validity (e.g., significant associations with body appreciation, body dissatisfaction, and disordered eating). Moreover, group comparisons showed minimal gender differences in functionality appreciation. However, significant age differences were found in functionality appreciation, with older ages generally associated with higher functionality appreciation. Overall, findings suggest that the FAS is a sound instrument to be used in the Chinese context. Furthermore, functionality appreciation was found to be higher in older adults than adolescents or young adults, suggesting the potential important role of aging in functionality appreciation.


Vitamin D3 Supplementation Prior to Total Knee Arthroplasty: A Randomized Controlled Trial.
The purpose of this randomized controlled trial was to determine if a one-time dose of vitamin D3 prior to total knee arthroplasty improves function and patient-reported outcomes, while decreasing complications. One hundred seven patients undergoing primary total knee arthroplasty were randomized to receive 50,000 international units vitamin D3 (57 patients) or placebo (50 patients) on the morning of surgery. Power analysis determined 45 patients were required in each cohort to detect a minimal clinically important difference of 6 points in the functional component of the 2011 version of the Knee Society Score (KSS), assuming an alpha of 0.05 and power of 80%. KSS and a Timed Up and Go Test (TUGT) were measured preoperatively and at 3 and 6 weeks postoperatively. There was no difference in improvement of KSS at 3 weeks (+4.8 points vitamin D3 versus +3.0 points placebo; P = .6) or 6 weeks (+14.5 points vitamin D3 versus +12.4 points placebo; P = .5) from baseline. There was no difference in change in TUGT at 3 weeks (+1.2 seconds vitamin D3 versus +0.6 seconds placebo; P = .6) or 6 weeks (-0.3 seconds vitamin D3 versus -0.9 seconds placebo; P = .6) from baseline. There were 4 complications in the placebo cohort within the first 90 days postoperatively and 5 complications in the vitamin D3 cohort (P = 1.0). Supplementation with 50,000 international units vitamin D3 on the day of surgery failed to demonstrate statistical significant differences in functional KSS, TUGT times, or complications in the early postoperative period compared to placebo. Level I, therapeutic study.


Characteristics of transcription profile, adhesion and migration of SETD2-loss Met-5A mesothelial cells exposed with crocidolite.
Asbestos is a fibrous silicate mineral exhibiting biopersistence and carcinogenic properties and contributes to mesothelioma. Despite the concept of gene-environmental interaction in pathogenesis of mesothelioma, the possible pathophysiological changes of mesothelial cells simultaneously with SET domain containing 2 (SETD2) loss and asbestos exposure remains obscure. Herein, CRISPR/Cas9-mediated SETD2 knockout Met-5A mesothelial cells (Met-5ASETD2-KO ) were established and exposed with crocidolite, an amphibole asbestos. Cell viability of Met-5ASETD2-KO appeared to dramatically decrease with ≥2.5 μg/cm2 crocidolite exposure as compared with Met-5A, although no cytotoxicity and apoptosis changes of Met-5ASETD2-KO and Met-5A was evident with 1.25 μg/cm2 crocidolite exposure for 48 h. RNA sequencing uncovered top 50 differentially expressed genes (DEGs) between 1.25 μg/cm2 crocidolite exposed Met-5ASETD2-KO (Cro-Met-5ASETD2-KO ) and 1.25 μg/cm2 crocidolite exposed Met-5A (Cro-Met-5A), and ITGA4, THBS2, MYL7, RAC2, CADM1, and CLDN11 appeared to be the primary DEGs involved with adhesion in gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Cro-Met-5ASETD2-KO had strong migration but mild adhesion behavior as compared with Cro-Met-5A. Additionally, crocidolite tended to increase migration of Met-5ASETD2-KO but inhibited migration of Met-5A when compared with their corresponding cells without crocidolite exposure, although no further adhesion property changes was evident for both cells in response to crocidolite. Therefore, crocidolite may affect adhesion-related gene expression and modify adhesion and migration behavior for SETD2-depleted Met-5A, which could provide preliminary insight regarding the potential role of SETD2 in the cell behavior of asbestos-related malignant mesothelial cell.


Complication rates following all-epiphyseal ACL reconstructions in skeletally immature patients: A retrospective case series study.
The aim was to evaluate the safety of a physeal-sparing anterior cruciate ligament reconstruction technique (ACLR), performed with Orthopediatrics (Warsaw, IN) equipment, by assessing complications.Skeletally immature patients who underwent all-epiphyseal ACLR between 2015 and 2017 with postoperative follow-up were included in this retrospective study. Complications, demographic, clinical, surgical, and imaging data was retrieved from an urban tertiary pediatric hospital database. Physeal status, limb-length discrepancies (LLD), and angular deformities were assessed on preoperative and postoperative radiographs, growth disturbances were reported, and initial and follow-up diameters of tunnels were compared.Nineteen ACLRs were included from 18 patients, 4 females and 14 males, with bone age at surgery of 13.3 ± 1.0 years. At a mean follow-up of 19.2 ± 10.1 months, there were no symptomatic growth disorders requiring intervention. There were: 2 (11.1%) unilateral early physeal closures, 2 (10.5%) new angular deformities (5°-10°), 4 (22.2%) LLD (1-2 cm), 1 (5.6%) contralateral ACLR, 1 (5.6%) femoral screw removal, 2 (10.5%) graft ruptures, and 1 meniscal tear (5.3%). Mean tunnel widening was 1.7 mm and 1.5 mm on the femoral and tibial side, respectively, and no massive osteolysis was recorded at the polyetheretherketone implant site.The complication rates were comparable to those in similar studies, with no growth-related complications at 19.2 months.


Fisetin targets phosphatidylinositol-3-kinase and induces apoptosis of human B lymphoma Raji cells.
Aberrant regulation of phosphatidylinositol-3-kinases (PI3Ks) is known to be involved in the progression of cancers. PI3K-binding flavonoids such as quercetin and myricetin have been shown to inhibit PI3K activity, but the direct targeting of fisetin to PI3K has not been established. Here, we carried out an in silico investigation of fisetin binding to PI3K and determined fisetin's inhibitory activity in enzymatic and cell-based assays. In addition, fisetin induced apoptosis in human Burkitt's lymphoma Raji cells by inhibiting both PI3Ks and mammalian target of rapamycin (mTOR). Our results indicate that fisetin may serve as a natural backbone for the development of novel dual inhibitors of PI3Ks and mTOR for the treatment of cancer.


Studies on cultured rat Schwann cells. II. Comparison with a rat Schwann cell line.
Cultured rat Schwann cells do not exhibit the ring-like changes in cell shape previously reported to be induced in the Schwann cell line RN22 by elevation of intracellular cyclic AMP. They do, however, undergo different shape changes on treatment with cholera toxin or low serum concentration. Furthermore, DNA synthesis in the cell line is inhibited by treatment with cholera toxin and unaffected by bovine pituitary extract, though both of these agents stimulate DNA synthesis in normal Schwann cells. Our results, therefore, do not support the hypothesis that elevation of intracellular cyclic AMP is a positive signal for myelination by the Schwann cell. Moreover, they illustrate the need for caution in drawing conclusions about normal cells of the nervous system from studies on neural cell lines.


In AF with recent ACS or PCI, apixaban improved 30-day outcomes vs. VKAs; aspirin effects varied vs. placebo.
Alexander JH, Wojdyla D, Vora AN, et al. Risk/benefit tradeoff of antithrombotic therapy in patients with atrial fibrillation early and late after an acute coronary syndrome or percutaneous coronary intervention: insights from AUGUSTUS. Circulation. 2020;141:1618-27. 32223444.


Fever in children less than 36 months of age--questions and strategies for management in the emergency department.
Fever is a common pediatric complaint in the Emergency Department. Emergency Physicians often must be conservative in their management of febrile children, as patient follow-up is not always available. A unified approach for the management of febrile infants will be discussed in this article.


Infraspinatus Muscle Fiber Moment Arms During Abduction: A Biomechanical Comparison of Values for Intact Rotator Cuff, Supraspinatus Tear, Superior Capsular Reconstruction, and Reverse Total Shoulder Arthroplasty.
Lines of action of the superior, middle, and inferior infraspinatus muscle fibers work together to produce moment arms that change throughout abduction in an intact shoulder, after a supraspinatus tear, and after superior capsular reconstruction (SCR) and reverse total shoulder arthroplasty (rTSA). To use moment arm values to indicate the efficacy of SCR and rTSA to restore infraspinatus function during shoulder abduction. Descriptive laboratory study. A total of 5 human cadaveric shoulders placed in a testing apparatus were each actively abducted (0°-90°) under the following 4 conditions: intact, complete supraspinatus tear, SCR, and rTSA. The 3-dimensional coordinates of points were tracked along the origin and insertion of the superior, middle, and inferior infraspinatus fibers during abduction. Moment arm values were calculated using the origin-insertion method to determine abduction contribution of infraspinatus fiber sections. Analysis of variance and post hoc Tukey testing were used to compare differences in moment arms between the 4 conditions and between fiber sections. In the intact condition, the superior infraspinatus fibers had an abduction moment that decreased with elevation until shifting to adduction. Conversely, the middle and inferior fibers had an adduction moment that turned to abduction (mean moment arm values from 0° to 90°: inferior, from -5.9 to 19.4 mm; middle, from -4.7 to 15.9 mm; superior, from 5.6 to -5.1 mm; P < .05). After a supraspinatus tear, superior fibers lacked any torque, and inferior and middle fibers lost adduction potential (inferior, from 4.8 to 14.0 mm; middle, from -0.2 to 9.6 mm; superior, from 1.0 to 0.7 mm; P < .05). SCR restored the initial superior fiber abduction moment (5.6 mm at 0°; P < .05); middle and inferior fibers had some restoration but were weaker than intact fibers. Loss of abduction moment in all fibers was seen with rTSA (inferior, from -9.6 to -1.6 mm; middle, from -10.5 to -3.6 mm; superior, from -1.7 to -4.6 mm; P < .05). Infraspinatus fiber groups had different and inverse moment arms during scapular plane elevation. SCR most closely resembled the intact shoulder, whereas rTSA transformed the infraspinatus into an adductor. These results support the efficacy of SCR at restoring biomechanical muscle function and suggest that the changes in moment arms for each fiber group be considered when choosing treatment modalities and rehabilitation protocols after rotator cuff tear.


Non-A, non-B hepatitis and dentistry.
Non-A, non-B hepatitis (hepatitis C) is a viral infection(s) transmitted mainly by blood and blood products. Infection is usually asymptomatic, but typically followed by chronic infection, frequently with chronic liver disease. Although probably less than 1% of the UK population (and hence dental patients) are infected, groups at high risk for other blood-borne infections are also at risk for non-A, non-B hepatitis. Immunisation against hepatitis B cannot protect against non-A, non-B hepatitis; recommended cross-infection procedures must suffice to protect patients and staff.


Parental Accompaniment in Operating Rooms Reduces Child Anxiety.
We believe that parental presence before the induction of anesthesia for surgery among children with a cleft palate/lip would be effective in mitigating their preoperative anxiety. We assessed the states of patients with a cleft palate/lip when their parents accompanied them into operating rooms and clarified their and their parents' cognition using a questionnaire. Data were collected via nursing observation when patients and their parents entered the operating room. Furthermore, an anonymous questionnaire was administered to patients and parents after the operation regarding their feelings about parental presence in the operating room. In total, nine patients cried when they entered the surgical room. Furthermore, six patients and three parents reported preoperative anxiety. In addition, eight patients agreed that they were satisfied with the presence of their parents before induction. Approximately half of the patients cried. However, the presence of parents before the induction of anesthesia was effective in reducing anxiety among most patients and their parents.


Electrical self-stimulation deficits in the anterior and posterior parts of the medial forebrain bundle after ibotenic acid lesion of the middle lateral hypothalamus.
The aim of the present study was to analyse the involvement of the intrinsic neurons located in the middle lateral hypothalamus in electrical self-stimulation measured with electrodes in the anterior and posterior parts of the medial forebrain bundle. In rats without hypothalamic lesions, self-stimulation rates from both anterior and posterior electrodes were similar on either side of the brain. For all rats with ibotenic acid-induced lesions in the lateral hypothalamus, self-stimulation rates were lower with electrodes in the area of the lesion, while self-stimulation on the contralateral side was normal. In rats with electrodes in the anterior hypothalamus, the lesion produced a large deficit when stimulation was applied to the anterior electrode ipsilateral to the lesion. Only three rats showed a decrease in self-stimulation with stimulation of the posterior hypothalamic electrode ipsilateral to the lesion; self-stimulation of the other three rats was normal. These results suggest that self-stimulation in the anterior part of the medial forebrain bundle is supported by long fibers originating in the middle part of the lateral hypothalamus, while self-stimulation in the posterior part of the lateral hypothalamus can be influenced by another system not involved in reward processes observed in the rostral part of the medial forebrain bundle.


Estrogenic activity of biological samples as a biomarker.
Biological assays can evaluate the cumulative effect of a mixture, considering synergistic/antagonistic interactions and effects of unknown/unconsidered compounds. Therefore, their application could increase in the next years also to analyse biological samples. The aim of this review is to discuss the methodological approach and the application of estrogenic activity assays in human biological samples. 75 research articles were analysed and divided according to whether they used these assays: i) to quantify the level of estrogens and/or as a biomarker of estrogenic status ii) as a biomarker of exposure to endocrine disrupting chemicals (EDCs). For the first purpose, some authors extracted biological samples while others tested them directly without any treatment. The study of these methodologies outlined that the methodology applied influenced the specificity of analysis. The estrogenic activity biomarker was used to analyse physiological variations of estrogens, pediatric diseases, hormone-dependent diseases and estrogen suppression/enhancement after pharmaceutical treatments. For the second purpose, some authors extracted samples while others tested them directly, some authors divided endogenous estrogens from xenoestrogens while others tested samples without separation. The analysis of these methodologies outlined some limitations related to the efficiency of extraction and the incorrect separation of some compounds. The studies which applied this EDC biomarker showed that it was correlated with some EDCs, it varied according to the exposure of the population and it allowed the identification of some relationships between EDC exposure and breast cancer, type 1 diabetes and adverse health effects on children. In conclusion, the estrogenic activity of biological samples can be a useful tool: to quantify low levels of 17β-estradiol, to assess the combined effect of endogenous estrogens and xenoestrogens, to estimate the estrogenic status providing considerable insight into physiological or pathological conditions, to evaluate EDC presence implementing the existing knowledge about EDC exposure and adverse health effects.


Observations on enzymes of ammonia assimilation in two different strains of Cyanidium caldarium.
Two strains of Cyanidium caldarium, one able to utilize nitrate as a substrate, and the other not, were tested for the presence of enzymes of ammonia assimilation. The nitrate-assimilating strain exhibits glutamate dehydrogenase activity. By contrast, the other strain lacks glutamate dehydrogenase; it possesses high alanine dehydrogenase and L-alanine aminotransferase activities which suggest that this strain may incorporate ammonia through reductive amination of pyruvate and may form glutamate from 2-ketoglutarate by a transamination reaction with alanine. Neither strain reveals glutamate synthase activity. Both strains contain similar levels of glutamine synthetase.


Crystal structure of pyridoxine 4-oxidase from Mesorhizobium loti.
Pyridoxine 4-oxidase (PNOX) from Mesorhizobium loti is a monomeric glucose-methanol-choline (GMC) oxidoreductase family enzyme, catalyzes FAD-dependent oxidation of pyridoxine (PN) into pyridoxal, and is the first enzyme in pathway I for the degradation of PN. The tertiary structures of PNOX with a C-terminal His6-tag and PNOX-pyridoxamine (PM) complex were determined at 2.2Å and at 2.1Å resolutions, respectively. The overall structure consisted of FAD-binding and substrate-binding domains. In the active site, His460, His462, and Pro504 were located on the re-face of the isoalloxazine ring of FAD. PM binds to the active site through several hydrogen bonds. The side chains of His462 and His460 are located at 2.7 and 3.1Å from the N4' atom of PM. The activities of His460Ala and His462Ala mutant PNOXs were very low, and 460Ala/His462Ala double mutant PNOX exhibited no activity. His462 may act as a general base for the abstraction of a proton from the 4'-hydroxyl of PN. His460 may play a role in the binding and positioning of PN. The C4' atom in PM is located at 3.2Å, and the hydride ion from the C4' atom may be transferred to the N5 atom of the isoalloxazine ring. The comparison of active site residues in GMC oxidoreductase shows that Pro504 in PNOX corresponds to Asn or His of the conserved His-Asn or His-His pair in other GMC oxidoreductases. The function of the novel proline residue was discussed.


Antihypertensive drug class in combination with lipid lowering treatment for primary prevention of cardiovascular disease in the elderly.
Antihypertensives and lipid-lowering therapy (LLT) are often used concurrently. To determine whether there was a difference in clinical outcomes when older patients with LLT were prescribed angiotensin-converting-enzyme-inhibitors (ACE-Is) compared with diuretics. This analysis included 648 LLT older users free of cardiovascular disease (CVD) from a trial comparing ACE-I versus diuretic-based therapy. Comparisons were made between LLT+ACE-I (n = 335) and LLT+diuretic groups (n = 313) using multivariable Cox proportional-hazard models. Primary endpoints were all-cause and CVD mortality (in-trial [4.1-year]+post-trial [6.9-year]) and secondary endpoints (in-trial) were the composite of all-cause mortality and first CVD events and its components, CVD mortality and incident diabetes. There were no significant differences between the two groups for the primary endpoints over the in-trial plus post-trial follow-up, nor was there a difference for any secondary outcomes over the in-trial follow-up. The LLT+ACE-I and LLT+diuretic combinations showed similar effects in CVD-free older individuals. Randomised trials are needed to provide conclusive evidence.


Expression of p53, MDM2, and p21 proteins in high-grade cervical intraepithelial neoplasia and relationship to human papillomavirus infection.
The relationship between human papillomavirus (HPV) infection and cell cycle regulators p53, MDM2, and p21 in cervical intraepithelial neoplasia (CIN) has not been investigated. p53, MDM2, and p21 immunoreactivity were analyzed with respect to HPV DNA status in high-grade CIN (CIN II-III). Formalin-fixed, paraffin-embedded tissue sections from 169 biopsy specimens with high-grade CIN were examined for HPV DNA by polymerase chain reaction with the L1 and E1 consensus primers Gp5+/6+ and CpI/CpIIG. HPV-positive specimens were typed with the E6 type-specific primers for HPV 16 and 18. The biopsy specimens were stained with the monoclonal antibodies p53, MDM2, and p21. The interpretation of nuclear staining was regarded as focal (< 5%), regional (5% to 50%), or diffuse (> 50%). HPV DNA was found in 156 cases (92%); 122 (78%) were positive for HPV 16, 18, or both. Immunohistochemically, p53 was detected in 50 specimens (30%); nuclear staining was mainly focal. Focal nuclear staining for MDM2 was found in 6 specimens (4%), and regional and diffuse nuclear staining for p21 was present in 137 (81%). Significant correlation was found only between p53 and MDM2 immunoreactivity. These results indicate that there is no correlation between HPV status and expression of the cell cycle regulators p53, MDM2, and p21. Inactivation of p21 and p53 protein may be important, and MDM2 abnormalities seem to play a minor role in the development of high-grade CIN.


[Correlation between podoplanin-positive lymphatic microvessel density and CT characteristics of non-small cell lung cancer].
It has been proven that ymphatic microvessel density (LMVD) was closely correlated with the lymphatic metastasis of non-small cell lung cancer (NSCLC). The aim of the present study is to explore the relationship between podoplanin-LMVD and multi-slice spiral computed tomography (MSCT) characteristics of NSCLC. MSCT scanning was performed on 34 cases of NSCLC (squamous carcinoma, 15 cases; adenocarcinoma, 15 cases; and adenosquamous carcinoma, 4 cases) prior to operation. Clinical pathology results, including lymph node metastasis, were obtained. CT characteristics, such as shape of the edge, internal structure, and adjacent structures, were described. LMVD in the central and peripheral areas examined respectively using SP immunohistochemical technique were analyzed. Lymph node metastasis was found to be associated with LMVD in the peripheral areas. LMVD in the peripheral areas of the resected lesions, the MSCT findings of which included spinous process, pleural indentation, and carcinomatous lymphangitis, was higher than that of the lesions without these MSCT characteristics (P<0.05). MSCT findings of spinous process, pleural indentation, or carcinomatous lymphangitis of NSCLC may suggest a higher level of tumor lymphangiogenesis with a higher risk of lymph node metastasis.


The percentage of myeloperoxidase-positive blast cells is a strong independent prognostic factor in acute myeloid leukemia, even in the patients with normal karyotype.
To examine whether the percentage of myeloperoxidase (MPO)-positive blast cells is useful as a prognostic factor for acute myeloid leukemia (AML), cytochemical analysis of MPO was performed in 491 patients who were registered to the Japan Adult Leukemia Study Group-AML92 study. Patients were divided into two using the percentage of MPO-positive blast (high [>or=50%] and low (<50%)). Complete remission rates were 85.4% in the former and 64.1% in the latter (P=0.001). The overall survival (OS) and the disease-free survival (DFS) were significantly better in the high MPO group (48.3 vs 18.7% for OS, and 36.3 vs 20.1% for DFS, P<0.001, respectively). Multivariate analysis showed that both karyotype and the percentage of MPO-positive blast cells were equally important prognostic factors. The high MPO group still showed a better survival even when restricted to the intermediate chromosomal risk group or the patients with normal karyotype (P<0.001). The OS of patients with normal karyotype in the high MPO group was almost equal with that of the favorable chromosomal risk group. The percentage of MPO-positive blast cells is a simple and highly significant prognostic factor for AML patients, and especially useful to stratify patients with normal karyotype.


Long non-coding RNA small nucleolar RNA host gene 1 alleviates the progression of epilepsy by regulating the miR-181a/BCL-2 axis in vitro.
Long non-coding RNAs (lncRNAs) have been reported to be involved in regulating epilepsy. The purpose of this study is to investigate the possibly regulatory mechanism of small nucleolar RNA host gene 1 (SNHG1) on epilepsy. Quantitative real-time PCR was utilized to detect the expression of SNHG1, microRNA (miR)-181a, and B-cell lymphoma-2 (BCL-2). Through an enzyme-linked immunosorbent assay, the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and cyclooxygenase-2 (COX-2) were determined. The viability and apoptosis of CTX-TNA2 cells were measured using MTT assay and flow cytometry analysis, respectively. Western blot assay was performed to analyze the protein levels of Bcl-2, BCL2-associated X, and Caspase-3. The relationships between miR-181a and SNHG1/BCL-2 were confirmed by the dual-luciferase reporter assay. SNHG1 expression was down-regulated in EP tissues and kainic acid (KA)-induced CTX-TNA2 cells. The apoptosis and release of inflammatory factors (TNF-α, IL-1β, IL-6, and COX-2) in KA-induced CTX-TNA2 cells were suppressed by SNHG1 overexpression and promoted by miR-181a up-regulation. In addition, we confirmed that SNHG1 targeted miR-181a, whereas BCL-2 was a target gene of miR-181a. Negative correlations between SNHG1 and miR-181a, as well as miR-181a and BCL-2 were exhibited. Both the up-regulation of miR-181a and down-regulation of BCL-2 reversed the inhibiting effects of SNHG1 on apoptosis and inflammatory response of KA-induced CTX-TNA2 cells, and the promoting effect upon cell viability. SNHG1 alleviated the progression of EP by modulating the miR-181a/BCL-2 axis in vitro, thus SNHG1 could act as a possible therapeutic target for treating EP.


Catheter-based interventions guided solely by a new phased-array intracardiac imaging catheter: in vivo experimental studies.
Intracardiac echocardiography (ICE) has had useful but limited use during interventional procedures because of technologic limitations. We used a novel phased-array ICE device (AcuNav) with 2-dimensional sector imaging and full Doppler capability to see whether it could guide cardiac interventions without fluoroscopy. Twelve dogs were studied, and we performed atrial septostomy, tricuspid, and pulmonary valve disruption using only ICE. Preinterventional and postinterventional anatomic and hemodynamic data were noted. All attempts were successful in the placement of the ICE catheter (100%). We attempted septostomy on 11 dogs and were successful 8 times (73%). Tricuspid valve disruption and balloon dilatation were performed successfully on 5 dogs (100%). We attempted pulmonary valve disruption on 4 dogs and could always correctly place the guidewire (100%). We performed pulmonary valve balloon dilatation on one dog (25%). A comprehensive echocardiographic examination was always possible. This new ICE device can guide interventions without fluoroscopy. However, further studies are needed to evaluate whether it can replace fluoroscopy.


Evaluation of spontaneous variability in the frequency of ventricular arrhythmias in Boxers with arrhythmogenic right ventricular cardiomyopathy.
To evaluate spontaneous variability in the frequency of ventricular arrhythmias and assess the influence of day of ECG recording and day of week on arrhythmia frequency in Boxers affected with arrhythmogenic right ventricular cardiomyopathy (ARVC). Prospective study. 10 Boxers with ARVC with prior ambulatory ECG recordings that included > or = 500 ventricular premature complexes/24 h. Consecutive 24-hour ambulatory ECG recordings were obtained during a 7-day period in each dog. The number of ventricular premature complexes and grade of the arrhythmia were obtained from each recording. For each dog, the number of ventricular premature complexes for each recording was evaluated to identify any differences relative to the day of recording (recording 1 to 7) and day of the week (Monday through Sunday). Spontaneous variability accounted for as much as 80% of the change in frequency of ventricular premature complexes in dogs with frequent arrhythmias; this value was almost 100% in dogs with less frequent arrhythmias. Grade of arrhythmia was less variable but was also inversely related to frequency of arrhythmia. No significant differences in frequency values were identified among days of recording or among days of the week. Changes of < or = 80% in the frequency of ventricular arrhythmias may be within the limit of spontaneous variability in dogs with ARVC. This degree of variability should be considered in evaluations of ambulatory ECG recordings, particularly in the assessment of the efficacy of antiarrhythmic drugs.


Expression of Cdx2 and hepatocyte antigen in gastric carcinoma: correlation with histologic type and implications for prognosis.
This study was designed to (a) analyze the correlation between the expression of Cdx2 and Hep and the clinicopathologic features of patients with gastric carcinoma, and (b) determine the value of combined analysis of Cdx2 and Hep expression in distinguishing histologic types and prognoses of gastric carcinomas. The expression of Cdx2 and Hep were studied using immunohistochemistry of paraffin-embedded tumor specimens from 109 patients who underwent D2 resection for gastric adenocarcinoma from 1995 to 1998. Nuclear Cdx2 and Hep expression was detected in 36.7% (40 of 109) and 54.1% (59 of 109) of gastric carcinoma cases, respectively. Expression of Cdx2 and Hep was significantly higher in intestinal-type carcinomas than in diffuse-type carcinomas (P = 0.027 and P = 0.037, respectively). There was a clear negative correlation between Cdx2 expression and lymph node metastasis (P = 0.029), as well as between Hep expression and depth of wall invasion (P = 0.011). The patients with Cdx2-positive or Hep-positive expression shows higher survival rate than those with Cdx2-negative or Hep-negative expression (P = 0.0008 and P = 0.003, respectively). Multivariate analysis revealed that the expression of Cdx2 and Hep were independent prognostic indicators of gastric carcinoma. The combination of Cdx2 and Hep expression was significantly lower in diffuse-type carcinoma than in intestinal or mixed-type carcinoma. Multivariate analysis revealed that Cdx2 and Hep expression was an independent prognostic indicator of gastric carcinoma (P < 0.001). These data suggest that combined analysis of Cdx2 and Hep has significant value in distinguishing histologic types and in predicting the prognosis of gastric carcinoma.


Studies of 3-aminopyridine adenine dinucleotide phosphate.
3-Aminopyridine adenine dinucleotide phosphate (AADP) was prepared from NADP and 3-amino-pyridine through the pig brain NADase-catalyzed pyridine base exchange reaction. The purified dinucleotide was chemically characterized and spectral properties of the compound were determined. The importance of the application of AADP in studies of NADP-requiring biochemical processes was indicated by the demonstration of AADP as an effective inhibitor of five NADP-requiring enzymes, by the demonstration of the fluorescence enhancement on the binding of AADP to yeast glucose-6-phosphate dehydrogenase when glucose-6-phosphate is present, and by the functioning of AADP as a fluorimetric substrate for snake venom nucleotide pyrophosphatase.


A new outbreak of sheep scab (Psoroptes ovis) in Lesotho and the measures taken to control it.
Psoroptic mange in sheep was reintroduced to Lesotho in 1975. The course of the disease outbreak, the problems encountered in attempting to limit its spread and the eventual introduction of a simultaneous dipping policy backed by legislation are described.


Leveraging Basic Science for the Clinic-From Bench to Bedside.
The tools and insights of behavioral neuroscience grow apace, yet their clinical application is lagging. This article suggests that associative learning theory may be the algorithmic bridge to connect a burgeoning understanding of the brain with the challenges to the mind with which all clinicians and researchers are concerned. Instead of giving up, talking past one another, or resting on the laurels of face validity, a consilient and collaborative approach is suggested: visiting laboratory meetings and clinical rounds and attempting to converse in the language of behavior and cognition to better understand and ultimately treat patients.


The medial preoptic area modulates cocaine-induced locomotion in male rats.
Cocaine-induced locomotion is mediated by dopamine in the nucleus accumbens (NAc). Recent evidence indicates that the medial preoptic area (mPOA), a region in the rostral hypothalamus, modulates cocaine-induced dopamine in the NAc. Specifically, rats with lesions of the mPOA experienced a greater increase in dopamine following cocaine administration than rats with sham lesions. Whether the mPOA similarly influences cocaine-induced locomotion is not known. Here we examined whether radiofrequency or neurotoxic lesions of the mPOA in male rats influence changes in locomotion that follow cocaine administration. Locomotion was measured following cocaine administration in male rats with neurotoxic, radiofrequency, or sham lesions of the mPOA. Results indicate that bilateral lesions of the mPOA facilitated cocaine-induced locomotion. This facilitation was independent of lesion type, as increased locomotion was observed with either approach. These findings support a role for the mPOA as an integral region in the processing of cocaine-induced behavioral response, in this case locomotor activity.


Endothelin-1 stimulates c-fos mRNA expression and acts as a modulator on cell proliferation of rat FRTL5 thyroid cells.
In FRTL5 thyroid cells, endothelin (ET)-1 alone had no effect on DNA synthesis but caused a transient increase in c-fos mRNA levels and stimulated IGF-I induced DNA synthesis and cell proliferation. By contrast, ET-1 inhibited the stimulatory effects of TSH actions on DNA synthesis, cell proliferation and c-AMP production. 8-Bromo-cAMP-induced DNA synthesis was also inhibited by ET-1, suggesting that ET-1 exerts its inhibitory effects at step(s) involving cAMP production and post cAMP pathway. ET-1-induced suppression of TSH actions were reversed by a C-kinase inhibitor, H-7. These results suggest that the effect of ET on functions of FRTL5 cells is, at least, in part mediated by C-kinase dependent pathway.


Selenium alleviates heart remodeling through Sirt1/AKT/GSK-3β pathway.
Selenium, reported as an important medium for maintaining the body's homeostasis, acts to have multiple bioeffects including anti-inflammatory, anti-oxidant and anti-apoptosis effects. However, its role in heart failure still remains unclear. In this study, we explored the effects of selenium on heart failure and its possible mechanism. The heart failure models were induced by aortic banding and isoproterenol. H&E, TUNEL and PSR staining were performed to detect the degree of cardiomyocyte hypertrophy, apoptosis rates and heart fibrosis, respectively. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect different mRNA levels, and western blot was applied to assess the expressions of relative proteins. Immunofluorescence staining was used to evaluate α-SMA density. We first found that treatment of selenium alleviated heart fibrosis and the development of heart failure but not cardiomyocyte cross sectional areas. Besides, selenium improved heart levels of superoxide dismutase2 (SOD2), glutathione peroxidase (Gpx) and glutathione (GSH) and the activity of SOD, accompanied by decreased apoptosis rate. In addition, our in vitro study has shown that selenium reduced mRNA levels of collagen Ⅰ and collagen III, expressions of a-SMA, p-AKT/AKT and p-GSK-3β/ GSK-3β, apoptosis rates and reactive oxygen species (ROS) levels in H9C2 cardio-myoblasts treated with TGF-β1. Moreover, the level of Sirt1 was found to be up-regulated by selenium which effects were weakened after the administration of small interfering RNA (siRNA)-Sirt1 or EX527 (inhibitor of Sirt1). Our current results have demonstrated that the protective effects of selenium on heart hypertrophy is through the regulation of Sirt1 and AKT/GSK-3β pathway.


Brucella melitensis infection associated with Guillain-Barré syndrome through molecular mimicry of host structures.
Brucella melitensis is a facultative intracellular bacterium that can survive inside macrophages and the causative agent of brucellosis. In the present study, we found that a lipooligosaccharide of B. melitensis has a GM1 ganglioside-like structure and shows a strong antibody response in mice. The cholera toxin B subunit, which binds to GM1 ganglioside specifically, reacted with the surface of B. melitensis. Immunization with B. melitensis induced the production of anti-GM1 ganglioside antibodies in mice and serum from immunized mice showed a cross-reaction with Guillain-Barré syndrome (GBS)-associated Campylobacter jejuni, but not non-GBS-associated C. jejuni. When B. melitensis was treated with a neuraminidase, antibody responses disappeared. B. melitensis immunization induced the production of anti-GM1 ganglioside antibodies in BALB/c mice but not in C57BL/6 and ddY mice, and for BALB/c mice, immunization with B. melitensis induced much greater production of anti-GM1 ganglioside than GBS-associated C. jejuni. Flaccid limb weakness was observed in B. melitensis immunized mice. These results suggest that B. melitensis is a new etiological agent for GBS and that immunological responses between it and GBS-associated C. jejuni in the mouse model may be different.


Nitrogen utilization efficiencies in mediterranean-climate shrubs of California and Chile.
Comparative studies of nitrogen utilization efficiencies (g assimilation mg-1 leaf nitrogen expended) for dominant chaparral shrubs of California and matorral shrubs of central Chile indicate varying relationships of these efficiencies to total shrub productivity and community dominance. In California where nitrogen is limiting for shrub growth, increasing nitrogen utilization efficiency is correlated with increased productivity, and species with the highest values are dominant on polar (north-facing) slopes. In Chile where soil nutrients are not strongly limiting, increased nitrogen utilization efficiency beyond a low threshold has little or no effect on productivity. This may be an important aspect of the relative ecological success of deciduous shrubs in Chile. High nitrogen utilization efficiency in Chile is associated with broad ecological amplitude rather than increased competitive ability through higher productivity.


Silencing long non-coding RNA XIST suppresses drug resistance in acute myeloid leukemia through down-regulation of MYC by elevating microRNA-29a expression.
Long non-coding RNAs (lncRNAs) are biomarkers participating in multiple disease development including acute myeloid leukemia (AML). Here, we investigated molecular mechanism of X Inactive-Specific Transcript (XIST) in regulating cellular viability, apoptosis and drug resistance in AML. XIST, miR-29a and myelocytomatosis oncogene (MYC) expression in AML bone marrow cells collected from 62 patients was evaluated by RT-qPCR and Western blot analysis. Besides, the relationship among XIST, miR-29a and MYC was analyzed by dual luciferase reporter assay, RIP, and RNA pull down assays. AML KG-1 cells were treated with anti-tumor drug Adriamycin. The role of XIST/miR-29a/MYC in cellular viability, apoptosis and drug resistance in AML was accessed via gain- and loss-of-function approaches. At last, we evaluated role of XIST/miR-29a/MYC on tumorigenesis in vivo. XIST and MYC were up-regulated, and miR-29a was down-regulated in AML bone marrow cells. Silencing XIST inhibited cellular activity and drug resistance but promoted cellular apoptosis of KG-1 cells by down-regulating MYC. XIST inhibited miR-29a expression to up-regulate MYC. Moreover, silencing XIST inhibited tumorigenesis of AML cells in vivo. Overall, down-regulation of XIST decreased MYC expression through releasing the inhibition on miR-29a, thereby reducing drug resistance, inhibiting viability and promoting apoptosis of AML cells.


Nitrofurantoin: another cause of drug-induced chronic active hepatitis? A report of a patient with HLA-B8 antigen.
Nitrofurantoin, an agent used extensively in chronic urinary tract infections, is rarely incriminated as a hepatotoxin. In this 27 year old women chronic active hepatitis first developed during exposures to nitrofurantoin, and she later suffered exacerbations. Earlier reported cases are reviewed which describe a spectrum of hepatotoxic reactions. This patient has HLA-B8, an antigen associated with autoimmune forms of chronic active hepatitis. It is postulated that the antigen may be associated with liver injury initiated by drugs such as nitrofurantoin.


Early life ionizing radiation exposure and cancer risks: systematic review and meta-analysis.
Ionizing radiation use for medical diagnostic purposes has substantially increased over the last three decades. Moderate to high doses of radiation are well established causes of cancer, especially for exposure at young ages. However, cancer risk from low-dose medical imaging is debated. To review the literature on cancer risks associated with prenatal and postnatal medical diagnostic ionizing radiation exposure among children and to assess this risk through a meta-analysis. A literature search of five electronic databases supplemented by a hand search was performed to retrieve relevant epidemiological studies published from 2000 to 2019, including patients younger than 22 years of age exposed to medical imaging ionizing radiation. Pooled odds ratio (ORpooled) and pooled excess relative risk (ERRpooled) representing the excess of risk per unit of organ dose were estimated with a random effect model. Twenty-four studies were included. For prenatal exposure (radiographs or CT), no significant increased risk was reported for all cancers, leukemia and brain tumors. For postnatal exposure, increased risk was observed only for CT, mostly for leukemia (ERRpooled=26.9 Gy-1; 95% confidence interval [CI]: 2.7-57.1) and brain tumors (ERRpooled=9.1 Gy-1; 95% CI: 5.2-13.1). CT exposure in childhood appears to be associated with increased risk of cancer while no significant association was observed with diagnostic radiographs.


Association of radioactive iodine treatment in differentiated thyroid cancer and cardiovascular death: a large population-based study.
The risk of cardiovascular diseases' death (CVD) in patients with differentiated thyroid cancer (DTC) treated with radioactive iodine (RAI) after surgery has not been adequately studied. Data of DTC patients who received RAI after surgery were retrieved from the Surveillance, Epidemiology, and End Result (SEER) database (2004-2015). Standardized mortality rate (SMR) analysis was used to evaluate the CVD risk in patients with RAI vs general population. A 1:1 propensity score matching (PSM) was applied to balance inter-group bias, and Pearson's correlation coefficient was used to detect collinearity between variables. The Cox proportional hazard model and multivariate competing risk model were utilized to evaluate the impact of RAI on CVD. At last, we curved forest plots to compare differences in factors significantly associated with CVD or cancer-related deaths. DTC patients with RAI treatment showed lower SMR for CVD than general population (RAI: SMR = 0.66, 95% CI 0.62-0.71, P < 0.05). After PSM, Cox proportional hazard regression demonstrated a decreased risk of CVD among patients with RAI compared to patients without (HR = 0.76, 95% CI 0.6-0.97, P = 0.029). However, in competing risk regression analysis, there was no significant difference (adjusted HR = 0.82, 95% CI 0.66-1.01, P = 0.11). The independent risk factors associated with CVD were different from those associated with cancer-related deaths. The CVD risk between DTC patients treated with RAI and those who did not was no statistical difference. Noteworthy, they had decreased CVD risk compared with the general population.


Increased revascularization efficacy after administration of an adenovirus encoding VEGF(121).
Adenovirus-mediated VEGF gene delivery is being evaluated in clinical trials as a treatment for patients with vascular diseases that stem from ischemia, such as diffuse coronary artery disease and peripheral vascular disease. Although adenoviral vectors are one of the most widely utilized vectors to deliver therapeutic genes to cells, they also have a major limitation in that their inherent immunogenicity leads to the production of neutralizing antibodies that block effective repeat administration. Although this may be true of intravenous, intranasal, and other routes of administration, recent studies have indicated that it may be possible to effectively readminister adenovirus to skeletal muscle. The present study found improved efficacy after administration of AdVEGF(121.10), an E1/E3-deleted adenovirus encoding human VEGF(121) under the control of a CMV promoter in a rat hindlimb ischemia model. As expected, repeat administration of adenovirus resulted in a marked increase of circulating neutralizing antibody, yet nanogram quantities of VEGF protein were still detectable within the hindlimb skeletal muscle after a second administration of vector. The amount of VEGF protein produced after repeat administration translated into improved efficacy as evidenced by increased blood flow as measured by laser Doppler, increased vessel number upon post-mortem angiography, and an increased number of CD31-positive vessels. These findings have important implications for increasing the efficacy of adenovirus-mediated gene therapy in the treatment of peripheral vascular disease and coronary artery disease.


Newly diagnosed enhancing lesions: Steroid initiation may impede diagnosis of lymphoma involving the central nervous system.
Establishing the pathologic diagnosis of central nervous system (CNS) lymphoma can be challenging, yet management of this potentially curable disease depends heavily on it. One avoidable impediment to obtaining an accurate and timely diagnosis is the pre-operative administration of steroids, which causes tumor involution and prevents appropriate sampling of viable tissue. We discuss a case of primary CNS lymphoma that highlights the evolution of the disease and the attempts to establish a diagnosis in the setting of prior administration of corticosteroids. Familiarity with these clinical scenarios will help others avoid delays in patient care that results from delayed diagnosis.


Removal of hexavalent chromium from groundwater by Mg/Al-layered double hydroxides using characteristics of in-situ synthesis.
This study aimed to develop a novel in-situ method to directly remove toxic hexavalent chromium anions from groundwater. The characteristics of Mg/Al-layered double hydroxides (LDH) involving in-situ synthesis and interlayer exchangeable anions can facilitate to remove Cr(VI) from solution. Two different methods of LDH preparation were employed to explore the adsorption efficiency of (di)chromates, such as traditional coprecipitation (CO3-LDH) and innovative in-situ synthesis (in-situ-LDH). The synthesized LDH samples were characterized using scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and zeta potential. The results demonstrated that the adsorptive amount of Cr(VI) for the in-situ synthesis process dramatically increased with an increase in initial Cr(VI) concentrations from 100 mg/L to 900 mg/L. The kinetic study indicated that the constant rate (k2) of the pseudo-second-order equation significantly decreased when the initial concentration of Cr(VI) exceeded 500 mg/L. The removal efficiency of Cr(VI) was slightly dependent on solution pH (5.0-12) values. The in-situ-LDH absorbent (339 mg/g) exhibited the significantly higher Langmuir maximum adsorption capacity than CO3-LDH (246 mg/g). The primary adsorption mechanism was anion exchange; meanwhile, the adsorption-coupled reduction mechanism also played an integral role. The advanced in-situ synthetic method can be developed to efficiently remove toxic hexavalent chromium anions from groundwater.


Splenogonadal fusion: case presentation and literature review.
Splenogonadal fusion is a rare congenital anomaly in which there is fusion of the spleen and the gonad or mesonephric derivatives. To date, approximately 150 cases have been reported since the condition was first described by Bostroem in 1883 (Bostroem E. Demonstration eines Praparates von Verwachsung der Milz mit dem lenken Hoden. Gesellschaft deutscher Naturforscher und Aerzte, Verhandlungen der 56 Versammlung, Freiburg; 1883. p. 149). Very few cases have been diagnosed preoperatively, and many cases presenting as a testicular swelling underwent an unnecessary orchiectomy with the suspicion of a testicular neoplasm. A case is presented and the related literature is reviewed.


A mechanism of erythrocyte lysis by lysophosphatidylcholine.
Lysophosphatidylcholine micelles liberate several cell surface polypeptides from erythrocyte membranes, inducing a sodium-selective permeability defect which leads to colloid osmotic lysis. Evidence is presented to support the hypothesis that at the lowest lytic lysophospholipid concentrations, selective disruption of membrane protein function, rather than gross structural reorganization of the membrane, is the primary lytic mechanism.


[Proliferation kinetics of MCF-7 cell cultures. II. Synchronization and cell recruitment induced by hormones].
The culture of MCF-7 cells in well known experimental conditions and the analysis of the cellular uptake of 3HTdR under the influence of estrogens (17-beta-E2) and antiestrogens (OH-TAM) at precise concentration levels (10(-6)/10(-9) M) have made possible the study of the growing kinetic process of the cellular cultured population and the determination of the action of such hormonal preparations on the same process. The main findings are as follows: the growing rate of the cultured cells appears to slow down in presence of OH-TAM; the reason for this slowing growth seems to be the "blockade" of the cultured cells in the last part of G1 phase, a phenomenon that has proved to be dose-dependent; by the stimulating effect of the 17-beta-E2, the MCF-7 cells, synchronized in G1, progress simultaneously in their vital cycle during, at least, three divisory cycles; and this "recruitment" effect seems to be characteristic of the estrogen since the synchronization process fades or disappears when the 17-beta-E2 is absent from the culture medium.


The clinical significance of mesenchyme forkhead 1 (FoxC2) in gastric carcinoma.
Mesenchyme forkhead 1 (FoxC2) is an epithelial-mesenchymal transition (EMT)-inducing factor. Previous studies have demonstrated that FoxC2 binds directly to the promoter region of p120-catenin (p120ctn). The aim of this study was to investigate the clinical significance of FoxC2 expression and the inter-relationship between FoxC2 and p120ctn, in gastric cancer. Immunohistochemistry was used to examine the expression of FoxC2 and p120ctn proteins in 325 gastric cancer samples. Staining for FoxC2 in cancer tissues was markedly stronger than in normal tissues. High FoxC2 expression was associated significantly with differentiation, invasion depth, lymph node metastasis and tumour stage. Patients with high FoxC2 expression or low p120ctn expression had a poor prognosis. In the high p120ctn expression group, the prognosis for patients with low FoxC2 expression was better than for the high FoxC2 group. Moreover, stepwise Cox regression showed that p120ctn was an independent prognostic factor, but FoxC2 in combination with p120ctn was not correlated significantly with survival. We found that FoxC2 and p120ctn play important roles in the progression and prognosis of gastric cancer. Moreover, FoxC2 and p120ctn should be evaluated further as novel biomarkers and therapeutic targets for gastric cancer treatment.


Use of modified Magee equations and histologic criteria to predict the Oncotype DX recurrence score.
Oncotype DX (Genomic Health, Redwood City, CA, USA, current list price $4,350.00) is a multigene quantitative reverse transcription-polymerase chain reaction-based assay that estimates the risk of distant recurrence and predicts chemotherapy benefit for patients with estrogen receptor (ER)-positive breast cancers. Studies have suggested that standard histologic variables can provide similar information. Klein and Dabbs et al have shown that Oncotype DX recurrence scores can be estimated by incorporating standard histologic variables into equations (Magee equations). Using a simple modification of the Magee equation, we predict the Oncotype DX recurrence score in an independent set of 283 cases. The Pearson correlation coefficient (r) for the Oncotype DX and average modified Magee recurrence scores was 0.6644 (n=283; P<0.0001). 100% of cases with an average modified Magee recurrence score>30 (n=8) or an average modified Magee recurrence score<9 (with an available Ki-67, n=5) would have been correctly predicted to have a high or low Oncotype DX recurrence score, respectively. 86% (38/44) of cases with an average modified Magee recurrence score≤12, and 89% (34/38) of low grade tumors (NS<6) with an ER and PR≥150, and a Ki-67<10%, would have been correctly predicted to have a low Oncotype DX recurrence score. Using an algorithmic approach to eliminate high and low risk cases, between 5% and 23% of cases would potentially not have been sent by our institution for Oncotype DX testing, creating a potential cost savings between $56,550.00 and $282,750.00. The modified Magee recurrence score along with histologic criteria may be a cost-effective alternative to the Oncotype DX in risk stratifying certain breast cancer patients. The information needed is already generated by many pathology laboratories during the initial assessment of primary breast cancer, and the equations are free.


At the intersection of science and theory: How the Nurse Role Integration Model reconciles the conflict.
As more nurses embrace precision science, there is a tendency to utilize theoretical frameworks from other disciplines thus, placing nursing at risk of losing its autonomy and independence. The discipline has fallen prey to internal binary opposition, eliminating opportunities to engage in civil discourse. To explore how the roles nurses select might fit together in a theoretical framework and help nurses understand how the roles they choose to support their identity as nurses, this paper introduced a model of nursing that includes the bench scientists, the policy activists, and bedside nurses, using the Neuman Systems Model (NSM). The Nurse Role Integration Model (NRIM) espouses the basic tenets of NSM: prevention counteracts stressors from penetrating the client's lines of defense thus, reducing stress response. Primary prevention reflects the work of the nurse bench scientists, investigating the underlying mechanisms behind pathophysiology; secondary prevention is applied nurse scientists who build upon nurse researchers' work, identifying and testing potential interventions; tertiary prevention is nurse policy activists, the fulcrum, who leverage primary and secondary findings to argue policy change at all levels. Once policy change is adopted, bedside nurses are educated and implement the change. This lens provides an opportunity to create greater solidarity, strengthening the unity and autonomy of the discipline.


Protected area co-management and perceived livelihood impacts.
Creation of protected areas to conserve biodiversity can have both positive and negative impacts, with impacts unequally distributed within local communities. A global shift towards local community involvement in protected area governance and co-management has aimed to reduce costs of protected area establishment and their uneven distribution. Yet, there is mixed evidence to support whether such initiatives are succeeding. Here, a protected area in Madagascar is used as a case study to explore how co-management governance processes impact upon livelihood strategies and outcomes, and how these impacts are distributed within and between villages. Focus groups, interviews and questionnaires were conducted in 2015/16 with households surrounding a protected area, co-managed by local community associations and a national NGO. Data analysis was framed around the Sustainable Livelihoods Framework. The majority of respondents perceived negative livelihood outcomes, and impacts were unevenly distributed between social groups. Respondents were more likely to report negative livelihood outcomes if they were from remote villages, poorer households and reliant on provisioning ecosystem services before protected area establishment. Qualitative data showed that the main drivers of this were protected area-related rules and regulations restricting forest activities. Drivers of improved livelihood outcomes were training and materials improving agricultural yields and increased community cohesion. Although co-managed protected areas may be overall more effective in meeting biological and socio-economic goals than protected areas of other governance types, the evidence here suggests that governance processes can lead to local perceptions of inequity.


Elimination of infused branched-chain amino-acids from plasma of patients with non-obese type 2 diabetes mellitus.
Increased plasma levels of branched-chain amino-acids (BCAA) have been demonstrated in poorly controlled diabetes mellitus, and related to absolute or relative insulin deficiency. To study the pathogenesis of this alteration, the elimination of BCAA from plasma was measured in 8 patients with non-obese type 2 diabetes mellitus and in 8 age-matched control subjects during steady-state BCAA concentrations induced by a primed-continuous infusion. Fasting BCAA levels were increased by 40-50% in patients with diabetes. The plasma clearances of valine, isoleucine, and leucine, calculated as infusion rate divided by steady-state concentration, were reduced by 20% in diabetics, despite 50% hyperinsulinemia (P < 0.01). Basal BCAA levels and BCAA clearance were negatively correlated (r(2) = 0.46 - 0.56). The endogenous basal appearance rates of BCAA, estimated by the basal concentrations multiplied by the plasma clearances, were normal in diabetics, and there was no difference in the apparent volumes of distribution of BCAA. The increased basal concentration of BCAA in poorly controlled type 2 diabetics (693 [SD 114; n = 8] mumol/l vs 479 [88; n = 8] in controls (P < 0.005) is attributable to changes in plasma clearances, without any change in the efflux of BCAA into plasma. This may be due to insulin resistance.


Design and Synthesis of New Transient Receptor Potential Vanilloid Type-1 (TRPV1) Channel Modulators: Identification, Molecular Modeling Analysis, and Pharmacological Characterization of the N-(4-Hydroxy-3-methoxybenzyl)-4-(thiophen-2-yl)butanamide, a Small Molecule Endowed with Agonist TRPV1 Activity and Protective Effects against Oxidative Stress.
4-(Thiophen-2-yl)butanoic acid was identified as a cyclic substitute of the unsaturated alkyl chain of the natural ligand, capsaicin. Accordingly, a new class of amides was synthesized in good yield and high purity and their molecular recognition against the target was investigated by means of docking experiments followed by molecular dynamics simulations, in order to rationalize their geometrical and thermodynamic profiles. The pharmacological properties of these new compounds were expressed as activation (EC50) and desensitization (IC50) potencies. Several compounds were found to activate TRPV1 channels, and in particular, derivatives 1 and 10 behaved as TRPV1 agonists endowed with good efficacy as compared to capsaicin. The most promising compound 1 was also evaluated for its protective role against oxidative stress on keratinocytes and differentiated human neuroblastoma cell lines expressing the TRPV1 receptor as well as for its cytotoxicity and analgesic activity in vivo.


Factors associated with delayed pediatric hypospadias surgery in Taiwan: a population-based, nationwide analysis.
Current guidelines recommend that hypospadias repair should be performed before age 18 months. This study aims to investigate the trends of surgical timing and to determine what factors are associated with age at surgery. The present study utilized a subset of the National Health Insurance Research Database, known as Longitudinal Health Insurance Database 2005, which contains the data of all paid medical benefit claims over the period from 1997 to 2007 for a subset of one million beneficiaries randomly drawn from the population of 22.72 million individuals in NHI program during any part of calendar year 2005. We analyzed claims data for all subjects with the diagnoses of hypospadias. Among 52,705 live male newborns, 218 were diagnosed with hypospadias and thus were included as subjects in our study. Among them, 89 received repair surgery. Approximately 60.6% of the study subjects received repair after the age of 18 months. Multivariate analysis showed that several factors were significantly associated with age at hypospadias surgery: specialty of clinics where first diagnosis was made; specialty of physician making the first diagnosis, age of physician making the first diagnosis; specialty of surgeon performing the surgery; number of years since surgeon's board certification; urbanization level of subject's residence; modality of surgery; concomitant cryptorchidism; concomitant prematurity and low birth weight; age at diagnosis; and number of well-baby clinic visits. This study addresses an important issue of delayed hypospadias surgery in Taiwan, which provides a potential opportunity for improvement in quality of care.


Highly sensitive immunoassay based on SERS using nano-Au immune probes and a nano-Ag immune substrate.
A super-high-sensitivity immunoassay based on surface-enhanced Raman scattering (SERS) was implemented using the nano-Au immune probes and nano-Ag immune substrate. Ultraviolet-visible extinction spectra, transmission electron microscopy (TEM) and scanning electron microscopy (SEM) images, and SERS spectra were used to characterise the nano-Au immune probes and the nano-Ag immune substrate. The nano-Ag immune substrate was prepared by the in situ growth of Ag nanoparticles and the subsequent linkage of these nanoparticles with anti-apolipoprotein B on a silicon wafer. The nano-Ag immune substrate exhibited strong SERS activity, excellent reproducibility, and high biospecificity. The nano-Au immune probes were prepared by immobilising 4-mercaptobenzoic acid (4MBA) molecules as a Raman reporter and anti-apolipoprotein B onto the surfaces of Au nanoparticles. It was found that 4MBA induced the aggregation of Au nanoparticles, resulting in the generation of vast hot spots. Moreover, the nano-Au immune probes exhibited strong SERS activity and high biospecificity. A sandwich-type immunoassay structure consisting of the nano-Au immune probes and nano-Ag immune substrate was used to detect the concentration of apolipoprotein B, where the detection limit was as low as 2 fg/mL (3.878×10(-18) mol/L). Taken together, the experimental results indicate that the proposed immunoassay protocol has a great potential application in biological sensing and clinical diagnostics.


A fully visualized arthroscopic disc suturing technique.
Advanced arthroscopic procedures, including disc suturing, are advantageous in managing temporomandibular joint disorders. These techniques are indicated in cases of long-standing closed lock, displaced discs with reduction, and hypermobility with chronic dislocation. Disc suturing procedures can be done blindly, partially blindly, or fully visualized. Fully visualized suturing techniques have obvious advantages, but can be time-consuming, difficult to perform, and traumatic. This article presents a new suturing technique that is fully visualized and is less time-consuming and relatively easy to perform.


Clearance of bone marrow mast cells after hypomethylating agent and venetoclax for systemic mastocytosis associated with myeloid neoplasia.
Systemic mastocytosis (SM) results from clonal proliferation of neoplastic mast cells that infiltrate bone marrow and other organs. A major subset of patients with SM has a clonally related myeloid neoplasm and the SM itself (SM-AMN). We evaluated the efficacy of hypomethylating agent and venetoclax (HMA-VEN) to target both the myeloid neoplasm and mast cell infiltrate in a patient with SM associated with acute myeloid leukemia arising from myelodysplastic syndrome and illustrate complete elimination of bone marrow mast cells and complete remission of MDS/AML. This case illustrates the potent activity of HMA-VEN both against the AMN as well as the associated SM.


Rapid intestinal glucuronidation and hepatic glucuronide recycling contributes significantly to the enterohepatic circulation of icaritin and its glucuronides in vivo.
Icaritin (ICT), a prenylflavonoid derivative extracted from the Epimedium genus, has exhibited antitumor effects in hepatocellular carcinoma (HCC) cells and safety and tolerance in clinical settings. However, ICT exhibits low blood concentration and the in vivo dominant plasma species of ICT is glucuronides [icaritin-3-glucuronide (G1), icaritin-7-glucuronide (G2) and icaritin-3, 7-diglucuronide (DIG)]. Therefore, how ICT reaches the liver and exerts its effect with low toxicity remains unknown. Therefore, pharmacokinetic experiments (p.o. 5 mg/kg with/out 50 mg/kg inhibitor combo), intestinal perfusion (2 μM ICT), portal vein infusion (1.6 μM ICT, 7.1 μM G1, 6.8 μM G2 and 4.4 μM DIG), and in vitro studies (the concentration range of substrates: 0.3-10 μM) were conducted in the present study. Ultimately, ICT was shown to undergo glucuronidation by the intestine and subsequent uptake by hepatocytes via organic anion transporting peptides (OATPs) as conjugates, followed by biliary excretion mainly as diglucuronide. In conclusion, we found for the first time that the intestine is considered as the major metabolic organ, liver as the main recycling organ for the enterohepatic recycling (EHR) of ICT. Moreover, DIG is the main species in the systemic circulation following oral administration of ICT which explains the low toxicity of ICT in clinical settings.


The Perception Gap: Recognizing and managing the risks that arise when we get risk wrong.
Many in the academic, science, and business communities are frustrated at how people perceive and respond to risk, lamenting that the lay public is sometimes more afraid of some threats than the evidence warrants, and less afraid of some dangers than the evidence warns. This is often ascribed to the alarmist way the news media cover risk-related subjects. That criticism is simplistic and unproductive, and ignores or dismisses the large body of research that finds that the perception of risk is not, and can never be, perfectly rational. Risk perception among members of the public, the media, and members of the academic, scientific, and business communities, is ultimately subjective. The gap between our fears and the evidence is not simply the product of alarmist media reporting. This 'Perception Gap' poses significant risks in and of itself, influencing the choices we make as individuals and as a society. The roots of the Perception Gap must be understood if we are to recognize the dangers that can arise when we sometimes get risk wrong, and in order that we may more wisely manage those risks as actively as we manage toxicological or food or other risks with which we are more familiar.


[Conservative treatment or surgery of Colles fracture? (author's transl)].
In Colles fracture good functional results can be achieved by conservative treatment. Surgical procedures should only be performed in rare cases of comminuted fractures.


Molecular and Serological Characteristics of Avian Pathogenic Escherichia coli Isolated from Various Clinical Cases of Poultry Colibacillosis in Poland.
Escherichia coli infections are a major problem in modern poultry production. Avian pathogenic E. coli (APEC) strains have several mechanisms that enable them to colonize various ecosystems. In this study, 290 E. coli isolates were recovered from clinical cases of colibacillosis in chicken and turkey broilers and from laying and breeding hens. The samples were taken from organs with pathological changes suggesting colibacillosis. The lesions were assigned to three groups depending on their advancement, of which the largest (60% of the isolates) was group 3, with the most extensive changes. The most common serotype was shown to be O78 (14%). The most frequently detected gene among those tested was iss, while papC was the least prevalent. An analysis of the number of genes present per isolate revealed that the presence of four genes was the most common (22%), while only 1% of the strains tested had all eight genes. The most frequently detected genes for each serotype were iss and iucD for O78; irp2 and cvi/cva for O1; irp2, iucD, and iss for O2, and iss and iucD for O8, for which the least frequent was papC. All O18 serotype strains had the iss gene, while none had the vat gene.


An introduction to Rasch measurement for scale development and person assessment.
This article: a) outlines some of the limitations of True Score Theory, b) discusses some advantages of Rasch measurement, and c) compares the results of Rasch and factor analytic techniques applied to a common data set. Using a mail survey, 206 female members of a national nursing association completed Ryckman's (1982) Perceived Physical Ability Scale. Exploratory factor analysis identified one factor with a Cronbach alpha of .78. Rasch fit statistics also identified one dimension with a person reliability of .76. Rasch methods were also used to investigate the rating scale functioning, additional construct validity issues, and person diagnosis. Discrepancies between the two estimates of internal consistency are discussed and differences in the utility of the two methodologies are reviewed.


[The IgA myeloma, personal contribution and review of the literature (author's transl)].
After reporting the most important differences between the IgA and IgG myeloma and between the two varieties on the IgA myeloma, the A. relate one uncommon case of IgA myeloma, with an alpha2-electrophoretic migration, a considerable increase of the myelomatosis paraprotein and an increase of the seric viscosithy, without the hyperviscosity syndrome.


Systemic computational investigation to identify potential inhibitors against cancer by targeting P21-activated kinase 4 and D(CGATCG).
Cancer accounts for more than 10 million deaths in the year 2020. Development of drugs that specifically target cancer signaling pathways and proteins attain significant importance in the recent past. The p21-activated kinase 4 enzyme, which plays diverse functions in cancer and is reported in elevated expression makes this enzyme an attractive anti-cancer drug target. Similarly, cancer cells' DNA could also serve as a good platform for anti-cancer drug development. Herein, a robust in silico framework is designed to virtually screen multiple drug libraries from diverse sources to identify potential binders of the mentioned cancer targets. The virtual screening process identified three compounds (BAS_01059603, ASN_10027856, and ASN_06916672) as best docked molecules with a binding energy score of ≤ -10 kcal/mol for p21-activated kinase 4 and ≤ -6 kcal/mol for D(CGATCG). In the docking analysis, the filtered compounds revealed stable binding to the same site to which controls bind in X-ray structures. The binding interactions of the compounds with receptors are dominated by van der Waals interactions. The average root mean square deviation (rmsd) value for p21-activated kinase 4 systems is noticed at ∼2 Å, while for D(CGATCG), the average rmsd is 2.7 Å. The MMGB/PBSA interpreted ASN_12674021 to show strong intermolecular binding energy compared to the other two systems and control in both receptors. Moreover, the entropy energy contribution is less than the mean binding energy. In short, the compounds are showing promising binding to the biomolecules and therefore must be evaluated for anti-cancer activity in experimental studies.Communicated by Ramaswamy H. Sarma.


Patients with alcohol problems in the emergency department, part 1: improving detection. SAEM Substance Abuse Task Force. Society for Academic Emergency Medicine.
Medical and social problems related to alcohol use are frequently seen in the ED. Often, the tempo of emergency medicine practice seems to preclude assessment beyond that required by the acute complaint. However, detection of ED patients with alcohol problems can occur using brief screening tools. This article was developed by members of the SAEM Substance Abuse Task Force, and describes screening tools that have been used successfully to identify at-risk and dependent drinkers. Their brevity, reproducibility, and accuracy vary somewhat, but screening can be realistically performed in the busy ED setting. The early detection of patients with alcohol problems would provide the opportunity for early intervention, and may reduce subsequent morbidity and mortality in this patient population.


Research Progress in Function and Regulation of E3 Ubiquitin Ligase SMURF1.
Smad ubiquitylation regulatory factor 1 (Smurf1) is an important homologous member of E6-AP C-terminus type E3 ubiquitin ligase. Initially, Smurf1 was reportedly involved in the negative regulation of the bone morphogenesis protein (BMP) pathway. After further research, several studies have confirmed that Smurf1 is widely involved in various biological processes, such as bone homeostasis regulation, cell migration, apoptosis, and planar cell polarity. At the same time, recent studies have provided a deeper understanding of the regulatory mechanisms of Smurf1's expression, activity, and substrate selectivity. In our review, a brief summary of recent important biological functions and regulatory mechanisms of E3 ubiquitin ligase Smurf1 is proposed.


A new type of cytocentrifuge, the valve-centrifuge.
A new type of cytocentrifuge has been developed in which the sedimentation process of the cells onto the slides is separated from the draining of the sedimentation fluid. This is realised by electrically controlled valves which can be closed and opened while the centrifuge is running. Sedimentation is carried out with closed valves, draining of adhering medium with open valves. The preparations, freed of adhering medium by the centrifugal force can be taken out and the cells can be fixed. Alternatively the valves can be closed again and fixative can be introduced through a central well, the cells still being under the influence of the centrifugal force. With subsequent draining of the fixative and introduction of washing and staining solutions through the central well, the whole process from sedimentation to staining can be carried out in the running centrifuge. The process seems well suited for complete automation. Using dilution series from a suspension of human buffy coat cells counted in a Buerker chamber, the cell counts in the centrifuge preparations showed virtually total recovery of cells, with no apparent selection or specific distribution of cell types. Draining of the sedimentation and fixative fluids at a slow rate was found to be vital for optimal recovery of cells. The morphology of different cell types sedimented on the slide was excellent. The flattening of nuclei thorugh gravity was studied by cytophotometry of Feulgen-stained leucocytes. The nuclear area of these cells was found to be approximately double that from cells in identically stained classical smears. With this type of valve-centrifuge a quantitative and unbiased recovery of uniformly spread and flattened cells on coverslips or slides may be obtained, thus making the procedure well suited to automated analysis based on cytophotometric principles and morphometric pattern recognition.


Determinants of Discordance Between Criteria for Inactive Disease and Low Disease Activity in Juvenile Idiopathic Arthritis.
To assess concordance among criteria for inactive disease (ID) and low disease activity (LDA) in juvenile idiopathic arthritis (JIA) and to seek factors driving discordance. The frequency of fulfillment of existing criteria was evaluated in information on 10,186 patients extracted from 3 cross-sectional data sets. Patients were divided up according to the functional phenotypes of oligoarthritis and polyarthritis. Concordance between criteria was examined using weighted Venn diagrams. The role of each individual component in explaining discordance between criteria was assessed by calculating the absolute number and percentage of instances in which the component was responsible for discrepancy between definitions. Criteria for ID were met by 28.6-41.1% of patients with oligoarthritis and by 24.0-33.4% of patients with polyarthritis. Criteria for LDA were met by 44.8-62.4% of patients with oligoarthritis and by 44.6-50.4% of patients with polyarthritis. There was a 57.9-62.3% overlap between criteria for ID and a 67.9-85% overlap between criteria for LDA. Parent and physician global assessments and acute-phase reactants were responsible for the majority of instances of discordance among criteria for ID (8.7-15.5%, 10.0-12.3%, and 10.8-17.3%, respectively). We found fair concordance between criteria for ID and LDA in JIA, with the main drivers of discordance for ID being physician and parent global assessments and acute-phase reactants. This observation highlights the need for further studies aimed to evaluate the impact of subjective physician and parent perception of disease remission and of laboratory measures of inflammatory activity on the definition of ID.


New insights into non-enzymatic glycation of human serum albumin biopolymer: A study to unveil its impaired structure and function.
Albumin glycation and subsequent formation of advanced glycation end products (AGEs) correlate with diabetes and associated complications. Human Serum Albumin (HSA) was modified with d-glucose for a 40day period under sterile conditions at 37°C. Modified samples along with native HSA (unmodified) were analyzed for impairment in biochemical characteristics ((fructosamine, carbonyl, thiol, lysine, arginine, hydroxymethyl furfural [HMF] content), electrochemical (electrical conductance), simulated gastric fluid assay, simulated intestinal fluid assay, spectroscopic properties (UV, fluorescence), optical (surface contact angle) and fluid dynamics (viscosity and Stokes radius). Impairment in drug binding capacity of glycosylated-HSA was assessed with molecular docking experiment using metformin. UV-absorbance and fluorescence measurement were performed for drug bound glycated and native-HSA. Extensively modified HSA has been used to study its relevance in diabetes mellitus. Glucose modified-HSA resulted in AGEs formation. It suggests deleterious impairment in biochemical, electrochemical, spectroscopic, optical and fluidity properties of HSA at high concentrations of glucose. The results of the present study can be useful to understand the phenomenon of proteins damage in hyperglycemic conditions.


Exploring a unique water ecosystem under long-term exposure to hexavalent chromium - An in situ study of natural diatom (Bacillariophyceae) communities.
This paper reports the third in a series of three studies of a unique aquatic phytobial consortium that developed in a polluted ditch situated near an old chromium waste landfill. The ditch is a specific ecological niche having increased loads of several chemical compounds, including extreme hexavalent chromium concentrations up to two thousand times the allowed limit (0.02 mg dm-3 in Poland) in the more polluted section B; the moderate concentrations in section A are twice the limit. We focus on the microscopic algae group of diatoms, one of the most important components of the phytobial consortium, and continue our novel attempt to analyze the bioremediation potential of the entire consortium under those environmental conditions. We used numerical methods to analyze differences in diatom biodiversity between sections A and B, and assessed the relations between diatoms and selected water chemistry properties, including hexavalent chromium, chlorides and sulphates, the latter two known to positively influence the resistance of algae to the impact of hexavalent chromium. We noted 37 diatom taxa in section A of the ditch and 30 in section B. The most frequently observed diatoms were cosmopolitan taxa and/or characteristic taxa of saline waters. Sulphates were the most important factor influencing the diatom composition in the ditch, explaining 52% of the total variability, followed by chlorides (30%) and hexavalent chromium (9%). Gomphonema acuminatum, Melosira varians and Nitzschia frustulum var. frustulum were found to be most resistant to hexavalent chromium and were selected for further experimental studies on their biotechnological usefulness.


Forced vital capacity and maximal respiratory pressures in patients with mild and moderate scoliosis.
Lung function and maximal respiratory pressures of 24 adolescent females with mild-to-moderate idiopathic scoliosis (spinal curvature 10-60 degrees) were determined and compared with 38 age- and sex-matched controls. Twelve patients with moderate scoliosis (Cobb angle 35-60 degrees) had significantly reduced mean values for FVC (% predicted) and maximal inspiratory pressure (MIP), as compared to the controls. Twelve patients with mild scoliosis (Cobb angle less than 35 degrees) had normal mean values for FVC and maximal respiratory pressures, but five individual patients had FVC values less than 80% predicted. All but one of the patients with mild scoliosis had normal MIP values. FVC (% predicted) was significantly correlated with the degree of spinal curvature (r = -0.466; P less than 0.05) but was not related to MIP. These results indicate that reduced FVC values do occur in patients with mild-to-moderate idiopathic scoliosis and suggest that these low FVC values can be attributed to the rib cage deformity rather than to an inability to generate adequate inspiratory pressures.


Evaluation of larvicidal activity and effects on post embrionary development of laboratory reared Lucilia cuprina (Wiedemann, 1830) (Diptera: Calliphoridae), treated with Brevibacillus laterosporus.
The blowfly Lucilia cuprina is an economically important livestock pest that is also associated with human myiasis. To date, methods including the application of chemical pesticides, plant extracts, insect growth regulators and a range of Bacillus thuringiensis strains have been used, with varying degrees of success, to control this pest. The present study evaluated the larvicidal activity and the induction of sub lethal effects upon post embrionary development following ingestion of 12 strains of Brevibacillus laterosporus, presented individually in the diet as spores. All strains were shown to be larvicidal, with corrected mortality levels of 29 to 54%. No significant differences were observed, in terms of larval weight at the time of abandoning the diet, in the time taken for the initiation of the pupation process, in the duration of the pupation process, the period of adult emergence or cumulative mortality during the transition from larvae to adult. However, an influence upon sex ratio was observed. This study suggests that strains of B. laterosporus hold potential for development as a tool in the biological control of L. cuprina.


MAGORINO: Magnitude-only fat fraction and R* 2 estimation with Rician noise modeling.
Magnitude-based fitting of chemical shift-encoded data enables proton density fat fraction (PDFF) and R 2 * $$ {R}_2^{\ast } $$ estimation where complex-based methods fail or when phase data are inaccessible or unreliable. However, traditional magnitude-based fitting algorithms do not account for Rician noise, creating a source of bias. To address these issues, we propose an algorithm for magnitude-only PDFF and R 2 * $$ {R}_2^{\ast } $$ estimation with Rician noise modeling (MAGORINO). Simulations of multi-echo gradient-echo signal intensities are used to investigate the performance and behavior of MAGORINO over the space of clinically plausible PDFF, R 2 * $$ {R}_2^{\ast } $$ , and SNR values. Fitting performance is assessed through detailed simulation, including likelihood function visualization, and in a multisite, multivendor, and multi-field-strength phantom data set and in vivo. Simulations show that Rician noise-based magnitude fitting outperforms existing Gaussian noise-based fitting and reveals two key mechanisms underpinning the observed improvement. First, the likelihood functions exhibit two local optima; Rician noise modeling increases the chance that the global optimum corresponds to the ground truth. Second, when the global optimum corresponds to ground truth for both noise models, the optimum from Rician noise modeling is closer to ground truth. Multisite phantom experiments show good agreement of MAGORINO PDFF with reference values, and in vivo experiments replicate the performance benefits observed in simulation. The MAGORINO algorithm reduces Rician noise-related bias in PDFF and R 2 * $$ {R}_2^{\ast } $$ estimation, thus addressing a key limitation of existing magnitude-only fitting methods. Our results offer insight into the importance of the noise model for selecting the correct optimum when multiple plausible optima exist.


OSa, a 'new' low-frequency red cell antigen.
A new low-frequency red cell antigen, OSa, in a Japanese blood donor is inherited as a Mendelian dominant. A family study showed that OSa is not controlled by ABO, P1, Rh, Kidd, or Diego loci, nor is the antigen X- or Y-borne.


Neurological manifestations of Borrelia burgdorferi-infections: the enlarging clinical spectrum.
We report on the clinical symptoms of 50 patients with serologically proven B. burgdorferi infection in stage 2 Lyme disease. Besides the typical pattern of the GBB-syndrom myelitis, encephalitis, cranial nerve neuritis others than Bell's palsy, painful neuritis without CSF-pleocytosis and meningitis without other neurological findings were observed.


Radionuclide probes for molecular imaging of pancreatic beta-cells.
Islet transplantation is a promising treatment option for patients with type 1 diabetes (T1D); however, the fate of the graft over time remains difficult to follow, due to the lack of available tools capable of monitoring graft rejection and inflammation prior to islet graft loss. Due to the challenges imposed by the location of the pancreas and the sparsely dispersed beta-cell population within the pancreas, currently, the clinical verification of beta-cell abnormalities can only be obtained indirectly via metabolic studies, which typically is not possible until after a significant deterioration in islet function has already occurred. The development of non-invasive imaging methods for the assessment of the pancreatic beta-cells, however, offers the potential for the early detection of beta-cell dysfunction prior to the clinical onset of T1D and type 2 diabetes (T2D). Ideal islet imaging agents would have an acceptable residence time in the human body, be capable of providing high-resolution images with minimal uptake in surrounding tissues (e.g., the liver), would not be toxic to islets, and would not require pre-treatment of islets prior to transplantation. A variety of currently available imaging techniques, including magnetic resonance imaging (MRI), bioluminescence imaging (BLI), and nuclear imaging have been tested for the study of beta-cell diseases. In this article, we summarize the recent advances made in nuclear imaging techniques for non-invasive imaging of pancreatic beta-cells. The use of radioactive probes for islet imaging is also discussed.


Medial orbital wall fracture with enophthalmos.
An isolated blow-out fracture of the medial orbital wall is uncommon, whereas the incidence in conjunction with an orbital floor fracture is high. The most striking features of an isolated medial wall fracture are diplopia on medial and lateral gaze and/or enophthalmos. The cases of two patients with a fracture of the medial orbital wall with enophthalmos are presented. One patient had an isolated medial wall fracture, whereas the other had a combined medial and inferior orbital wall fracture. Treatment of the enophthalmos consisted of exposure of the medial wall fracture site using a bicoronal flap, freeing of the herniated soft tissues and reconstruction of the defect with an autogenous medial iliac bone graft. The incidence, aetiology, pathogenesis, signs and symptoms and surgical treatment of the isolated orbital medial blow-out fracture are discussed.


The Impact of Hydration and Dehydration on the Mobility and Location of Ibuprofen Molecules in the Voids of Ultra-Stable Zeolite Y.
Mesoporous dealuminated zeolites are used as hosts for ibuprofen. This drug experiences high mobility when confined in mesopores, which is largely dependent on the water content. Zeolites are materials that are naturally hydrated under ambient conditions. Nitrogen adsorption and X-ray diffraction (XRD) show that the samples with the content of ibuprofen up to 38% have the guest phase residing only in mesopores. 1H and 13C MAS NMR studies of samples in ambient conditions, after dehydration, and in hydration prove the impact of water for increased mobility of ibuprofen. Increased mobility of the introduced phase was also detected for samples with no water content. It was ascribed to ibuprofen located outside mesopores, which experiences a prolonged time of cooling to room temperature. This phenomenon is important for all the future uses of the melting method in guest-host systems and the future use of zeolites for biomedical applications.


Robust outer volume suppression utilizing elliptical pulsed second order fields (ECLIPSE) for human brain proton MRSI.
The robust and reliable utilization of proton magnetic resonance spectroscopic imaging (MRSI) at high fields is hampered by several key technical difficulties, including contamination from extracranial lipids. To that end, this work presents novel lipid suppression sequences for proton MRSI in the human brain utilizing elliptical localization with pulsed second-order fields (ECLIPSE). Two lipid suppression methods were implemented with the ECLIPSE gradient insert. One method is a variable power, 4-pulse sequence optimized to achieve outer volume suppression (OVS) and compared against a standard, 8-slice OVS method. The second ECLIPSE method is implemented as an inversion recovery (IR) sequence with elliptical inner volume selection (IVS) and compared against a global IR method. The ECLIPSE-OVS sequence provided a 116-fold mean lipid suppression (range, 104-134), whereas an optimized 8-slice OVS sequence achieved 15-fold suppression (range, 13-18). Furthermore, the superior ECLIPSE-OVS suppression was achieved at 30% of the radiofrequency (RF) power required by 8-slice OVS. The ECLIPSE-based IR sequence suppressed skull lipids by 155-fold (range, 122-257), compared to 16-fold suppression (range, 14-19) achieved with IR. OVS and IVS executed with ECLIPSE provide robust and effective lipid suppression at reduced RF power with high immunity to variations in B1 and T1 .


Epigenetic regulation of hepatic stellate cell activation.
Activation of hepatic stellate cells (HSC) to a myofibroblast-like phenotype is the pivotal event in liver fibrosis. In uninjured liver, HSC are quiescent and non-dividing, but upon liver injury these cells undergo a dramatic change in phenotype which generates activated myofibroblast-like HSC. The change in phenotype is underpinned by a global change in gene expression with hundreds of genes being up- or downregulated. Molecular events that orchestrate changes in gene expression take place at the level of chromatin packaging which is altered through three main processes: histone modifications, DNA methylation, and silencing by non-coding RNAs. The present review focuses on the epigenetic regulation of HSC activation.


Rapid Onset of Efficacy of Baricitinib in Chinese Patients with Moderate to Severe Rheumatoid Arthritis: Results from Study RA-BALANCE.
Baricitinib is an oral, selective inhibitor of Janus kinase which demonstrates clinical efficacy in patients with rheumatoid arthritis (RA). This report aims to analyze the onset time of baricitinib in Chinese patients with moderately to severely active RA who had an inadequate response to methotrexate. This post hoc analysis evaluated clinical improvements of Chinese patients treated with baricitinib 4 mg once daily compared with placebo, based on data from a phase 3 study RA-BALANCE. Efficacy measures including American College of Rheumatology 20% (ACR20) response, ACR core set values, Disease Activity Score modified to include the 28 diarthrodial joint count (DAS28) using high-sensitivity C-reactive protein (hsCRP), DAS28-erythrocyte sedimentation rate, Simplified Disease Activity Index, Clinical Disease Activity Index, DAS28-hsCRP ≤ 3.2 response (low disease activity), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were evaluated at weeks 1, 2, 4, 8, 12, 14, 16, 20, and 24 (except for FACIT-F evaluated every 4 weeks). A logistic regression model and an analysis of covariance model were used to analyze treatment comparisons of categorical and continuous measures, respectively. Statistically significant (p ≤ 0.05) improvements were observed as early as week 1 or 2 for the baricitinib group compared to placebo in almost all main efficacy measures. For other outcomes including 66 swollen joint count, 68 tender joint count, FACIT-F, and DAS28-hsCRP ≤ 3.2 response rate, differences were evident (p ≤ 0.05) by week 4 in the baricitinib group compared with placebo. Significant improvements in all efficacy measures were sustained through 24 weeks. Baricitinib demonstrated a rapid onset of efficacy on ACR20 response, ACR core set values, disease activity, and patient-reported outcome improvements in Chinese patients from RA-BALANCE. ClinicalTrials.gov identifier, NCT02265705.