Mortality and morbidity in elderly patients with fracture neck of femur treated by hemiarthroplasty.
To determine mortality and morbidity in elderly patients with fracture neck of femur treated by hemiarthroplasty (Austin Moore Prosthesis) during one year postoperatively. Descriptive, analytical study. Department of Orthopaedics, Postgraduate Medical Institute/Hayatabad Medical Complex, Peshawar, from June 2001 to May 2002. During the study period, all patients with fracture neck of femur, who were 65 years of age or above and treated by Austin Moore Prosthesis (AMP), were included. The patients were followed for one year at intervals of 2 weeks, 4 weeks, 6 months, and one year. All surviving patients were assessed for complications, both general and mechanical, related to the implant. The mortality and morbidity were compared for various age subgroups, and in patients with and without systemic co-morbidities.Chi square test was applied to see the significance of results. The total number of patients was 46 with average age of 70 years. Male to female ratio was 1:2. There were 70% patients who had one or more associated systemic disease. The mortality at 2 weeks was 4.3%, 17.4% at 6 months and 26% at one year. The overall dislocation rate was 4.3%. Two patients had infection and 17.4% patients had thigh pain at one year. The mortality and morbidity was high in patients with systemic co-morbidities, and those above 70 years of age, but this was statistically not significant (p value >0.05). The functional assessment of surviving patients at one year was graded as excellent or good in 76.4% of patients. In this series, Austin Moore Prosthesis in elderly patients was associated with dislocation, infection and thigh pain in short-term follow-up. The postoperative mortality was high, but it was age and systemic co-morbidity-related rather than due to the surgical procedure. The functional assessment of hip at one year was excellent or good in majority of surviving patients.


The causes of the municipal solid waste and the greenhouse gas emissions from the waste sector in the United States.
The United States generated approximately 730kg of waste per capita in 2013, which is the highest amount of waste among OECD countries. The waste has adverse effects to human health and the environment. One of the most serious adverse effects is greenhouse gas emissions, especially methane (CH4), which causes global warming. However, the United States' amount of waste generation is not decreasing, and the recycling rate is only 26%, which is lower than other OECD countries. In order to decrease waste generation and greenhouse gas emissions, identifying the causality of the waste generation and greenhouse gas emissions from waste sector should be made a priority. The research objective is to verify whether the Environmental Kuznets Curve relationship is supported for waste generation and GDP across the U.S. Moreover, it also confirmed that total waste generation and recycling of waste influences carbon dioxide emissions from the waste sector. Based on the results, critical insight and suggestions were offered to policymakers, which is the potential way to lower the solid waste and greenhouse gas emissions from the waste sector. This research used annually based U.S. data from 1990 to 2012, and these data were collected from various data sources. To verify the causal relationship, the Granger causality test was applied. The results showed that there is no causality between GDP and waste generation, but total waste and recycling generate significantly increasing and decreasing greenhouse gas emissions from the waste sector, respectively. This implies that waste generation will not decrease even if GDP increases. And, if waste generation decreases or the recycling rate increases, greenhouse gas emission will decrease. Based on these results, increasing the recycling rate is first suggested. The second suggestion is to break the causal relationship between MSW and greenhouse gas emission from the waste sector. The third is that the U.S. government should benchmark a successful case of waste management. Based on the research, it is expected that waste generation and carbon dioxide emission from the waste sector can be decreased more efficiently.


Oral administration of leucine stimulates phosphorylation of 4E-bP1 and S6K 1 in skeletal muscle but not in liver of diabetic rats.
Leucine performs a signaling role to enhance protein synthesis by phosphorylating eukaryotic initiation factor (eIF) 4E-binding protein 1 (4E-BP1) and 70-kDa ribosomal protein S6 kinase (S6K1), two key regulatory proteins involved in the initiation of mRNA translation. The purpose of the current study was to assess whether the phosphorylation of 4E-BP1 and S6K1 was increased in skeletal muscle and liver by an oral administration of leucine to diabetic rats and to determine the in vivo contribution of insulin to a leucine-dependent induction of 4E-BP1 and S6K1 phosphorylation. Food-deprived (18 h) normal and diabetic rats were orally administered 135 mg/ 100 g body weight L-leucine and sacrificed at 1 h after administration. Leucine administration resulted in enhanced phosphorylation of 4E-BP1 and S6K1 in skeletal muscle and in liver of nondiabetic rats. The stimulatory action of leucine on the phosphorylation of 4E-BP1 and S6K1 in skeletal muscle was not abolished in rats with streptozotocin-induced diabetes. In contrast, leucine administration did not stimulate the phosphorylation of 4E-BP1 and S6K1 in the liver of diabetic rats. These findings suggest that in skeletal muscle, leucine functions as a nutritional signaling molecule that independently regulates the phosphorylation states of 4E-BP1 and S6K1. In contrast to skeletal muscle, insulin is essential in mediating the leucine-dependent induction of 4E-BP1 and S6K1 phosphorylation in liver. leucine, 4E-BP1, S6K1, translation initiation, diabetes


TFAP2 paralogs regulate melanocyte differentiation in parallel with MITF.
Mutations in the gene encoding transcription factor TFAP2A result in pigmentation anomalies in model organisms and premature hair graying in humans. However, the pleiotropic functions of TFAP2A and its redundantly-acting paralogs have made the precise contribution of TFAP2-type activity to melanocyte differentiation unclear. Defining this contribution may help to explain why TFAP2A expression is reduced in advanced-stage melanoma compared to benign nevi. To identify genes with TFAP2A-dependent expression in melanocytes, we profile zebrafish tissue and mouse melanocytes deficient in Tfap2a, and find that expression of a small subset of genes underlying pigmentation phenotypes is TFAP2A-dependent, including Dct, Mc1r, Mlph, and Pmel. We then conduct TFAP2A ChIP-seq in mouse and human melanocytes and find that a much larger subset of pigmentation genes is associated with active regulatory elements bound by TFAP2A. These elements are also frequently bound by MITF, which is considered the "master regulator" of melanocyte development. For example, the promoter of TRPM1 is bound by both TFAP2A and MITF, and we show that the activity of a minimal TRPM1 promoter is lost upon deletion of the TFAP2A binding sites. However, the expression of Trpm1 is not TFAP2A-dependent, implying that additional TFAP2 paralogs function redundantly to drive melanocyte differentiation, which is consistent with previous results from zebrafish. Paralogs Tfap2a and Tfap2b are both expressed in mouse melanocytes, and we show that mouse embryos with Wnt1-Cre-mediated deletion of Tfap2a and Tfap2b in the neural crest almost completely lack melanocytes but retain neural crest-derived sensory ganglia. These results suggest that TFAP2 paralogs, like MITF, are also necessary for induction of the melanocyte lineage. Finally, we observe a genetic interaction between tfap2a and mitfa in zebrafish, but find that artificially elevating expression of tfap2a does not increase levels of melanin in mitfa hypomorphic or loss-of-function mutants. Collectively, these results show that TFAP2 paralogs, operating alongside lineage-specific transcription factors such as MITF, directly regulate effectors of terminal differentiation in melanocytes. In addition, they suggest that TFAP2A activity, like MITF activity, has the potential to modulate the phenotype of melanoma cells.


NgAgo-gDNA system efficiently suppresses hepatitis B virus replication through accelerating decay of pregenomic RNA.
Covalently closed circular DNA (cccDNA) in the hepatocytes nucleus is responsible for persistent infection of Hepatitis B virus (HBV). Current antiviral therapy drugs nucleos(t)ide analogs or interferon fail to eradicate HBV cccDNA. Genome editing technique provides an effective approach for HBV treatment through targeting viral cccDNA. Natronobacterium gregoryi Argonaute (NgAgo)-guide DNA (gDNA) system with powerful genome editing prompts us to explore its application in inhibiting HBV replication. Preliminary function verification indicated that NgAgo/EGFP-gDNA obviously inhibited EGFP expression. To further explore the potential role of NgAgo in restricting HBV replication, 10 of gDNAs targeting the critical region of viral genome were designed, only S-142, P-263 and P-2166 gDNAs led to significant inhibition on HBsAg, HBeAg and pregenomic RNA (pgRNA) level in Huh7 and HepG2 cells transfected with pcDNA-HBV1.1 plasmid. Similar results were also found in HBV infected HLCZ01 cells and Huh7-NTCP cells. However, we failed to detect any DNA editing in S-142, P-263 and P-2166 targeting region through T7E1 assay and Sanger sequencing. Remarkably, we found that NgAgo/P-2166 significantly accelerated the decay of viral pgRNA. Taken together, our results firstly demonstrate the potential of NgAgo/gDNA in inhibiting HBV replication through accelerating pgRNA degradation, but not DNA editing.


Cessation of neoangiogenesis in Alzheimer's disease follows amyloid-beta immunization.
Pathogenic neoangiogenesis in Alzheimer's disease (AD) is due to amyloid-beta (Aβ) and results in blood-brain barrier (BBB) leakiness in AD. It likely occurs as a compensatory response to impaired cerebral blood flow and provides a strong link between brain vascularity and AD. Aβ immunotherapy is an experimental treatment for AD; however, unexpected negative vascular side effects seen in early human clinical trials demonstrate that our knowledge of Aβ and AD pathogenesis is incomplete. We demonstrate that immunization with Aβ peptides neutralizes the amyloid trigger leading to neoangiogenesis and reverses hypervascularity in Tg2576 AD mice. This process resolves plaque burden suggesting that neoangiogenesis is a key mechanism underlying plaque formation. A meta-analysis demonstrated that hypervascular reversion in vaccinated Alzheimer's patients. This appears to be the first example of vascular reversion following any therapeutic intervention and supports the conclusion that modulation of neoangiogenesis may repair damage in the AD brain.


Vibrationally hot bands of the SiCN Ã 2Δ - X̃ 2Π system.
We have generated SiCN in supersonic free jet expansions and observed the laser induced fluorescence (LIF) spectrum. In addition to the vibronic bands from the vibrationless level of the X̃ (2)Π state, the hot bands from the bending vibrational level, à (01(1)0) (2)Φ - X̃ (01(1)0) (2)Δ and à (01(1)0) (2)Π - X̃ (01(1)0) (2)Σ((-)), have been measured. The rotational energy levels were reasonably analyzed as those of the (2)K' - (2)K″ transitions, but their line intensities calculated from the Hönl-London factors derived in the intermediate case between Hund's case (a) and (b) could not reproduce the observed spectra. The Hönl-London factors derived in the (2)Λ' - (2)Λ″ ((2)Δ - (2)Π) transition reasonably reproduced the spectra. It indicates that coupling between the electronic orbital and vibrational angular momenta is weak in the SiCN (2)Δ - (2)Π system, and a basis set of |Λ v2 l Σ;J P MJ>, the so-called "l-basis", better describes the system than that of |Λ v2 K Σ;J P MJ>.


Gas-liquid chromatographic determination of cholesterol and other sterols in foods.
A gas-liquid chromatographic (GLC) method, using the butyryl esters of sterols, has been developed for the measurement of cholesterol, stigmasterol, sitosterol, and campesterol in foods. An immobile phase of 1% SE-30 coated on 100-120 mesh Gas-Chrom Q packed in a 6 inch X 4 mm id glass column operated at 255 degrees C was the most satisfactory of 7 column packings evaluated. Extraction with chloroform-methanol gave 98.7% recovery with a coefficient of variation of 1.8% for cholesterol added to a variety of foods. When cholesteryl palmitate was added to vegetable oil and the butyryl derivative was prepared, followed by GLC analysis, the recovery was 99.3% with a coefficient of variation of 0.9%. Amounts as low as 1 mg/100 g food can be detected with a precision of 2.5%. The results of the analysis of a variety of foods for cholesterol, campesterol, sitosterol, and stigmasterol are given.


Autoantibodies to the high-affinity IgE receptor in patients with asthma.
Autoimmune diseases have been implicated as a cause of intrinsic asthma; however, there is little data on the role of autoimmunity in the pathogenesis of asthma. The purpose of this study was to investigate circulating autoantibodies against the high-affinity IgE receptor Fc(epsilon)RI in patients with asthma. Seventy-eight patients with asthma and 32 healthy individuals as control subjects were included. All subjects were tested with basophil histamine releasing assay and immunoblotting to assess for the potential presence of receptor Fc(epsilon)RI autoantibodies. Of the 78 asthma patients total subjects, 25 (32.1%) had a positive by basophil histamine releasing assay and 23 (29.5%) by immunoblotting. Both of them were significant higher than the positive rate, 9.4% (p < 0.05) and 9.4% (p < 0.05), respectively. Our data demonstrated that aberrant autoantibodies against the high-affinity IgE receptor Fc(epsilon)RI were found in some patients with asthma implies that the autoimmunity may be one factor in intrinsic asthma pathogenesis.


The inflammatory response-related robust machine learning signature in endometrial cancer: Based on multi-cohort studies.
Uterine corpus endometrial carcinoma (UCEC) is a prevalent form of cancer in women, affecting the inner lining of the uterus. Inflammation plays a crucial role in the progression and prognosis of cancer, making it important to identify inflammatory response-related subtypes in UCEC for targeted therapy and personalized medicine. This study discovered significant variation in immune response within UCEC tumors based on molecular subtypes of inflammatory response-related genes. Subtype A showed a more favorable prognosis and better response to immunotherapies like anti-CTLA4 and anti-PDCD1 therapy. Functional analysis revealed subtype-specific differences in immune response, with subtype A exhibiting higher expression of genes related to cytokine signaling pathways, NK cell-mediated cytotoxicity pathways and inflammatory processes. Subtype A also showed increased sensitivity to three chemotherapeutic agents. A 12-gene inflammatory response-related signature was found to have prognostic value for 1, 2 and 3 year survival in UCEC patients. Additionally, a validated machine learning-based signature demonstrated significant differences in clinical traits between low-risk and high-risk cohorts. Elevated risk scores were associated with higher pathological grading, older age, advanced stage and immune subtype C2. Low-risk groups had higher infiltration of immune cell types such as CD8 + T cells and activated CD4 + cells. However, the abundance of cytotoxic immune cells decreased with increasing risk scores. Finally, PCR was applied to test the different expression in P2PX4. P2RX4 knockdown inhibited the proliferation and proliferation of the endometrial carcinoma Ishikawa cell line. In conclusion, this developed signature can serve as a clinical prediction index and reveal distinct immune expression patterns. Ultimately, this study has the potential to enhance targeted therapy and personalized medicine for UCEC patients.


Structure and agency in development-induced forced migration: the case of Brazil's Belo Monte Dam.
This paper examines how structure and agency interact to shape forced migration outcomes. Specifically, I ask how structural factors such as compensation policies as well as social, financial, and human capital may either foster or constrain migration aspirations and capabilities. I use longitudinal, semi-structured interview data to study forced migration among farmers displaced by the Belo Monte Dam in the Brazilian Amazon. Results from baseline interviews indicate that nearly all community members aspired to purchase rural land in the region and maintain livelihoods as cacao farmers or cattle ranchers. Constraints limiting the ability to attain aspirations included strict requirements on land titles for properties, delays in receiving compensation, rising land prices, and the lack of power to negotiate for better compensation. Despite these constraints, most migrants succeeded in attaining aspirations, as they were able to mobilize resources such as social networks, financial capital, skills, and knowledge. These findings highlight the importance of considering the relationship between structure and agency within forced migration research. I conclude by discussing how the findings may inform resettlement policies for future cases of development- or environment-induced forced migration.


Fertility preservation in female classic galactosemia patients.
Almost every female classic galactosemia patient develops primary ovarian insufficiency (POI) as a diet-independent complication of the disease. This is a major concern for patients and their parents, and physicians are often asked about possible options to preserve fertility. Unfortunately, there are no recommendations on fertility preservation in this group. The unique pathophysiology of classic galactosemia with a severely reduced follicle pool at an early age requires an adjusted approach. In this article recommendations for physicians based on current knowledge concerning galactosemia and fertility preservation are made. Fertility preservation is only likely to be successful in very young prepubertal patients. In this group, cryopreservation of ovarian tissue is currently the only available technique. However, this technique is not ready for clinical application, it is considered experimental and reduces the ovarian reserve. Fertility preservation at an early age also raises ethical questions that should be taken into account. In addition, spontaneous conception despite POI is well described in classic galactosemia. The uncertainty surrounding fertility preservation and the significant chance of spontaneous pregnancy warrant counseling towards conservative application of these techniques. We propose that fertility preservation should only be offered with appropriate institutional research ethics approval to classic galactosemia girls at a young prepubertal age.


Dimensional reduction study of piezoelectric ceramics constitutive equations from 3-D to 2-D and 1-D.
Accurate performance evaluation is crucial to the design and development of macro/micro-sized piezoelectric devices, and key to this is the proper use of the stiffness/ compliance and piezoelectric coefficients of the piezoelectric ceramics involved. Although the literature points out effective piezoelectric coefficients e(31,f) and d(33,f) for thin film materials and reduced dimensionality of equations for bulk material, the elastic and piezoelectric coefficients remain unchanged from the 3-D equations in most reported 1-D and 2-D analyses of the macro/micro-sized devices involving the e form of the constitutive equations. The use of unchanged coefficients leads to variations between numerically predicted and experimental results in most devices. To understand effects of the dimensional reduction from 3-D to 2-D and 1-D on stiffness/compliance and piezoelectric coefficients, this paper derives the 2-D and 1-D constitutive equations from the 3-D equations, focusing on the discussion of often-required device configurations for sensor and actuator design and analysis. Two modified coefficients are proposed, termed reduced and enhanced, which enable better understanding of effects of the dimensional reduction and also effects on the design and analysis of sensors and actuators.


Approximate Analytical Solutions for the Euler Equation for Second-Row Homonuclear Dimers.
This work presents a new method how to obtain approximate analytical solutions for the Euler equation for second-row homonuclear dimers. In contrast to the well-known Kohn-Sham method where a system of N nonlinear coupled differential equations must be solved iteratively, orbital-free density functional theory allows to access the minimizing electron density directly via the Euler equation. For simplified models, here, an atom-centered monopole expansion with one free parameter, solutions of the electron density can be obtained analytically by solving the Euler equation at the bond critical point. The procedure is exemplarily carried out for N2, C2, and B2, yielding bound molecules with an internuclear distance of 2.01, 2.43, and 3.07 bohr, respectively.


Oak moss extracts in the diagnosis of fragrance contact allergy.
Oak moss absolute is one of the eight ingredients of the fragrance mix (FM) used for diagnosing perfume allergy. Oak moss absolute is an extract prepared from the lichen Evernia prunastri growing on oak trees. It has been shown that the oak moss patch test material from one producer contained resin acids which are ingredients of another lichen, tree moss. Resin acids, e.g. abietic acid and dehydroabietic acid, are also the main allergens in colophonium. The aim of the study was to assess whether the contamination of oak moss absolute and thus the FM with resin acids had affected their diagnostic value so that they, instead of indicating fragrance allergy, had become indicators of allergy to resin acids and thus colophonium. Two studies were undertaken. First the relationship between patch test reactions to FM, oak moss absolute, both with contents of resin acids, and colophonium were assessed in 885 consecutive patients. A significant relationship between reactions to colophonium and FM was seen (p < 0.001) as well as a significant relationship between oak moss absolute and colophonium (p < 0.001). The relationship between colophonium and FM was still significant when all reactions to oak moss absolute were disregarded (p < 0.001), showing a relationship also between colophonium and fragrance ingredients other than oak moss absolute. Second, 119 consecutive patients were tested with an old and a new version of oak moss absolute containing resin acid (0.05%) and no measurable resin acid, respectively, and with the corresponding FM. No overall difference in reactivity to the old and new version of oak moss absolute/FM was seen. It is concluded the diagnostic value of oak moss absolute as indicator fragrance contact allergy has been and is unaffected by the resin acid contamination.


Reinforcement of thoracolumbar burst fractures with calcium phosphate cement. A biomechanical study.
A biomechanical study on the stabilization of thoracolumbar burst fractures. To demonstrate that the addition of a calcium phosphate cement into the fractured vertebral body through a transpedicular approach is a feasible technique that improves the stiffness of a transpedicular screw construct. Short segment pedicle screw instrumentation is a commonly used method for reduction and stabilization of unstable burst fractures. Recent investigators, however, have reported a high rate of instrumentation failure and sagittal collapse when there is a loss of anterior column support. In this study, the ability of a new hydroxyapatite cement to augment anterior column support was investigated in a burst fracture model. A cadaveric L1 burst fracture model was stabilized using short segment pedicle screw instrumentation. Specially instrumented-pedicle screws recorded screw-bending moments. The L1 vertebral body was reinforced with the hydroxyapatite cement through a transpedicular approach. Mechanical testing of the instrumented and instrumented-reinforced constructs were performed in flexion, extension, side bending, and torsion. Construct stiffness and screw-bending moments were recorded. Transpedicular vertebral body reconstruction with hydroxyapatite cement reduced pedicle screw-bending moments by 59% in flexion and 38% in extension. Mean initial stiffness in the flexion-extension plane was increased by 40% (P < 0.05). There were no statistically significant differences in these parameters with lateral bending or torsional movements. This hydroxyapatite cement compound augments anterior column stability in a burst fracture model. This technique may improve outcomes in burst fracture patients without the need for a secondary anterior approach.


[International health: various current concepts].
This study is a theoretical approach on international health with the purpose to point out some aspects which can enhance the understanding of the International Health field and its operational and conceptual elements in the socio-economic process of integration of neighboring countries.


De Novo Discovery of Thiopeptide Pseudo-natural Products Acting as Potent and Selective TNIK Kinase Inhibitors.
Bioengineering of ribosomally synthesized and post-translationally modified peptides (RiPPs) is an emerging approach to explore the diversity of pseudo-natural product structures for drug discovery purposes. However, despite the initial advances in this area, bioactivity reprogramming of multienzyme RiPP biosynthetic pathways remains a major challenge. Here, we report a platform for de novo discovery of functional thiopeptides based on reengineered biosynthesis of lactazole A, a RiPP natural product assembled by five biosynthetic enzymes. The platform combines in vitro biosynthesis of lactazole-like thiopeptides and mRNA display to prepare and screen large (≥1012) combinatorial libraries of pseudo-natural products. We demonstrate the utility of the developed protocols in an affinity selection against Traf2- and NCK-interacting kinase (TNIK), a protein involved in several cancers, which yielded a plethora of candidate thiopeptides. Of the 11 synthesized compounds, 9 had high affinities for the target kinase (best KD = 1.2 nM) and 10 inhibited its enzymatic activity (best Ki = 3 nM). X-ray structural analysis of the TNIK/thiopeptide interaction revealed the unique mode of substrate-competitive inhibition exhibited by two of the discovered compounds. The thiopeptides internalized to the cytosol of HEK293H cells as efficiently as the known cell-penetrating peptide Tat (4-6 μM). Accordingly, the most potent compound, TP15, inhibited TNIK in HCT116 cells. Altogether, our platform enables the exploration of pseudo-natural thiopeptides with favorable pharmacological properties in drug discovery applications.


Recent advances of the nanocomposite hydrogel as a local drug delivery for diabetic ulcers.
Diabetic ulcer is a serious complication of diabetes. Compared with that of healthy people, the skin of patients with a diabetic ulcer is more easily damaged and difficult to heal. Without early intervention, the disease will become increasingly serious, often leading to amputation or even death. Most current treatment methods cannot achieve a good wound healing effect. Numerous studies have shown that a nanocomposite hydrogel serves as an ideal drug delivery method to promote the healing of a diabetic ulcer because of its better drug loading capacity and stability. Nanocomposite hydrogels can be loaded with one or more drugs for application to chronic ulcer wounds to promote rapid wound healing. Therefore, this paper reviews the latest progress of delivery systems based on nanocomposite hydrogels in promoting diabetic ulcer healing. Through a review of the recent literature, we put forward the shortcomings and improvement strategies of nanocomposite hydrogels in the treatment of diabetic ulcers.


Naamidines H and I, cytotoxic imidazole alkaloids from the Indonesian marine sponge Leucetta chagosensis.
Two new imidazole alkaloids, naamidines H ( 1) and I ( 2), were isolated from the marine sponge Leucetta chagosensis, collected in North Sulawesi, Indonesia. The compounds ( 1 and 2) showed cytotoxicity against HeLa cells with IC50 values of 5.6 and 15 microg/mL, respectively.


Aberrant expression of monoclonal antibody-defined colonic mucosal antigens in inflammatory bowel disease.
Human proximal colon from patients with inflammatory bowel disease and from controls was studied by two techniques to detect tumor-associated antigen expression. A panel of four murine monoclonal antibodies that recognize tumor-associated antigens was used to test purified colonic mucins for epitope expression by radioimmunoassay and to test formalin-fixed, deparaffinized sections of colon by the immunoperoxidase technique. The panel included monoclonal antibodies 19-9, B72.3, DU-PAN-2, and CSLEX1. Colonic mucins were purified from uninvolved surgical specimens by gel filtration with Sepharose 4B and cesium chloride-guanidine hydrochloride density gradient ultracentrifugation. Purified mucins from uninvolved colonic mucosal specimens from 4 of 7 patients with ulcerative colitis expressed one or more of these epitopes by radioimmunoassay, whereas mucins from 6 disease controls did not. Reactivity patterns were heterogeneous. Immunoperoxidase testing demonstrated staining with two or more antibodies in 14 of 18 involved inflammatory bowel disease segments, whereas control sections rarely stained with these antibodies, with the exception of 19-9. Sections of uninvolved mucosa from 4 of 9 patients with ulcerative colitis stained with two or more antibodies. Staining patterns were heterogeneous. The results demonstrate that colonic expression of tumor-associated epitopes occurs frequently in involved segments from both patients with ulcerative colitis and with Crohn's disease, whereas only patients with ulcerative colitis frequently expressed these epitopes in uninvolved segments.


Transcriptome analysis reveals the regulation of cyclic nucleotide-gated ion channels in response to exogenous abscisic acid and calcium treatment under drought stress in tomato.
Background: Drought stress can limit the growth and development of tomato seedlings and cause considerable loss of tomato yield. Exogenous abscisic acid (ABA) and calcium (Ca2+) can effectively alleviate the damage of drought stress to plants in part because Ca2+ acts as a second messenger in the drought resistance pathway. Although cyclic nucleotide-gated ion channels (CNGCs) are common non-specific Ca2+ osmotic channels in cell membranes, a thorough understanding of the transcriptome characteristics of tomato treated with exogenous ABA and Ca2+ under drought stress is necessary to characterize the molecular mechanism of CNGC involved in tomato drought resistance. Results: There were 12,896 differentially expressed genes in tomato under drought stress, as well as 11,406 and 12,502 differentially expressed genes after exogenous ABA and Ca2+ application, respectively. According to functional annotations and reports, the 19 SlCNGC genes related to Ca2+ transport were initially screened, with 11 SlCNGC genes that were upregulated under drought stress and downregulated after exogenous ABA application. After exogenous Ca2+ application, the data showed that two of these genes were upregulated, while nine genes were downregulated. Based on these expression patterns, we predicted the role of SlCNGC genes in the drought resistance pathway and their regulation by exogenous ABA and Ca2+ in tomato. Conclusion: The results of this study provide foundational data for further study of the function of SlCNGC genes and a more comprehensive understanding of drought resistance mechanisms in tomato.


Asymmetric dimethylarginine is not a good predictor of ischemia using myocardial perfusion scintigraphy.
Asymmetric dimethylarginine (ADMA) plays role in the pathogenesis of coronary artery disease and related mortality and morbidity through a number of mechanisms. We hypothesized that plasma ADMA levels would be increased in the presence of reversible ischemia as measured by GATED single photon emission computed tomography (SPECT) myocardial perfusion scintigraphy (MPS). Fasting i.v. blood samples were drawn before testing. All patients underwent 99mTc-sestamibi GATED SPECT MPS with a one-day stress-rest protocol; the images were visually analyzed. Post-stress GATED parameters, including ejection fraction, end systolic and end diastolic volumes, and automatic stress defect scores, were recorded. The plasma ADMA levels were higher in the ischemic group than in the non-ischemic group (0.46 ± 0.19 vs. 0.40 ± 0.15; P = 0.016). Plasma ADMA levels (odds ratio [OR] = 13.5; 95% confidence interval [CI] = 1.7-109.01; P = 0.015) and sex (OR = 2.49, 95% CI = 1.18-5.26; P = 0.017) were independent predictors of ischemia. There was no linear correlation between plasma ADMA levels and both the GATED SPECT and stress test parameters. Our data support the hypothesis that increased baseline ADMA levels are independently related with the presence of reversible ischemia.


Composite catalyst of rosin carbon/Fe3O4: highly efficient counter electrode for dye-sensitized solar cells.
A composite catalyst of rosin carbon/Fe3O4 with marvellous morphology was synthesized and applied as a counter electrode (CE) in dye-sensitized solar cells (DSCs), demonstrating notable electrocatalytic activity for the reduction of I3(-). Based on this CE, a high power conversion efficiency of 8.11% was achieved, comparable to that of the traditional Pt CE.


Intramolecular Nitrofuran Diels-Alder Reactions: Extremely Substituent-Tolerant Cycloadditions via Asynchronous Transition States.
Nitrofurans undergo intramolecular Diels-Alder reactions with tethered electron-poor dienophiles more rapidly and in higher yield than non-nitrated furans. Computational studies indicate that increased stabilization of a partial positive charge on the nitro-substituted carbon in both transition state and product is the driving force for these reactions. Frontier molecular orbital energy differences indicate a switch from normal to inverse electron demand upon nitration. There does not appear to be a contribution from any differences in aromatic stabilization energy between furans and nitrofurans. Calculations show that the nitrofuran reactions proceed via a highly asynchronous transition state allowing easier bond formation between two sterically hindered carbons.


Pd-NHC catalysed regioselective activation of B(3,6)-H of o-carborane - a synergy between experiment and theory.
Regioselective B-H activation of o-carboranes is an effective way for constructing o-carborane derivatives, which have broad applications in medicine, catalysis and the wider chemical industry. However, the mechanistic basis for the observed selectivities remains unresolved. Herein, a series of density functional theory (DFT) calculations were employed to characterise the palladium N-heterocyclic carbene (Pd-NHC) catalysed regioselective B(3,6)-diarylation of o-carboranes. Computational results at the IDSCRF(ether)-LC-ωPBE/BS1 and IDSCRF(ether)-LC-ωPBE/BS2 levels showed that the reaction undergoes a Pd(0) → Pd(II) → Pd(0) oxidation/reduction cycle, with the regioselective B(3)-H activation being the rate-determining step (RDS) for the full reaction profile. The computed RDS free energy barrier of 24.3 kcal mol-1 agrees well with the 82% yield of B(3,6)-diphenyl-o-carborane in ether solution at 298 K after 24 hours of reaction. The Ag2CO3 additive was shown to play a crucial role in lowering the RDS free energy barrier and facilitating the reaction. Natural charge population (NPA) and molecular surface electrostatic potential (ESP) analyses successfully predicted the experimentally observed regioselectivities, with electronic effects being revealed to be the dominant contributors to product selectivity. Steric hindrance was also shown to impact the reaction rate, as revealed by experimental and computational characterisation studies of substituents and ligand effects. Furthermore, computational predictions aligned with the experimental findings that NHC ligands outperform the phosphine ones for this particular reaction. Overall, the observed trends reported in this work are expected to assist in the rational optimisation of the efficiency and regioselectivity of this and related reactions.


Does plantar skin abrasion affect cutaneous mechanosensation?
In humans, plantar cutaneous mechanoreceptors provide critical input signals for postural control during walking and running. Because these receptors are located within the dermis, the mechanical properties of the overlying epidermis likely affect the transmission of external stimuli. Epidermal layers are highly adaptable and can form hard and thick protective calluses, but their effects on plantar sensitivity are currently disputed. Some research has shown no effect of epidermal properties on sensitivity to vibrations, whereas other research suggests that vibration and touch sensitivity diminishes with a thicker and harder epidermis. To address this conflict, we conducted an intervention study where 26 participants underwent a callus abrasion while an age-matched control group (n = 16) received no treatment. Skin hardness and thickness as well as vibration perception thresholds and touch sensitivity thresholds were collected before and after the intervention. The Callus abrasion significantly decreased skin properties. The intervention group exhibited no change in vibration sensitivity but had significantly better touch sensitivity. We argue that touch sensitivity was impeded by calluses because hard skin disperses the monofilament's standardized pressure used to stimulate the mechanoreceptors over a larger area, decreasing indentation depth and therefore stimulus intensity. However, vibration sensitivity was unaffected because the vibrating probe was adjusted to reach specific indentation depths, and thus stimulus intensity was not affected by skin properties. Since objects underfoot necessarily indent plantar skin during weight-bearing, calluses should not affect mechanosensation during standing, walking, or running.


Relationships among veteran status, gender, and key health indicators in a national young adult sample.
Although many risk behaviors peak during young adulthood, little is known about health risk factors and access to care. This study assessed health indicators and health care access in a national sample of young adult veterans and civilians. Data were from the 2010 Behavioral Risk Factor Surveillance System, a national telephone survey. Of 27,471 participants, ages 19-30 years, 2.2% were veterans (74.6% were male) and 97.7% were civilians (37.6% were male). Gender-stratified comparisons assessed health indicators and health care access by veteran status. Multivariate logistic regression was used to examine health indicators and health care access as a function of gender and veteran status. In the overall sample, women were more likely than men to have insurance, to have a regular physician, and to have had a routine checkup and yet were more likely to report financial barriers to care. Women also were more likely than men to report general medical and mental distress and higher lifetime anxiety and depressive disorders, whereas men were more likely to be overweight or obese and to report tobacco use and high-risk drinking. Adjusted analyses revealed a higher likelihood of general medical distress and higher rates of lifetime anxiety disorders among veterans compared with civilians, although there were no differences between veterans and civilians regarding health care utilization and hazardous drinking. Findings extend the literature on health care status and modifiable risk factors for young adults by identifying differences between men and women and between veterans and civilians. Interventions may need to be tailored on the bases of gender and veteran status because of several differences in mental health and general health needs.


Assessing the dietetic needs of different patient groups receiving enteral tube feeding in primary care.
To examine the nature of all contacts between adult tube-fed patients and the dietetic service and to refine the current dietetic protocols to reflect the findings of the study with a view to improving patient care. All adult patients referred to the Community Nutrition and Dietetic Service within a 6-month period were included in the study. Using a proforma developed from a retrospective case-note analysis, data were collected on the complications that prompted more frequent contacts than the department protocol. Data were analysed using the Statistical Package for the Social Sciences. The most common indication for home enteral feeding in this group of adult patients was a swallowing disorder resulting from a cerebrovascular accident (59.5%) followed by cancer (21.5%). There was a trend for cancer patients to need more intervention compared with those patients with other medical conditions. A significant difference was observed in the total contacts and telephone calls given to those patients in there own homes (P=0.019) and there was a trend towards more domicilary visits with this group. The department protocols have been revised to include a planned review within 2-6 weeks of initial dietetic assessment in the community for those patients who were identified to have the greatest need. More intensive dietetic monitoring has clear implications for dietetic services in the community.


An approach to the study of gene expression in hepatocarcinogenesis initiation.
In carcinogenesis, determination of gene and protein expression profiles is important for prevention and treatment. Caffeic acid phenethyl ester (CAPE) in a single dose administered before carcinogenic initiation induced by diethylnitrosamine (DEN) prevents the appearance of preneoplastic lesions. On the basis of this approach, the main purpose of this work was to compare the gene expression profiles induced by DEN or a previously administered single dose of CAPE. Using a modified hepatocarcinogenesis-resistant hepatocyte model, male Fischer-344 rats were administered with one intraperitoneal dose of CAPE (20 mg/kg) 12 hours before DEN administration (200 mg/kg). Livers were removed and processed for microarray analysis and reverse transcription-polymerase chain reaction 12 hours after CAPE dosing and 24 hours after DEN administration with or without CAPE. CAPE alone did not alter the expression profile. DEN treatment modified the expression of 665 genes, and CAPE plus DEN induced changes in 1371 genes. DEN treatment increased the expression of genes associated with oxidative stress such as glutathione reductase, genes involved in cell cycle regulation including p53, and modified cytochrome P450. CAPE plus DEN diminished the expression of cytochrome involved in DEN bioactivation such as CYP2B1 as well as the expression of regulators of oxidative stress such as glutathione reductase, GST-kappa and GST-theta, and cell cycle regulators such as p53. Using CAPE as a tool, we uncovered new approaches for studying the altered expression of reactive genes and identifying proteins that will help to propose well-sustained and concrete hypothesis of DEN mechanism of hepatocarcinogenesis initiation.


Educational Preparation, Roles, and Competencies to Guide Career Development for Cardiac Rehabilitation Nurses.
Cardiac rehabilitation is one of the most widely recommended strategies to reduce the burden of cardiovascular disease. The multicomponent nature of cardiac rehabilitation programs requires a multidisciplinary team of healthcare professionals including nurses who are equipped with extensive knowledge and skills. However, there is a lack of a comprehensive, explicit career pathway that contains academic and clinical development to prepare nurses to become cardiac rehabilitation specialists. The aim of this study is to identify the 3 essential components for cardiac rehabilitation professionals: (1) educational preparation, (2) role/responsibility, and (3) competency to inform the framework of career development for cardiac rehabilitation nurses. Through scoping review, 4 stages from the methodological framework of scoping review by Arksey and O'Malley (Int J Soc Methodol. 2005;8:19-32) were used. Some attempts have been made in developing frameworks of career development for cardiac rehabilitation professionals with these 3 components through guidelines/standards and core curriculum development worldwide, among which the United States is the only country with a well-established system including guidelines for cardiac rehabilitation/secondary prevention programs, a position statement in terms of competencies, and certification examination for cardiac rehabilitation professionals. Nevertheless, further development and integration of these efforts, specifically for cardiac rehabilitation nurses, are required. It is vital to raise the awareness of the significant contribution that appropriately educated and trained nurses make in reducing the global burden of cardiovascular disease through cardiac rehabilitation. Therefore, action on establishing a system of comprehensive, clearly defined career development pathway for cardiac rehabilitation nurses worldwide is of immediate priority.


Transcription Factor Nrf2 Modulates Lipopolysaccharide-Induced Injury in Bovine Endometrial Epithelial Cells.
Endometritis in high-yield dairy cows adversely affects lactation length, milk quality, and the economics of dairy products. Endoplasmic reticulum stress (ERS) in bovine endometrial epithelial cells (BEECs) occurs as a consequence of diverse post-natal stressors, and plays a key role in a variety of inflammatory diseases. Nuclear-factor-erythroid-2-related factor 2 (Nrf2) is an important protective regulatory factor in numerous inflammatory responses. However, the mechanism by which Nrf2 modulates inflammation by participating in ERS remains unclear. The objective of the present study was to explore the role of Nrf2 in lipopolysaccharide (LPS)-induced injury to BEECs and to decipher the underlying molecular mechanisms of this injury. The expression of Nrf2- and ERS-related genes increased significantly in bovine uteri with endometritis. Isolated BEECs were treated with LPS to stimulate the inflammatory response. The expression of Nrf2 was significantly higher in cells exposed to LPS, which also induced ERS in BEECs. Activation of Nrf2 led to enhanced expression of the genes for the inflammation markers TNF-α, p65, IL-6, and IL-8 in BEECs. Moreover, stimulation of Nrf2 was accompanied by activation of ERS. In contrast, Nrf2 knockdown reduced the expression of TNF-α, p65, IL-6, and IL-8. Additionally, Nrf2 knockdown decreased expression of ERS-related genes for the GRP78, PERK, eIF2α, ATF4, and CHOP proteins. Collectively, our findings demonstrate that Nrf2 and ERS are activated during inflammation in BEECs. Furthermore, Nrf2 promotes the inflammatory response by activating the PERK pathway in ERS and inducing apoptosis in BEECs.


Autologous fibrin sealant (Vivostat) for mesh fixation in laparoscopic transabdominal preperitoneal hernia repair.
The use of fibrin glue derived from humans or animals has been reported as an alternative method of mesh fixation, instead of staples, in inguinal hernia repair. However, fibrin sealants involve the potential risks of virus transmission or immunological reactions to foreign proteins. This risk could be avoided by using autologous fibrin derived from the patient. A feasibility study on the use of autologous fibrin was therefore carried out in patients undergoing laparoscopic transabdominal inguinal hernia repair. In a series of 10 patients undergoing laparoscopic transabdominal inguinal hernia repair, autologous fibrin was produced from 120 ml of the patient's blood during the hernia repair. The process took an average of 20 min. The perioperative and postoperative results were compared with those in a control group of 20 patients in whom conventional fibrin was used. Producing and applying the autologous fibrin was uncomplicated. No differences in the outcome were observed between the two groups. One patient in the conventional fibrin group developed a seroma. None of the patients reported persistent pain. No recurrences were observed after a mean follow-up period of 9 months (range 6 - 12 months) in the conventional fibrin group and 7 months (range 6 - 8 months) in the autologous fibrin group. This feasibility study suggests that autologous fibrin sealant allowed adequate mesh fixation that did not differ from that in a control group in whom conventional fibrin glue was used. Autologous fibrin may be an interesting alternative for a variety of laparoscopic and endoscopic applications.


A rare type of dual left anterior descending artery distribution demonstrated by multislice cardiac computerized tomography in a patient with anterior wall infarction.
Dual left anterior descending coronary artery (LAD) distribution with either of the vessels originating from the left main coronary artery (LMCA) and the right aortic sinus of Valsalva is an extremely rare coronary artery anomaly. Here we discuss a 45-year-old male who presented with non-ST-elevation anterior wall myocardial infarction due to near-total occlusion of the LAD immediately after its origin from the LMCA. The distal interventricular septum was supplied by an additional LAD arising from the right aortic sinus with a long septal course. The anomalous origin and septal course of the latter vessel were confirmed with multislice cardiac computerized tomography. The binary distribution of the LAD limited the extent of ischemic insult to the anterior wall in this case.


Resistant starch, fermented resistant starch, and short-chain fatty acids reduce intestinal fat deposition in Caenorhabditis elegans.
Obesity is a growing global public health dilemma. The objective of this project is to develop and validate a screening mechanism for bioactive compounds that may reduce body fat and promote health. Resistant starch (RS) reduces body fat in rodents. Amylose starch that has a high content of RS, endogenous compounds obtained from the ceca of amylose starch fed mice (fermented RS), and individual short-chain fatty acids (SCFA) were tested. The Caenorhabditis elegans model and Nile red staining were selected to determine the intestinal fat deposition response to bioactive components. The fluorescence intensity of Nile red was reduced to 76.5% (amylose starch), 78.8% (fermented RS), 63.6% (butyrate), or 28-80% (SCFAs) of controls, respectively (P < 0.001). The reduced intestinal fat deposition suggests reduced food intake or increased energy expenditure. C. elegans is a practical animal model to screen for bioactive compounds that may prevent or treat obesity.


Age-related differences in mammography use and in breast cancer knowledge, attitudes, and behaviors.
This study examined age differences in breast cancer knowledge, attitudes, and early-detection behaviors in a multi-ethnic sample of economically disadvantaged women participating in a breast-cancer education outreach program. Age differences in breast cancer knowledge, perceptions of risk of breast cancer, barriers to mammography, recommendations of mammography by health professionals, health promotion behaviors, and mammography use and intention were investigated. The subjects were 139 women aged 30 or older who were categorized in one of three age groups: 30 to 39, 40 to 49, and 50 years old or older. One fourth of the women between the ages of 30 and 39 reported both that they had had mammography in the past and that they intended to have it in the next year. Fifty percent of those in their forties reported mammography use at some time in the past, and 56% intended to obtain it in the coming year. Fifty percent of those 50 or older reported that they had had mammography in the past year. Women aged 40 or older were more likely than those in their thirties to report that their healthcare providers had encouraged them to get mammograms. No significant age differences were observed in breast cancer knowledge or perceptions of personal risk of breast cancer. The fact that the three age groups were similar in their perceptions of personal risk of breast cancer suggests that older women may not be accurately assessing their risk and thus may be obtaining screening mammography at less-than-optimal levels.


Risk assessment of malignancy in solitary pulmonary nodules in lung computed tomography: a multivariable predictive model study.
Computed tomography images are easy to misjudge because of their complexity, especially images of solitary pulmonary nodules, of which diagnosis as benign or malignant is extremely important in lung cancer treatment. Therefore, there is an urgent need for a more effective strategy in lung cancer diagnosis. In our study, we aimed to externally validate and revise the Mayo model, and a new model was established. A total of 1450 patients from three centers with solitary pulmonary nodules who underwent surgery were included in the study and were divided into training, internal validation, and external validation sets (n = 849, 365, and 236, respectively). External verification and recalibration of the Mayo model and establishment of new logistic regression model were performed on the training set. Overall performance of each model was evaluated using area under receiver operating characteristic curve (AUC). Finally, the model validation was completed on the validation data set. The AUC of the Mayo model on the training set was 0.653 (95% confidence interval [CI]: 0.613-0.694). After re-estimation of the coefficients of all covariates included in the original Mayo model, the revised Mayo model achieved an AUC of 0.671 (95% CI: 0.635-0.706). We then developed a new model that achieved a higher AUC of 0.891 (95% CI: 0.865-0.917). It had an AUC of 0.888 (95% CI: 0.842-0.934) on the internal validation set, which was significantly higher than that of the revised Mayo model (AUC: 0.577, 95% CI: 0.509-0.646) and the Mayo model (AUC: 0.609, 95% CI, 0.544-0.675) (P < 0.001). The AUC of the new model was 0.876 (95% CI: 0.831-0.920) on the external verification set, which was higher than the corresponding value of the Mayo model (AUC: 0.705, 95% CI: 0.639-0.772) and revised Mayo model (AUC: 0.706, 95% CI: 0.640-0.772) (P < 0.001). Then the prediction model was presented as a nomogram, which is easier to generalize. After external verification and recalibration of the Mayo model, the results show that they are not suitable for the prediction of malignant pulmonary nodules in the Chinese population. Therefore, a new model was established by a backward stepwise process. The new model was constructed to rapidly discriminate benign from malignant pulmonary nodules, which could achieve accurate diagnosis of potential patients with lung cancer.


A small plasmid in Shigella dysenteriae 1 specifies one or more functions essential for O antigen production and bacterial virulence.
The role of plasmids in the virulence of Shigella dysenteriae 1 W30864, which contains at least five species, was investigated. By means of a standard plasmid-curing procedure, that is, bacterial cultivation at an elevated temperature, five virulence-deficient derivatives were obtained. One of these lacked a small, 6-megadalton plasmid, designated pHW400, exhibited reduced invasiveness for HeLa cells, and failed to produce the somatic antigen. Transposon tagging of the pHW400 plasmid to produce pHW401 and the transfer of this derivative into a variant of strain W30864 lacking pHW400 confirmed the conclusion that the pHW400 plasmid encodes one or more functions involved in O antigen (lipopolysaccharide) biosynthesis and bacterial virulence. A plasmid of similar size was detected in all of the three other strains of S. dysenteriae 1 examined.


Primate B-1 cells generate antigen-specific B cell responses to T cell-independent type 2 antigens.
Ab responses to T cell-independent type 2 (TI-2) Ags, such as bacterial capsular polysaccharides, are critical for host defense. In mice, B-1b cells expressing a CD11b(+)FSC(hi)CD21(lo/-)CD19(hi) phenotype play a key role in producing Abs against TI-2 Ags. In primates, a distinct IgM(+)CD27(+) "memory" B cell population is thought to generate TI-2 Ab responses, and evidence for a B-1b-like cell population participating in these responses is lacking. In this article, we demonstrate that nonhuman primates (NHPs; African green monkeys and cynomolgus macaques) harbor serosal B cells expressing a CD11b(+)FSC(hi)CD21(lo/-)CD80(+/-)CD19(hi) phenotype, constitutively active Stat3, and increased reactivity with phosphorylcholine, similar to murine peritoneal B-1a and B-1b cell populations. Like what is observed for murine B-1b cells, NHP CD11b(+)FSC(hi)CD21(lo/-)CD19(hi) B cells dominate the Ag-specific B cell response and Ab production against the TI-2 Ag trinitrophenyl-Ficoll. Although Ag-specific IgM(+) B cells expressing CD27 were not detected prior to immunization, Ag-specific CD11b(+)CD19(hi) B cells expressed and maintained an IgM(+)IgD(lo)CD27(+)CD80(+) phenotype following immunization. Thus, the murine and NHP B cell populations responding to trinitrophenyl-Ficoll are highly similar, with the main exception being that Ag-specific NHP B-1-like cells express CD27 following TI-2 Ag encounter. Therefore, murine B-1b and primate IgM(+)CD27(+) "memory" B cell subsets proposed to produce TI-2 Ab responses may be highly related, if not identical. Overall, these data not only support that B-1-like cells are present in NHPs but also provide evidence that these cells perform the same functions attributed to murine B-1b cells.


Topical review: sleep bruxism and the role of peripheral sensory influences.
Sleep bruxism (SB) is an unusual orofacial movement described as a parafunction in dentistry and as a parasomnia in sleep medicine. Since several peripheral influences could be involved in sleep-wake regulation and the genesis of rhythmic jaw movements, the authors have reviewed the relevant literature to facilitate understanding of mechanisms possibly involved in SB genesis. Various animal and human studies indicate that during either wakefulness or anesthesia, orofacial sensory inputs (e.g., from periodontium, mucosa, and muscle) could influence jaw muscle activity. However, the role of these sensory inputs in jaw motor activity during sleep is unclear. Interestingly, during sleep, the jaw is usually open due to motor suppression; tooth contact most likely occurs in association with sleep arousal. Recent physiologic evidence supports an association between sleep arousal and SB; a sequential change from autonomic (cardiac) and brain cortical activities precede SB-related jaw motor activity. This suggests that the central and/or autonomic nervous systems, rather than peripheral sensory factors, have a dominant role in SB genesis. However, some peripheral sensory factors may exert an influence on SB through their interaction with sleep-wake mechanisms. The intent of this review is to integrate various physiologic concepts in order to better understand the mechanisms underlying the genesis of SB.


Sexistential Crisis: An Intersectional Analysis of Gender Expression and Sexual Orientation in Masculine Overcompensation.
Masculine overcompensation-a phenomenon where men react to masculinity threats by endorsing hypermasculine ideals-has been demonstrated among straight men but has yet to be examined among gay men. The current study therefore proposed to examine whether gay men overcompensate similarly to their straight counterparts by providing participants with randomized feedback that threatened their masculinity. Overcompensation was measured in 867 online respondents by administering a series of questionnaires regarding views of pornography, rape, sex roles, and political orientation. Although our hypothesis was not confirmed, results revealed the intersectionality of both sexual orientation and self-reported gender expression regarding the formation of different views and beliefs. Specifically, masculinity was differentially related to homophobic attitudes, more callous views toward victims of sexual assault, and various components of attitudes toward pornography in gay and straight men. Masculine gay males held stereotypically masculine views less strongly than their masculine straight counterparts, providing evidence that gay males adopt a different type of masculinity than straight males-something of a "masculinity lite." Such findings point to the converging influence of sexual orientation and gender expression as contributors relevant to the attitudes of gay and straight men. This information adds to a growing body of literature on differences between gay and straight men and can be used to inform theory, education, and clinical practice, particularly in settings where men grapple with the implications of their masculinity.


Mistletoe (viscum album) lectins as cytokine inducers and immunoadjuvant in tumor therapy. A review.
Therapy of cancer with a Viscum extract has been carried out in Europe for over six decades in thousands of patients with uncertain advantages. This approach has been bedeviled by major problems such as variable composition of the extract, lack of knowledge of active component(s) and mechanism of action, to cite a few. However the recent standardization of Viscumin in terms of galactoside-binding lectin activity has allowed to clarify that it can act as powerful inflammatory mediator able to stimulate the immune system. Merits and demerits of this approach have been reviewed and although the active component has probably not unique immunoenhancing properties, it may be useful as an adjuvant in the biological therapy of cancer and it should not be ignored any longer. As usual, medical progress depends upon experimentation and not exclusively on intuition and emotion.


Overexpressed Histocompatibility Minor 13 was Associated with Liver Hepatocellular Carcinoma Progression and Prognosis.
Among primary liver carcinoma cases, the proportion of liver hepatocellular carcinoma (LIHC) cases is 75%-85%. Current treatments for LIHC include chemotherapy, surgical excision, and liver transplantation, which are effective for early LIHC treatment. Nevertheless, the early symptoms of liver carcinoma are atypical, so a large proportion of LIHC patients are diagnosed at an advanced stage. Histocompatibility minor 13 (HM13), located in the endoplasmic reticulum, is responsible for catalysing the hydrolysis of some signal peptides after cleavage from the precursor protein. Here, we studied the role of HM13 in LIHC development through bioinformatics analysis. Database analysis showed that HM13 was of great significance for LIHC tumorigenesis. Compared to normal liver tissues, HM13 expression was increased to a greater extent in LIHC tissues. After analysis of Kaplan‒Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA) datasets, we discovered that highly expressed HM13 exhibited an association with shorter overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS). We conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to analyse HM13-related genes, and the data indicated that these genes obviously participated in rRNA processing, ribosome biogenesis, spliceosome, Huntington's disease, and ATP-dependent helicase activity. The Cell Counting Kit-8 (CCK-8) assay and Transwell assay showed that reducing HM13 expression hindered LIHC cell proliferation, migration, and invasion. In conclusion, these findings indicate that HM13 is a biomarker and is related to the poor prognosis of LIHC. Our results are conducive to discovering new targets for LIHC treatment.


Sequential learning in individuals with agrammatic aphasia: evidence from artificial grammar learning.
We examined sequential learning in individuals with agrammatic aphasia (n = 12) and healthy age-matched participants (n = 12) using an artificial grammar. Artificial grammar acquisition, 24-hour retention, and the potential benefits of additional training were examined by administering an artificial grammar judgment test (1) immediately following auditory exposure-based training, (2) one day after training, and (3) after a second training session on the second day. An untrained control group (n = 12 healthy age-matched participants) completed the tests on the same time schedule. The trained healthy and aphasic groups showed greater sensitivity to the detection of grammatical items than the control group. No significant correlations between sequential learning and language abilities were observed among the aphasic participants. The results suggest that individuals with agrammatic aphasia show sequential learning, but the underlying processes involved in this learning may be different than for healthy adults.


Effect of inhomogeneous broadening on time-resolved photoluminescence in CaAlSiN3:Eu2+.
The decay behavior of CaAlSiN(3):Eu(2+) was monitored as a function of the detection wavelength on the Eu(2+) emission band for various Eu(2+) concentrations from 0.0005 to 0.05. The decay at the higher-energy side was faster and less linear than the lower-energy side decay for all Eu(2+) concentrations. This was due to an inhomogeneous broadening induced by the random distribution of Al and Si ions at a crystallographic site in the CaAlSiN(3) structure and to the successive site-to-site energy transfer. This phenomenon caused a redshift of the Eu(2+) emission band as the Eu(2+) concentration increased.


Restoration of endothelial function after repaired coarctation of the aorta--a case report.
According to current literature, there is no clinical report regarding coronary spasm in the presence of aortic coarctation. There are no cases in which endothelial function was restored after the repair of aortic coarctation. A 29-year-old woman with aortic coarctation and acute myocardial infarction due to coronary spasm experienced restoration of endothelial function after the repair of aortic coarctation. This case may increase knowledge of the mechanism of coronary damage in human coronary arteries not only with a coarcted aorta but also with hypertensive heart.


Animal models of spontaneous autoimmune disease: type 1 diabetes in the nonobese diabetic mouse.
The nonobese diabetic (NOD) mouse represents probably the best spontaneous model for a human autoimmune disease. It has provided not only essential information on type 1 diabetes (T1D) pathogenesis, but also valuable insights into mechanisms of immunoregulation and tolerance. Importantly, it allows testing of immunointervention strategies potentially applicable to man. The fact that T1D incidence in the NOD mouse is sensitive to environmental conditions, and responds, sometimes dramatically, to immunomanipulation, does not represent a limit of the model, but is likely to render it even more similar to its human counterpart. In both cases, macrophages, dendritic cells, CD4+, CD8+, and B cells are present in the diseased islets. T1D is a polygenic disease, but, both in human and in NOD mouse T1D, the primary susceptibility gene is located within the MHC. On the other hand, T1D incidence is significantly higher in NOD females, although insulitis is similar in both sexes, whereas in humans, T1D occurs with about equal frequency in males and females. In addition, NOD mice have a more widespread autoimmune disorder, which is not the case in the majority of human T1D cases. Despite these differences, the NOD mouse remains the most representative model of human T1D, with similarities also in the putative target autoantigens, including glutamic acid decarboxylase IA-2, and insulin.


NONMEM and NPEM2 population modeling: a comparison using tobramycin data in neonates.
Nonlinear mixed effects modeling (NONMEM) and nonparametric expectation maximization (NPEM2) have both been used in population modeling of tobramycin. We compared both methods for differences in population pharmacokinetic parameters in relation to error models used. Predictive performance was compared between models. A group of 470 neonates who had received tobramycin according to a gestational age (GA)-dependent dosing interval was analyzed according to a one-compartment model with NONMEM and NPEM2. Additional models were constructed where the assay error pattern in NPEM2 mimicked NONMEM residual error and vice versa. Individual pharmacokinetic parameter estimates were compared. Predictive performance was evaluated in a separate group of 61 patients. Population estimates and variation coefficients (CV) for optimal models were NONMEM K(el) 0.071 h(-1) (27%), V(d) 0.59 L/kg (9%); NPEM2 K(el) 0.079 h(-1) (42%), V(d) 0.65 L/kg (48%). Forcing NONMEM to use the NPEM2 error pattern as residual error or vice versa resulted in smaller differences in CVs of the estimates. NONMEM gave less bias (P < 0.05) than NPEM2 and comparable precision with this approach. In conclusion NONMEM and NPEM2 are dissimilar in population estimates. Differences in ranges of pharmacokinetic parameter estimates between NONMEM and NPEM2 are largely determined by the method of incorporating error patterns in both programs.


Disease duration and herpes zoster infection related to neutropenia in patients with systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is an autoimmune disease involving several organs. Neutropenia in patients with SLE may be a factor associated with infection leading to higher morbidity and mortality. There are several inconsistent predictors of neutropenia in patients with SLE. The present study is a retrospective, analytical study, which aimed to identify other predictors of neutropenia in patients with SLE. Patients with SLE who had been regularly followed up for ≥1 year were included in this study. Clinical factors, including history of disease, comorbidities, previous infection, laboratory results and treatment, were collected. The primary analyzed indicator was the occurrence of neutropenia. Factors associated with neutropenia were calculated by multivariate logistic regression analysis. A total of 84 patients met the study criteria. Of those 84 patients, 36 (42.86%) developed neutropenia. There were seven factors placed in the predictive model for neutropenia. Two factors were independently associated with the presence of neutropenia: Disease duration and herpes zoster infection. The first factor was negatively related with neutropenia with an adjusted odds ratio of 0.70 (95% confidence interval, 0.54, 0.92), whereas herpes zoster infection was an independent risk factor for neutropenia with an adjusted odds ratio of 8.46 (95% confidence interval, 1.30, 54.80). In conclusion, the present study revealed that short duration of disease and herpes zoster infection are predictors of neutropenia in patients with SLE.


Haematuria in patients with haemophilia and its influence on renal function and proteinuria.
To investigate renal function in a group of patients with a history of haemophilia and haematuria. We reviewed 32 medical records of the patients with haemophilia and gross haematuria identified through a computerized haemophilia registry, from January 1993 to December 2004. In all patients but three (two refused to participate and one died) clinical and laboratory tests were performed by the nephrologist. One patient had chronic renal failure because of diabetic nephropathy. In two patients reduced renal function was detected by creatinine clearance measurements, and one of them had Duchenne muscular dystrophy. In four patients minimal proteinuria was diagnosed by the biuret method. Mild reduction in renal function of unknown cause was found in only one of the 29 patients tested.


The experience of auditory implant recipients undergoing magnetic resonance imaging: Factors associated with pain.
Many patients with cochlear implants (CI) and auditory brainstem implants (ABI) require magnetic resonance imaging (MRI) following implantation. This study explores the patient experience of MRI, identifying factors associated with pain, and the effect of interventions designed to enhance comfort and safety. A prospective observational case series from a tertiary referral unit. Tight head bandaging ± local anaesthetic injection (devices with non-MRI-compatible magnets) or observation alone (implants with MRI-compatible magnets) were employed for 1.5 T MRI of consecutive adult patients with CI or ABI without magnet removal. Pain was recorded via visual analogue scale (1 = no pain, 5 = extreme pain) at three time points; (1) baseline, (2) head bandage applied (3) during scanning. Patient age, device type, body area imaged and total scan time were recorded as variables, alongside adverse events. Data were collected for 227 MRI scans (34 patients with ABI, 32 with CI). In patients managed with bandaging, pain score after bandaging but prior to scanning (median 2.2) did not differ from pain during scanning (2.1), but both were significantly higher than baseline (1.4, both P ≤ 0.001). Scanning areas other than the head/cervical spine was associated with higher pain scores (P = 0.036). Pain during MRI differed between different manufacturers implants (P ≤ 0.001). Adverse events occurred in 8/227 scans (3.5%), none occurring with devices containing an MRI-compatible magnet. MRI scanning with auditory implant magnets in situ is safe and well tolerated by patients.


BMI and BMI Changes to All-cause Mortality among the Elderly in Beijing: a 20-year Cohort Study.
To explore the association between body mass index (BMI) and all-cause mortality among the elderly in Beijing. This analysis was based on the Beijing multidimensional longitudinal study of aging (BLSA), which included 2,090 subjects over 55 years old and was followed-up from 1992 to 2012. BMI-mortality curves were drawn to find the optimal BMI range with the lowest mortality. Cox proportional hazard models were used to obtain the hazard ratios (HRs) for BMI and BMI changes in the overall population and in specific stratified populations. During follow-up, 1,164 deaths were recorded; BMI-mortality curve was U-shaped, with the lowest mortality at a BMI of approximately 25 kg/m2. After adjusting for gender, age, smoking, drinking and some pre-existing diseases, HRs for underweight, overweight and obesity compared with normal weight were 1.372 (95% CI: 1.154-1.631), 0.767 (95% CI: 0.666-0.884) and 0.871 (95% CI: 0.830-1.246), respectively. HR for BMI drop was 3.245 (95% CI: 0.824-12.772) in the underweight group and 1.892 (95% CI: 0.830-1.246) in the normal weight group, HR for BMI rise was 1.795 (95% CI: 1.243-2.591) in normal weight group and 1.962 (95% CI: 1.202-3.203) in the overweight group. Keeping BMI in an overweight status and stable is related to a reduced mortality.


Understanding the interactions between cephalopods and marine litter: A research evaluation with identification of gaps and future perspectives.
Litter is known to negatively affect numerous marine organisms, but the extent of such impacts is not well known for several groups, including cephalopods. Considering the ecological, behavioral and economic importance of these animals, we reviewed the types of interactions between cephalopods and litter in the scientific literature, to evaluate impacts and knowledge gaps. We found 30 papers, which included records of microplastic ingestion and the transfer of synthetic microfibers along the food web. The largest number of records involved litter use as shelter, and the common octopus was the most frequent species. At first sight, litter use as shelter could appear to be a potential positive effect, but it is necessary to clarify the implications of this choice and its long-term consequences. Regarding ingestion and trophic transfer, further research is needed to elucidate its occurrence and impacts on cephalopods and their predators, including humans.


Some novel polymeric nanocomposites.
The nanocomposites described here all involve polymers and were chosen because they are already of commercial importance, show some promise of becoming so, or simply seem interesting. The field is so broad that some topics are mentioned only very briefly, and there is considerable emphasis on the polysiloxane nanocomposites studied by the author's research group. Some are typically prepared using techniques very similar to those used in the new sol-gel approach to ceramics, with either the polymer or the ceramic being the continuous phase. Other dispersed phases include particles responsive to an applied magnetic field, intercalated or exfoliated platelets obtained from clays, mica, or graphite, silsesquioxane nanocages, nanotubes, dual fillers, porous particles, spherical and ellipsoidal polymeric particles, and nanocatalysts. Also described are some typical studies involving theory or simulations on such particle reinforcement. Experiments on ceramics modified by dispersed polymers are equally interesting, but there is less relevant theory. Many of the fields mentioned have become so vast that the approach taken here is simply to describe general approaches and characteristics of the composites, list some specific examples, and provide leading references (with some emphasis on studies that are relatively recent or in the nature of reviews).


Modulation of human T cell production of migration inhibitory lymphokines by cytokines derived from human leukocyte dialysates.
Human leukocyte dialysates contain components capable of amplifying cutaneous delayed-type hypersensitivity (DTH) reactions. In the present study, two such amplifiers, both less than 3500 m.w., were partially purified from human leukocyte dialysates by gel filtration on Sephadex G-10 followed by high pressure reverse-phase liquid chromatography. These amplifiers of DTH were examined for their effects on production of the migration inhibitory lymphokines leukocyte migration inhibition factor (LIF) and macrophage migration inhibition factor (MIF). The amplifiers were found to increase LIF and MIF production by antigen- or alloantigen-stimulated human peripheral blood lymphocytes in a dose-dependent fashion. Further analysis demonstrated that although antigen-stimulated T4 and T8 cell subpopulations could produce LIF activity under the assay conditions employed, amplification of lymphokine production by modulator was only observed with the T4 subset.


Ameliorative effects of snake (Deinagkistrodon acutus) oil and its main fatty acids against UVB-induced skin photodamage in mice.
The effects of topically administered snake (Deinagkistrodon acutus) oil and its main fatty acid components on skin photodamage were explored. Epidermal thickness, mice body weight, antioxidant enzymes (superoxide dismutase, glutathione peroxidase, catalase), inflammatory cytokines (tumor necrosis factor alpha and interleukin-6), skin histology, collagen content, and metalloproteinase-1 indicators were analyzed. The results show that topical application of both snake oil and its main fatty acids recovered ultraviolet B (UVB) irradiation induced antioxidant enzymes depletion, prevented metalloproteinase-1. Snake oil and its main fatty acids suppressed dermal infiltration of inflammatory cells and reduced inflammatory cytokines levels. Notably, there was no significant difference in the antioxidant activity but a significant difference in the anti-inflammatory activity between fatty acids and snake oil under the same dose. Finally, snake oil and its main fatty acids inhibited UVB-induced histological damage such as epidermal thickening, collagen fiber and elastic fiber destruction. Our study demonstrated for the first time in KM mice that snake oil exhibited prominent photoprotection activity by protecting the activity of antioxidant enzymes and inhibiting inflammatory factors, as well as reducing the generation of MMP-1. What's more, the main fatty acids in snake oil play an important role in preventing photo-damage especially in protecting antioxidant enzyme activity.


RGS6: a novel gene associated with congenital cataract, mental retardation, and microcephaly in a Tunisian family.
The object of this study is to identify the underlying genetic defect in a consanguineous Tunisian family affected with autosomal recessive congenital cataract associated with mental retardation and microcephaly. A whole-genome scan was performed with polymorphic microsatellites in the axiom data for the screened members. Homozygous regions were analyzed with integrated Systems Tool for Eye gene Discovery (iSyTE), to identify candidate genes with lens-enriched expression that were potentially associated with cataract. Then we screened for mutations by direct sequencing. Structure and function of the mutant gene were analyzed by bioinformatics analysis. Using whole-genome scanning, we identified six runs of homozygosity shared among affected members of the studied family. Analysis of these regions by iSyTE allowed us to select 3 genes (RGS6, PCNX, and P4HA1) according to their expression in 3 critical stages of lens development. Upon screening for mutations by sequencing analysis, we found a novel mutation in RGS6, the splice-acceptor variant c.1369-1G>C that was not previously reported in congenital cataract phenotypes. Our study identified a new gene to be included in the large spectrum of cataract-associated genes. Importantly, the study demonstrated that, in addition to lens-enriched genes that exhibit high expression levels, genes identified by iSyTE that are highly lens-enriched but have lower absolute expression may also represent candidates for potential function in the lens.


Calciuric effects of short-term dietary loading of protein, sodium chloride and potassium citrate in prepubescent girls.
Studies using adult human subjects indicate that dietary protein and sodium chloride have negative effects on the retention of calcium by increasing urinary calcium excretion, while alkaline potassium improves calcium retention along with decreasing urinary calcium losses. This study investigated the effect of these dietary factors on acute urinary calcium excretion in 14 prepubescent girls age 6.7 to 10.0 years. Subjects provided a fasting urine sample then consumed a meal containing one of five treatments: moderate protein (MP) providing 11.8 g protein, moderate protein plus 26 mmol sodium chloride (MP+Na), high protein (HP) providing 28.8 g protein, high protein plus 26 mmol sodium chloride (HP+Na), or high protein plus 32 mmol potassium as tripotassium citrate (HP+K). Urine was collected at 1.5 and 3.0 hours after the meal. Supplemental protein was given as 80:20 casein:lactalbumin. Test meals were isocaloric, and unless intentionally altered, components of interest except phosphate were equal between treatments. Each subject completed all five treatments. Urinary calcium excretion rose after the meal, peaking at 1.5 hours. There were no significant differences in calcium excretion between treatments at any time point. The high protein treatments did not result in a significant increase in either net acid or sulfate excretion at 1.5 hours compared to moderate protein. Dietary sodium chloride had no effect on urinary sodium or calcium excretion over the 3 hours. After the potassium treatment, sodium excretion increased (p< or =0.002) and net acid excretion decreased (p<0.001) compared to other treatments at 1.5 hours. In children, a simultaneous increase in protein and phosphorus due to increased milk protein intake did not increase acute urinary calcium excretion. An effect of dietary sodium chloride on acute urinary calcium excretion was not observed. Both these findings were similar to those of adult studies previously conducted in the same laboratory using similar format and treatments. Potassium citrate was not hypocalciuric in children, a response differing from that for adults, who have shown a decrease in acute urinary calcium excretion in response to alkaline potassium treatment. Further characterization of calciuric responses to dietary factors is required for children, who may differ from adults in many respects.


Laterality and Lateralization in Autism Spectrum Disorder, Using a Standardized Neuro-Psychomotor Assessment.
A detailed assessment of laterality in children with Autism Spectrum Disorder (ASD) was realized, including handedness and other measures (muscle tone, manual performance, dominant eye), using a standardized battery for the developmental assessment of neuro-psychomotor functions. The results of the laterality tests relating to cerebral hemisphere organization (spontaneous gestural laterality and tonic laterality) were different in ASD children, and indicate that the cerebral organization could be disrupted. These assessments, added to the observations of usual laterality most often reported in the literature, provide better understanding of the developmental organization from the pathophysiological point of view in children with ASD.


Previous Mental Load and Incentives Influence Anticipatory Arousal as Indexed by the Baseline Pupil Diameter in a Speech-in-Noise Task.
Listening effort and fatigue are common experiences when conversing in noisy environments. Much research has investigated listening effort in relation to listening demand using the speech-in-noise paradigm. Recent conceptualizations of listening effort postulate that mental fatigue should result in decreased arousal and a reluctance to invest further effort, particularly when the effort is not worthwhile. The aim of the study was to investigate the influence of fatigue on listening effort, in interaction with listening demands and motivation. To induce fatigue 30 adults with normal hearing completed a 40-minute long speech-in-noise task ("load sequence"). Pre- and post-load sequence listening effort was probed in easy and hard listening demands (individually adjusted signal-to-noise ratios); with high and low motivation (manipulated with monetary incentives). Subjective effort, estimated performance, and tendency to quit listening were collected using rating scales. Baseline pupil diameter and mean pupil dilation were recorded as indices of anticipatory arousal and objective effort. Self-reported effort and mean pupil dilation were overall larger during hard SNR as compared to easy SNR. Baseline pupil diameter declined from pre- to post-load sequence, suggesting an overall decrease in arousal. Monetary incentives had no influence on the baseline pupil diameter for the easy SNR condition, but for the hard SNR condition larger incentives led to larger baseline pupil diameter. These results suggest that anticipatory arousal may be influenced by fatigue and motivation effects. Models of listening effort should account for the independent influence of motivation and previous load on anticipatory arousal and effort in distinct parameters.


[Successful further prolongation of immature twin pregnancy by tocolysis and re-cerclage following unavoidable delivery of the first foetus after emergency cerclage (author's transl)].
The article reports on a twin pregnancy with EPH gestosis in a 20-year old primipara which could be prolonged by tocolysis and emergency cerclage after signs of premature delivery and prolapse of the amniotic sac in the 28th/29th pregnancy week. At the beginning of the 30th gestation week there was an unavoidable delivery of the first twin (920 g) who survived for 5 days only due to immaturity and hypotrophy. Directly after delivery of the first twin the pregnancy for the second twin was prolonged by renewed tocolysis and renewed circular suture of the cervix. This enabled the second child, whose growth had been retarded like that of the first one, to continue to grow for some time. Unavoidable delivery of the second twin (1,650 g) eventually occurred at the beginning of the 32nd week of pregnancy. The eutrophic child survived without the slightest complication. This case is presented in detail and discussed, including the histology of the placenta. The most important points for enabling the survival of a twin foetus are sufficient tocolysis, a satisfactory technique for occlusion of the os uteri, as well as exclusion and prevention of chorioamnionitis.


Outcome After Reperfusion Therapies in Patients With Large Baseline Diffusion-Weighted Imaging Stroke Lesions: A THRACE Trial (Mechanical Thrombectomy After Intravenous Alteplase Versus Alteplase Alone After Stroke) Subgroup Analysis.
Stroke patients with large diffusion-weighted imaging (DWI) volumes are often excluded from reperfusion because of reckoned futility. In those with DWIvolume >70 mL, included in the THRACE trial (Mechanical Thrombectomy After Intravenous Alteplase Versus Alteplase Alone After Stroke), we report the associations between baseline parameters and outcome. We examined 304 patients with anterior circulation stroke and pretreatment magnetic resonance imaging. Variables were extracted from the THRACE database, and DWI volumes were measured semiautomatically. Among 53 patients with DWIvolume >70 mL, 12 had favorable outcome (modified Rankin Scale score, ≤2) at 3 months; they had less coronary disease (0/12 versus 12/38; P=0.046) and less history of smoking (1/10 versus 12/31; P=0.013) than patients with modified Rankin Scale score >2. None of the 8 patients >75 years of age reached modified Rankin Scale score ≤2. Favorable outcome occurred in 12 of 37 M1-occluded patients but in 0 of 16 internal carotid-T/L-occluded patients (P=0.010). Favorable outcome was more frequent (6/13) when DWI lesion was limited to the superficial middle cerebral artery territory than when it extended to the deep middle cerebral artery territory (6/40; P=0.050). Stroke patients with DWI lesion >70 mL may benefit from reperfusion therapy, especially those with isolated M1 occlusion or ischemia restricted to the superficial middle cerebral artery territory. The benefit of treatment seems questionable for patients with carotid occlusion or lesion extending to the deep middle cerebral artery territory.


Binding, oligomerization, and pore formation by streptolysin O in erythrocytes and fibroblast membranes: detection of nonlytic polymers.
Streptolysin O (SLO) is a representative of the family of cholesterol-binding cytolysins that form large pores in target cell membranes. Aggregation of the toxin to polymeric structures is required for pore formation. However, it is not known whether, vice versa, polymers may under certain circumstances remain nonfunctional, and whether this might be the cause underlying the relative resistance of certain cells towards toxin action. In the present study, we applied radioiodinated, functionally active SLO to human, rabbit, and mouse erythrocytes and to human fibroblasts and keratinocytes. Binding and polymerization were quantified and correlated with membrane damage. At low toxin concentrations, human and rabbit but not mouse erythrocytes were lysed, but binding and polymerization of SLO were essentially identical in all cases. Nonlytic polymers were also detected on human fibroblasts and keratinocytes treated with subcytotoxic concentrations of SLO, and quantitative estimates indicated that nonpermeabilized cells could carry hundreds of polymers on their surface. When applied at low concentrations to fibroblasts, much of the toxin remained in monomer form and was subsequently shed from the cells. This was shown by monitoring the fate of radioiodinated toxin and also by using a sensitive cell enzyme-linked immunosorbent assay that permitted immunological detection of surface-exposed SLO. Thus, relative resistance of cells towards the permeabilizing action of SLO may be due to their ability to tolerate formation of a limited number of SLO polymers and to shedding of nonoligomerized toxin from their surface.


Design, Synthesis and Biological Evaluation of 7-Chloro-9H-pyrimido[4,5-b]indole-based Glycogen Synthase Kinase-3β Inhibitors.
Glycogen synthase kinase-3β (GSK-3β) represents a relevant drug target for the treatment of neurodegenerative pathologies including Alzheimer's disease. We herein report on the optimization of a novel class of GSK-3β inhibitors based on the tofacitinib-derived screen hit 3-((3R,4R)-3-((7-chloro-9H-pyrimido[4,5-b]indol-4-yl)(methyl)amino)-4-methylpiperidin-1-yl)-3-oxopropanenitrile (1). We synthesized a series of 19 novel 7-chloro-9H-pyrimido[4,5-b]indole-based derivatives and studied their structure-activity relationships with focus on the cyanoacetyl piperidine moiety. We unveiled the crucial role of the nitrile group and its importance for the activity of this compound series. A successful rigidization approach afforded 3-(3aRS,7aSR)-(1-(7-chloro-9H-pyrimido[4,5-b]indol-4-yl)octahydro-6H-pyrrolo[2,3-c]pyridin-6-yl)-propanenitrile (24), which displayed an IC50 value of 130 nM on GSK-3β and was further characterized by its metabolic stability. Finally, we disclosed the putative binding modes of the most potent inhibitors within the ATP binding site of GSK-3β by 1 µs molecular dynamics simulations.


Catheter-based revascularization of the hepatic artery to treat coronary steal from a gastroepiploic artery bypass graft.
During diagnostic cardiac catheterization for symptoms of progressive angina, a high-grade ostial stenosis of an aberrant hepatic artery was identified. The common hepatic artery, which originated directly from the aorta rather than the celiac artery, supplied an in situ gastroepiploic artery bypass graft to the distal right coronary artery. Reduced flow within the bypass graft was observed consistent with a steal phenomenon from the coronary artery. This report describes successful angioplasty and stenting of the hepatic artery to salvage the gastroepiploic bypass graft and resolve the patient s ischemic symptoms.


Metered Cryospray™: a novel uniform, controlled, and consistent in vivo application of liquid nitrogen cryogenic spray.
In this article, a novel cryotherapy approach using a uniform, controlled, and consistent in vivo application of liquid nitrogen (LN2) spray as a Metered Cryospray™ (MCS) process is described. Although MCS may be used for many potential clinical applications, this paper focuses on the development that led to the controlled and consistent delivery of radial LN2 cryogen spray in order to generate a uniform circumferential effect and how the amount of MCS can be adapted to specifically ablate targeted diseases within a patient's lumen such as an airway or esophagus.


CD147 promotes Src-dependent activation of Rac1 signaling through STAT3/DOCK8 during the motility of hepatocellular carcinoma cells.
Metastasis is considered a dynamic process in tumor development that is related to abnormal migration and invasion. Tumor cells can move as individual cells in two interconvertible modes: mesenchymal-type and amoeboid. Previously, we reported that the interaction between CD147 and Annexin II can inhibit the amoeboid movement in hepatocellular carcinoma (HCC) cells. However, the mechanism of CD147 involved in mesenchymal movement is still unclear. Notably, our results show overexpression of CD147 led to mesenchymal-type movement in HCC cells. Evidence indicated that the mesenchymal-type cell movement induced by CD147 was Src dependent, as observed by confocal microscopy and Rac1 activity assay. The phosphorylation of Src (pY416-Src) can be up-regulated by CD147, and this regulation is mediated by focal adhesion kinase (FAK). Next, we identified DOCK8 as a GEF for Rac1, a key molecule driving mesenchymal-type movement. We also found that Src promotes STAT3 phosphorylation and STAT3 facilitates DOCK8 transcription, thus enhancing DOCK8 expression and Rac1 activation. This study provides a novel mechanism of CD147 regulating mesenchymal-type movement in HCC cells.


Trace elements in shellfish on the Danish market.
Different kinds of shellfish have been investigated for their contents of the trace elements cadmium, lead, mercury, nickel, chromium, arsenic and selenium. The investigation included shrimps, mussels, lobster, langoustine, crayfish, crab claws and oyster. None of the Danish action levels for cadmium, lead and mercury respectively were exceeded, but the highest concentration of lead was very close to the Danish action levels. Shellfish do not contribute significantly to the intake of the trace elements investigated.


[An improved operation approach for bipedal rat model construction].
To explore an improved operation approach to make up the ethical deficiency of classical bipedal rat model. 20 SD rats were randomly divided into an improved group and a traditional group averagely. Improved group were operated with plexus brachialis nerve amputation, while traditional group with forelimbs amputation close to shoulder joint. Forelimb and shoulder joint movements were observed and electromyography of the peripheral muscles around shoulder joint were recorded to make certain the paralytic scope. Operation duration and axillary artery hurt probability of both the improved and traditional operation were compared to evaluate the operation risk of improved approach. Mean total upright time on 2 d, 1 w, 2 w, 4 w and 6 w post-operation and upright posture on 6 w post-operation were recorded to evaluate the human-upright-posture-simulating effect of bipedal rats operated with improved approach. Compared with classical amputation approach, improved approach exhibited simpler operation procedure, shorter operation duration and lower axillary artery hurt probability. Electromyography revealed that all forelimb muscles and most shoulder-peripheral muscles were denervated, forelimbs of the improved bipedal rats were absolutely paralyzed and shoulder joint reserved only slight abduction function. The mean total upright time of improved bipedal rats was longer than the classical ones after 2 w post-operation, while upright posture showed no difference with classical bipedal rats. The improved operation approach not only simplified operation procedures, but also achieved even better effect than classical amputation operation and exempted bipedal rat model from the ethical shadow.