Probiotic properties of Lactobacillus strains isolated from Tibetan kefir grains.
The objective of this study was to evaluate the functional properties of lactic acid bacteria (LAB) isolated from Tibetan kefir grains. Three Lactobacillus isolates identified as Lactobacillus acidophilus LA15, Lactobacillus plantarum B23 and Lactobacillus kefiri D17 that showed resistance to acid and bile salts were selected for further evaluation of their probiotic properties. The 3 selected strains expressed high in vitro adherence to Caco-2 cells. They were sensitive to gentamicin, erythromycin and chloramphenicol and resistant to vancomycin with MIC values of 26 µg/ml. All 3 strains showed potential bile salt hydrolase (BSH) activity, cholesterol assimilation and cholesterol co-precipitation ability. Additionally, the potential effect of these strains on plasma cholesterol levels was evaluated in Sprague-Dawley (SD) rats. Rats in 4 treatment groups were fed the following experimental diets for 4 weeks: a high-cholesterol diet, a high-cholesterol diet plus LA15, a high-cholesterol diet plus B23 or a high-cholesterol diet plus D17. The total cholesterol, triglyceride and low-density lipoprotein cholesterol levels in the serum were significantly (P<0.05) decreased in the LAB-treated rats compared with rats fed a high-cholesterol diet without LAB supplementation. The high-density lipoprotein cholesterol levels in groups B23 and D17 were significantly (P<0.05) higher than those in the control and LA15 groups. Additionally, both fecal cholesterol and bile acid levels were significantly (P<0.05) increased after LAB administration. Fecal lactobacilli counts were significantly (P<0.05) higher in the LAB treatment groups than in the control groups. Furthermore, the 3 strains were detected in the rat small intestine, colon and feces during the feeding trial. The bacteria levels remained high even after the LAB administration had been stopped for 2 weeks. These results suggest that these strains may be used in the future as probiotic starter cultures for manufacturing novel fermented foods.


Similarities and differences in the pathogenesis of alcoholic and nonalcoholic steatohepatitis.
Subpopulations of individuals with alcohol-induced fatty livers and nonalcoholic steatosis develop steatohepatitis. Steatohepatitis is defined histologically: increased numbers of injured and dying hepatocytes distinguish this condition from simple steatosis. The increased hepatocyte death is generally accompanied by hepatic accumulation of inflammatory cells and sometimes increases in myofibroblastic cells, leading to hepatic fibrosis and eventually, cirrhosis. The purpose of this review is to summarize similarities and differences in the pathogenesis of steatohepatitis in alcoholic fatty liver disease and nonalcoholic fatty liver disease.


Atypical Presentation of an Epidural Hematoma in a Patient Receiving Rivaroxaban After Total Hip Arthroplasty.
The authors report a case of a 69-year-old woman who presented with a spontaneous spinal epidural hematoma (SSEH) 10 days after a total hip arthroplasty. The patient had been receiving 10 mg/d of rivaroxaban for 5 days for venous thromboembolism prophylaxis. She had a sudden onset of severe neck pain, followed by quadriplegia below C4. A dorsal SSEH was revealed by computed tomography. While preparing for the emergency evacuation of the SSEH, the neurological symptoms resolved spontaneously in 4 hours. The 1-month follow-up magnetic resonance imaging confirmed that the SSEH had completely resolved. The pathogenesis of SSEH is unclear, but anticoagulant therapy is a known risk factor. It is a relatively rare disorder. Only 1 case of SSEH has been reported, and that patient was receiving a nonsteroidal anti-inflammatory drug besides rivaroxaban, which is another known risk factor for bleeding disorders. [Orthopedics. 2016; 39(3):e558-e560.].


[Relation of the time course of Japanese Pediatric Asthma Control Test (JPAC) and Childhood Asthma Control Test (C-ACT) score with respiratory function and fractional exhaled nitric oxide (FENO)].
Two major convenient questionnaires of asthma control in childhood, Japanese Pediatric Asthma Control Program (JPAC) and Childhood Asthma Control Test (C-ACT) have been available in Japan. The aim of this study is to evaluate relationship of two questionnaires in terms of the changes of respiratory function and fractional nitric oxide (FENO) in each individual. The 102 samples from patients with asthma aged 6 to 11 years old and their parents' answers for the two questionnaires at regular visits were collected. At the same time, respiratory functions and FENO were measured. The correlations of each difference of scores (+/-JPAC or +/-C-ACT), correlations of +/-JPAC or +/-C-ACT and increased ratio of respiratory functions and FENO (DeltaFENO%) were examined. We analyzed the factors that influences on respiratory functions and FENO. Moreover, the correlations of increased ratio of respiratory functions and DeltaFENO% were examined. Changes of JPAC and C-ACT correlated with each other. (rho=0.725, p<0.0001) DeltaFENO% was influenced by medications, especially ICS. +/-JPAC weakly correlated with DeltaFEV1% and DeltaFEF25-75% and DeltaPEF%, so did C-ACT. +/-JPAC correlated most strongly with the change of DeltaFEF25-75% among the parameters of respiratory functions. (rho=0.357, p=0.0003)+/-JPAC, but not +/-C-ACT weakly correlated with DeltaFENO%. (rho=-0.2045, p=0.0401) JPAC and C-ACT reflect the change of the respiratory function of each patient rather than those at random visit. Furthermore, JPAC may reflect FENO. In conclusion, recognition of the changes of the scores of these questionnaires may increase the utilities of the same scores obtained at a single visit. It is needed further study how to use FENO added on these questionnaires.


Retinal degeneration increases susceptibility to myopia in mice.
Retinal diseases are often associated with refractive errors, suggesting the importance of normal retinal signaling during emmetropization. For instance, retinitis pigmentosa, a disease characterized by severe photoreceptor degeneration, is associated with myopia; however, the underlying link between these conditions is not known. This study examines the influence of photoreceptor degeneration on refractive development by testing two mouse models of retinitis pigmentosa under normal and form deprivation visual conditions. Dopamine, a potential stop signal for refractive eye growth, was assessed as a potential underlying mechanism. Refractive eye growth in mice that were homozygous for a mutation in Pde6b, Pde6b(rd1/rd1) (rd1), or Pde6b(rd10/rd10) (rd10) was measured weekly from 4 to 12 weeks of age and compared to age-matched wild-type (WT) mice. Refractive error was measured using an eccentric infrared photorefractor, and axial length was measured with partial coherence interferometry or spectral domain ocular coherence tomography. A cohort of mice received head-mounted diffuser goggles to induce form deprivation from 4 to 6 weeks of age. Dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels were measured with high-performance liquid chromatography in each strain after exposure to normal or form deprivation conditions. The rd1 and rd10 mice had significantly greater hyperopia relative to the WT controls throughout normal development; however, axial length became significantly longer only in WT mice starting at 7 weeks of age. After 2 weeks of form deprivation, the rd1 and rd10 mice demonstrated a faster and larger myopic shift (-6.14±0.62 and -7.38±1.46 diopter, respectively) compared to the WT mice (-2.41±0.47 diopter). Under normal visual conditions, the DOPAC levels and DOPAC/dopamine ratios, a measure of dopamine turnover, were significantly lower in the rd1 and rd10 mice compared to the WT mice, while the dopamine levels were similar or higher than WT in the rd10 mice. Lower basal levels of DOPAC were highly correlated with increasing myopic shifts. Refractive development under normal visual conditions was disrupted toward greater hyperopia from 4 to 12 weeks of age in these photoreceptor degeneration models, despite significantly lower DOPAC levels. However, the retinal degeneration models with low basal levels of DOPAC had increased susceptibility to form deprivation myopia. These results indicate that photoreceptor degeneration may alter dopamine metabolism, leading to increased susceptibility to myopia with an environmental visual challenge.


Soluble VCAM-1 binding to alpha4 integrins is cell-type specific and activation dependent and is disrupted during apoptosis in T cells.
Soluble vascular cell adhesion molecule-1 (sVCAM-1) is generated during inflammation and can alter lymphocyte functions. The authors report that the binding of sVCAM-1 to alpha4 integrin-bearing cells is a dynamically regulated, active cellular process. Binding of recombinant sVCAM-1 to alpha4 integrins on peripheral blood mononuclear cells was cell-type specific. Circulating CD16+ NK cells constitutively bound sVCAM-1 with high affinity, whereas a subpopulation of T-lymphocytes, primarily CD45RO+ (memory), bound sVCAM-1 only after phorbol ester stimulation. sVCAM-1 binding to homogenous stable cell lines was also cell-type specific, and required active cellular processes because it was blocked by the inhibition of ATP synthesis and by Fas-induced apoptosis. Indeed, the loss of high-affinity VCAM-1 binding was an early event in apoptosis. Furthermore, an H-Ras/Raf-initiated signaling pathway also suppressed sVCAM-1 binding to alpha4beta1 integrins. Collectively, these results showed that the capacity of alpha4 integrins to bind VCAM-1 is actively regulated and that this regulation may control alpha4 integrin-dependent cellular functions. (Blood. 2000;95:602-609)


Update: influenza activity--United States, 1991-92 season.
From October 23, 1991, through January 18, 1992, 46 state health departments reported regional or widespread influenza activity for 1 or more weeks. For the week ending January 4, 34 states reported regional or widespread activity, the most during any single week this season. From late October through mid-December, influenza outbreaks reported from 11 states involved primarily school children. Reports of outbreaks among adults began in mid-November and continued through January and involved persons in a variety of settings (e.g., a business in California; a hospital in Ohio; a county jail in Tennessee; and nursing homes in Maryland, Missouri, New York, Ohio, Utah, and Wisconsin).


[Is cholecystectomy a risk factor for colorectal cancer? A meta-analysis].
The number of patients subjected to cholecystectomy has increased since the introduction of laparoscopic methods. Therefore, the question of an association between colorectal cancer (CR-Ca) and cholecystectomy (CHE) is again topical. Several studies have been performed investigating the possibility of a link between cholecystectomy and large bowel cancer. The findings recorded in these studies have been varied and in some cases contradictory. In meta-analyses of the different types of studies (prospective and retrospective) the main question, "Is the risk of colorectal cancer higher after cholecystectomy?" was examined. In prospective matched-pairs studies, 1158 patients who had undergone CHE were compared with 1222 controls. The relative risk (RR) was 1.48, and this result was not significant. The four prospective cohort studies compared the frequency of CR-Ca of 22,783 CHE patients with the expected frequency in the population (RR = 0.99). The retrospective studies compared the frequency of previous CHE in 11,797 patients with CR-Ca with the frequency in 33,940 controls without CR-Ca. The calculated odds ratio (O. R.) of the meta-analysis was 1.15, a significant but not clinically relevant increase in risk. Similar results was shown for evaluation of sex difference both in the prospective studies, with an RR of 0.99 for women and 1.00 for men, and in the retrospective studies, with a RR of 1.17 (p < 0.05) for women and 1.09 (n.s.) for men. The results for different location of the tumour show no significant risk differences in prospective studies either for the colon or for the rectum.(ABSTRACT TRUNCATED AT 250 WORDS)


Influence of Spoilage Flora and Temperature on Growth of Staphylococcus aureus in Turkey Meat.
Staphylococcus aureus isolated from a turkey processing plant grew in ground turkey muscle, either leg or breast, contaminated with spoilage bacteria with incubation at 15,20 or 23°C. No growth occurred with incubation at 7 or 10°C. The rate and extent of growth of S. aureus at 15 and 20°C were increased by cooking the muscle before inoculation. Toxin production during growth of S. aureus on turkey muscle was demonstrated on one occasion only.


Rapid and exceptional response to Sonidegib in a patient with multiple locally advanced basal cell carcinomas.
Locally advanced basal cell carcinoma (laBCC) represents a rare but possible occurrence in the vast scenario of dermatological diseases. It is well known that most BCC has a pathological activation of the hedgehog pathway, making them susceptible to targeted therapy with selective inhibitors. Sonidegib, approved for the treatment of laBCC on the basis of the results of the basal cell carcinoma outcomes with LDE225 treatment study, demonstrated rapid efficacy and a manageable safety profile. Here, we describe the case of a patient affected by multiple laBCC treated with Sonidegib. The patient experienced an important regression of tumors after only 2 months of therapy, with few side effects. This result confirms the role of Sonidegib as a valid and well-tolerated therapeutic option for laBCC.


Late activation of stress kinases (SAPK/JNK) by genotoxins requires the DNA repair proteins DNA-PKcs and CSB.
Although genotoxic agents are powerful inducers of stress kinases (SAPK/JNK), the contribution of DNA damage itself to this response is unknown. Therefore, SAPK/JNK activation of cells harboring specific defects in DNA damage-recognition mechanisms was studied. Dual phosphorylation of SAPK/JNK by the genotoxin methyl methanesulfonate (MMS) occurred in two waves. The early response (< or = 2 h after exposure) was similar in cells knockout for ATM, PARP, p53, and CSB or defective in DNA-PK(cs) compared with wild-type cells. The late response however (> or = 4 h), was drastically reduced in DNA-PK(cs) and Cockayne's syndrome B (CSB)-deficient cells. Similar results were obtained with human cells lacking DNA-PK(cs) and CSB. Activation of SAPK/JNK by MMS was not affected upon inhibition of base excision repair (BER), indicating base damage itself does not signal to SAPK/JNK. Because SAPK/JNK activation was attenuated in nongrowing cells, DNA replication-dependent processing of lesions, involving DNA-PK(cs) and CSB, appears to be required. DNA-PK(cs) coprecipitates with SEK1/MKK4 and SAPK/JNK, supporting a role of DNA-PK(cs) in SAPK/JNK activation. In this process, Rho GTPases are involved since inhibition of Rho impairs MMS-induced signaling to SAPK/JNK. The data show that sensing of DNA damage by DNA-PK(cs) and CSB causes a delayed SEK1/MKK4-mediated dual phosphorylation of SAPK/JNK.


Changing trends in sulfur emissions in Asia: implications for acid deposition, air pollution, and climate.
In the early 1990s, it was projected that annual SO2 emissions in Asia might grow to 80-110 Tg yr(-1) by 2020. Based on new high-resolution estimates from 1975 to 2000, we calculate that SO2 emissions in Asia might grow only to 40-45 Tg yr(-1) by 2020. The main reason for this lower estimate is a decline of SO2 emissions from 1995 to 2000 in China, which emits about two-thirds of Asian SO2. The decline was due to a reduction in industrial coal use, a slowdown of the Chinese economy, and the closure of small and inefficient plants, among other reasons. One effect of the reduction in SO2 emissions in China has been a reduction in acid deposition not only in China but also in Japan. Reductions should also improve visibility and reduce health problems. SO2 emission reductions may increase global warming, but this warming effect could be partially offset by reductions in the emissions of black carbon. How SO2 emissions in the region change in the coming decades will depend on many competing factors (economic growth, pollution control laws, etc.). However a continuation of current trends would result in sulfur emissions lower than any IPCC forecasts.


Plasmid-Based Stat3 siRNA Delivered by Functional Graphene Oxide Suppresses Mouse Malignant Melanoma Cell Growth.
RNA interference (RNAi) has been used for cancer gene therapy in recent years. However, the application of RNAi is hindered in the absence of safe and efficient gene delivery. In this article, a novel vehicle of graphene oxide functionalized with polyethylenimine and polyethylene glycol (GO-PEI-PEG) was successfully synthetized and then used to deliver plasmid-based Stat3 siRNA. The carrier can readily bind plasmid with high transfection efficiency. Moreover, molecular biology studies reveal that Stat3-related gene and protein expressions were significantly inhibited, suggesting that the formation of GO-PEI-PEG complexes could be utilized as a promising gene delivery in cancer therapy.


Geometrical Optimization Approach to Isomerization: Models and Limitations.
We study laser-driven isomerization reactions through an excited electronic state using the recently developed Geometrical Optimization procedure. Our goal is to analyze whether an initial wave packet in the ground state, with optimized amplitudes and phases, can be used to enhance the yield of the reaction at faster rates, driven by a single picosecond pulse or a pair of femtosecond pulses resonant with the electronic transition. We show that the symmetry of the system imposes limitations in the optimization procedure, such that the method rediscovers the pump-dump mechanism.


Development of a dynamic interactive web tool to enhance understanding of multi-state model analyses: MSMplus.
Multi-state models are used in complex disease pathways to describe a process where an individual moves from one state to the next, taking into account competing states during each transition. In a multi-state setting, there are various measures to be estimated that are of great epidemiological importance. However, increased complexity of the multi-state setting and predictions over time for individuals with different covariate patterns may lead to increased difficulty in communicating the estimated measures. The need for easy and meaningful communication of the analysis results motivated the development of a web tool to address these issues. MSMplus is a publicly available web tool, developed via the Shiny R package, with the aim of enhancing the understanding of multi-state model analyses results. The results from any multi-state model analysis are uploaded to the application in a pre-specified format. Through a variety of user-tailored interactive graphs, the application contributes to an improvement in communication, reporting and interpretation of multi-state analysis results as well as comparison between different approaches. The predicted measures that can be supported by MSMplus include, among others, the transition probabilities, the transition intensity rates, the length of stay in each state, the probability of ever visiting a state and user defined measures. Representation of differences, ratios and confidence intervals of the aforementioned measures are also supported. MSMplus is a useful tool that enhances communication and understanding of multi-state model analyses results. Further use and development of web tools should be encouraged in the future as a means to communicate scientific research.


The use of complete-case and multiple imputation-based analyses in molecular epidemiology studies that assess interaction effects.
In molecular epidemiology studies biospecimen data are collected, often with the purpose of evaluating the synergistic role between a biomarker and another feature on an outcome. Typically, biomarker data are collected on only a proportion of subjects eligible for study, leading to a missing data problem. Missing data methods, however, are not customarily incorporated into analyses. Instead, complete-case (CC) analyses are performed, which can result in biased and inefficient estimates. Through simulations, we characterized the performance of CC methods when interaction effects are estimated. We also investigated whether standard multiple imputation (MI) could improve estimation over CC methods when the data are not missing at random (NMAR) and auxiliary information may or may not exist. CC analyses were shown to result in considerable bias and efficiency loss. While MI reduced bias and increased efficiency over CC methods under specific conditions, it too resulted in biased estimates depending on the strength of the auxiliary data available and the nature of the missingness. In particular, CC performed better than MI when extreme values of the covariate were more likely to be missing, while MI outperformed CC when missingness of the covariate related to both the covariate and outcome. MI always improved performance when strong auxiliary data were available. In a real study, MI estimates of interaction effects were attenuated relative to those from a CC approach. Our findings suggest the importance of incorporating missing data methods into the analysis. If the data are MAR, standard MI is a reasonable method. Auxiliary variables may make this assumption more reasonable even if the data are NMAR. Under NMAR we emphasize caution when using standard MI and recommend it over CC only when strong auxiliary data are available. MI, with the missing data mechanism specified, is an alternative when the data are NMAR. In all cases, it is recommended to take advantage of MI's ability to account for the uncertainty of these assumptions.


The epithelial cell cytoskeleton and intracellular trafficking. I. Shiga toxin B-subunit system: retrograde transport, intracellular vectorization, and more.
Many intracellular transport routes are still little explored. This is particularly true for retrograde transport between the plasma membrane and the endoplasmic reticulum. Shiga toxin B subunit has become a powerful tool to study this pathway, and recent advances on the molecular mechanisms of transport in the retrograde route and on its physiological function(s) are summarized. Furthermore, it is discussed how the study of retrograde transport of Shiga toxin B subunit allows one to design new methods for the intracellular delivery of therapeutic compounds.


Importance of Corneal Angiography in Subclinical Limbitis in a Case of Atopic Keratoconjunctivitis.
The aim of this study was to report corneal angiography features in subclinical limbitis in a patient with atopic keratoconjunctivitis. This is a case report. A 22-year-old woman with a medical history of atopic keratoconjunctivitis was referred for bilateral corneal neovascularization with scarring. On examination, no signs of active disease were noticed at the slit lamp. Ocular surface angiography detected active corneal limbitis, showing as limbal leakage at fluorescein angiography in the early phase and leakage after indocyanine green angiography in the late phase. The patient was treated with topical corticosteroid. At follow-up, the fluorescein angiography and indocyanine green angiography no longer showed limbal leakage, whereas the slit lamp examination was unchanged. Active allergic corneal limbitis may present as subclinical inflammation, with no signs of activity at the slit lamp examination. Therefore, its diagnosis can be challenging without the use of corneal angiography.


Sennoside B inhibits PDGF receptor signaling and cell proliferation induced by PDGF-BB in human osteosarcoma cells.
To address the possibility that sennoside B inhibition of cell proliferation is mediated via interference with platelet-derived growth factor (PDGF) signaling. Human osteosarcoma MG63 cells were treated with PDGF in the presence or absence of sennoside B. Activation of the PDGF signaling pathway was monitored using western immunoblotting with specific antibodies against the PDGF receptor, phosphotyrosine and components of the downstream signaling cascade. Activation of cell metabolism and proliferation was assessed by chromogenic reduction of MTT. Sennoside B was found to inhibit PDGF-BB-induced phosphorylation of the PDGF receptor (PDGFR) in human MG63 osteosarcoma cells. Downstream signaling was also affected; pre-incubation of PDGF-BB with sennoside B inhibited the phosphorylation of pathway components including Ak strain transforming protein (AKT), signal transducer and activator of transcription 5 (STAT-5) and extracellular signal-regulated kinase 1/2 (ERK1/2). Further, we found that sennoside B can bind directly to the extracellular domains of both PDGF-BB and the PDGF-beta receptor (PDGFR-beta). The effect was specific for sennoside B; other similar compounds including aloe-emodin, rhein and the meso isomer (sennoside A) failed to inhibit PDGFR activation or downstream signaling. Sennoside B also inhibited PDGF-BB stimulation of MG63 cell proliferation. These results indicate that sennoside B can inhibit PDGF-stimulated cell proliferation by binding to PDGF-BB and its receptor and by down-regulating the PDGFR-beta signaling pathway. Sennoside B is therefore of potential utility in the treatment of proliferative diseases in which PDGF signaling plays a central role.


Sustaining a successful RN compensation model through transparency and communication.
In the March 2005 issue of The Journal of Nursing Administration, authors from an academic medical center outlined a new RN salary program that addressed recruitment and retention of valued resources and established an approach for pay and pay practices for staff RNs across an integrated practice. This follow-up article describes experiences in implementing the program and the successful outcomes achieved.


Providing sex education to persons with learning disabilities in the era of HIV/AIDS: tensions between discourses of human rights and restriction.
Research suggests that disabled people may be at increased risk for HIV infection, yet are excluded from HIV prevention campaigns. Historically people with learning disabilities have been constructed as either being asexual or sexually uninhibited, and sex education considered to be unnecessary or potentially harmful. This article reports on findings of a qualitative study exploring the challenges expressed by participants who provide sex education for persons with learning disabilities, revealing a tension between a human rights discourse and a discourse of restriction of sexual behaviours. Sex education, in the context of HIV/AIDS, may potentially construct sex as dangerous, echoing past constructions of disabled people's sexuality as problematic.


Ga(2,2'-bipy)(HPO(4))(H(2)PO(4)): first layered inorganic-organic hybrid gallium phosphate with a neutral framework.
A novel gallium phosphate, Ga(2,2'-bipy)(HPO(4))(H(2)PO(4)) (denoted FJ-12; FJ = Fujian Institute of Research on the Structure of Matter), which is the first example of layered inorganic-organic hybrid gallium phosphate with neutral framework, has been hydrothermally synthesized and structurally characterized by single-crystal X-ray diffraction. This compound crystallizes in the monoclinic system, space group P2(1)/c (No. 14), with a = 10.9443(9), b = 15.8253(13), and c = 8.4201(7) A, beta = 108.898(2) degrees, V = 1379.7(2) A(3), and Z = 4. The structure consists of HPO(4) and H(2)PO(4) tetrahedra and unusual GaO(4)N(2) octahedra which are linked through their vertexes forming an undulated sheetlike structure with 4.12-net. The adjacent layers are stably packed together and exhibit interesting 3-D supramolecular arrays pi-pi interactions of the 2,2'-bipy groups.


Comparative analysis of imaging modalities in the preoperative assessment of nodal metastasis in esophageal cancer.
Preoperative radiological findings of nodal status in 74 patients, using endoscopic ultrasonography (EUS), computed tomography (CT), ultrasonography (US), and magnetic resonance imaging (MRI), were compared to histopathology reports following transthoracic total esophagectomy with radical lymphadenectomy (TTE), involving complete dissection of the mediastinal and abdominal nodes and lower cervical lymph nodes. Accuracy, sensitivity, and specificity of each radiological investigation were calculated for each anatomic group of nodes. Statistical analysis revealed that EUS is more accurate and significantly more sensitive (P<0.01) for lymph nodes along the right recurrent laryngeal nerve and those in the upper and mid-periesophageal, infracarinal locations. Paratracheal and lower paraesophageal nodes are assessed better using CT whereas MRI is better for mid-paraesophageal and infra-aortic nodes. US is most accurate and sensitive for evaluation of cervical and abdominal nodes (P<0.01).


[Ejaculation induced by electrostimulation in men with spinal cord injuries].
Five men (aged 29-43 years) with ejaculatory dysfunction and spinal cord injuries for 10-41 years and level of complete lesions from C6 to T10 underwent electrostimulation. Antegrade ejaculate was obtained in all five participants and simultaneous retrograde ejaculation in four. In general, the total number of spermatozoa was greatest in the retrograde ejaculates and highly variable between the subjects both in the antegrade (0.2-5330 mill.) and in the retrograde ejaculates (0.4-5690 mill.). The percentage of immobile and morphologically abnormal spermatozoa was increased compared with normal values. In connection with the electrostimulation procedures no cases of autonomous hyperreflexia or rectal mucosal injury were observed.


Destabilization and phase separation of particle suspensions in emulsions.
Yield stress fluids are widely used in industrial application to arrest dense solid particles, which can be studied by using a concentrated emulsion as a model fluid. We show in experiments that particle sedimentation in emulsions cannot be predicted by the classical criterion for spheres embedded in a yield stress fluid. Phase separation processes take place, where a liquid layer forms and particle sedimentation is enhanced by the emulsion drainage. In addition, emulsion drainage can be arrested or enhanced by the amount of particles embedded in the emulsion. A minimal mathematical model is developed and solved in numerical simulations to describe the emulsion drainage in the presence of particles, which favorably compares with the experimental stability diagram and the sedimentation dynamics.


Bilayer Lateral Heterostructures of Transition-Metal Dichalcogenides and Their Optoelectronic Response.
Two-dimensional lateral heterojunctions based on monolayer transition-metal dichalcogenides (TMDs) have received increasing attention given that their direct band gap makes them very attractive for optoelectronic applications. Although bilayer TMDs present an indirect band gap, their electrical properties are expected to be less susceptible to ambient conditions, with higher mobilities and density of states when compared to monolayers. Bilayers and few-layers single domain devices have already demonstrated higher performance in radio frequency and photosensing applications. Despite these advantages, lateral heterostructures based on bilayer domains have been less explored. Here, we report the controlled synthesis of multi-junction bilayer lateral heterostructures based on MoS2-WS2 and MoSe2-WSe2 monodomains. The heterojunctions are created via sequential lateral edge-epitaxy that happens simultaneously in both the first and the second layers. A phenomenological mechanism is proposed to explain the growth mode with self-limited thickness that happens within a certain window of growth conditions. With respect to their as-grown monolayer counterparts, bilayer lateral heterostructures yield nearly 1 order of magnitude higher rectification currents. They also display a clear photovoltaic response, with short circuit currents ∼103 times larger than those extracted from the as-grown monolayers, in addition to room-temperature electroluminescence. The improved performance of bilayer heterostructures significantly expands the potential of two-dimensional materials for optoelectronics.


Conformal organohalide perovskites enable lasing on spherical resonators.
Conformal integration of semiconductor gain media is broadly important in on-chip optical communication technology. Here we deploy atomic layer deposition to create conformally deposited organohalide perovskites--an attractive semiconducting gain medium--with the goal of achieving coherent light emission on spherical optical cavities. We demonstrate the high quality of perovskite gain media fabricated with this method, achieving optical gain in the nanosecond pulse regime with a threshold for amplified spontaneous emission of 65 ± 8 μJ cm(-2). Through variable stripe length measurements, we report a net modal gain of 125 ± 22 cm(-1) and a gain bandwidth of 50 ± 14 meV. Leveraging the high quality of the gain medium, we conformally coat silica microspheres with perovskite to form whispering gallery mode optical cavities and achieve lasing.


Predictors of satisfaction and quality of life following post-mastectomy breast reconstruction.
Breast reconstruction is associated with multiple psychological benefits. However, few studies have identified clinical and psychological factors associated with improved satisfaction and quality of life. This study examined factors, which predict satisfaction with breast appearance, outcome satisfaction and quality of life following post-mastectomy breast reconstruction. Women who underwent post-mastectomy breast reconstruction between 2010 and 2016 received a postal questionnaire consisting of The BREAST-Q Patient Reported Outcomes Instrument, The European Organisation for Research and Treatment of Cancer QLQ-30 Questionnaire, The Patient and Observer Scar Assessment Scale, and a series of Visual-Analogue Scales. One hundredforty-eight women completed the questionnaire, a 56% response rate. Hierarchical multiple regression analyses revealed psychosocial factors accounted for 75% of the variance in breast satisfaction, 68% for outcome satisfaction, and 46% forquality of life. Psychosocial well-being emerged as a significant predictor of satisfaction with breast appearance (β = .322) and outcome satisfaction (β = .406). Deep inferior epigastric perforator flap patients reported greater satisfaction with breast appearance (β = .120) and outcome satisfaction (β = .167). This study extends beyond the limited research by distinguishing between satisfaction with breast appearance and outcome satisfaction. The study provides evidence for the role of psychosocial factors predicting key patient reported outcomes and demonstrates the importance of psychosocial well-being and reconstruction type. The findings also highlight the need for healthcare providers to consider the psychosocial well-being of patients both preoperatively and post operatively and provide preliminary evidence for the use of deep inferior epigastric perforator reconstructions over other types of reconstructive procedures.


Optimizing syndromic health surveillance in free ranging great apes: the case of Gombe National Park.
1. Syndromic surveillance is an incipient approach to early wildlife disease detection. Consequently, systematic assessments are needed for methodology validation in wildlife populations. 2. We evaluated the sensitivity of a syndromic surveillance protocol for respiratory disease detection among chimpanzees in Gombe National Park, Tanzania. Empirical health, behavioural and demographic data were integrated with an agent-based, network model to simulate disease transmission and surveillance. 3. Surveillance sensitivity was estimated as 66% (95% Confidence Interval: 63.1, 68.8%) and 59.5% (95% Confidence Interval: 56.5%, 62.4%) for two monitoring methods (weekly count and prevalence thresholds, respectively), but differences among calendar quarters in outbreak size and surveillance sensitivity suggest seasonal effects. 4. We determined that a weekly detection threshold of ≥2 chimpanzees with clinical respiratory disease leading to outbreak response protocols (enhanced observation and biological sampling) is an optimal algorithm for outbreak detection in this population. 5. Synthesis and applications. This is the first quantitative assessment of syndromic surveillance in wildlife, providing a model approach to detecting disease emergence. Coupling syndromic surveillance with targeted diagnostic sampling in the midst of suspected outbreaks will provide a powerful system for detecting disease transmission and understanding population impacts.


[Radiological diagnosis of benign dysphagia].
In the diagnostic work-up of the benign dysphagia modern radiology must not only describe morphologic alterations but also has to keep in mind the great importance of motility disorders. Dysfunction of the esophagus can be assessed by fluoroscopy alone. The superior method to analyze the motility disorders of the oropharyngeal and pharyngo-esophageal transport is high-speed cineradiography at a frame-rate of 50 frames/sec on 35-mm film because of the very fast and complex patterns of motion during oropharyngeal deglutition, which occurs within only 0.5 to 0.7 sec. The upper esophageal sphincter turned out to play a very important role in many motility disorders of the pharynx and the esophagus, which often secondarily leads to permanent structural lesions. Examples are given, in which kinds of disorders cineradiography contributes to diagnosis and therapy. In some cases it turned out to be the method of first choice, as for example for aspiration.


Pityriasis lichenoides in children: a long-term follow-up of eighty-nine cases.
Pityriasis lichenoides is usually classified into an acute and a chronic form. From a review of 89 cases of the disease seen since 1974 it seems that a more realistic classification into three main groups, according to the distribution of pityriasis lichenoides lesions, could be made, namely, a diffuse, a central, and a peripheral form, each characterized by a different clinical course. Conversely, no correlations were detected in our series between the severity of skin lesions and their distribution or the overall course of the disease. None of our cases suggests the possible evolution of pityriasis lichenoides into lymphomatoid papulosis. Although no infectious causative agent has been identified, a viral origin seems likely in some cases. Most patients responded favorably to UVB irradiation. Our conclusions are (1) that pityriasis lichenoides is probably a clinical disorder with a diverse etiology and (2) that its classification by distribution seems more useful than its subdivision into an acute and a chronic form.


Effects of Light and of Fusarium solani on Synthesis and Activity of Phenylalanine Ammonia-Lyase in Peas.
Phenylalanine ammonia-lyase was purified from peas, and a specific antiserum against the enzyme was produced in rabbits. The antiserum was used to study the first 8 hours of the phenylalanine ammonia-lyase activity response in two different organs of the pea from different developmental stages and in response to two different stimuli. Etiolated seedlings were pulse-labeled with l-[(35)S]methionine after either no light exposure or after specific periods of irradiation with blue light. Immature pods were pulse labeled with mixed l-[(3)H]amino acids after specific time periods following inoculation of the pod endocarp surfaces with macroconidia of Fusarium solani. Immunoprecipitates isolated from extracts of each group were analyzed with sodium dodecyl sulfate disc gel electrophoresis and were found to contain a radioactive protein with an electrophoretic mobility identical to that of the phenylalanine ammonia-lyase subunit (M(r) 81,000). The radioactivity contained in the subunit band was interpreted as being due to de novo synthesis of the enzyme. The net rate of phenylalanine ammonia-lyase labeling, found to be initially low in both tissue types, rose dramatically, peaking at approximately a six- to ten-fold greater level at 4 hours after the beginning of the stimulus. Thereafter, the rate of labeling declined slowly. Inoculation with F. solani f. sp. pisi, a true pathogen of peas, caused a fifty per cent greater rate of peak labeling than did inoculation with a nonpathogen, F. solani f. sp. phaseoli. The time profile of the changing rate of labeling correlates with the changing activity level of the enzyme which peaks at 12 hours after the onset of the stimulus. The data presented favor a model which explains the changing activity of phenylalanine ammonia-lyase as being due to a changing rate of synthesis or degradation (or both) of the enzyme rather than due to the activation of a preformed zymogen.


Genomic and Phylogenetic Analysis of Lactiplantibacillus plantarum L125, and Evaluation of Its Anti-Proliferative and Cytotoxic Activity in Cancer Cells.
Lactiplantibacillus plantarum is a diverse species that includes nomadic strains isolated from a variety of environmental niches. Several L. plantarum strains are being incorporated in fermented foodstuffs as starter cultures, while some of them have also been characterized as probiotics. In this study, we present the draft genome sequence of L. plantarum L125, a potential probiotic strain presenting biotechnological interest, originally isolated from a traditional fermented meat product. Phylogenetic and comparative genomic analysis with other potential probiotic L. plantarum strains were performed to determine its evolutionary relationships. Furthermore, we located genes involved in the probiotic phenotype by whole genome annotation. Indeed, genes coding for proteins mediating host-microbe interactions and bile salt, heat and cold stress tolerance were identified. Concerning the potential health-promoting attributes of the novel strain, we determined that L. plantarum L125 carries an incomplete plantaricin gene cluster, in agreement with previous in vitro findings, where no bacteriocin-like activity was detected. Moreover, we showed that cell-free culture supernatant (CFCS) of L. plantarum L125 exerts anti-proliferative, anti-clonogenic and anti-migration activity against the human colon adenocarcinoma cell line, HT-29. Conclusively, L. plantarum L125 presents desirable probiotic traits. Future studies will elucidate further its biological and health-related properties.


The public's knowledge and beliefs about obsessive compulsive disorder.
Obsessive compulsive disorder (OCD) is a disabling condition associated with significant personal and societal burdens. Despite the availability of efficacious treatments, in most cases, the disorder remains unrecognized and untreated. Lack of knowledge (i.e. poor mental health literacy, MHL) regarding OCD may be an impediment to seeking treatment. Therefore, the current study assessed public knowledge and beliefs about OCD and examined factors influencing MHL. Five hundred seventy-seven US adults participated in a telephone survey. After hearing a vignette describing someone with OCD, participants' MHL for OCD was assessed across three domains as follows: recognition of OCD, knowledge and beliefs about available help, and concerns about being negatively evaluated for reporting symptoms. The majority of participants (90.9%) reported that the symptoms were a cause for concern and that the person in the vignette should seek professional help (89.5%). However, only one-third of respondents correctly labeled the disorder as OCD. More respondents were optimistic about the likely success of psychotherapy than medication, but primary care physicians were the most frequently reported source of professional help. Finally, less education, lower income, and being in an older cohort were associated with poorer recognition of OCD. When presented with brief vignettes describing a person with OCD, most community members can recognize the benefits of seeking professional help. However, recognition of the disorder and knowledge of treatment options can be improved.


Evaluation of an active population-based surveillance system for major birth defects in South Carolina.
Birth defects are common, costly, and contribute substantially to infant mortality. The South Carolina Birth Defects Program (SCBDP) employs active population-based surveillance to monitor major birth defects statewide. We evaluated SCBDP's system attributes using published CDC guidelines. To determine timeliness, completeness, and accuracy of birth defects information, we examined SCBDP's reports, program and education materials, advisory group meeting minutes, and strategic plan. We also met with program staff and stakeholders (n = 10) to discuss program goals and data utilization. We calculated the percentage of birth defects cases found 6 months after a birth cohort year for 2016-2018. SCBDP identifies 900-1,200 birth defects cases for a birth population of approximately 55,000 live births annually through active case reviews. SCBDP uses trained medical staff to abstract detailed information from maternal and infant medical records; SCBDP also has established auto-linkage with state vital statistics to capture demographic and birth data. SCBDP is timely and captures 97.1% (range 96.7-97.6%) of birth defects cases within 6 months after the birth cohort year closes. Active case identification using medical records as the primary data source improves quality assurance and completeness, while prepopulating demographic information improves timeliness. Given that birth defects significantly contribute to infant morbidity and mortality, monitoring these conditions is important to understand their impact on communities and to drive public health actions. SCBDP active surveillance and rigorous data quality practices provide the program with timely, complete, and accurate birth defects data.


Inhibition of the cholinergic neurotransmission in human airways via prejunctional alpha-2-adrenoceptors.
Previous investigations on guinea-pig airways indicate that the excitatory, cholinergic neurotransmission can be inhibited via prejunctional alpha-2-adrenoceptors. The aim of this study was to investigate whether a similar inhibition of the cholinergic neurotransmission is present in human airways. Ring preparations of human bronchi were mounted for recording of isometric tension and immersed in oxygenated Krebs solution. Electrical field stimulation of the preparations elicited atropine-sensitive twitch contractions. Exogenous noradrenaline (in the presence of cocaine and propranolol) inhibited the electrically evoked contractions. The noradrenaline-induced inhibition could be antagonized by yohimbine whereas prazosin was ineffective, indicating that the inhibition was mediated by alpha-2-adrenoceptors. Contractions evoked by exogenous acetylcholine (in the presence of cocaine and propranolol) was unaffected by the addition of noradrenaline, which suggests that the alpha-2-adrenoceptors have a prejunctional localization. In conclusion, this report gives evidence that the human bronchial, cholinergic neurotransmission can be inhibited by stimulation of prejunctional alpha-2-adrenoceptors.


APOE Effects on Default Mode Network in Chinese Cognitive Normal Elderly: Relationship with Clinical Cognitive Performance.
Functional connectivity in default mode network (DMN) may be changed in Alzheimer's disease (AD) patients and related risk populations, such as amnestic mild cognitive impairment (aMCI) patients and APOE ε4 carriers. Exploring DMN changes and related behavioral performance of APOE ε4 population might provide valuable evidence for better understanding the development of AD. Subjects were enrolled from a population-based cohort established in a multi-center study in China. Forty-nine cognitive normal individuals were enrolled after standardized cognitive evaluations, MRI examination and APOE genotyping. Regions of interest (ROI)-based functional connectivity analyses were performed, and voxel-based analyses were used to validate these findings. The correlation between DMN functional connectivity and behavioral performance was further evaluated between APOE ε4ε3 and ε3ε3 carriers. Comparing to ε3ε3 carriers, functional connectivity between left parahippocampal gyrus and right superior frontal cortex (LPHC-R.Sup.F), left parahippocampal gyrus and medial prefrontal cortex (ventral) (LPHC-vMPFC) were significantly increased in ε4ε3 carriers, while connectivity between cerebellar tonsils and retrosplenial was decreased. LPHC-R.Sup.F connectivity was positively correlated with the changes of delay recall from baseline to follow-up (r = 0.768, p = 0.009), while LPHC-vMPFC connectivity had a positive correlation with MMSE at baseline (r = 0.356, p = 0.018), and a negative correlation with long-delayed recognition at follow-up (r = -0.677, p = 0.031). Significantly increased functional connectivity in vMPFC was confirmed in voxel-based analyses by taking LPHC as seed region. APOE ε4 carriers present both increased and decreased functional connectivity in DMN, which is correlated with clinical cognitive performances. DMN changes might be an early sign for cognitive decline.


A herpesvirus entry mediator mutein with selective agonist action for the inhibitory receptor B and T lymphocyte attenuator.
The human cytomegalovirus opening reading frame UL144 is an ortholog of the TNF receptor superfamily member, herpesvirus entry mediator (HVEM; TNFRSF14). HVEM binds the TNF ligands, LIGHT and LTa; the immunoglobulin inhibitory receptor, B and T lymphocyte attenuator (BTLA); and the natural killer cell-activating receptor CD160. However, UL144 selectively binds BTLA, avoiding activation of inflammatory signaling initiated by CD160 in natural killer cells. BTLA and CD160 cross-compete for binding HVEM, but the structural basis for the ligand selectivity by UL144 and how it acts as an anti-inflammatory agonist remains unclear. Here, we modeled the UL144 structure and characterized its binding with BTLA. The UL144 structure was predicted to closely mimic the surface of HVEM, and we also found that both HVEM and UL144 bind a common epitope of BTLA, whether engaged in trans or in cis, that is shared with a BTLA antibody agonist. On the basis of the UL144 selectivity, we engineered a BTLA-selective HVEM protein to understand the basis for ligand selectivity and BTLA agonism to develop novel anti-inflammatory agonists. This HVEM mutein did not bind CD160 or TNF ligands but did bind BTLA with 10-fold stronger affinity than wild-type HVEM and retained potent inhibitory activity that reduced T-cell receptor, B-cell receptor, and interferon signaling in B cells. In conclusion, using a viral immune evasion strategy that shows broad immune-ablating activity, we have identified a novel anti-inflammatory BTLA-selective agonist.


Effect of Engineered Nickel Oxide Nanoparticle on Reactive Oxygen Species-Nitric Oxide Interplay in the Roots of Allium cepa L.
Scientists anxiously follow instances of heavy metals augmenting in the environment and undergoing bioaccumulation and trace their biomagnification across food webs, wary of their potent toxicity on biological entities. Engineered nanoparticles supplement natural pools of respective heavy metals and can mimic their effects, exerting toxicity at higher concentrations. Thus, a thorough understanding of the underlying mechanism of this precarious interaction is mandatory. Most urban and industrial environments contain considerable quantities of nickel oxide nanoparticles. These in excess can cause considerable damage to plant metabolism through a significant increase in cellular reactive oxygen species and perturbation of its cross-talk with the reactive nitrogen species. In the present work, the authors have demonstrated how the intrusion of nickel oxide nanoparticles (NiO-NP) affected the exposed roots of Allium cepa: starting with disruption of cell membranes, before being interiorized within cell organelles, effectively disrupting cellular homeostasis and survival. A major shift in the reactive oxygen species (ROS) and nitric oxide (NO) equanimity was also observed, unleashing major altercations in several crucial biochemical profiles. Altered antioxidant contents and upregulation of stress-responsive genes, namely, Catalase, Ascorbate peroxidase, Superoxide dismutase, and Rubisco activase, showing on average 50-250% rise across NiO-NP concentrations tested, also entailed increased cellular hydrogen peroxide contents, with tandem rise in cellular NO. Increased NO content was evinced from altered concentrations of nitric oxide synthase and nitrate reductase, along with NADPH oxidase, when compared with the negative control. Though initially showing a dose-dependent concomitant rise, a significant decrease of NO was observed at higher concentrations of NiO-NP, while cellular ROS continued to increase. Modified K/Na ratios, with increased proline concentrations and GABA contents, all hallmarks of cellular stress, correlated with ROS-NO perturbations. Detailed studies showed that NiO-NP concentration had a significant role in inducing toxicity, perturbing the fine balance of ROS-NO, which turned lethal for the cell at higher dosages of the ENP precipitating in the accumulation of stress markers and an inevitable shutdown of cellular mechanisms.


[Tissue distribution of arsenic of liushen pills and realgar].
This study is to report the tissue distribution of arsenic after giving different doses of realgar and Liushen pills to Beagle dogs, in order to provide basis for the safety evaluation of Liushen pills. ICP-MS was used to measure arsenic concentration, and HPLC-ICP-MS was used to analyze arsenic speciation. The concentration of total arsenic and As(III) + DMA (arsenite + dimethylarsenic acid) increased with dosing of realgar. Total arsenic concentration in most tissues and As(III) + DMA concentration in all tissues of Liushen pills group are lower than that of realgar group, but AsB concentration in liver, spleen and kidney of Liushen pills group increased. The concentration of total arsenic showed a dose-dependent manner with dosage administered. It was indicated that components in Liushen pills can reduce solubility of arsenic in realgar, which may decrease toxicity of realgar.


HSD17B13: A Potential Therapeutic Target for NAFLD.
Nonalcoholic fatty liver disease (NAFLD), especially in its inflammatory form (steatohepatitis, NASH), is closely related to the pathogenesis of chronic liver disease. Despite substantial advances in the management of NAFLD/NASH in recent years, there are currently no efficacious therapies for its treatment. The biogenesis and expansion of lipid droplets (LDs) are critical pathophysiological processes in the development of NAFLD/NASH. In the past decade, increasing evidence has demonstrated that lipid droplet-associated proteins may represent potential therapeutic targets for the treatment of NAFLD/NASH given the critical role they play in regulating the biogenesis and metabolism of lipid droplets. Recently, HSD17B13, a newly identified liver-enriched, hepatocyte-specific, lipid droplet-associated protein, has been reported to be strongly associated with the development and progression of NAFLD/NASH in both mice and humans. Notably, human genetic studies have repeatedly reported a robust association of HSD17B13 single nucleotide polymorphisms (SNPs) with the occurrence and severity of NAFLD/NASH and other chronic liver diseases (CLDs). Here we briefly overview the discovery, tissue distribution, and subcellular localization of HSD17B13 and highlight its important role in promoting the pathogenesis of NAFLD/NASH in both experimental animal models and patients. We also discuss the potential of HSD17B13 as a promising target for the development of novel therapeutic agents for NAFLD/NASH.


Short and medium-term influence of physical activity on immune parameters.
Physical stress induces different changes in immune parameters depending on effort schedule and/or customary physical training. The mechanisms whereby they take place and the occurrence of possible tolerance after repeated effort have not been conclusively elucidated. We studied short and medium-term exercise-induced changes in immune parameters after a standard physical effort (24' of cycle ergometer up to the 80% of maximal heart rate, daily for 5 days) in a group of healthy untrained controls. White Blood Cells, lymphocyte subsets, plasmatic catecholamine and cortisol levels, IgG and IL2receptor (IL2R) levels were determined. Most of the observed changes were strictly acute effort-related and disappeared within 3 hours (except for shifts in CD4+ CD45RA+ and CD4+ CD45RA- lymphocytes): they were concomitant to a transient sympathetic activation proved by heart rate (HR) and Norepinephrine (NE) increase. The medium-term effects of repeated daily effort included only a questionable rise in CD19+ and CD3+ CD4- CD8- cells. As far as possible tolerance mechanisms are concerned, we did not detect any change in either the direction or the entity of effort-induced changes in our controls after repeated effort. Study of strictly standardized exercise protocols is mandatory before clinical applications of physical activity in the approach to the treatment of disimmune diseases.


[NOEY2 gene mRNA expression in breast cancer tissue and its relation to clinicopathological parameters].
To investigate the expression of NOEY2 gene in breast cancer tissue and its relation to clinicopathological and other molecular parameters. The mRNA expression of NOEY2 gene was monitored in benign and malignant breast lesions by RT-PCR and in situ hybridization (ISH) with transcripted antisense RNA probes. The protein expression of estrogen receptor (ER), Ki67, p27 and p21(WAF1) in the 60 breast cancer lesions was detected by immunohistochemical method. All 6 benign lesions, and 13 (72.2%) of the 18 breast cancers were NOEY2 positive by RT-PCR. By ISH, positive NOEY2 was obtained in all 10 benign lesions but only in 31 (51.7%) of the 60 breast cancer lesions. The difference was statistically significant (P = 0.025). NOEY2 positive rate tended to decrease with the increase of histological grade. However, NOEY2 expression was negatively correlated with the status of axillary lymph nodes. The positive NOEY2 rate was 75% in those without lymph node metastasis but only 26.7% in those with metastasis (P < 0.001). No correlation with other clinicopathological parameters including ER, Ki67, p27 or p21(WAF1) were found. NOEY2 gene may be related with the pathogenesis of breast cancer. A link between NOEY2 loss expression and the spreading mechanism of breast cancer may possibly exist.


Gating Effects for Ion Transport in Three-Dimensional Functionalized Covalent Organic Frameworks.
The development of bioinspired nano/subnano-sized (<2 nm) ion channels is still considered a great challenge due to the difficulty in precisely controlling pore's internal structure and chemistry. Herein, for the first time, we report that three-dimensional functionalized covalent organic frameworks (COFs) can act as an effective nanofluidic platform for intelligent modulation of the ion transport. By strategic attachment of 12-crown-4 groups to the monomers as ion-driver door locks, we demonstrate that gating effects of functionalized COFs can be activated by lithium ions. The obtained materials exhibit an outstanding selective ion transmission performance with a high gating ratio (up to 23.6 for JUC-590), which is among the highest values in metal ion-activated solid-state nanochannels reported so far. Furthermore, JUC-590 offers high tunability, selectivity, and recyclability of ion transport proved by the experimental and simulated studies.


Fasting Plasma Glucose Level Independently Predicts the Mortality of Patients with Coronavirus Disease 2019 Infection: A Multicenter, Retrospective Cohort Study.
Coronavirus disease 2019 (COVID-19) has become a global pandemic, which prompts a consensus for the necessity to seek risk factors for this critical disease. Risk factors affecting mortality of the disease remain elusive. Diabetes and hyperglycemia are known to negatively affect a host's antiviral immunity. We evaluated the relationship between a history of diabetes, fasting plasma glucose (FPG) levels and mortality among severely ill patients with COVID-19. This was a retrospective cohort study that assessed 106 adult inpatients (aged ≥18 years) from two tertiary hospitals in Daegu, South Korea. The participants were transferred to tertiary hospitals because their medical condition required immediate intensive care. The demographic and laboratory data were compared between COVID-19 patients who survived and those who did not. Compared with the survivor group, age, and the proportions of diabetes, chronic lung disease and FPG were significantly higher in the deceased group. In the Cox proportional hazards regression model for survival analysis, FPG level and age were identified as significant predictors of mortality (P<0.05). The threshold values for predicting high mortality were age >68 years and FPG of 168 mg/dL, respectively. Among those without diabetes, high FPG remained a significant predictor of mortality (P<0.04). High FPG levels significantly predicted mortality in COVID-19, regardless of a known history of diabetes. These results suggest intensive monitoring should be provided to COVID-19 patients who have a high FPG level.


Advanced heart block and atrial flutter in a patient with HLA B27 spondyloarthropathy.
An athletic 43-year-old man presented with symptomatic bradycardia and atrial flutter after being diagnosed with HLA B27 associated spondyloarthropathy several months earlier. The patient was admitted and underwent electrophysiology evaluation with ablation of his atrial flutter and eventually underwent pacemaker implantation. His cardiac workup showed a structurally normal heart and strongly suggested that his HLA B27 associated spondyloarthropathy was responsible for his presentation. A review of the literature suggests that HLA B27 spondyloarthropathy related heart block may be an often overlooked cause of heart block in otherwise healthy patients.


Single molecule conductance, thermopower, and transition voltage.
We have measured the thermopower as well as other important charge transport quantities, including conductance, current-voltage characteristics, and transition voltage of single molecules. The thermopower has little correlation with the conductance, but it decreases with the transition voltage, which is consistent with a theory based on Landauer's formula. Since the transition voltage reflects the molecular energy level alignment, our finding also shows that the thermopower provides valuable information about the relative alignment between the molecular energy levels and the electrodes' Fermi energy level.


A Greener Amidoximation Process for Fabrication of Popular Uranium Complexing Fiber Using Water as the Single Solvent.
A mixed water-organic solvent used for amidoximation increased the production cost of an amidoxime-based polymer sorbent and was not environmentally friendly as well. In this work, the amidoximation of an ultrahigh molecular weight polyethylene fiber co-grafted with acrylonitrile and methacrylic acid was carried out in aqueous solution without the use of an organic solvent. The effects of amidoximation parameters including NH2OH concentration, temperature, time, and various solvents on the uranium adsorption performances in both uranium-spiked brine and simulated seawater were investigated. Results indicated that the optimal amidoximation parameters were 5% (w/v) NH2OH, 80 °C, and 24 h. The uranium adsorption capacities of the sorbents amidoximated in aqueous solution were comparable with those of sorbents amidoximated in the various mixed water-organic solvents. Moreover, in comparison with both acidic (pH ∼3) and alkalic (pH ∼11) aqueous solution, the sorbent amidoximated in neutral (pH ∼7) NH2OH aqueous solution achieved higher uranium adsorption capacities in both uranium-spiked brine (112.4 mg/g) and simulated seawater (7.4 mg/g). Additionally, potassium hydroxide (KOH) treatment was a necessary process and indeed significantly increased the uranium adsorption capacity.


Effect of promoter mutations and upstream deletions on the expression of genes coding for small, acid-soluble spore proteins of Bacillus subtilis.
The sspB and sspE genes code for major small, acid-soluble proteins of Bacillus subtilis spores and are transcribed during sporulation by RNA polymerase containing sigma G. Analysis of the expression in vivo and the sigma G-dependent transcription in vitro of sspB and sspE genes carrying upstream deletions or point mutations in -10 and -35 promoter regions is consistent with sigma G being the only major transcriptional regulator of these genes. These data also provide information on the residues in -10 and -35 regions which are most important for sigma G recognition.


Solid-phase synthesis of dual alpha4beta1/alpha4beta7 integrin antagonists: two scaffolds with overlapping pharmacophores.
Two structural classes of dual alpha4beta1/alpha4beta7 integrin antagonists were investigated via solid-phase parallel synthesis. Using an acylated amino acid backbone, lead compounds containing biphenylalanine or tyrosine carbamate scaffolds were optimized for inhibition of alpha4beta1/VCAM and alpha4beta7/MAdCAM. A comparison of the structure-activity relationships in the inhibition of the alpha4beta7/MAdCAM interaction for substituted amines employed in both scaffolds suggests a similar binding mode for the compounds.


Profuse and acute hemorrhagic gastroesophageal injury after cryotherapy in a cardiac surgery patient.
Upper gastrointestinal injury associated with cryoablation and under placement of transesophageal echocardiography (TEE) during cardiac surgery is a rare complication but potentially fatal. During the cryoablation for the treatment of atrial fibrillation, delivered cryoenergy can adversely affect the esophagus, resulting in gastroesophageal ulceration. The TEE probe itself also can induce adverse effects like esophageal ulceration or perforation. In this case report, we describe a case of emergent gastroesophageal injury with massive bleeding that occurred after manipulation of a TEE probe during cryoablation therapy in a cardiac surgery patient.


The cell biology of ras-induced transformation: insights from studies utilizing an inducible hybrid oncogene system.
The c-Ha-ras oncogene has been implicated as a causative agent in the development of tumors in humans as well as mice. The molecular nature of the ras-induced tumorigenic process remains unclear, however. To address this question directly we have constructed a cell line which carries a zinc-inducible metallothionein-ras hybrid oncogene, transformant 212. Upon exposure to zinc for 24-48 hr, 212 cells assume a highly transformed morphology, concomitant with the induction of ras-expression. Natural killer cells constitute a subpopulation of lymphoid effector cells which have for a long time been hypothesized to be involved in the earliest stages of antitumor surveillance. Central to this hypothesis is the prediction that NK sensitivity arises during cellular transformation. By carrying out cytotoxicity assays against the 212 transformant, we showed that, indeed, increased sensitivity to NK-mediated lysis correlated with expression of the ras oncogene, which is consistent with the above hypothesis. We then addressed the question of the biochemical mechanism of ras-induced transformation. Owing to their similarity to G proteins, regulatory elements interposed between cell-surface receptors and their effector enzymes, it has been postulated that p21, the ras oncogene protein, mediates its transforming effects by constitutive activation of proliferative signal transduction pathways. We studied the effect of ras expression on the regulation of adenylate cyclase (A.C.), key enzyme of one such major pathway. We found that ras expression correlated with a dampening of responsiveness of A.C. to several stimuli, including hormones such as isoproterenol and other agents such as GMP-PNP, forskolin and fluoride-ion. Accumulation of cAMP as measured by RIA in intact cells, as basal or in response to stimulation of A.C. activity with forskolin, was also decreased (approximately 10-fold) with ras expression. Because the regulation of calcium, another important second messenger is dependent, in part, upon cAMP and GTP-binding proteins, we investigated the possible influence of ras expression on the intracellular concentration of calcium. Steady-state intracellular free Ca2+ concentration, as measured by fluorimetry, was indeed increased by approximately 50-125% in association with ras expression. Finally, we studied the possible influence of p21ras on protein kinase C (PKC), which is a key enzyme in the important signal transduction pathway of phosphatidylinositol lipid turnover. We assessed PKC activity directly, in a cell-free system, by measuring the ability of the enzyme to transfer radiolabelled phosphate from gamma-32P-ATP to histone, and exogenous substrate.(ABSTRACT TRUNCATED AT 400 WORDS)


Radiofrequency Ablation with an Internally Cooled Monopolar Directional Electrode: Ex Vivo and in Vivo Experimental Studies in the Liver.
To evaluate the feasibility of using an internally cooled directional electrode (ICDE) to create sufficient directional ablation in the desired area and to investigate whether use of the ICDE reduces thermal injury to the adjacent organs. The animal care and use committee approved this animal study. In ex vivo studies of bovine livers and colons, temperature was measured in both ablation and nonablation directions with the ICDE, temperature at the liver-colon interface and the presence of burns on the colon were evaluated with each ICDE and internally cooled conventional electrode (ICCE), and the ablation area with the use of three ICDEs in the switching multichannel mode was evaluated. In an in vivo study of 10 pigs, 11 ablations were performed by using three ICDEs in the switching multichannel mode. In addition, the difference in thermal injury to the gallbladder and stomach was compared between use of the ICDE and the ICCE. Mann-Whitney test and the Fisher exact test were used for statistical analysis. In the ex vivo study, the hepatic temperature in the nonablation direction was lower than 50°C; temperature higher than 47°C was maintained for less than 3 minutes, even 0.5 cm away from the ICDE; and the temperature at the liver-colon interface did not increase above 50°C. In the switching multichannel mode, a fused coagulation zone was created. In the in vivo study, confluent ablation was created in the inner circle of three ICDEs with a mean interelectrode distance of less than 2.6 cm. Use of the ICDE did not create a moderate-to-severe gallbladder wall injury in any of the pigs, but use of the ICCE caused injury in three of the five pigs (P > .05). The ICDE caused moderate-to-severe gastric wall injury at one of eight ablations, and the ICCE caused injury at eight of nine ablations (P < .05). Use of an ICDE can create a sufficient ablation in the desired direction and can decrease thermal injury to the adjacent organs.


Improved method for converting an unmodified peptide to an energy-transfer substrate for a proteinase.
This paper describes refinements to a method for generating energy-transfer-based fluorogenic substrates for proteinases [Geoghegan, K. F., et al. (1993) Bioconjugate Chem. 4, 537-544]. An unprotected peptide is taken as starting material and coupled by three steps of chemistry to two dyes that form an energy donor-energy acceptor pair. The donor group is Lucifer Yellow CH (lambda cx 420-430 nm, lambda em 530 nm), and the acceptor is 5-carboxytetramethylrhodamine, a strong chromophore that effectively quenches Lucifer Yellow fluorescence in intact substrates. Periodate oxidation of N-terminal Ser gives the peptide an alpha-N-glyoxylyl moiety, OHC-CO-peptide, which is allowed to react with Lucifer Yellow CH (a carbohydrazide derivative) to attach the dye through an adequately stable hydrazone bond. Derivatization is completed by allowing the succinimidyl ester of 5-carboxytetramethylrhodamine to react with the epsilon-amino group of a single Lys placed near the C terminus. In the revised method, the first two steps of chemistry are completed sequentially in a single vessel to eliminate the labor and losses associated with isolating the alpha-N-glyoxylyl intermediate. In addition, peptides taken as starting material for this method are now designed according to the scheme (Ser)-(cleavable sequence)-(Lys-Arg). The addition of Arg at the C terminus promotes aqueous solubility of the final substrate without complicating the chemistry; multiple Arg might also be used, through this has not been tried here. It has also been found that relative reversed-phase HPLC retention of Lucifer Yellow/5-carboxytetramethylrhodamine substrates is predictable on the basis of the hydrophobicity of the original peptide. Substrates prepared from peptides with Bull and Breese indices of > 200 cal/ mol are readily separated from residual dye in the second and final chromatographic step of the synthesis, simplifying the only moderately difficult step in the preparation. As with all fluorogenic substrates, assays using these substrates are subject to internal filtering effects that can lead to serious error. This problem becomes significant at a range of substrate concentration that is predictable when the size and geometry of the fluorescence cell are taken into account. The reasoning applied in determining this range is applicable to substrates constructed with any donor-acceptor pair.


[Psychological changes in the victims of the Gdańsk Shipyard hall fire in the period of 1995-1999].
The aim of this paper was to answer two questions. First--has a particular traumatic event (the Gdańsk Shipyard concert-hall fire) caused any psychopathological changes in the victims? Secondly--if yes, how do the dynamics of these changes manifest themselves? The authors used two psychological methods. Adjective Check List, which measures the structure of psychological needs, and in some way, the picture of oneself (before and after the fire) and HADS-M, which measures the intensity of negative emotions (anxiety, depressiveness and aggression). The first investigation in 1995 included two groups: 46 victims of the fire and a control group (47 youngsters, who did not participate in this particular concert). The investigation of the victims group was then repeated twice, in 1996 (35 persons) and in 1999 (39 persons). The series of investigations lead to the conclusion that the traumatic event (Gdańsk Shipyard hall fire) caused statistically significant, psychopathological changes in the victims (the first investigation). The changes concerned the worsening of the picture of oneself and an increase in the intensity of negative emotions (anxiety, depressiveness, aggression). All these changes still exist, despite the time which passed since the traumatic event (the repeated investigations).


Cerebellar hemorrhage as a complication of spine surgery.
The association between remote cerebellar hematoma (RCH) and spinal surgery is poorly understood and rarely reported. We present seven cases of RCH after spinal surgery. Seven patients were diagnosed with RCH utilizing computed tomography and/or magnetic resonance, between 2012 and 2016. Their clinical presentations, imaging data, treatment modalities, and outcome were analyzed. There were five females and two males with an average age of 55.8 ± 8.4 years. The age of onset ranged from 43 to 67 years and the time to clinical presentation ranged from 3 h to 5 days. Patients presented with: diplopia/strabismus (one patient), dysphagia/urinary incontinence (one patient), respiratory arrest (one patient), meningismus (one patient), and dysarthria (two patients), along with other symptoms/signs. Three patients were successfully managed without surgery, two required external ventricular drainage, and two were treated with posterior fossa decompression plus ventriculostomy. Four patients recovered completely, two showed mild residual deficits at discharge, while one expired 7 days postoperatively. RCH is an uncommon and underdiagnosed complication of spine surgery. It should be suspected when intracranial symptoms occur after spinal procedures.


The factor V Leiden mutation is not a common cause of pregnancy-induced hypertension in Japan.
Recent studies in Caucasian populations have shown an association of the Leiden mutation in factor V with preeclampsia (PE). It consists of a substitution of a G (G1691) with an A (A1691) at nucleotide position 1691 in exon 10, resulting in arginine instead of glutamine at residue 506 at the factor V cleavage site for activated protein C (APC); it contributes to the resistance to APC. The purpose of this study was to determine whether the Leiden mutation is associated with pregnancy-induced hypertension (PIH), including PE, in Japanese women. We examined the genotypes of factor V of 71 Japanese patients with PIH and 109 controls. None of the 180 Japanese women carried the factor V Leiden mutation. To date, the factor V Leiden mutation is rare and not a common cause of PIH in Japan. The results may suggest that there is a significant ethnic difference in the role of the Leiden mutation in compounding the risk factors in the pathogenesis of PIH between Japanese and Caucasian populations.


[Patophysiology of osteoarthritis].
Osteoarthritis (OA) is slowly evolving disease of articular cartilage degneration characterized by the gradual development of joint pain, stiffness and limitation of motion. Musculoskeletal diseases are growing medical, social and economic problem. OA among them takes leading position with incidence, morbidity and poor quality of life. In the last few decades there is increasing interest for better knowledge of all aspects of the disease, especially with regard to its pathophysiology. This paper focuses the recent aspects of patophysiology of OA, because knowledge of patophysiology means the challenge for the clinician to find a way to best prevent articular cartilage degradation, preserve joint function, treat joint pain and treat concurrent inflammation.


Chronic hyperglycemia triggers loss of pancreatic beta cell differentiation in an animal model of diabetes.
Differentiated pancreatic beta cells are unique in their ability to secrete insulin in response to a rise in plasma glucose. We have proposed that the unique constellation of genes they express may be lost in diabetes due to the deleterious effect of chronic hyperglycemia. To test this hypothesis, Sprague-Dawley rats were submitted to a 85-95% pancreatectomy or sham pancreatectomy. One week later, the animals developed mild to severe chronic hyperglycemia that was stable for the next 3 weeks, without significant alteration of plasma nonesterified fatty acid levels. Expression of many genes important for glucose-induced insulin release decreased progressively with increasing hyperglycemia, in parallel with a reduction of several islet transcription factors involved in beta cell development and differentiation. In contrast, genes barely expressed in sham islets (lactate dehydrogenase A and hexokinase I) were markedly increased, in parallel with an increase in the transcription factor c-Myc, a potent stimulator of cell growth. These abnormalities were accompanied by beta cell hypertrophy. Changes in gene expression were fully developed 2 weeks after pancreatectomy. Correction of blood glucose by phlorizin for the next 2 weeks normalized islet gene expression and beta cell volume without affecting plasma nonesterified fatty acid levels, strongly suggesting that hyperglycemia triggers these abnormalities. In conclusion, chronic hyperglycemia leads to beta cell hypertrophy and loss of beta cell differentiation that is correlated with changes in c-Myc and other key transcription factors. A similar change in beta cell differentiation could contribute to the profound derangement of insulin secretion in human diabetes.


Structure and specificity of the T cell antigen receptor.
The antigen receptor on T lymphocytes is a multi-chain complex of which two chains determine its specificity for antigen. Although these receptor chains possess genetic and structural similarities with membrane-bound immunoglobulin, the B cell antigen receptor, they endow T cells with a distinct specificity. Unlike B cells, T cells recognize foreign antigenic properties only in the form of proteolytic fragments bound to molecules encoded by the major histocompatibility complex. In addition, one stage of the development of T cells in the thymus is dependent upon an antigen receptor-mediated event. Utilizing the response to a well defined antigen as a model system, we discuss the relationship between receptor structure and the specificity of these recognition events.


Intrahippocampal infusions of anisomycin produce amnesia: contribution of increased release of norepinephrine, dopamine, and acetylcholine.
Intra-amygdala injections of anisomycin produce large increases in the release of norepinephrine (NE), dopamine (DA), and serotonin in the amygdala. Pretreatment with intra-amygdala injections of the beta-adrenergic receptor antagonist propranolol attenuates anisomycin-induced amnesia without reversing the inhibition of protein synthesis, and injections of NE alone produce amnesia. These findings suggest that abnormal neurotransmitter responses may be the basis for amnesia produced by inhibition of protein synthesis. The present experiment extends these findings to the hippocampus and adds acetylcholine (ACh) to the list of neurotransmitters affected by anisomycin. Using in vivo microdialysis at the site of injection, release of NE, DA, and ACh was measured before and after injections of anisomycin into the hippocampus. Anisomycin impaired inhibitory avoidance memory when rats were tested 48 h after training and also produced substantial increases in local release of NE, DA, and ACh. In an additional experiment, pretreatment with intrahippocampal injections of propranolol prior to anisomycin and training significantly attenuated anisomycin-induced amnesia. The disruption of neurotransmitter release patterns at the site of injection appears to contribute significantly to the mechanisms underlying amnesia produced by protein synthesis inhibitors, calling into question the dominant interpretation that the amnesia reflects loss of training-initiated protein synthesis necessary for memory formation. Instead, the findings suggest that proteins needed for memory formation are available prior to an experience, and that post-translational modifications of these proteins may be sufficient to enable the formation of new memories.


Antielevation syndrome after unilateral anteriorization of the inferior oblique muscle.
To report antielevation syndrome with restriction of elevation on abduction in the operated eye and overaction (OA) of the inferior oblique muscle (IO) of the contralateral eye after unilateral IO anteriorization (AT). Medical records were reviewed retrospectively in 8 of 24 patients who underwent unilateral IOAT. Four patients were referred from other hospitals after the same surgery. Four patients had infantile esotropes. The rest showed accommodative esotropia, superior oblique palsy, exotropia, and consecutive exotropia. The mean amount of hyperdeviation was 16.3 PD (10 approximately 30). The mean restriction of elevation on abduction in the operated eye was -1.6 (-1 approximately -4) and IOOA of the contralateral eye was +2.7 (+2 approximately +3). IOAT of nonoperated eyes in 4 patients, IO weakening procedure of anteriorized eyes in 2 patients, and IO myectomy on an eye with IOAT in 1 patient were performed. Ocular motility was improved after surgery in all patients. Unilateral IOAT may result in antielevation syndrome. Therefore bilateral IOAT is recommended to balance antielevation in both eyes. A meticulous caution is needed when performing unilateral IOAT.


Changing trends of splenectomy in hereditary spherocytosis: The experience of a reference Centre in the last 40 years.
We describe the clinical/haematological characteristics of 446 patients with hereditary spherocytosis diagnosed in the last 40 years in a reference centre. The frequency of splenectomy decreased over time (44% before 1990 to 7% in 2011-2020), notwithstanding a confirmed good efficacy. Age at splenectomy progressively increased (63% in children before 1990 to 88% in patients aged ≥20 years in 2011-2020). Our real-life experience showed that even a fraction of patients in the trait/mild categories (19/92, 21%) were splenectomised, whilst 30/78 (38%) in the moderate/severe groups were not. Overall, these data pinpoint to the increasing awareness about post-splenectomy thromboses and infections.


A functional ex vivo assay to detect PARP1-EJ repair and radiosensitization by PARP-inhibitor in prostate cancer.
Here, we present a functional assay to detect the repair switch to the alternative PARP1-dependent end joining (PARP1-EJ) pathway and the associated susceptibility to PARPi-mediated radiosensitization in freshly collected tumor samples from prostate cancer (PCa) patients, thereby facilitating the selection of patients who should benefit from combined PARPi plus radiotherapy (RT) treatment. Our optimized ex-vivo approach sustains tumor slices for up to 15 days under culture conditions that maintain proliferation and oxygenation rates, as measured by EdU incorporation and pimonidazole staining, respectively. We present a robust system to analyze DSB repair using, for the first time in an ex vivo tumor slice setting, two DSB-markers simultaneously i.e. γH2AX and 53BP1. A computer-based processing method (i) controls variations in DNA content and slicing on the number of repair foci and (ii) measures the PARPi-mediated enhancement ratio on DSB foci numbers to ensure inter-patient-comparability. We validated this approach using a PC3 xenograft model with its previously described repair switch to PARP1-EJ. More importantly, we show that approximately 30% of the analyzed tumor tissue samples collected from PCa patients display a switch to PARP1-EJ, as indicated by the enhanced number of residual γH2AX/53BP1 foci exclusively after PARPi+RT. Furthermore, normal prostatic tissues show no repair switch to PARP1-EJ, indicating that this repair switch and its associated radiosensitizing effect is tumor-specific. Collectively, we present here a predictive assay for the switch to PARP1-EJ that enables individualization of anti-cancer treatment using a combination of RT and radiosensitizing anticancer agents such as PARPi in PCa.


Macrophage interactions with Candida.
The monocyte/macrophage, in comparison to the neutrophil, would appear to have a limited role in protection against C. albicans. This statement is based on the observations of several investigators who report that these cells have very little killing capacity unless they are activated by cytokines such as IFN-gamma and GM-CSF. The mechanisms of killing by these cells appear to include both oxidative and nonoxidative mechanisms, the latter perhaps being more important. The mechanisms of killing may be different for monocytes and macrophages. Granulocyte-macrophage colony-stimulating factor and its effect on monocytes has been studied using Candida as a target organism. Two explanations for the enhancement of monocyte killing by this cytokine have been proposed: GM-CSF augments both superoxide anion and the level of mannose receptors on treated monocytes. Both of these changes could be significant in the increased killing capacity of these cells.


Torsade de pointes caused by polypharmacy and substance abuse in a patient with human immunodeficiency virus.
Drug-induced QT prolongation is a potentially dangerous adverse effect of some medication combinations. When QT prolongation progresses to torsade de pointes, life-threatening or fatal outcomes may result. A 57-year-old man with a history of human immunodeficiency syndrome on abacavir, nevirapine, tenofovir, voriconazole, and methadone presented to the emergency department with a chief complaint of new-onset seizures. The physical exam was unremarkable. The electrocardiogram demonstrated sinus bradycardia and a prolonged QT(c) interval of 690 ms. In the emergency department, he had several episodes of torsade de pointes (TdP) and ventricular tachycardia that resolved spontaneously. These episodes were accompanied by an alteration in mentation and generalized twitching. Magnesium and amiodarone were effective in terminating the dysrhythmia. The patient had multiple risk factors for prolonged QT syndrome including human immunodeficiency virus infection, methadone therapy, and polypharmacy leading to potential drug interactions. Physicians must be aware of multidrug interactions potentiating QT prolongation and leading to torsade de pointes.


Structure and cathodoluminescence of individual ZnS/ZnO biaxial nanobelt heterostructures.
We report on a controlled synthesis of two novel semiconducting heterostructures: heterocrystalline-ZnS/single-crystalline-ZnO biaxial nanobelts and side-to-side single-crystalline ZnS/ZnO biaxial nanobelts via a simple one-step thermal evaporation method. In the first heterostructure, a ZnS domain is composed of the heterocrystalline superlattice (3C-ZnS) N /(2H-ZnS) M [111]-[0001] with the atomically smooth interface between wurtzite and zinc blende ZnS fragments. High-spatial resolution cathodoluminescence studies on individual heterostructures for the first time reveal a new ultraviolet emission peak ( approximately 355 nm), which is not observed in separate ZnS or ZnO nanostructures. The present hererostructures are expected to become valuable not only with respect to fundamental research but also for a design of new broad-range ultraviolet nanoscale lasers and sensors.


Detailed analyses of individual neutral lipid classes of Pneumocystis.
Individual neutral lipid classes of Pneumocystis carinii carinii were isolated and purified by thin-layer chromatography. The fatty acids in steryl esters, triglycerides, free fatty acids, diglycerides, and monoglycerides were quantified by gas-liquid chromatography. The fatty acid compositions of these lipids were similar to those of the neutral lipid classes in whole rat lung controls, unlike comparable studies of phospholipid classes. The free fatty alcohols of rat lung controls and P. carinii were also identified and quantified; only saturated fatty alcohols were detected.


Intraspinal microstimulation produces over-ground walking in anesthetized cats.
Spinal cord injury causes a drastic loss of motor, sensory and autonomic function. The goal of this project was to investigate the use of intraspinal microstimulation (ISMS) for producing long distances of walking over ground. ISMS is an electrical stimulation method developed for restoring motor function by activating spinal networks below the level of an injury. It produces movements of the legs by stimulating the ventral horn of the lumbar enlargement using fine penetrating electrodes (≤50 μm diameter). In each of five adult cats (4.2-5.5 kg), ISMS was applied through 16 electrodes implanted with tips targeting lamina IX in the ventral horn bilaterally. A desktop system implemented a physiologically-based control strategy that delivered different stimulation patterns through groups of electrodes to evoke walking movements with appropriate limb kinematics and forces corresponding to swing and stance. Each cat walked over an instrumented 2.9 m walkway and limb kinematics and forces were recorded. Both propulsive and supportive forces were required for over-ground walking. Cumulative walking distances ranging from 609 to 835 m (longest tested) were achieved in three animals. In these three cats, the mean peak supportive force was 3.5 ± 0.6 N corresponding to full-weight-support of the hind legs, while the angular range of the hip, knee, and ankle joints were 23.1 ± 2.0°, 29.1 ± 0.2°, and 60.3 ± 5.2°, respectively. To further demonstrate the viability of ISMS for future clinical use, a prototype implantable module was successfully implemented in a subset of trials and produced comparable walking performance. By activating inherent locomotor networks within the lumbosacral spinal cord, ISMS was capable of producing bilaterally coordinated and functional over-ground walking with current amplitudes <100 μA. These exciting results suggest that ISMS may be an effective intervention for restoring functional walking after spinal cord injury.


Microvascular system of the lumbar dorsal root ganglia in rats. Part II: neurogenic control of intraganglionic blood flow.
The dorsal root ganglion (DRG) should not be overlooked when considering the mechanism of low-back pain and sciatica, so it is important to understand the morphological features of the vascular system supplying the DRG. However, the neurogenic control of intraganglionic blood flow has received little attention in the past. The authors used an immunohistochemical technique to investigate the presence and distribution of autonomic and sensory nerves in blood vessels of the DRG. Ten Wistar rats were used. To investigate the mechanism of vasomotion on the lumbar DRG, the authors used immunohistochemical methods. Sections were incubated overnight with antisera to tyrosine hydroxylase (TH), aromatic L-amino-acid decarboxylase (AADC), 5-hydroxytryptamine, substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), somatostatin (SOM), neuropeptide Y (NPY), leucine-enkephalin, and cholineacetyl transferase (Ch-E). The avidin-biotin complex method was used as the immunohistochemical procedure, and the sections were observed under a light microscope. In the immunohistochemical study, TH-, AADC-, SP-, CGRP-, VIP-, SOM-, NPY-, and Ch-E-positive fibers were seen within the walls of blood vessels in the DRG. This study revealed the existence of a comprehensive perivascular adrenergic, cholinergic, and peptidergic innervation of intraganglionic blood vessels, with a possible role in neurogenic regulation (autoregulation) of intraganglionic circulation. The presence of perivascular nerve plexuses around intraganglionic microvessels suggests that autonomic nerves play an important role in intraganglionic circulation.


[A wireless telemetry study on the electrical activity in nucleus accumbens of heroin-induced place preference rats].
To analyze the electrical activity property changes in nucleus accumbens (NAc) of heroin-induced conditioned place preference (CPP) rats during different stages of heroin dependence and to explore NAc's roles in the formation of drug dependence. Recording electrodes were bilaterally embedded into the NAcs of rats with the aid of stereotaxic apparatus, followed by establishment of heroin-dependent rat model. The NAc electrical activity during 3 different stages of heroin dependence, including heroin pre-exposure, immediate post-exposure and heroin withdrawal, were respectively recorded using EEG wireless telemetry techniques. The frequency distribution (ranging from 0.5 to 30 Hz) and the amplitude of NAc electrical activity were analyzed and measured. Heroin-dependent rat models were successfully established and their withdrawal symptoms were evident. All rats showed a conditioned place preference (CPP) for the white box after 5-10 days of heroin-exposure, and displayed a maximum withdrawal symptoms on 2d after heroin- withdrawal. During all statges of heroin-dependence, the NAc electrical activity contained the highest proportion of delta rhythm and the lowest proportion of alpha2 rhythm. The discharge frequence band was similar across different stages. There was a significantly increased ratio of low-frequency discharges (delta rhythm) and decreased ratio of high-frequency discharges (beta rhythm) in NAc of rats during the immediate post- heroin exposure stage when compared with that during pre-exposure and heroin withdrawal stages. During the withdrawal stage, the ratio of at rhythm was significantly lower than during pre- and post-heroin exposure stages (P < 0.01). Further, the mean discharge amplitude in NAcs during immediate post-exposure and withdrawal stages was significantly increased relative to pre-exposure stage. However, the mean discharge amplitude during heroin withdrawal stage was significantly lower than during immediate post-exposure stage. The electrical activity properties in rat NAcs showed a significant change during different stages of heroin-dependence, which suggested that neuronal activities in NAcs might contribute to the modulation of drug-dependence.


Molecular genetics of too much bone.
Bone remodelling is an important process both throughout growth and in adult life. The homeostasis of bone tissue is maintained by the balanced processes of bone resorption and formation. Imbalance can give rise to a broad spectrum of skeletal pathologies, of which osteoporosis, characterized by a decrease in bone density leading to increased fracture risk, is the best known because of its high prevalence and consequently high socio-economic impact. At the opposite end of the spectrum, several genetic conditions displaying too much bone are situated. Mainly because of their monogenic nature-in contrast to the multifactorial character of osteoporosis-the underlying molecular genetic causes for several of these conditions have been revealed recently. In this review, the most important gene identifications of the last years and their impact on the understanding of bone biology are discussed.