Attitude of bachelor of dental surgery students and interns toward teaching-learning process in Government Dental College, Kottayam, Kerala, India.
The educational environment affects the academic performance of students. One of the most widely utilized tools for measuring the educational environment is Dundee Ready Education Environment Measure (DREEM). The objective of the study was to assess the attitude toward study environment, as measured using DREEM questionnaire, and to find out the differences in perception of various batches of dental students. All Bachelor of Dental Surgery students from Government Dental College, Kottayam, Kerala, India, were included in the study. They were given the well-established DREEM questionnaire. A total of 234 students took part in the study, belonging to 2009, 2010, 2011, 2012, 2013, and 2014 batches. DREEM subcategories were analyzed for significance using analysis of variance. The significance of DREEM score across the different batches was further analyzed using post hoc test. Overall, DREEM score was positive (111.14), but there is need for improvement. Individual questions also were given positive score for most questions. The maximum score was obtained for 3rd year students. Similar results are obtained for three of the five subcategories of DREEM. The total DREEM score was positive (111.14). The total score as well as the scores for the subcategories was highest in 3rd year dental students. The increase might be due to the excitement of clinical exposure for the first time in 3rd year students.


Interstitial deletion of the short arm of chromosome 4.
A 17 year old girl investigated for mental retardation and minor anomalies was found to have an interstitial deletion of 4p. Her clinical and cytogenetic findings are compared with previous reported case of interstitial 4p deletion and with terminal 4p--deletions (Wolf-Hirschhorn syndrome).


Acylated flavonoid glycosides from Barringtonia racemosa.
Using various chromatographic separations, three new acylated flavonoid glycosides, namely barringosides G-I (1-3), were isolated from the water-soluble extract of Barringtonia racemosa branches and leaves. The structure elucidation was performed by extensive analysis of the 1D and 2D NMR and HR-QTOF-MS data. Of the isolated compounds, barringoside I (3) showed moderate inhibitory effects on LPS-induced NO production in RAW264.7 cells with an IC50 of 52.48 ± 1.04 µM.


Primary precursor B-cell lymphoblastic lymphoma of the ovary: case report and review of the literature.
Primary ovarian lymphoma is a rare disease, and its definition is still controversial. Many cases of primary ovarian lymphoma are diagnosed as diffuse large B-cell type, whereas the precursor lymphoblastic type is extremely rare. Herein, we describe a case of precursor B-cell lymphoblastic lymphoma of the ovary that was successfully treated with surgery and chemotherapy. A 19-year-old woman presented ovarian tumors and paraaortic lymphoadenopathy, which were suggestive of advanced ovarian cancer. Exploratory laparotomy and right salpingo-oophorectomy were performed, and the diagnosis of precursor B-cell lymphoblastic lymphoma was established. The patient was treated with a combination of chemotherapy and is currently disease-free 1 year after surgery. To our best knowledge, this is the fourth reported case of precursor lymphoblastic lymphoma of the ovary.


Driving the quadricyclane-to-norbornadiene isomerization by charge separation with perylenediimide as electron acceptor.
Through comprehensive photo-assays, this study investigates the reaction coordinate governing the interconversion between quadricyclane (QC) and norbornadiene (NBD) upon photo-irradiation up to a wavelength of 550 nm. To harness this spectroscopic range for energy release, we link the NBD-core with a highly electron-accepting perylenediimide (PDI) with broad absorption, achieving strong electronic coupling between them. We detail the successful synthesis and present extensive DFT calculations to determine the amount of stored energy. By means of transient absorption spectroscopy, an oxidative electron transfer is observed during the QC-to-NBD isomerization following the initial PDI photoexcitation. This charge-separated state is key to triggering the back-isomerization with visible light excitation.


Methodology and feasibility of a structured education program for diabetes education in India: The National Diabetes Educator Program.
India has over 62 million people with diabetes. Unfortunately, there are no trained diabetes educators in India although many are self-taught through experience. The National Diabetes Educator Program (NDEP) was initiated with the primary aim to educate and train diabetes educators in India. The first cycle of NDEP was conducted during the period June 2011 to March 2012 in 96 training centers in India and trained 1032 diabetes educators mainly drawn from various diabetes clinics across the country. Structured modules were taught by diabetologists/endocrinologists or experienced educators. A majority of the trainees attended all sessions and 95% of the trainees acknowledged that the program met its objective and was beneficial to them. This article elaborates the methodology of the program and its evaluation based on feedback received from the participants and trainers.


How Heavy Lifting Lightens Our Lives: Content Analysis of Perceived Outcomes of Masters Weightlifting.
Although the benefits of sport participation for older adults has been well-documented, the traditionally masculine sport of weightlifting has only recently become popular among older women, who now participate at rates comparable to men in the United States. This study describes the self-reported effects of participating in Masters-level Olympic weightlifting on other aspects of life. Contrasting with previous studies of Masters athletes in other sports, the gender balance and broad age range of our sample allowed us to explore whether the self-reported impact of sport on older adults was similar or different across age groups (35-44, 45-59, 60, and older) for both men and women. A total of 352 (191 women, 159 men, 2 other) who completed a survey of Masters lifters registered with the United States national organization (USAW) responded to an open-ended question about how weightlifting has affected other aspects of their life. Across gender and age categories, responses indicated that weightlifting has a positive impact on physical health (strength, mobility, fitness) and on psychological (mental health benefits, stress reduction) and social aspects such as community connections. Female lifters mentioned psychological benefits such as increased confidence and help with stress and depression more commonly than male lifters; older lifters were more likely than middle-aged lifters to mention physical health benefits. Competition was a prominent theme across genders and age groups. The themes mentioned by participants are consistent with previous literature on sports that are less strongly gender-typed than weightlifting.


Characteristics of inner reading voices.
This study examined the phenomenological characteristics of inner speech during silent reading (inner reading voices or IRVs), a type of inner speech that may be particularly amenable to empirical study. A survey was conducted in the general population to assess IRV frequency, location, number, identity, and controllability, and auditory qualities of IRVs. Of 570 survey respondents, 80.7% reported sometimes or always hearing an inner voice during silent reading, and the remaining 19.3% reported always understanding words being read without hearing an inner voice. Results indicated that IRVs are a routine experience for many, with 34.2% of respondents with IRVs hearing an IRV every time something was read, and 45% reporting an IRV often. Most respondents reported IRVs with specific auditory qualities such as gender, accent, pitch, loudness, and emotional tone. IRVs were reported in participants' own voices, as well as in the voices of other people. Some respondents reported being unable to control any aspect of their IRVs, while others could control one or several aspects. These results indicate that there is considerable individual variation in inner speech during silent reading.


Prognostic Impact of Preoperative Osteosarcopenia for Patients with Pancreatic Ductal Adenocarcinoma After Curative Resection.
The clinical significance of preoperative osteosarcopenia in pancreatic ductal adenocarcinoma (PDAC) has not been fully studied. The purpose of this study was to evaluate the role of preoperative osteosarcopenia in predicting the survival of patients with PDAC. We retrospectively analyzed 265 patients who underwent curative surgical resection for PDAC between 2012 and 2018 in two Japanese institutes. The skeletal muscle index at the L3 vertebrae and the bone mineral density at the Th11 vertebra were calculated for the evaluation of osteosarcopenia before surgery. The relationship between perioperative osteosarcopenia and clinicopathological factors and prognosis was analyzed. The median overall survival (OS) and disease-free survival (DFS) of patients with osteosarcopenia were significantly shorter than those of patients without osteosarcopenia (OS: 23 and 48 months, respectively, P < 0.001; DFS: 13.4 and 21.2 months, respectively, P = 0.004). On multivariate analysis, osteosarcopenia was found to be an independent factor associated with OS (hazard ratio [HR] 1.98; 95% confidence interval [CI] 1.40-2.80; P < 0.001) and DFS (HR 1.53; 95% CI 1.11-2.10; P = 0.009). Preoperative osteosarcopenia may be a useful prognostic factor in patients with PDAC who undergo surgical resection. Further studies are needed to assess whether perioperative, nutritional interventions and rehabilitation contribute to improving the prognosis of these patients.


Relationship between shift assignments, organizational justice, and turnover intention: A cross-sectional survey of Japanese shift-work nurses in hospitals.
Shift management and planning processes for shift-working nurses are important for their continued work. This study aimed to determine the association between shift assignments, organizational justice, and their interaction with turnover intention among shift-work nurses. This cross-sectional study used an online questionnaire administered to Japanese nurses between January and February 2020. Enquiries pertaining to their daily start and end times for each shift type, the shift assignments, organizational justice, and their turnover intention were made. To examine the association with turnover intention, logistic regression analysis was performed with shift assignments, organizational justice, and their interaction terms as independent variables. A total of 386 nurses participated in the final analysis. Of these, 161 nurses (41.7%) had turnover intention. Unequal work assignments and procedural justice were significantly associated with turnover intention. However, the interaction between these factors was not significant. The results suggest that procedural justice in the workplace and turnover intention are related, but in shift planning, even procedural justice cannot buffer unequal work from leading to turnover intention. This study provides valuable insights for nursing managers who manage the schedules of shift-working nurses.


Encouraging microRNA-based Therapeutic Strategies for Hepatocellular Carcinoma.
Hepatocellular carcinoma (HCC) is one of the most common and rapidly fatal malignancies worldwide with poor prognosis. Most of the HCC patients died quickly because of the rapid tumor progression with no effective therapy except for liver resection or transplantation. Recently, microRNAs (miRNAs) have emerged as key factors involved in a series of biological processes ranging from embryogenesis to programmed cell death with aberrant expression profiles, potentially attractive diagnosis, prognosis or therapeutic applications for related-diseases. Accumulating evidences have indicated the roles of miRNAs as tumor suppressor in hepatocyte malignant transformation including development, differentiation, proliferation and tumorigenesis. This article reviews that the recent progress underlies the development of novel miRNA-based HCC therapeutic strategies in the coming future.


"Snooping" as a Distinct Parental Monitoring Strategy: Comparisons With Overt Solicitation and Control.
Parents can use solicitation (asking questions) and control (disclosure rules) to obtain information about adolescents, but only if youths comply. Snooping might uncover additional information, but also strongly violates privacy expectations. Three studies of parents and adolescents examined distinctions between snooping, solicitation, and control. Differences existed in terms of factor structure and frequency (Studies 1-2), links to perceived invasion (Study 1), correlations with problematic communication, behavior, and relationships (Study 2), and parent-adolescent (dis)agreement about acceptability (Study 3). Snooping is a relatively infrequent monitoring behavior, compared to solicitation and control, but appears to be a stronger indicator of problems in adolescent and family functioning. We discuss implications regarding the necessity and appropriateness of particular parental monitoring behaviors.


CAD-Based Virtual Humans : Design and Safety Assessment of MRI Coils.
Magnetic resonance imaging (MRI) is a ubiquitous tool used in clinical settings around the world to provide detailed three-dimensional information on the internal anatomy and physiology of human patients without the use of ionizing radiation, which is the primary safety concern associated with computed tomography. This information is obtained noninvasively and can be used in the diagnosis of pathological conditions as well as the monitoring of treatments.


Drug use among a sample of males admitted to an alcohol detoxication center.
Urine samples were obtained from 93% of a sample of 111 consecutive male admissions to a nonmedical detoxication center in Toronto. Analysis of these samples revealed that 51 (50%) had traces of drugs other than alcohol and that 12 (12%) were alcohol free. Benzodiazepines were the most frequently detected drugs and these were found in 32% of all samples. Barbiturates were detected in seven (7%) samples and cannabinoids in 10 (10%) samples. A wide range of urine alcohol concentrations was found and some samples had zero or low concentrations. Although alcohol urine concentrations were generally lower in samples containing other drugs, the distribution of urine alcohol concentrations was similar for samples containing only alcohol and those containing alcohol and some other drug. Of the 51 samples found to contain drugs other than alcohol, subjects' self-reports were concordant in 27 cases (53%). Most of the discrepancies between self-reports and urine analysis were due to the under-reporting of the use of benzodiazepines. Subjects with drugs in their urine tended to be younger than others, but they were not distinguished with respect to their behaviors while in the detoxication center or length of stay. Those with the highest urine alcohol concentrations had shorter stays in the detoxication center. Implications for further studies are discussed.


Nocardia farcinica spinal osteomyelitis.
A case of disseminated Nocardia farcinica infection with spine involvement is reported. To describe the first case of Nocardia farcinica spinal osteomyelitis, and to propose spine instrumentation with debridement and multiple antibiotics for treatment of nocardia spinal osteomyelitis. Only 11 cases involving Nocardia asteroides spinal osteomyelitis have been reported over the past 40 years. These case reports describe various presentations and treatments of nocardia spinal osteomyelitis. A 54-year-old nonambulant, paraparetic man was admitted to the authors' hospital with acutely increased low back pain, fever, and signs of dementia. A disseminated Nocardia farcinica infection including spinal osteomyelitis at T11, T12, L1, L2, and L4; epidural abscess T10-L4, L5-S1 discitis, empyemas, cerebral abscess, and bilateral psoas abscess was noted. Antibiotic therapy, multiple debridements, and posterior instrumentation were performed to palliate the Nocardia farcinica infection. At a recent 3-year follow-up assessment, the patient was independent and ambulant. He had been off antibiotics for 5 months. Previous case reports of nocardia spinal osteomyelitis describe treatment with antibiotics, debridements, and arthrodesis with autologous bone graft. Prolonged recumbency ensued. In the reported case, a combination of antibiotics, debridements, arthrodesis, and posterior instrumentation for immediate stabilization of the spine resulted in a favorable outcome at 3 years.


Metal free, one pot 1,6-Conjugate Addition of Diol on para-Quinone Methide followed by ipso cyclization: An Approach to Spiro 1,4-Dioxane cyclohexadienone Derivatives.
A novel one-pot transition metal-free and Brönsted acid mediated 1,6-conjugate addition of bisnuleophilic diol on biselectrophilc para-quinone methide followed by ipso cyclization assisted by NBS has been developed under mild reaction conditions, offers a new approach to synthesize spiro 1,4-dioxane cyclohexadienone derivatives. This strategy features broad substrate scope of p-QMs with high functional group tolerance and good yields of spirocyclic scaffolds (60-92 %). N-Bromo succinimide an important role in an ipso spirocyclization with high efficiency.


[Specific function of STAT5 in regulation of proliferation of chronic leukemia K562 cells: inhibitory effect of WHI-P131].
In this study, we examined the possible role of JAK/STAT signaling pathway in regulation of proliferation of chronic leukemia cells K562. The thyrosine phosphorylation of STAT3 and STAT5 was used as a marker of an activation status of STAT proteins. We demonstrate that in growing culture of K562 both STAT3 and STAT5 are constitutively activated. To determine the significance of STATs activity in maintaining the high level of K562 proliferation we tested two JAK inhibitors: AG-490 (JAK2 and JAK3 inhibitor) and WHI-P131 (a new specific JAK3 inhibitor). We showed that in long-tern cultures (48 h) of K562 cells with AG-490 or WHI-P132 the cells remain viable. It was found that treatment with WHI-P131 (30-100 microM) decreased the thyrosine phosphorylation of STAT5 being without effect on the high level of STAT3 phosphorylation. In proliferating K562 cells, AG-490 (25-50 microM) did not influence STAT3 and STAT5 phosphorylation. The flow cytometry analysis revealed a dose-dependent decrease in G1 and S phases and an increase in G2/M phases in WHI-P131-treated K562 cell cultures and no changes in cell cycle structure in AG-490-treated cells. Thus, our findings indicate a preferential role for STAT5 (not constitutively active STAT3) in proliferation of leukemia to other JAK drugs which stimulate apoptosis and decrease proliferation, WHI-P131 prevents K562 cells growth by arresting in G2/M phases of cell cycle.


Coupling instantaneous energy-budget models and behavioural mode analysis to estimate optimal foraging strategy: an example with wandering albatrosses.
How foragers move across the landscape to search for resources and obtain energy is a central issue in ecology. Direct energetic quantification of animal movements allows for testing optimal foraging theory predictions which assumes that animals forage so as to maximise net energy gain. Thanks to biologging advances, we coupled instantaneous energy-budget models and behavioural mode analysis to test optimal foraging theory predictions on wandering albatross Diomedea exulans during the brooding period. Specifically, the instantaneous energy-budget model considered the energetic balance (i.e., the difference between empirical energy gain data and modelled energy expenditure via heart rate values) along the trajectory of a given individual. Four stereotypic instantaneous behavioural modes were identified based on trajectory properties (e.g., speed and turning angle) by applying a new algorithm called Expectation Maximization Binary Clustering. Previous studies on this species have shown that foraging-in-flight is the optimal foraging strategy during the incubation period when albatrosses undertake long-distance movements but no specific foraging strategy has been determined for shorter foraging movements (e.g., brooding period). The output of our energy-budget model (measured as net energy gain) highlighted the potential optimality of alternative search strategies (e.g., sit-and-wait) during brooding, when birds may be subjected to specific energetic trade-offs and have to adapt their foraging strategies accordingly. However, not all birds showed this pattern, revealing the importance of considering individual variability in foraging strategies, as well as any switching among strategies, before drawing population-level generalizations. Finally, our study unveils the importance of considering fine scale activities to make realistic estimates of trip energy expenditure for flying birds at sea. The up-scaling of accurately measured fine-scale energy patterns is essential to quantify energy balances, and their fluctuations by season of different activities among individuals or populations. In particular, we offer new insights for the energetic quantification of the effect of changing oceanic winds on the biology of pelagic predators in the southern oceans.


Vascular and transsynovial forces of the isolated stationary equine joint.
To provide quantitative assessment of forces affecting filtration of synovial fluid in response to incremental changes in arterial and venous hemodynamics. 7 clinically normal adult horses. Using a stationary, isolated metacarpophalangeal joint preparation, blood flow (Qa[cir]), tissue perfusion, arterial pressure (Pa[cir]), venous pressure (Pv[cir]), transsynovial fluid flow, total vascular resistance, vascular compliance, and tissue compliance were evaluated before and after arterial and venous pressure manipulations. At isogravimetric conditions, pre- and postcapillary resistance and ratios, osmotic reflection coefficient (sigma[d]), capillary pressure, net filtration pressure, and transitional microvascular pressure were determined. Synovial tissue blood flow was similar before, immediately after, and 3.5 hours after joint isolation. The sigma(d) for the joint was low, owing to the high oncotic pressure of synovial fluid at filtration-independent states. Transsynovial flow occurred in preference to lymph flow because of the high permeability of synovial tissue (low sigma[d]). Synovial fluid production and transfluid flow (synovium weight gain) increased at Pa(cir) > 200 mm of Hg, indicating a threshold phenomenon for synovial filtration. Net filtration pressure > 6 mm of Hg is needed to effect an increase in synovial fluid flow, and pressure of approximately 11 mm of Hg is necessary to increase lymphatic flow. Vascular compliance in the joint was low, but increased markedly with Pv(cir). Vascular and tissue compliance increased with increased Pa(cir). Vascular compliance changes caused by increased arterial pressure were minimal, compared with those caused by increased venous pressure owing to the greater elastance of arteries and the larger muscular arterial wall. This isolated joint preparation permitted evaluation of codependent hemodynamic, microvascular, and transsynovial flow responses to hemodynamic manipulations. Synovial tissue permeability was markedly affected by increased vascular forces altering filtration pressures toward synovial fluid production.


Effect of Montmorillonite Nanogel Composite Fillers on the Protection Performance of Epoxy Coatings on Steel Pipelines.
Montmorillonite (MMT) clay mineral is widely used as filler for several organic coatings. Its activity is increased by exfoliation via chemical modification to produce nanomaterials. In the present work, the modification of MMT to form nanogel composites is proposed to increase the dispersion of MMT into epoxy matrices used to fill cracks and holes produced by the curing exotherms of epoxy resins. The dispersion of MMT in epoxy improved both the mechanical and anti-corrosion performance of epoxy coatings in aggressive marine environments. In this respect, the MMT surfaces were chemically modified with different types of 2-acrylamido-2-methyl propane sulfonic acid (AMPS) nanogels using a surfactant-free dispersion polymerization technique. The effect of the chemical structure, nanogel content and the interaction with MMT surfaces on the surface morphology, surface charges and dispersion in the epoxy matrix were investigated for use as nano-filler for epoxy coatings. The modified MMT nanogel epoxy composites showed excellent resistance to mechanical damage and salt spray resistance up to 1000 h. The interaction of MMT nanogel composites with the epoxy matrix and good response of AMPS nanogel to sea water improve their ability to act as self-healing materials for epoxy coatings for steel.


Molecular typing of HLA-E.
Human leukocyte antigen-E (HLA-E) is a non-classical HLA class I gene that shows a limited degree of polymorphism compared to the classical HLA genes. The HLA-E molecule can bind peptides derived from the leader sequence of various HLA class I alleles and some viral homologues, including CMV. The HLA-E peptide complex can act as a ligand for the CD94/NKG2 receptors expressed on the surface of natural killer cells and T cell subsets. Differences in expression levels between the different HLA-E alleles have been reported and a role for HLA-E polymorphism in stem cell transplantation has been postulated. This chapter focuses on routine technologies for HLA-E typing: the sequence-specific primer-PCR method that uses sequence-specific primers, the PCR sequence-specific oligonucleotides Luminex method, using sequence-specific probes attached to beads and the sequencing-based typing method, where sequencing of the alleles is performed.


[Fifth-line chemotherapy for metastatic gastric cancer--a case responding to modified FOLFOX 6].
According to the National Comprehensive Cancer Network (NCCN) clinical practice guideline for gastric cancer (2006, the first edition), 5-FU/Leucovorin (LV), 5-FU-based, cisplatin (CDDP)-based, oxaliplatin (L-OHP)-based, taxane-based, and irinotecan (CPT-11)-based, ECF are recommended. We used modified FOLFOX 6 (mFOLFOX 6) for pretreatment, that is oxaliplatin-based chemotherapy, for a patient who had received 5-FU-based, CDDPbased, taxane-based, and CPT-11-based treatment for an unresectable gastric cancer case responding to mFOLFOX 6. A 73-year-old male admitted to our hospital for treatment of advanced gastric cancer was diagnosed to be inoperable. A combination chemotherapy docetaxel and CDDP and S-1 as first-line treatment, CPT-11 and CDDP as second-line treatment, weekly paclitaxel treatment as third-line treatment, and MTX and 5-FU as fourth-line treatment were performed. He had progressed after 5-FU-based, CDDP-based, taxane-based, and CPT-11-based chemotherapy. There are no effective approved drugs for gastric cancer in Japan. Oxaliplatin was reportedly effective for metastatic gastric cancer, but it is still non-approved in Japan. After receiving an explanation of oxaliplatin-based therapy, he gave informed consent. Oxaliplatin-based therapy for this patient was then evaluated and approved under an institutional review board of Higashi Sapporo Hospital. mFOLFOX 6 used for the oxaliplatin-based therapy. After 2 courses of mFOLFOX 6, he showed a partial response. Oxaliplatin-based treatment was thought to be promising for previously CDDP-treated patients with unresectable gastric cancers.


Divergent regulation of gonadotropin subunit mRNA levels by androgens in the female rat.
To examine the effects of gonadal steroids on the pretranslational regulation of the gonadotropin subunits in the female, adult female rats, beginning 7 or 28 days after ovariectomy, received daily injections of testosterone propionate (T), dihydrotestosterone propionate (D), or estradiol benzoate (E) for 7 days. Intact cycling females and ovariectomized rats that received vehicle served as controls. Serum was obtained for LH and FSH levels to assess changes in gonadotropin secretion. Total RNA from individual rats was recovered and analyzed by blot hybridization with specific radiolabeled cDNA probes for the alpha, LH beta, and FSH beta subunits. Autoradiographic bands were quantitated and standardized to mRNA levels in the intact animals. Ovariectomy resulted in a rise in serum gonadotropin levels and all three gonadotropin subunit mRNA levels. Estrogen replacement resulted in suppression of alpha, LH beta, and FSH beta mRNAs whether given at 7 or 28 days after ovariectomy. In contrast, whereas androgen replacement decreased alpha and LH beta mRNAs, D or T did not consistently suppress FSH beta mRNAs. We conclude that chronic estrogen administration to the castrated female rat uniformly suppresses all three gonadotropin subunit mRNA levels. In female rats, as in male rats, chronic androgen administration fails to negatively regulate FSH beta mRNAs.


Revealing the Penumbra through Imaging Elemental Markers of Cellular Metabolism in an Ischemic Stroke Model.
Stroke exacts a heavy financial and economic burden, is a leading cause of death, and is the leading cause of long-term disability in those who survive. The penumbra surrounds the ischemic core of the stroke lesion and is composed of cells that are stressed and vulnerable to death, which is due to an altered metabolic, oxidative, and ionic environment within the penumbra. Without therapeutic intervention, many cells within the penumbra will die and become part of the growing infarct, however, there is hope that appropriate therapies may allow potential recovery of cells within this tissue region, or at least slow the rate of cell death, therefore, slowing the spread of the ischemic infarct and minimizing the extent of tissue damage. As such, preserving the penumbra to promote functional brain recovery is a central goal in stroke research. While identification of the ischemic infarct, and the infarct/penumbra boundary is relatively trivial using classical histology and microscopy techniques, accurately assessing the penetration of the penumbra zone into undamaged brain tissue, and evaluating the magnitude of chemical alterations in the penumbra, has long been a major challenge to the stroke research field. In this study, we have used synchrotron-based X-ray fluorescence imaging to visualize the elemental changes in undamaged, penumbra, and infarct brain tissue, following ischemic stroke. We have employed a Gaussian mixture model to cluster tissue areas based on their elemental characteristics. The method separates the core of the infarct from healthy tissue, and also demarcates discrete regions encircling the infarct. These regions of interest can be combined with elemental and metabolic data, as well as with conventional histology. The cell populations defined by clustering provide a reproducible means of visualizing the size and extent of the penumbra at the level of the single cell and provide a critically needed tool to track changes in elemental status and penumbra size.


Functional Smiles: Tools for Love, Sympathy, and War.
A smile is the most frequent facial expression, but not all smiles are equal. A social-functional account holds that smiles of reward, affiliation, and dominance serve basic social functions, including rewarding behavior, bonding socially, and negotiating hierarchy. Here, we characterize the facial-expression patterns associated with these three types of smiles. Specifically, we modeled the facial expressions using a data-driven approach and showed that reward smiles are symmetrical and accompanied by eyebrow raising, affiliative smiles involve lip pressing, and dominance smiles are asymmetrical and contain nose wrinkling and upper-lip raising. A Bayesian-classifier analysis and a detection task revealed that the three smile types are highly distinct. Finally, social judgments made by a separate participant group showed that the different smile types convey different social messages. Our results provide the first detailed description of the physical form and social messages conveyed by these three types of functional smiles and document the versatility of these facial expressions.


Microbial Screening Based on the Mizoroki-Heck Reaction Permits Exploration of Hydroxyhexylitaconic-Acid-Producing Fungi in Soils.
Recently, we developed a unique microbial screening method based on the Mizoroki-Heck reaction for itaconic acid (IA)-producing fungi. This method revealed that 37 out of 240 fungal strains isolated from soils produce vinyl compounds, including IA. In this study, we further characterized these compounds in order to verify that the screening method permits the isolation of fungi that produce other vinyl compounds, excluding IA. HPLC analysis showed that 11 out of 37 isolated strains produced IA, similar to Aspergillus terreus S12-1. Surprisingly, the other 8 isolated strains produced two vinyl compounds with HPLC retention times different from that of IA. From these strains, the vinyl compounds of Aspergillus niger S17-5 were characterized. Mass spectrometric and NMR analyses showed that they were identical to 8-hydroxyhexylitaconic acid (8-HHIA) and 9-HHIA. This finding showed that 8-HHIA- and 9-HHIA-producing fungi, as well as IA-producing fungi, are ubiquitously found in soils. Neither 8-HHIA nor 9-HHIA showed antibacterial or anti-inflammatory activities. Interestingly, 8-HHIA and 9-HHIA showed cytotoxicity against the human cervical cancer cell line (HeLa) and human diploid cell line (MRC-5), and MRC-5 only, respectively, compared to IA at the same concentration. This study indicates that the screening method could easily discover fungi producing 8-HHIA and 9-HHIA in soils.


Comparison of bone mineral density with dual energy x-ray absorptiometry, quantitative ultrasound and single energy x-ray absorptiometry.
We conducted this prospective study to establish the correlation between dual energy x-ray absorptiometry (DXA), quantitative ultrasound (QUS) and single energy x-ray absorptiometry (SXA) and to establish the role of QUS and SXA as a screening tool for osteoporosis. We carried out measurements of bone mineral density (BMD) of lumbar spine and femoral neck using DXA, QUS of heel using ultrasound densitometer, and BMD of forearm using SXA. We performed all the measurements at the Nuclear Medicine Division of King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia between 2002 and 2004. We obtained the measurements of 437 female adult patients, aged 20-87 years. We expressed all the values as mean +/- SD. The BMD (g/cm2) of lumbar spine was 1 +/- 0.18, and femoral neck was 0.88 +/- 0.17. The broad band ultrasound attenuation (BUA) of the heel was 74.9 +/- 39.1 dB/MHz, the speed of sound (SOS) was 1542.5 +/- 81.4 m/s, and the estimated BMD was 0.52 +/- 0.15 (g/cm2). The BMD of forearm showed a value of 0.44 +/- 0.10 g/cm2. The best correlation was between absolute values of BMD of lumbar spine and femoral neck (r=0.71, p=0.000). The correlation between BMD of lumbar spine, QUS heel and forearm BMD was significant, but low to moderate (r=0.43-0.64, p=0.000). A strong correlation existed between the various parameters of heel, namely, BUA, SOS and estimated BMD (r=0.85-0.96, p=0.000). We used the World Health Organization (WHO) criterion of T-score to diagnose the patients with osteoporosis or osteopenia with each modality. We diagnosed a maximum number of patients to have osteoporosis with BMD estimation of lumbar spine (31%), followed by femoral neck (14%), forearm (11%), and heel (6%). The correlation between all modalities was significant, but varied from high to low. It was high between lumbar spine and femoral neck, moderate between lumbar spine and forearm and low between lumbar spine and QUS of heel. When we used the same WHO criterion of T-score (more than -2.5 SD below normal), QUS detected significantly less numbers with osteoporosis. We conclude that with the present cut-off of T-score, the QUS may not be used as a screening tool. It may need some modification of T-score. However, we need larger multi-center studies with a larger number of patients for further validation.


Association of Waist-to-Height Ratio, Metabolic Syndrome, and Carotid Atherosclerosis in Individuals with a High Risk of Stroke: A Cross-Sectional Study of 9605 Study Participants.
Background: To determine the association of waist-to-height ratio (WHtR), metabolic syndrome (MetS), and carotid atherosclerosis (CAS) in individuals with a high risk of stroke. Methods: We performed a cross-sectional analysis of 9605 study responders from eight urban area communities in Northern China. Height, weight, waist circumference, blood pressure (BP), and blood lipid were measured. Information of population characteristics, smoking status, alcohol consumption, physical activity, and diet were determined by validated questionnaire. Results: A total of 9605 study responders were included in this study. The average age was 60 ± 9 years with 5911 (61.5%) patients being females. The prevalence of MetS and CAS was 26.2% and 75.1%, respectively. WHtR was significantly associated with CAS using our final adjusted model [odds ratio (OR): 1.233, 95% confidence interval (CI): 1.096-1.378]. The association of CAS with hypertension and hyperglycemia were statistically significant among factors that constitute MetS. Additional risk factors affecting the development of CAS included age, previous stroke, and smoking history (P < 0.05). Conclusion: WHtR was determined to perform better compared with other traditional indicators for correlating CAS. We believe that WHtR is a better indicator for the early identification of CAS in individuals with a high risk of stroke. This will facilitate the early detection and intervention of CAS.


Metastatic angiosarcoma of the spleen. A case report and treatment approach.
We report a case of a 28-year-old man with angiosarcoma of the spleen and liver metastases. The aim of this paper is to underline the importance of planned splenectomy in these patients even if they have metastatic disease, and to propose an intensive chemotherapy regimen consisting of anthracyclines, ifosfamide and mesna with G-CSF support.


Diverse contributions of MYC2 and EIN3 in the regulation of Arabidopsis jasmonate-responsive gene expression.
Derepression of transcription factors is the key mechanism for triggering plant jasmonate (JA) responses. Unlike regulating certain physiological functions for the majority of transcription factors in JA signaling, MYC2 and EIN3 control more diverse aspects. MYC2 predominantly participates in wounding response, metabolism, and root growth inhibition, while EIN3 (and its closest homolog EIL1) regulates defense gene expression and root hair development. Recently, it was reported that MYC2 and EIN3/EIL1 proteins mutually interact with each other and suppress their interaction partner's transcriptional activities. To understand their contributions in the modulation of transcriptomic network, we initially identified 1,495 differentially expressed jasmonate (JA)-responsive genes in wild-type Arabidopsis through RNA-seq analysis. Among them, 25% or 4.2% were independently regulated by EIN3/EIL1 or MYC2, respectively. Further analysis showed that EIN3/EIL1 and MYC2 interdependently regulate 16.3% of the JA-regulated transcriptome, including downregulation of three auxin-related genes, which might confer JA-inhibited root elongation. Lastly, we found that <30 genes were antagonistically regulated by MYC2 and EIN3/EIL1. We conclude that EIN3/EIL1 play a dominant role while MYC2 largely relies on EIN3/EIL1 for executing its transcriptional activity, either synergistically or antagonistically.


Comparison of two-stage open versus percutaneous pedicle screw fixation in treating pyogenic spondylodiscitis.
Percutaneous pedicle screw instrumentation is a minimally invasive surgical technique; however, the effects of using percutaneous pedicle screw fixation in treating patients with spinal infections have not yet been well demonstrated. The aim of this study, therefore, was to determine whether percutaneous posterior pedicle screw instrumentation is superior to the traditional open approach in treating pyogenic spondylodiscitis. We retrospectively reviewed data for 45 patients treated for pyogenic spondylodiscitis with anterior debridement and interbody fusion followed by a second-stage procedure involving either traditional open posterior pedicle screw fixation or percutaneous posterior pedicle screw fixation. Twenty patients underwent percutaneous fixation and 25 patients underwent open fixation. Demographic, operative, and perioperative data were collected and analyzed. The average operative time for the percutaneous procedure was 102.5 minutes, while the average time for the open procedure was 129 minutes. The average blood loss for the percutaneous patients was 89 ml versus a 344.8 ml average for the patients in the open group. Patients who underwent the minimally invasive surgery had lower visual analogue scale scores and required significantly less analgesia afterwards. After two years of follow-up, neither recurrent infection nor intraoperative complications, such as wound infection or screw loosening, were found in the percutaneous group. Moreover, there was no significant difference in outcome between the two groups in terms of Oswestry Disability Index scores. Anterior debridement and interbody fusion with bone grafting followed by minimally invasive percutaneous posterior instrumentation is an alternative treatment for pyogenic spondylodiscitis which can result in less intraoperative blood loss, shorter operative time, and reduced postoperative pain with no adverse effect on infection control.


Virulence and antibiotic resistance genes in Campylobacter spp. in the Czech Republic.
Thermotolerant species of the genus Campy-lobacter are the important agents causing human foodborne infections throughout the world. The aims of this study were to evaluate the presence of nine putative virulence genes in Campylobacter spp. isolated from patients and from foods (poultry meat, pork liver), to determine the resistance of Campylobacter isolates to eight antibiotic agents and to detect four resistance genes.Matherial and methods: The presence of the virulence genes cdtA, cdtB, cdtC, virB11, ciaB, wlaN, iam, dnaJ and racR was detected by polymerase chain reaction (PCR) in 94 Campylobacter spp. isolates from humans and 123 campylobacters from foods. The phenotypic resistance to selected antimicrobial agents was tested with microdilution method in 82 human isolates and 91 food isolates. The isolates with antibiograms were tested for the presence of blaOXA-61, tet(O), aph-3-1 and cmeB genes by PCR with specific primers. In both human and food C. jejuni isolates the preva-lence of the studied virulence genes, especially dnaJ, racR, ciaB genes and the toxigenic genes cdtA, cdtB, cdtC, was considerably higher than in C. coli isolates. The only exception was the iam gene identified in only C. coli. The tested isolates of both C. jejuni and C. coli were highly resistant to quinolone antibiotics. Additionally, C. coli was also more resistant to erythromycin, streptomycin and, in case of isolates from pork liver, to tetracycline. High prevalence rates of genes encoding antibiotic resistance was noted for the blaOXA-61 and tet(O) genes in both Campylobacter species. The presented study is the first to assess the presence of genes for virulence and resistance to antibiotics in thermotolerant Campylobacter spp. isolated from humans and foods in the Czech Republic. The resistance of Campylobacter isolates to eight antibiotic agents was also assessed. The prevalence of genes responsible for virulence and resistance is rather varied in thermotolerant Campylobacter spp.


Distinct focal adhesion protein modules control different aspects of mechanotransduction.
Focal adhesions (FAs) are macromolecular complexes that regulate cell adhesion and mechanotransduction. By performing fluorescence recovery after photobleaching (FRAP) and fluorescence loss after photoactivation (FLAP) experiments, we found that the mobility of core FA proteins correlates with their function. Structural proteins such as tensin, talin and vinculin are significantly less mobile in FAs than signaling proteins such as FAK (also known as PTK2) and paxillin. The mobilities of the structural proteins are directly influenced by substrate stiffness, suggesting that they are involved in sensing the rigidity of the extracellular environment. The turnover rates of FAK and paxillin, as well as kindlin2 (also known as FERMT2), are not influenced by substrate stiffness. By using specific Src and FAK inhibitors, we reveal that force-sensing by vinculin occurs independently of FAK and paxillin phosphorylation. However, their phosphorylation is required for downstream Rac1-driven cellular processes, such as protrusion and cell migration. Overall, we show that the FA is composed of different functional modules that separately control mechanosensing and the cellular mechano-response.


A placebo-controlled study of high dose buprenorphine in opiate dependents waiting for medication-assisted rehabilitation in Oslo, Norway.
To evaluate whether buprenorphine. even without additional control and psychosocial treatment and support, alleviates the problems faced by patients waiting for medication assisted rehabilitation (MAR). A randomized, double-blind, 12-week study of Subutex versus placebo without additional support as an interim therapy. One hundred and six patients, 70 males and 36 females, waiting for MAR in Oslo. The average age was 38 years with an average history of heroin use of 20 years. Fifty-five patients were assigned to buprenorphine and 51 to a placebo. Subutex or placebo sublingual tablets were given under supervision in a daily dose of 16 mg with the exception of a double dose on Saturday and no dose on Sunday. Retention, compliance, self-reported drug-abuse, wellbeing and mental health. The average number of days of participation was significantly higher in the buprenorphine group, 42 (median: 29) compared to 14 (median: 11) for the placebo group (P < 0.001). The retention of patients after 12 weeks was 16 patients in the buprenorphine group and one patient in the placebo group. The buprenorphine group had a larger decrease in reported opioid use (p < 0.001) and in reported use of other drugs, tablets and alcohol abuse (p < 0.01). The group also showed a stronger increase in wellbeing (p < 0.01) and life satisfaction (p < 0.05). None of the participants died. The patients waiting for MAR benefited significantly from the buprenorphine as an interim therapy according to retention, self-reported use of drugs and wellbeing. However, the patients had difficulties in remaining in treatment over time without psychosocial support.


Diagnostic criteria for the classification of cancer-associated weight loss.
Existing definitions of clinically important weight loss (WL) in patients with cancer are unclear and heterogeneous and do not consider current trends toward obesity. Canadian and European patients with cancer (n = 8,160) formed a population-based data set. Body mass index (BMI) and percent WL (%WL) were recorded, and patients were observed prospectively until death. Data were entered into a multivariable analysis controlling for age, sex, cancer site, stage, and performance status. Relationships for BMI and %WL to overall survival were examined to develop a grading system. Mean overall %WL was -9.7% ± 8.4% and BMI was 24.4 ± 5.1 kg/m(2), and both %WL and BMI independently predicted survival (P < .01). Differences in survival were observed across five categories of BMI (< 20.0, 20.0 to 21.9, 22.0 to 24.9, 25.0 to 27.9, and ≥ 28.0 kg/m(2); P < .001) and five categories of %WL (-2.5% to -5.9%, -6.0% to -10.9%, -11.0% to -14.9%, ≥ -15.0%, and weight stable (± 2.4%); P < .001). A 5 × 5 matrix representing the five %WL categories within each of the five BMI categories was graded based on median survival and prognostic significance. Weight-stable patients with BMI ≥ 25.0 kg/m(2) (grade 0) had the longest survival (20.9 months; 95% CI, 17.9 to 23.9 months), and %WL values associated with lowered categories of BMI were related to shorter survival (P < .001), as follows: grade 1, 14.6 months (95% CI, 12.9 to 16.2 months); grade 2, 10.8 months (95% CI, 9.7 to 11.9 months); grade 3, 7.6 months (95% CI, 7.0 to 8.2 months); and grade 4, 4.3 months (95% CI, 4.1 to 4.6 months). Survival discrimination by grade was observed within specific cancers, stages, ages, and performance status and in an independent validation sample (n = 2,963). A robust grading system incorporating the independent prognostic significance of both BMI and %WL was developed.


Curve matching to predict growth in patients receiving growth hormone therapy: An interpretable & explainable method.
Curve matching may be used to predict growth outcomes using data of patients whose growth curves resemble those of a new patient with growth hormone deficiency (GHD) and those born small for gestational age (SGA). We aimed to investigate the validity of curve matching to predict growth in patients with GHD and those born SGA receiving recombinant human growth hormone (r-hGH). Height data collected between 0-48 months of treatment were extracted from the easypod™ connect ecosystem and the easypod™ connect observational study. Selected patients with height standard deviation scores (HSDS) [-4, <-1] and age [3, <16y] at start were included. The 'Matching Database' consisted of patients' monthly HSDS obtained by the broken stick method and imputation. Standard deviation (SD) was obtained from the observed minus the predicted HSDS (error) based on matched patients within the 'Matching Database'. Data were available for 3,213 patients in the 'Matching Database', and 2,472 patients with 16,624 HSDS measurements in the observed database. When ≥2 HSDS measurements were available, the error SD for a one-year prediction was approximately 0.2, which corresponds to 1.1 cm, 1.3 cm, and 1.5 cm at 7, 11, and 15 years of age, respectively. Indication and age at treatment start (<11 vs ≥11 years) had a small impact on the error SD, with patients born SGA and patients aged <11 years at treatment start generally having slightly lower values. We conclude that curve matching is a simple and valid technique for predicting growth in patients with GHD and those born SGA.


[Purpura fulminans: a rare complication of chickenpox].
A 3.5-year-old boy presented with purpura on the buttocks extending towards both legs. Two weeks earlier, he had had chickenpox. Because of the rapidly progressing purpura with clinical signs of hypovolaemic shock, he was treated with fresh frozen plasma, packed red blood cells, intravenous immunoglobulins, prednisolone, acyclovir and ceftriaxone. The purpura stopped spreading. In the next few days, the skin at the site of the purpura became necrotic and was excised, as was the subcutis and part of the fascia on both legs and flanks. The right lower leg was amputated and a temporary colostomy was created to prevent faecal contamination of the wounds. The patient recovered and was discharged after three months. Purpura fulminans is a rare complication after a primary infection with varicella zoster virus. A varicella infection may lead to protein S deficiency resulting in diffuse intravascular coagulation and severe skin defects.


Enhancing the Performance of Perovskite Solar Cells by Introducing 4-(Trifluoromethyl)-1H-imidazole Passivation Agents.
Defects in perovskite films are one of the main factors that affect the efficiency and stability of halide perovskite solar cells (PSCs). Uncoordinated ions (such as Pb2+, I-) act as trap states, causing the undesirable non-radiative recombination of photogenerated carriers. The formation of Lewis acid-base adducts in perovskite directly involves the crystallization process, which can effectively passivate defects. In this work, 4-(trifluoromethyl)-1H-imidazole (THI) was introduced into the perovskite precursor solution as a passivation agent. THI is a typical amphoteric compound that exhibits a strong Lewis base property due to its lone pair electrons. It coordinates with Lewis acid Pb2+, leading to the reduction in defect density and increase in crystallinity of perovskite films. Finally, the power conversion efficiency (PCE) of PSC increased from 16.49% to 18.97% due to the simultaneous enhancement of open-circuit voltage (VOC), short circuit current density (JSC) and fill factor (FF). After 30 days of storage, the PCE of the 0.16 THI PSC was maintained at 61.9% of its initial value, which was 44.3% for the control device. The working mechanism of THI was investigated. This work provides an attractive alternative method to passivate the defects in perovskite.


Role of ATP sensitive potassium channel in extracellular potassium accumulation and cardiac arrhythmias during myocardial ischaemia.
Extracellular potassium rises rapidly during myocardial ischaemia, correlating with the onset of ventricular arrhythmias. The extracellular accumulation of potassium can induce abnormalities in both impulse conduction and impulse generation. Inhomogeneities of potassium conductance will elicit regional differences in action potential duration and repolarisation. The resulting spatial dispersion of refractory period will allow for fragmentation of impulse conduction on ensuing beats, the formation of irregular reentrant pathways and ventricular fibrillation. In a similar manner, the spread of injury current from the ischaemic tissue to surrounding normal tissue can trigger extrasystoles (depolarisation induced automaticity). It has been hypothesised that the activation of the ATP sensitive potassium channel contributes significantly to reductions in action potential duration and increases in extracellular potassium accumulation during myocardial ischaemia. ATP sensitive potassium channel antagonists prevent ischaemically induced reductions in action potential duration and the dispersion of refractory period but may induce oscillatory afterpotentials under some conditions (for example, calcium overload). In contrast, potassium channel agonists enhance the dispersion of refractory period ischaemia, which promotes the formation of re-entrant arrhythmias. The pharmacological modulation of the ATP sensitive potassium channels could therefore offer a novel approach for the management of cardiac arrhythmias in patients with ischaemic heart disease. In general, channel antagonists prevent ventricular fibrillation, while high (hypotensive) doses of channel agonists can induce malignant arrhythmias during ischaemia in animal models. However, recent evidence also suggests that potassium channel agonists may promote a better preservation of myocardial mechanical performance during reperfusion while ATP sensitive potassium channel antagonists exacerbate mechanical depression during ischaemia in experimental models.(ABSTRACT TRUNCATED AT 250 WORDS)


Lysine Requirements of Healthy Pregnant Women are Higher During Late Stages of Gestation Compared to Early Gestation.
Lysine is the first limiting amino acid in cereal proteins and is found mainly in animal-derived products. Current Dietary Reference Intake (DRI) recommendations extrapolate lysine requirements during pregnancy from nonpregnant adult data, and may underestimate true requirements. Our objective is to define a quantitative lysine requirement in healthy pregnant women and to determine whether requirements vary between 2 phases of gestation. Fourteen pregnant women in early (12-19 wk) and 19 women in late (33-39 wk) gestation were studied using the indicator amino acid oxidation technique. Individual lysine intakes (6-84 mg · kg-1 · d-1, deficient to excess) were tested on each study day as a crystalline amino acid mixture based on egg protein composition. Isonitrogenous diets maintained protein intake at 1.5 g · kg-1 · d-1 and calorie intake at 1.7 times resting energy expenditure during each study day. Phenylalanine and tyrosine intakes were held constant across all lysine intakes. Breath and urine samples were collected at baseline and isotopic steady state. Lysine requirements were determined by measuring the oxidation of L-[1-13C]-phenylalanine to 13CO2 (F13CO2). Biphase linear regression crossover analysis was used to determine a breakpoint (which represents the estimated average requirement, EAR) in F13CO2. The EAR for lysine during early gestation was determined to be 36.6 mg · kg-1 · d-1 (R2 = 0.484, upper 95% CI = 46.2 mg · kg-1 · d-1), similar to an earlier adult requirement of 36 mg · kg-1 · d-1. The EAR for lysine during late gestation was determined to be 50.3 mg · kg-1 · d-1 (R2 = 0.664, upper 95% CI = 60.4 mg · kg-1 · d-1), 23% higher than the current pregnancy DRI EAR recommendation of 41 mg · kg-1 · d-1. Our results suggest that lysine requirements are higher during late gestation compared to early gestation, and that current dietary lysine recommendations during late stages of pregnancy may be underestimated. The results have implications for populations consuming cereal-based diets as their primary source of protein. This trial was registered at clinicaltrials.gov as NCT01776931.


A placebo-controlled trial of flumazenil given by continuous infusion in severe benzodiazepine overdosage.
A controlled trial was performed to study the effect and any adverse reactions of continuously infused flumazenil in severe benzodiazepine overdosage. The study comprised 51 adults admitted to an intensive care unit with poisoning. Enrollment criteria were unconsciousness on admission and a clear response within 5 min after an i.v. bolus injection of 1 mg flumazenil. The level of consciousness was assessed according to a modified Glasgow coma scale immediately before and at defined intervals up to 12 h after injection. A double-blind infusion was started 15 min after the bolus injection and administered for 5 h. The patients were randomly allocated to one of three groups: a group given flumazenil 0.5 mg/h, a group given flumazenil 0.1 mg/h and a placebo group. The groups were comparable in age, sex and toxicological laboratory results. There were no significant differences between the groups in the average coma score on admission or 15 min after the bolus injection. In the flumazenil 0.5 mg/h group the level of consciousness remained unchanged between the 15-min recording and the subsequent assessments. In the two other groups the level of consciousness decreased significantly during the course of the infusion. The infusions were well tolerated. It is concluded that a continuous infusion of 0.5 mg of flumazenil per hour can prevent relapse into coma in patients with severe benzodiazepine poisoning aroused with a single injection of the antagonist.


The use of unallowed excipients.
The laws governing the U.S. Food and Drug Administration (FDA) do not provide for the approval of stand-alone excipients. Current regulations do not permit the use of excipients, but allow their use. The acceptance process for excipients is slow and only recently did the FDA propose draft guidance for nonclinical studies for pharmaceutical excipients. The FDA has made four suggestions to the U.S. Pharmacopoeia concerning including excipient monographs in the National Formulary for excipients not yet allowed. This article reviews these four proposals to identify the proposal that is most appropriate.


Modulation of cytochrome C oxidase-va is possibly involved in metallothionein protection from doxorubicin cardiotoxicity.
Previous studies using a cardiac-specific metallothionein (MT)-overexpressing transgenic (MT-TG) mouse model have demonstrated that MT protects from doxorubicin (DOX)-induced oxidative heart injury. The molecular mechanisms that underlie this cardioprotection, however, have yet to be defined. In the present study, we tested the hypothesis that MT overexpression activates cytoprotective mechanisms, leading to cardiac protection from DOX toxicity. MT-TG mice and nontransgenic wild-type (WT) controls were treated i.p. with DOX at a single dose of 20 mg/kg and sacrificed on the third day after the treatment. An expression proteomic analysis involving two-dimensional gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry was used to identify MT-induced changes in cytoprotection-related proteins. We identified 18 proteins that were modified by DOX treatment in the heart. These proteins included those involved in cellular antioxidant defense, enzymes of the mitochondrial electron transport chain, enzymes involved in beta-oxidation of fatty acids and glycolysis, and proteins involved in regulation of cardiac muscle contraction. However, the most dominant modification by MT is the cytochrome c oxidase subunit Va (CCO-Va). In response to DOX treatment, a specific isoform of CCO-Va was enhanced in the MT-TG but not in the WT mouse hearts. Because CCO-Va is a critical component in the mitochondrial electron transport chain, the results suggest that the cardioprotective effect of MT may be related to an increased expression or a differential modification of CCO-Va.


[Relationship of the kallistatin gene expression with male spermatogenic dysfunction and its possible mechanism].
To explore the role of the kallistatin gene in male spermatogenesis and its possible mechanism, and provide some new ideas for the clinical treatment of spermatogenic dysfunction. We collected semen samples from the patients with oligospermia (OS) or non-obstructive azoospermia (NOAS) as well as testis tissue from testicular puncture. We detected the differential expression of kallistatin in the seminal plasma and the mRNA and protein expression levels of kallistatin, KLK1, B2R, Bcl-2, casepase-3, Bax and other molecules in the testis tissue, assessed the testicular spermatogenic function using Johnsen's scores, examined the interstitial fibrosis in the testis by Masson and Sirius staining, and analyzed the correlation of the expression level of kallistatin with spermatogenesis, apoptosis and fibrosis. Kallistatin was highly expressed in the seminal plasma and testis tissue. The expression of kallistatin was significantly decreased in the seminal plasma (P < 0.05) and so were those of kallistatin, KLK1 and B2R in the testis tissue of the NOAS and OS patients compared with those in the normal controls (P < 0.01), but no statistically significant difference was found between the expression levels of kallistatin and KLK1 within the same group (P > 0.05). The expression of Bcl-2 in the testis tissue was significantly lower (P < 0.01) and those of Bax and Casepase-3 dramatically higher in the OS and NOAS patients than in the normal males (P < 0.01). Cell apoptosis was negatively correlated with the expression of kallistatin. The results of Masson and Sirius staining showed that the fibrosis of the testis tissue and the ratio of type I/III collagen fibers were markedly increased in the OS and NOAS patients in comparison with the normal controls, even more significantly in the NOAS than in the OS group. Decreased expression of kallistatin may be related to spermatogenic dysfunction, and the kallistatin expression plays a regulatory role in the testicular spermatogenesis, probably by regulating cell apoptosis and fibrosis in the testis tissue, but the specific mechanism needs to be confirmed by further studies.


[Private mutations in the myophosphorylase gene: the first case in a patient of Latin American descent].
McArdle's disease (glycogenoses type V) is a common metabolic myopathy caused by deficient myophosphorylase activity. The disease is due to mutations in the myophosphorylase (PYGM) gene and is present in a large number of countries. A 13-year-old male who suffered an episode of muscle pain and offered increased levels of creatinkinase in plasma, myoglobinuria and mild weakness of the proximal muscles, after short but vigorous exercise. The patient was born in Ecuador and was adopted by a Spanish family. The myophosphorylase gene was analysed completely and the patient was found to be a carrier of a missense mutation, a homozygous change where a G is replaced by an A in exon 11, changing a valine for a methionine in codon 456 (V456M). The mutation described above affects an amino acid that is conserved in the enzyme and which was not present in the control population that was studied. These findings show the presence of McArdle's disease in several ethnic groups and confirm that the ethnic origin of the patient is important when it comes to deciding what mutations should be analysed first in molecular diagnosis studies.


Polymeric micelles encapsulating fisetin improve the therapeutic effect in colon cancer.
The natural flavonoid fisetin (3,3',4',7-tetrahydroxyflavone) was discovered to possess antitumor activity, revealing its potential value in future chemotherapy. However, its poor water solubility makes it difficult for intravenous administration. In this study, the monomethyl poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) copolymer was applied to prepare nanoassemblies of fisetin by a self-assembly procedure. The prepared fisetin micelles gained a mean particle size of 22 ± 3 nm, polydisperse index of 0.163 ± 0.032, drug loading of 9.88 ± 0.14%, and encapsulation efficiency of 98.53 ± 0.02%. Compared with free fisetin, fisetin micelles demonstrated a sustained and prolonged in vitro release behavior, as well as enhanced cytotoxicity, cellular uptake, and fisetin-induced apoptosis in CT26 cells. As for in vivo studies, fisetin micelles were more competent for suppressing tumor growth and prolonging survival time than free fisetin in the subcutaneous CT26 tumor model. Furthermore, histological analysis, terminal deoxynucleotidyl transferase-mediated nick-end labeling assay, immunohistochemical detection of Ki-67, and microvessel density detection were conducted, demonstrating that fisetin micelles gained increased tumor apoptosis induction, proliferation suppression, and antiangiogenesis activities. In conclusion, we have successfully produced a MPEG-PCL-based nanocarrier encapsulating fisetin with enhanced antitumor activity.


[Effects of Methionine Restriction on Proliferation, Cell Cycle, and Apoptosis of Human Acute Leukemia Cells].
To investigate the effects of methionine restriction on proliferation, cell cycle and apoptosis of human acute leukemia cells. Cell Counting Kit-8 (CCK-8) assay was used to detect the effect of methionine restriction on HL-60 and Jurkat cells proliferation. The effect of methionine restriction on cell cycle of HL-60 and Jurkat cells was examined by PI staining. Annexin V-FITC / PI double staining was applied to detect apoptosis of HL-60 and Jurkat cells following methionine restriction. The expression of cell cycle-related proteins cyclin B1, CDC2 and apoptosis-related protein Bcl-2 was evaluated by Western blot assay. Methionine restriction significantly inhibited the proliferation of HL-60 and Jurkat cells in a time-dependent manner (HL-60: r =0.7773, Jurkat: r =0.8725), arrested the cells at G2/M phase (P < 0.001), and significantly induced apoptosis of HL-60 and Jurkat cells (HL-60: P < 0.001; Jurkat: P < 0.05). Furthermore, Western blot analysis demonstrated that methionine restriction significantly reduced the proteins expression of Cyclin B1 (P < 0.05), CDC2 (P < 0.01) and Bcl-2 (P < 0.001) in HL-60 and Jurkat cells. Acute leukemia cells HL-60 and Jurkat exhibit methionine dependence. Methionine restriction can significantly inhibit the proliferation, promote cell cycle arrest and induce apoptosis of HL-60 and Jurkat cells, which suggests that methionine restriction may be a potential therapeutic strategy for acute leukemia.


Loss of MSH2 and MSH6 due to heterozygous germline defects in MSH3 and MSH6.
Lynch Syndrome (LS) is the most common dominantly inherited colorectal cancer (CRC) predisposition and is caused by a heterozygous germline defect in one of the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, or PMS2. High microsatellite instability (MSI-H) and loss of MMR protein expression in tumours reflecting a defective MMR are indicators for LS, as well as a positive family history of early onset CRC. MSH2 and MSH6 form a major functional heterodimer, and MSH3 is an alternative binding partner for MSH2. So far, the role of germline MSH3 variants remains unclear, as to our knowledge heterozygous truncating variants are not regarded causative for LS, but were detected in patients with CRC, and recently biallelic MSH3 defects have been identified in two patients with adenomatous polyposis. By gene screening we investigated the role of MSH3 in 11 LS patients with truncating MSH6 germline variants and an unexplained MSH2 protein loss in their corresponding MSI-H tumours. We report the first two LS patients harbouring heterozygous germline variants c.1035del and c.2732T>G in MSH3 coincidentally with truncating variants in MSH6. In the patient with truncating germline variants in MSH3 and MSH6, two additional somatic second hits in both genes abrogate all binding partners for the MSH2 protein which might subsequently be degraded. The clinical relevance of MSH3 germline variants is currently under re-evaluation, and heterozygous MSH3 defects alone do not seem to induce a LS phenotype, but might aggravate the MSH6 phenotype in affected family members.


Interplay of oxygen-evolution kinetics and photovoltaic power curves on the construction of artificial leaves.
An artificial leaf can perform direct solar-to-fuels conversion. The construction of an efficient artificial leaf or other photovoltaic (PV)-photoelectrochemical device requires that the power curve of the PV material and load curve of water splitting, composed of the catalyst Tafel behavior and cell resistances, be well-matched near the thermodynamic potential for water splitting. For such a condition, we show here that the current density-voltage characteristic of the catalyst is a key determinant of the solar-to-fuels efficiency (SFE). Oxidic Co and Ni borate (Co-B(i) and Ni-B(i)) thin films electrodeposited from solution yield oxygen-evolving catalysts with Tafel slopes of 52 mV/decade and 30 mV/decade, respectively. The consequence of the disparate Tafel behavior on the SFE is modeled using the idealized behavior of a triple-junction Si PV cell. For PV cells exhibiting similar solar power-conversion efficiencies, those displaying low open circuit voltages are better matched to catalysts with low Tafel slopes and high exchange current densities. In contrast, PV cells possessing high open circuit voltages are largely insensitive to the catalyst's current density-voltage characteristics but sacrifice overall SFE because of less efficient utilization of the solar spectrum. The analysis presented herein highlights the importance of matching the electrochemical load of water-splitting to the onset of maximum current of the PV component, drawing a clear link between the kinetic profile of the water-splitting catalyst and the SFE efficiency of devices such as the artificial leaf.


Perfluorodecalin enhances in vivo confocal microscopy resolution of Arabidopsis thaliana mesophyll.
*Air spaces in the leaf mesophyll generate deleterious optical effects that compromise confocal microscopy. *Leaves were mounted in the nontoxic, nonfluorescent perfluorocarbon, perfluorodecalin (PFD), and optical enhancement and physiological effect were assessed using confocal microscopy and chlorophyll fluorescence. *Mounting leaves of Arabidopsis thaliana in PFD significantly improved the optical qualities of the leaf, thereby enabling high-resolution laser scanning confocal imaging over twofold deeper into the mesophyll, compared with using water. Incubation in PFD had less physiological impact on the mounted specimen than water. *We conclude that the application of PFD as a mounting medium substantially increases confocal image resolution of living mesophyll and vascular bundle cells, with minimal physiological impact.


Bifidobacterium pseudolongum-generated acetate suppresses non-alcoholic fatty liver disease-associated hepatocellular carcinoma.
Recent studies have highlighted the role of the gut microbiota and their metabolites in non-alcoholic fatty liver disease-associated hepatocellular carcinoma (NAFLD-HCC). We aimed to identify specific beneficial bacterial species that could be used prophylactically to prevent NAFLD-HCC. The role of Bifidobacterium pseudolongum was assessed in two mouse models of NAFLD-HCC: diethylnitrosamine + a high-fat/high-cholesterol diet or + a choline-deficient/high-fat diet. Germ-free mice were used for the metabolic study of B. pseudolongum. Stool, portal vein and liver tissues were collected from mice for non-targeted and targeted metabolomic profiles. Two human NAFLD-HCC cell lines (HKCI2 and HKCI10) were co-cultured with B. pseudolongum-conditioned media (B.p CM) or candidate metabolites. B. pseudolongum was the top depleted bacterium in mice with NAFLD-HCC. Oral gavage of B. pseudolongum significantly suppressed NAFLD-HCC formation in two mouse models (p < 0.01). Incubation of NAFLD-HCC cells with B.p CM significantly suppressed cell proliferation, inhibited the G1/S phase transition and induced apoptosis. Acetate was identified as the critical metabolite generated from B. pseudolongum in B.p CM, an observation that was confirmed in germ-free mice. Acetate inhibited cell proliferation and induced cell apoptosis in NAFLD-HCC cell lines and suppressed NAFLD-HCC tumor formation in vivo. B. pseudolongum restored heathy gut microbiome composition and improved gut barrier function. Mechanistically, B. pseudolongum-generated acetate reached the liver via the portal vein and bound to GPR43 (G coupled-protein receptor 43) on hepatocytes. GPR43 activation suppressed the IL-6/JAK1/STAT3 signaling pathway, thereby preventing NAFLD-HCC progression. B. pseudolongum protected against NAFLD-HCC by secreting the anti-tumor metabolite acetate, which reached the liver via the portal vein. B. pseudolongum holds potential as a probiotic for the prevention of NAFLD-HCC. Non-alcoholic fatty liver disease-associated hepatocellular carcinoma (NAFLD-HCC) is an increasing healthcare burden worldwide. There is an urgent need to develop effective agents to prevent NAFLD-HCC progression. Herein, we show that the probiotic Bifidobacterium pseudolongum significantly suppressed NAFLD-HCC progression by secreting acetate, which bound to hepatic GPR43 (G coupled-protein receptor 43) via the gut-liver axis and suppressed the oncogenic IL-6/JAK1/STAT3 signaling pathway. Bifidobacterium pseudolongum holds potential as a novel probiotic for NAFLD-HCC prevention.


The growth and transformation of American ego psychology.
The roots of ego psychology trace back to Sigmund Freud's The Ego and the Id (1923) and "Inhibitions, Symptoms and Anxiety" (1926), works followed by two additional fundaments, Anna Freud's The Ego and the Mechanisms of Defense (1936) and Heinz Hartmann's Ego Psychology and the Problem of Adaptation (1939). It was brought to full flowering in post-World War II America by Hartmann and his many collaborators, and for over two decades it maintained a monolithic hegemony over American psychoanalysis. Within this framework the conceptions of the psychoanalytic psychotherapies evolved as specific modifications of psychoanalytic technique directed to the clinical needs of the spectrum of patients not amenable to psychoanalysis proper. This American consensus on the ego psychology paradigm and its array of technical implementations fragmented several decades ago, with the rise in America of Kohut's self psychology, geared to the narcissistic disorders, and with the importation from Britain of neo-Kleinian and object-relational perspectives, all coinciding with the rapid growth of the varieties of relational psychoanalysis, with its shift in focus to the two-person, interactive, and co-constructed transference-countertransference matrix. Implications of this intermingled theoretical pluralism (as contrasted with the unity of the once dominant ego psychology paradigm) for the evolution of the American ego psychology are spelled out.


Synthesis of Water-Based Dispersions of Polymer/TiO₂ Hybrid Nanospheres.
We develop a strategy for preparing water-based dispersions of polymer/TiO₂ nanospheres that can be used to form composite materials applicable in various fields. The formed hybrid nanospheres are monodisperse and possess a hierarchical structure. It starts with the primary TiO₂ nanoparticles of about 5 nm, which first assemble to nanoclusters of about 30 nm and then are integrated into monomer droplets. After emulsion polymerization, one obtains the water-based dispersions of polymer/TiO₂ nanospheres. To achieve universal size, it is necessary to have treatments with intense turbulent shear generated in a microchannel device at different stages. In addition, a procedure combining synergistic actions of steric and anionic surfactants has been designed to warrant the colloidal stability of the process. Since the formed polymer/TiO₂ nanospheres are stable aqueous dispersions, they can be easily mixed with TiO₂-free polymeric nanoparticle dispersions to form new dispersions, where TiO₂-containing nanospheres are homogeneously distributed in the dispersions at the nanoscale, thus leading to various applications. As an example, the proposed strategy has been applied to generate polystyrene/TiO₂ nanospheres of about 100 nm in diameter.


Helper-Independent Sleeping Beauty transposon-transposase vectors for efficient nonviral gene delivery and persistent gene expression in vivo.
Transposon-based vectors represent promising new tools for chromosomal transgene insertion and establishment of persistent gene expression in vivo. Here, we report the development of helper-independent transposon-transposase (HITT) vectors, which contain on single plasmids (i) a Sleeping Beauty (SB) transposon containing the transgene and (ii) a SB transposase expression cassette. To obtain an optimal level of transposase expression from HITT vectors, we determined the relative strength of a panel of different promoters in mouse liver and used these promoters to drive transposase expression from injected HITT vectors carrying a human alpha(1)-antitrypsin (hAAT) expression cassette flanked by transposon inverted repeats. By correlating promoter strength with stabilized serum hAAT levels, a narrow expression window supporting high-level transposition in the liver was defined. Peak levels of long-term gene expression were obtained with promoters 30- to 40-fold less active than CMV in mouse liver, whereas reduced stable levels of hAAT were detected with both weaker and stronger promoters. Injected HITT vectors induced transposase-dependent insertion of transposon DNA into the genome of at least 5-6% of transfected hepatocytes, generating levels of persistent hAAT expression that were 2- to 4-fold higher than with an optimized two-plasmid approach. In addition, we show that HITT vectors carrying a human factor IX (hFIX)-containing transposon support (i) long-term hFIX expression in normal mice and (ii) partial phenotypic correction in a mouse model of hemophilia B. SB-based HITT vectors represent a major advance in the establishment of persistent transgene expression from nonviral gene delivery systems and should prove useful for gene transfer to tissues or cell types in which transfection efficiencies are low.


Incremental value of multiplanar cross-referencing for prostate cancer staging with endorectal MRI.
The purpose of this study was to assess whether use of the PACS cross-referencing tool in 3D MRI improves tumor staging of prostate cancer when pathologic findings are used as the reference standard. The institutional review board granted a waiver of informed consent for the study. Endorectal MRI at 1.5 T was performed before radical prostatectomy in 255 consecutive patients. Two radiologists unaware of the clinical data retrospectively and independently interpreted MR images without and with cross-referencing to predict the presence of extracapsular extension (ECE) and seminal vesicle invasion (SVI). Histopathologic findings were used as the reference standard. Area under the receiver operating characteristics curve (AUC), sensitivity and specificity, and weighted kappa statistics were calculated. At histologic examination, 68 (27%) of the patients were found to have ECE and 13 (5%) of the patients to have SVI; the latter all had ECE. In detecting ECE, both reviewers had a higher AUC using cross-referencing (p < 0.001 for both). The weighted kappa value was 0.56 for MRI alone and 0.76 for MRI with cross-referencing, indicating fair to good interobserver agreement. Sensitivity and specificity for ECE with MRI alone and with cross-referencing were 43% and 94% and 57% and 100% for reviewer 1 and 40% and 93% and 59% and 98% for reviewer 2, respectively. In detecting SVI, both reviewers had a higher AUC with cross-referencing (p = 0.007 and p = 0.056 for reviewers 1 and 2, respectively). Reviewer 1 benefited much more from cross-referencing than did reviewer 2. The weighted kappa statistic was 0.69 for MRI alone and the same with cross-referencing, indicating good interobserver agreement. Sensitivity and specificity for SVI with MRI alone and with cross-referencing, respectively, were 23% and 83% and 46% and 93% for reviewer 1 and 31% and 91% and 54% and 95% for reviewer 2. PACS cross-referencing significantly improves tumor staging of prostate cancer with 3D MRI. Some reviewers benefit more than others from use of this tool.


Thyrotropin Suppressive Therapy for Low-Risk Small Thyroid Cancer: A Propensity Score-Matched Cohort Study.
Thyrotropin (TSH) suppression has improved the clinical outcomes of patients with differentiated thyroid cancer (DTC). However, the efficacy of TSH suppressive therapy (TST) is unclear in patients with low-risk DTC. This study aimed to evaluate the efficacy of TST and optimal TSH levels of patients with low-risk DTC. This retrospective propensity score-matched cohort study included DTC patients (n = 446) who underwent lobectomy from 2002 to 2008 with or without TST (TST group and No-TST group). Disease-free survival (DFS) and dynamic risk stratification were compared between both groups using serum TSH levels. Approximately 74% of TST patients and 11% of No-TST patients had suppressed serum TSH levels (<2 mIU/L). The median follow-up period was 8.6 years. During follow-up, the disease recurred in 10 (2.7%) patients, with no significant difference in DFS between the groups (p = 0.63). The proportion of patients with excellent treatment response was similar between the TST (65.2%) and No-TST (64.4%) groups. Incomplete biochemical response was noted in 17.2% of the TST group patients and 9.4% of the No-TST group patients. No significant difference was observed in the DFS between both groups by comparing serum TSH level (p = 0.57). TST did not improve clinical outcomes, and serum TSH levels were not associated with recurrence in patients with low-risk small DTC. No clinical benefits were shown for TSH suppression in low-risk patients who underwent lobectomy. Thus, levothyroxine is not necessary for patients without evidence of hypothyroidism.


Potential for biosimilars in rheumatology in Africa.
Biosimilars are products which are highly similar to a reference biologic product (RBP). In Africa, regulatory frameworks for biosimilar approval are still in development in many countries and few biosimilars for rheumatic diseases are currently available. The use of biosimilar medicines in Africa provides an important opportunity to treat more rheumatology patients with biologic drugs. This editorial aims to shed a light on the potential benefits, challenges and current efforts, regarding the use of biosimilars in Africa in Rheumatology.


UV emission spectrometer using a non-periodic grating.
A UV emission spectrometer using a non-periodic spherical grating has been designed, which can be attached to the linear or helical undulator beamlines of the HiSOR light source at the Hiroshima Synchrotron Radiation Centre. The useful range of emitted photons from 10 to 100 eV is covered by two gratings with nominal groove spacings of 1/600 and 1/1200 mm. The energy resolution with a 100 micro m entrance slit width and the 1/600 mm grating is better than 0.2 eV below 50 eV.


Unwarranted variations in the quality of health care: can the law help medicine provide a remedy/remedies?
This Article reviews the essential findings of studies of variations in quality of care according to three categories of care: effective care, preference-sensitive care, and supply-sensitive care. It argues that malpractice liability and informed consent laws should be based on standards of practice that are appropriate to each category of care. In the case of effective care, the legal standard should be that virtually all of those in need should receive the treatment, whether or not it is currently customary to provide it. In the case of preference-sensitive care, the law should recognize the failure of the doctrine of informed consent to assure that patient preferences are respected in choice of treatment; we suggest that the law adopt a standard of informed patient choice in which patients are invited, not merely to consent to a recommended treatment, but to choose the treatment that best advances their preferences. In the case of supply-sensitive care, we suggest that physicians who seek to adopt more conservative patterns of practice be protected under the "respectable minority" or "two schools of thought" doctrine.


[Investigation of influence on apical sealability generated by root canal sealer placement].
To investigate the influence of sealer placement on apical sealability in root canal treatment. 100 extracted single root canal teeth were selected. All canals were prepared by manual Protaper instrument in a step-back way. The samples were divided into 5 groups randomly. A group: 30 samples, sealer placement by chief gutta percha; B group: 30 samples, sealer placement by K file; C group: 30 samples, sealer placement by spreader; D group: 5 samples, a positive control; E group: 5 samples, a negative control. There were 2 subsets in each experimental group which were obturated by lateral gutta percha with or without sealer. Glucose oxidase method was used to measure the apical leakage at the 1st 2nd, 4th, 7th, 10th, 15th, 20th, 25th, 30th day of the experiment. Apical sealability varied with different sealer placement methods (F=4.832, P=0.001). Sealer placement by chief gutta percha (A group) had the best instant apical sealability. However, lateral gutta percha with or without sealer didn't affect the apical sealibility. Placing the same kind sealer in different ways can affect the apical sealability. There were no significant differences of the apical leakage no matter the lateral gutta percha with or without sealer. In order to get better instant apical sealability and simplify the clinic operation, placing the sealer with a chief gutta percha while the lateral gutta percha without sealer is recommended.


Cloning and expression of Bombyx mori silk gland elongation factor 1gamma in Escherichia coli.
Elongation factor 1 (EF-1) from the silk gland of Bombyx mori consists of alpha-, beta-, gamma-, and delta-subunits. EF-1alpha GTP catalyzes the binding of aminoacyl-tRNA to ribosomes concomitant with the hydrolysis of GTP. EF-1betagammadelta catalyzes the exchange of EF-1alpha-bound GDP for exogenous GTP and stimulates the EF-1alpha-dependent binding of aminoacyl-tRNA to ribosomes. EF-1gamma cDNA, which contains an open reading frame (ORF) encoding a polypeptide of 423 amino acid residues, was amplified and cloned by PCR from a silk gland cDNA library. The calculated molecular mass and predicted pI of the product were 48,388 Da and 5.84, respectively. The silk gland EF-1gamma shares 67.3% amino acid identity with Artemia salina EF-lgamma. The N-terminal domain (amino acid residues 1-211) of silk gland EF-lgamma is 29.3% identical to maize glutathione S-transferase. We demonstrated that silk gland EF-lgamma bound to glutathione Sepharose, suggesting that the N-terminal domain of EF-1gamma may have the capacity to bind to glutathione.


Electrocardiographic findings of Wellens syndrome due to coronary artery-pulmonary artery fistula.
A coronary artery fistula (CAF) is an abnormal connection between a coronary artery and any of the four cardiac chambers, the large vessels, or other vascular structures. Wellens syndrome is an ST-segment elevation myocardial infarction equivalent. Although both Wellens syndrome and CAFs have been reported in the literature, they have rarely been reported in the same patient. We herein report a case clinically diagnosed as Wellens syndrome by electrocardiography (ECG) findings; coronary angiography subsequently showed a fistula originating from the left anterior descending artery and draining into the pulmonary artery. The ECG findings then returned to normal after the fistula had been closed by controlled-release coils. These events confirmed that the abnormal ECG findings of Wellens syndrome were due to the CAF.


Pathobiology of focal sclerosis.
This paper briefly reviews recent experimental data derived from work in animals and cell cultures that have increased our understanding of the pathobiologic pathways leading to focal sclerosis. These pathways include glomerular visceral epithelial cell damage, leukocyte infiltration, hyperplasia and matrix accumulation in the mesangium, and endothelial injury.


Inhibition of oxytocin receptor function by direct binding of progesterone.
The steroid hormone progesterone (P4) is essential for establishing and maintaining pregnancy in mammals. One of its functions includes maintenance of uterine quiescence by decreasing uterine sensitivity to the uterotonic peptide hormone oxytocin. Although it is generally held that steroid hormones such as P4 act at a genomic level by binding to nuclear receptors and modulating the expression of specific target genes, we show here that the effect of P4 on uterine sensitivity to oxytocin involves direct, non-genomic action of P4 on the uterine oxytocin receptor (OTR), a member of the G-protein-coupled receptor family. P4 inhibits oxytocin binding to OTR-containing membranes in vitro, binds with high affinity to recombinant rat OTR expressed in CHO cells, and suppresses oxytocin-induced inositol phosphate production and calcium mobilization. These effects are highly steroid- and receptor-specific, because binding and signalling functions of the closely related human OTR are not affected by P4 itself but by the P4 metabolite 5beta-dihydroprogesterone. Our findings provide the first evidence for a direct interaction between a steroid hormone and a G-protein-coupled receptor and define a new level of crosstalk between the peptide- and steroid-hormone signalling pathways.


Differential contribution of troponin I phosphorylation sites to the endothelin-modulated contractile response.
Cardiac troponin I is a phosphorylation target for endothelin-activated protein kinase C. Earlier work in cardiac myocytes expressing nonphosphorylatable slow skeletal troponin I provided evidence that protein kinase C-mediated cardiac troponin I phosphorylation accelerates relaxation. However, replacement with the slow skeletal isoform also alters the myofilament pH response and the Ca2+ transient, which could influence endothelin-mediated relaxation. Here, differences in the Ca2+ transient could not explain the divergent relaxation response to endothelin in myocytes expressing cardiac versus slow skeletal troponin I nor could activation of Na+/H+ exchange. Three separate clusters within cardiac troponin I are phosphorylated by protein kinase C, and we set out to determine the contribution of the Thr144 and Ser23/Ser24 clusters to the endothelin-mediated contractile response. Myocyte replacement with a cardiac troponin I containing a Thr144 substituted with the Pro residue found in slow skeletal troponin I resulted in prolonged relaxation in response to acute endothelin compared with control myocytes. Ser23/Ser24 also is a target for protein kinase C phosphorylation of purified cardiac troponin I, and although this cluster was not acutely phosphorylated in intact myocytes, significant phosphorylation developed within 1 h after adding endothelin. Replacement of Ser23/Ser24 with Ala indicated that this cluster contributes significantly to relaxation during more prolonged endothelin stimulation. Overall, results with these mutants provide evidence that Thr144 plays an important role in the acute acceleration of relaxation, whereas Ser23/Ser24 contributes to relaxation during more prolonged activation of protein kinase C by endothelin.


A computer controlled mock circulatory system for mono- and biventricular assist device testing.
The clinical use of heart assist devices for heart recovery, implies the problem of their in vitro testing and training to use. In a mock circulatory system developed to this aim, the main problem is reproducing interaction among the device, the ventricle and the circulatory network. This can be analysed by the position, on the p-v plane, of the working point defined by the intersection between end systolic ventricular (ESPVR) and arterial elastance lines. The system developed on this basis, connectable to mono- and biventricular parallel assist devices, was a closed loop model including systemic and pulmonary circulation. The arterial trees were reproduced by two windkessels with adjustable peripheral resistance, and the Starling's law of the heart by a variable elastance model. The software controls and monitors circulatory parameters and variables. Results showed the behavior of the system with preload or afterload changes. Further, the reproduction of physiological, pathological (obtained by modifying slope and volume intercept of the ESPVR line) and LVAD assisted circulatory conditions was shown. The assistance effect was underlined by the changes in the ventricular work cycle and in hemodynamics variables. The evaluation of the effect of device control strategy on the ventricle and its energetics (on p-v plane) were among the main characteristics of this system, which ought to be further improved to test devices such as the IABP, which requires a different aortic model.


[Effect of sinusoidal electricity magnetic fields on the proliferation and differentiation of osteoblasts in vitro].
To investigate the effect of sinusoidal electricity magnetic fields (SEMFs) on the proliferation and differentiation of osteoblasts in vitro. Calvarial osteoblasts of newborn rats were isolated by enzyme digestion and randomly divided into 3 groups after subculture. Two groups of cells were exposed to 50 Hz 1.8 mT SEMFs for 30 min/d in parallel and vertical, respectively. Those without SEMFs exposure served as control. The cells were observed under the contrast phase microscope each day. After 48 h, cell proliferation was assayed by MTT method. The alkaline phasphatase (ALP) activities and calcium contents were measured after 3, 6, 9, and 12 days. The ALP positive colonies were histochemically stained after 10 days and the calcified nodules were stained by Alizarin Bordeaux after 12 days. Expressions of ALP, bone morphogenetic protein-2 (BMP-2) and Osterix (OSX) mRNA were measured at 0 h, 24 h, 48 h and 96 h. The cells exposed to the SEMFs were arranged in spiral appearance after 3 days. Compared with control, SEMFs inhibited cell proliferation (P < 0.01 or P < 0.05), but enhanced the maturation and mineralization of the osteoblasts. The results showed that SEMFs improved ALP activities, promoted calcium contents, increased calcified nodulues numbers, boosted expressions of ALP, BMP-2 and OSX mRNA. SEMFs with magnetic lines of force in parallel has stronger activities than those in vertical. The SEMFs at 1.8 mT and 50 Hz inhibit the proliferation of osteoblasts, but enhance the maturation and mineralization of osteoblasts.


Iron oxide nanoparticles attenuate T helper 17 cell responses in vitro and in vivo.
Iron oxide nanoparticles (IONPs) have been shown to attenuate T helper (Th)1 and Th2 cell-mediated immunity in ovalbumin (OVA)-sensitized mice. The objective of this study is to investigate the effects of IONPs on the immune responses of Th17 cells, a subset of T cells involved in various inflammatory pathologies. For in vivo study, a murine model of delayed-type hypersensitivity (DTH) was employed. BALB/c mice received a single dose of IONPs (0.2-10 mg iron/kg) via the tail vein 1 h prior to ovalbumin (OVA) sensitization. Their footpads were subcutaneously challenged with OVA to induce DTH reactions. The expression of Th17 cell-related molecules in inflamed footpads were examined by immunohistochemistry. For in vitro study, OVA-primed splenocytes were directly exposed to IONPs (1-100 μg iron/mL), and then re-stimulated with OVA in culture. The expression of Th17 cell-related molecules were measured by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. IONP administration attenuated the number of interleukin (IL)-6, IL-17, the transcription factor ROR-γ, and chemokine receptor 6 positive cells in OVA-challenged footpads, whereas the number of transforming growth factor-β, IL-23 and chemokine (C-C motif) ligand 20 positive cells was not altered. Direct exposure of OVA-primed splenocytes to IONPs suppressed the production of IL-6 and IL-17, and the mRNA expression of IL-17 and ROR-γt. These data indicate that exposure to IONPs attenuates Th17 cell responses in vivo and in vitro.