Integrated multimedia electronic patient record and graph-based image information for cerebral tumors.
Current electronic patient record (EPR) implementations do not incorporate medical images, nor structural information extracted from them, despite images increasing role for diagnosis. This paper presents an integration framework into EPRs of anatomical and pathological knowledge extracted from segmented magnetic resonance imaging (MRI), applying a graph of representation for anatomical and functional information for individual patients. Focusing on cerebral tumors examination and patient follow-up, multimedia EPRs were created and evaluated through a 3D navigation application, developed with open-source libraries and standards. Results suggest that the enhanced clinical information scheme could lead to original changes in the way medical experts utilize image-based information.


Pediatric Persistent Inflammation, Immunosuppression, and Catabolism Syndrome Prevalence in Sepsis-Related Mortalities: A 23-Year Institutional History.
Delayed mortality in sepsis often is linked to a lack of resolution in the inflammatory cascade termed persistent inflammation, immunosuppression, and catabolism syndrome (PICS). Limited research exists on PICS in pediatric patients with sepsis. What is the prevalence of pediatric PICS (pPICS) in patients who died of sepsis-related causes and what associated pathogen profiles and comorbidities did they have compared with those patients without pPICS who died from sepsis? A retrospective study of a single institution using a de-identified database from 1997 through 2020 for all patients aged 21 years or younger who died of culture-positive sepsis from a known source and who had laboratory data available were evaluated for the presence of pPICS. Among records extracted from the institutional database, 557 patients had culture-positive sepsis, with 262 patients having pPICS (47%). Patients with pPICS were more likely to have underlying hematologic or oncologic disease or cardiac disease. In addition, patients who had pPICS showed increased odds of associated fungal infection compared with those patients who did not (OR, 2.69; 95% CI, 1.59-4.61; P < .001). When assessing laboratory criteria, having a sustained absolute lymphocyte count of < 1.0 × 103/μL was most closely associated with having pPICS compared with other laboratory parameters. Finally, the results of multivariate logistic regression analysis indicated that patients with pPICS were more common in the cardiac ICU, as opposed to the PICU (OR, 3.43; CI, 1.57-7.64; P = .002). Pediatric patients who died of a sepsis-related cause have a pPICS phenotype nearly one-half of the time. These patients are more likely to be in the cardiac ICU than the pediatric ICU and have associated fungal infections. Special attention should be directed toward this population in future research.


Combined action of uranium and stress in the rat. I. Behavioral effects.
The influence of restraint stress on uranium (U)-induced behavioral effects was assessed in adult male rats. Eight groups of animals received uranyl acetate dihydrate (UAD) in the drinking water at doses of 0, 10, 20 and 40 mg/kg/day during 3 months. Rats in four groups were concurrently subjected to restraint during 2 h per day throughout the study. At the end of the period of uranium exposure, the following behavioral tests were carried out: open-field activity, passive avoidance and Morris water maze. Uranium concentrations in brain were also determined. At 10 and 20 mg/kg/day of UAD restraint significantly affected the total distance traveled in the open-field during the first and third periods tested, respectively, while no significant differences between groups were observed on the passive avoidance test. In the Morris water maze test, the influence of restraint was only significant on the latency time measured on Day 3 in rats exposed at 10 mg/kg/day. Restraint stress did not affect significantly the uranium levels in brain of rats. Although the results of the present study scarcely show uranium-induced behavioral effects at the oral doses of UAD here administered, these effects, as well as the slight influence of restraint stress noted in some tests should not be underrated.


A modified push-pull system for the localised perfusion of brain tissue.
A method for monitoring the outflow of a push-pull perfusion system is presented. This modification possesses the following important advantages: (1) Inadvertent induction of expansion lesions is avoided, (2) Flow rates can be reduced from the usual 50-200 microliter/min to 0.6-1.7 microliter without decreasing the probability of detecting occlusions, (3) Incidence of occlusions is reduced, (4) Up to 30--40 perfusions can be performed at each of several sites in the brain of a single animal over a period of several months. The modified system has been used successfully to administer neurohumoral agents to the brain of rats and to determine the release of endogenous substances into the perfusate.


Sonochemical production of nanoparticle metal oxides for potential use in dentistry.
Two types of ultrasonic instruments used in dentistry have been compared with a sonochemical horn for the production of copper oxide and zinc oxide nanoparticles. The nanoparticles can be produced from benign reagents using dental instruments as the source of sonochemical enhancement. The process has been operated in resin models of teeth in a preliminary exploration of the potential of the method for enhancing procedures such as root canal surgery. The technique is potentially useful but further work is needed for a full assessment of using in-situ generated nanoparticles as an aid to disinfection during some types of dental surgery.


Enantio- and diastereodivergent dual catalysis: α-allylation of branched aldehydes.
An important challenge in asymmetric synthesis is the development of fully stereodivergent strategies to access the full complement of stereoisomers of products bearing multiple stereocenters. In the ideal case, where four products are possible, applying distinct catalysts to the same set of starting materials under identical conditions would in a single step afford any given stereoisomer. Herein, we describe the realization of this concept in a fully stereodivergent dual-catalytic synthesis of γ,δ-unsaturated aldehydes bearing vicinal quaternary/tertiary stereogenic centers. The reaction is enabled by chiral iridium and amine catalysts, which activate the allylic alcohol and aldehyde substrates, respectively. Each catalyst exerts high local stereocontrol irrespective of the other's inherent preference.


Natural course of large spontaneous pneumothorax.
A large pneumothorax was detected on chest x-ray film in a 41-year-old woman. She declined recommendations for evacuation of the air trapped in her right chest. The condition spontaneously resolved during 3 months after being detected.


Elm1 kinase activates the spindle position checkpoint kinase Kin4.
Budding yeast asymmetric cell division relies upon the precise coordination of spindle orientation and cell cycle progression. The spindle position checkpoint (SPOC) is a surveillance mechanism that prevents cells with misoriented spindles from exiting mitosis. The cortical kinase Kin4 acts near the top of this network. How Kin4 kinase activity is regulated and maintained in respect to spindle positional cues remains to be established. Here, we show that the bud neck-associated kinase Elm1 participates in Kin4 activation and SPOC signaling by phosphorylating a conserved residue within the activation loop of Kin4. Blocking Elm1 function abolishes Kin4 kinase activity in vivo and eliminates the SPOC response to spindle misalignment. These findings establish a novel function for Elm1 in the coordination of spindle positioning with cell cycle progression via its control of Kin4.


[Nursing tutor, working closely with students].
Appreciating the chance to work independently as well as interacting with the different nursing teams in her hospital, a nursing tutor tells us of the pleasure she gets out of dedicating herself to supporting student nurses. A way of approaching care from a different perspective.


Rapid morphologic plasticity of peri-infarct dendritic spines after focal ischemic stroke.
Focal stroke is associated with cell death, abnormal synaptic activity, and neurologic impairments. Given that many of these neuropathologic processes can be attributed to events that occur shortly after injury, it is necessary to understand how stroke affects the structure of neurons in surviving peri-infarct regions, particularly at the level of the dendritic spines, which transmit normal and potentially abnormal and injurious synaptic signaling. Recently, we described ischemia-induced changes in the structure of layer 1 dendritic tufts of transgenic mice expressing YFP in layer 5 cortical neurons. However, these in vivo imaging experiments could not address ischemia-related phenomena that occur in deeper cortical structures/layers, other cortical regions, or submicron changes in dendritic spine structure. Focal stroke was induced in the forelimb sensorimotor cortex by the photothrombotic method. Two, 6, and 24 hours after stroke, brains were processed for Golgi-Cox staining to permit a detailed analysis of primary apical dendritic spine structure from layer 2/3 and 5 cortical pyramidal neurons. Photothrombotic stroke caused a rapid deterioration of neurons, as revealed by Golgi-Cox labeling, in the infarct core that could be readily distinguished from surviving peri-infarct regions. Analysis of >15,000 dendritic spines revealed that although many spines were lost in the peri-infarct cortex during the first 24 hours after stroke (approximately 38% lost), spines that remained were significantly longer (approximately 25% at 6 hours). Furthermore, these effects were found in both layer 2/3 and 5 neurons and were restricted primarily to peri-infarct regions (<200 mum from the infarct border). These rapid changes in dendritic spine number and length may reflect an early adaptive response of potentially vulnerable peri-infarct neurons coping with postischemic spreading depression-like depolarizations and the loss of presynaptic contacts.


Hemostasis and thromboembolism in children with nephrotic syndrome: differences from adults.
Eleven of 204 children with nephrotic syndrome had thrombotic complications: arterial thrombosis in five, venous thrombosis in four, and pulmonary embolism in two. Fifty-one episodes of thromboembolism were recognized in 116 adult patients with nephrotic syndrome. Despite the lower incidence, thromboembolic complications tended to be more severe in children. In vitro indices of hemostasis and clinical evidence of thromboembolic complications were compared in children and adults. Antithrombin III concentrations and activities were abnormal in seven of 10 children, but in only two of 32 adults. In both groups, alpha 2-macroglobulin was elevated, but more markedly so in children. No evidence for circulating granulocyte-derived proteases (elastase/antielastase complexes) was noted in either group. Protein C was significantly elevated in children with nephrotic syndrome, but was normal in adults. Children also differed from adults with nephrotic syndrome in laboratory evidence of subthreshold disseminated intravascular coagulation (i.e., elevated soluble fibrinogen monomeric complexes and fibrin degradation products) and indicators of in vivo platelet activation (elevated beta-thromboglobulin). The more severe coagulation abnormalities in children may be linked to the more pronounced hypoalbuminemia.


Expression, immunolocalization and serodiagnostic value of a myophilin-like protein from Schistosoma japonicum.
The cDNA of a Schistosoma japonicum myophilin-like protein was cloned, sequenced, and expressed in Escherichia coli as a recombined protein (rSj myophilin-like protein), and the protein was purified by affinity chromatography. The deduced amino acid sequences of the Sj myophilin-like protein showed significant homology to myophilin, calponin, Np22 and Mp20. Northern blot and RT-PCR analyzes revealed expression of the Sj myophilin-like protein mRNA in eggs, sporocysts, cercariae, hepatic schistosomula and adult worms. Confocal fluorescence microscopy localized the native protein to the muscle of the adult worm. In schistosome-infected rabbits, the rSj myophilin-like protein antibody level, assessed by ELISA, was elevated after infection but was reduced after praziquantel treatment. In humans, the myophilin-like protein antibody level was evaluated by ELISA in sera from 33 non-infected humans and 61 schistosomiasis patients; the results showed a highly significant difference between the two groups with a sensitivity of 57.4%. Taken together, the myophilin-like protein may prove useful for monitoring the therapeutic effect of praziquantel rather than in serodiagnosis of schistosomiasis.


Calculation of prefectural disability-adjusted life expectancy (DALE) using long-term care prevalence and its socioeconomic correlates in Japan.
The objectives of this study were: (1) to determine the disability weight, "utility", for calculation of disability-adjusted life expectancy (DALE) using the prevalence of long-term care; (2) to calculate prefectural DALE; and (3) to clarify the relation between DALE and area socioeconomic conditions in Japan. Disability utility by care level (support and levels I-V) of long-term care insurance was determined by a survey of 236 professionals with four standard utility measures: EuroQol-5D, time trade-off, standard gamble, and visual analogue scale. DALE at age 65 (DALE65) and age-adjusted weighted disability prevalence (WDP) of 47 prefectures were calculated using the determined utilities, prevalence of long-term care, and life tables. The relationships of DALE and WDP to mortality from major causes and socioeconomic indicators were examined by correlation analysis. The determined utilities were: support, 0.78; level I, 0.68; level II, 0.64; level III, 0.44; level IV, 0.34; and level V, 0.21. The prefectural DALE65 ranged from 17.11 to 15.29 years for men and from 20.21 to 18.42 years for women. Strong correlations were found between DALE65 and mortality for both sexes. Male DALE65 was correlated with no socioeconomic indicators, while female DALE65 was correlated with some indicators. WDP was positively associated with indicators representing socioeconomic disadvantage, such as unemployment rate and percentage of elderly single households. The socioeconomic correlates of DALE and WDP suggested that favorable socioeconomic policies, in addition to a decrease in mortality from major causes, will contribute to significant extension of the independence period in the elderly. The method proposed here encourages the practical use of health expectancy in health policy, especially at local and regional levels.


Preliminary validation of an assessment for evaluating administration of a structured exercise counseling protocol.
Preliminary testing suggested acceptable reliability and validity for a 10-item assessment used to rate the performance in 9 facilities of 59 exercise counselors' administration of a structured treatment protocol intended to improve maintenance of exercise.


Allovalency observed by transferred NOE: interactions of sulfated tyrosine residues in the N-terminal segment of CCR5 with the CCL5 chemokine.
The N-terminal segment of the chemokine receptor Human CC chemokine receptor 5 (CCR5), Nt-CCR5, contains four tyrosine residues, Y3, Y10, Y14, and Y15. Sulfation of at least two of these tyrosine residues was found to be essential for high-affinity binding of CCR5 to its chemokine ligands. Here, we show that among the monosulfated Nt-CCR5(8-20) peptide surrogates (sNt-CCR5) those sulfated at Y15 and Y14 have the highest affinity for the CC chemokine ligand 5 (CCL5) chemokine in comparison with monosulfation at position Y10. Sulfation at Y3 was not investigated. A peptide sulfated at both Y14 and Y15 has the highest affinity for CCL5 by up to a factor of 3, in comparison with the other disulfated (sNt-CCR5) peptides. Chemical shift perturbation analysis and transferred nuclear Overhauser effect measurements indicate that the sulfated tyrosine residues interact with the same CCL5-binding pocket and that each of the sulfated tyrosines at positions 10, 14, and 15 can occupy individually the binding site on CCL5 in a similar manner, although with somewhat different affinity, suggesting the possibility of allovalency in sulfated Nt-CCR5 peptides. The affinity of the disulfated peptides to CCL5 could be increased by this allovalency and by stronger electrostatic interactions.


Spatio-temporal free-form registration of cardiac MR image sequences.
In this paper we present two registration algorithms for the spatio-temporal alignment of cardiac MR image sequences. Both algorithms have the ability to correct spatial misalignment between the images sequences caused by global and local shape differences. In addition, they have the ability to correct temporal misalignment caused by differences in the length of the cardiac cycles and by differences in the dynamic properties of the hearts. The algorithms use a 4D deformable transformation model which is separated into spatial and temporal components. The first registration algorithm optimizes the spatial and temporal transformation models simultaneously, while the second registration algorithm optimizes the temporal transformation component before optimizing the spatial component. For the evaluation of the spatio-temporal registration methods we have acquired 15 MR image sequences from healthy volunteers. The registration methods were quantitatively evaluated by measuring the overlap and surface distance of anatomical regions and qualitatively by visual inspection. The results demonstrate that a significant improvement in the alignment of the image sequences is achieved by the use of the deformable spatio-temporal transformation model. We demonstrate the use of the method for the construction of a probabilistic MR cardiac atlas representing the anatomy and function of a healthy heart.


Infected left atrial myxoma with mitral valve endocarditis.
We report a rare case of infected left atrial myxoma associated with mitral valve endocarditis. The tumor and a small amount of vegetative growth on the anterior mitral leaflet were surgically excised. Subsequent antibiotic therapy may have prevented the infection from recurring. Histological findings showed myxoma cells embedded in mucinous stroma at the tumor base and an organized thrombus with bacterial colonization at the tumor tip.


Comparison of stir bar sorptive extraction and membrane-assisted solvent extraction for the ultra-performance liquid chromatographic determination of oxazole fungicide residues in wines and juices.
The present study compares two new sample preparation methods, stir bar sorptive extraction (SBSE) and membrane-assisted solvent extraction (MASE) coupled to the novel technique of ultra-performance liquid chromatography (UPLC) for the sensitive, selective and solvent-free determination of six oxazole fungicide residues (hymexazol, drazoxolon, vinclozolin, chlozolinate, oxadixyl and famoxadone) in wine and juices. The analytes were separated on a rapid resolution C(18) column (50 mm x 4.6 mm, I.D., 1.8 microm) thermostated at 50 degrees C with isocratic elution using a 50/50 (v/v) water/acetonitrile (ACN) mobile phase at a flow-rate of 1 mL min(-1) and detected by diode-array detection (DAD). The UPLC method rapidly separates the fungicides (7 min). The best results as regards sensitivity, repeatability and analyte recovery were obtained using SBSE with a polydimethylsiloxane (PDMS) twister, at 60 degrees C for 30 min with stirring at 1700 rpm in the presence of a 0.1M acetate/acetic acid buffer (pH 5) and 20% (m/v) sodium chloride. Liquid desorption was performed with 100 microL of a 80/20 (v/v) ACN/water solution in a desorption time of 15 min. With the PDMS polymer, an apolar phase, hymexazol and oxadixyl were not extracted. Consequently, the SBSE procedure can only be applied to the other four fungicides. Detection limits ranged from 0.05 to 2.5 microgL(-1) at a signal to noise ratio of 3, depending on the compound. Recoveries obtained for spiked samples were satisfactory (83-113%) for all compounds. The proposed method was successfully applied to the analysis of different samples, residues of chlozolinate and drazoxolon being found in samples of red wine and grape juice, respectively.


Human pharmaceuticals modulate P-gp1 (ABCB1) transport activity in the fish cell line PLHC-1.
The ubiquitous presence of pharmaceuticals in aquatic systems is a challenging problem as their potential chronic effects on aquatic organisms remain largely unknown. The ATP-binding cassette (ABC) transport proteins contributing to the multidrug/multixenobiotic resistance (MDR/MXR) phenomenon seem to have an important role in the elimination of xenobiotics in aquatic organisms. Modulation of their efflux activities by contaminants may lead to substantial increase in intracellular accumulation and toxic effects of other xenobiotics. The aim of our work was to analyse a series of pharmaceuticals for their potential to modulate the activity of xenobiotic efflux transporters from the ABCB and ABCC sub-family in the Poeciliopsis lucida hepatoma cell (PLHC-1) fish cell line (PLHC-1/wt) and a doxorubicin (DOX) resistant PLHC-1 subclone (PLHC-1/dox) characterized by an elevated expression of the P-glycoprotein (ABCB1). Cellular accumulation of the model fluorescent substrates calcein-AM and rhodamine123 were used to determine an inhibitory effect on P-gp1 and/or MRP-like efflux transporters. 18 out of 33 tested pharmaceuticals showed MXR inhibitory activity with IC50 values occurring in the lower micromolar to millimolar range. Further, cytotoxic effects of pharmaceuticals were evaluated in PLHC-1/dox cells. Co-exposure of resistant cells to model P-gp1 inhibitor cyclosporine A (CyA) resulted in up to five times increased cytotoxicity of pharmaceuticals. In addition, some pharmaceuticals lead to a marked increase in cytotoxicity of doxorubicin, a model P-gp1 substrate. The modulation of toxicity by MDR inhibitors indicates their role in influencing cellular toxicity. In conclusion, the results of our study revealed significant inhibitory effects of environmentally relevant pharmaceuticals on P-gp1 and MRP-like transporters in fish. Our findings correspond well with data from mammalian systems indicating that the specificity and roles of the related efflux transporters may be similar in fish. Furthermore, due to the presence of active and inducible ABC transport proteins, the PLHC-1 cells appear to be a reliable in vitro system for the investigation of MDR/MXR mechanisms in fish.


Feasibility of vaccination against Macrobrachium rosenbergii nodavirus infection in giant freshwater prawn.
The giant freshwater prawn/giant river prawn, Macrobrachium rosenbergii is one of the high market value crustaceans cultured worldwide. The intensified aquaculture of the species has led to the outbreak of infectious diseases, prominently, the white tail disease (WTD). It is caused by the infection of Macrobrachium rosenbergii nodavirus (MrNV), which was classified in the family of Nodaviridae. To-date, there are no effective prophylactic and therapeutic agents available against MrNV infection. Vaccination is known to be the most effective prophylactic agent in disease prevention. However, vaccine development against virus infection in crustaceans is equivocal. The feasibility of vaccination in conferring immune protection in crustaceans against infectious diseases is disputable. The argument lies in the fact that crustaceans do not possess adaptive immunity, which is the main immune component that functions to establish immunological memory upon vaccination. Nevertheless, an increasing number of literatures has been documented, which concerns the development of vaccines against infectious diseases in crustaceans. The current review deliberates different approaches in vaccine development against MrNV, which were documented in the past years. It is noteworthy that the live-attenuated MrNV vaccine has not been experimented by far. Thus, the potential of live-attenuated MrNV vaccine in conferring long-term immune protection through the establishment of innate immune memory is currently being discussed.


Heavy-metal content and oxidative damage in Hypsiboas faber: the impact of coal-mining pollutants on amphibians.
It has been identified worldwide that amphibians are experiencing massive population declines. This decrease could be further enhanced by the exposure of amphibians to pollutants, which would enhance reactive oxygen species production and cause subsequent alterations in oxidant defense levels. The present study was aimed at understanding the impact of mineral coal on amphibians. For this purpose, chemical elemental contents and oxidative stress indexes in Hypsiboas faber from coal-mining areas and in an unpolluted area in the Catarinense Coal Basin, Brazil, were assessed. The highest contents of sulfur, chlorine, iron, zinc, and bromine were registered in specimens from the coal-mining area, whereas the highest contents of potassium calcium, and silicon were registered in specimens from the control area. It was found that there was a significant increase (p < 0.05) in the activity of super oxide dismutase (SOD) and glutathione peroxidase (GPx) in the animals from the coal-mining area, whereas the level of catalase showed no differences between the animal groups. The levels of TBARS showed no differences between the tested groups. However, carbonylation decreased significantly (p < 0.05) in animals from the coal-mining area, and there was a significant increase (p < 0.05) in the formation of total thiols in animals from the coal-mining area. In conclusion, the antioxidant system of H. faber is sensitive to pollutants present in coal-mining wastes, and its SOD and GPx activity may be a potential biomarker for monitoring the level of contaminants in the environment.


Identification of small molecules as potential inhibitors of interleukin 6: a multi-computational investigation.
IL(interleukin)-6 is a multifunctional cytokine crucial for immunological, hematopoiesis, inflammation, and bone metabolism. Strikingly, IL-6 has been shown to significantly contribute to the initiation of cytokine storm-an acute systemic inflammatory syndrome in Covid-19 patients. Recent study has showed that blocking the IL-6 signaling pathway with an anti-IL-6 receptor monoclonal antibody (mAb) can reduce the severity of COVID-19 symptoms and enhance patient survival. However, the mAb has several drawbacks, such as high cost, potential immunogenicity, and invasive administration due to the large-molecule protein product. Instead, these issues could be mitigated using small molecule IL-6 inhibitors, but none are currently available. This study aimed to discover IL-6 inhibitors based on the PPI with a novel camelid Fab fragment, namely 68F2, in a crystal protein complex structure (PDB ID: 4ZS7). The pharmacophore models and molecular docking were used to screen compounds from DrugBank databases. The oral bioavailability of the top 24 ligands from the screening was predicted by the SwissAMDE tool. Subsequently, the selected molecules from docking and MD simulation illustrated a promising binding affinity in the formation of stable complexes at the active binding pocket of IL-6. Binding energies using the MM-PBSA technique were applied to the top 4 hit compounds. The result indicated that DB08402 and DB12903 could form strong interactions and build stable protein-ligand complexes with IL-6. These potential compounds may serve as a basis for further developing small molecule IL-6 inhibitors in the future.


Treatment of interface keratitis with oral corticosteroids.
To describe the results of treating interface keratitis using a combination of intensive topical and oral corticosteroids. Casey Eye Institute, Portland, Oregon, USA. Thirteen eyes treated for grade 2 to 3 interface keratitis using an oral corticosteroid (prednisone 60 to 80 mg) as well as an hourly topical corticosteroid were retrospectively reviewed. The best corrected visual acuity (BCVA) was used as an objective guide of whether to treat with intense topical and oral corticosteroids, flap irrigation, or both. Predisposing factors such as intraoperative epithelial defects or a history of severe allergies or atopy were also looked for. All 13 eyes responded favorably to the combination of intensive topical and oral corticosteroids and had a BCVA of 20/20 after the keratitis resolved. In 6 eyes (46%), the patients had a history of severe seasonal allergies. One day postoperatively, 3 eyes (23%) had an epithelial defect and 2 eyes (15%), lint particles or debris embedded in the interface. With oral corticosteroid use, 3 patients (23%) noted mild stomach irritation and 2 (15%) noted nervousness. All 5 side effects resolved without sequelae. No patient developed a serious side effect. A short, intense course of an oral corticosteroid was an effective treatment in patients with grade 2 or higher interface keratitis when combined with a topical corticosteroid administered hourly. The BCVA is a helpful objective measure of the severity of interface keratitis and can be used to guide the clinician in the therapeutic strategy.


Linoleic acid and coronary heart disease.
The extent to which higher intakes of linoleic acid (LA) affect risk for coronary heart disease (CHD) is examined by reviewing a wide variety of study types, mostly in humans. In experimental studies, LA has been shown to lower serum levels of low-density lipoprotein cholesterol (LDL-C), especially when substituted for saturated fatty acids. Such an effect would be expected to reduce risk for CHD. In observational studies in which the dietary intake or serum content of LA were either cross-sectionally or prospectively related risk for CHD, higher LA intakes or serum levels have usually been associated with reduced risk. The pooled results from 5 randomized trials where LA was substituted for saturated fatty acids revealed a significant decrease in risk for CHD events with an LA intake 2-3 times current levels. Thus, current recommendations to consume 5-10% of energy from LA are evidence-based, and should not be reduced.


A Reappraisal of Charles Darwin's Engagement with the Work of William Sharp Macleay.
Charles Darwin, in his species notebooks, engaged seriously with the quinarian system of William Sharp Macleay. Much of the attention given to this engagement has focused on Darwin's attempt to explain, in a transmutationist framework, the intricate patterns that characterized the quinarian system. Here, I show that Darwin's attempt to explain these quinarian patterns primarily occurred before he had read any work by Macleay. By the time Darwin began reading Macleay's writings, he had already arrived at a skeptical view of the reality of these patterns. What most interested Darwin, as he read Macleay, was not the quinarian system itself. Rather, Darwin's notes on his reading primarily concerned certain background principles animating Macleay's work, in particular: (a) the non-existence of a saltus between human and animal minds, (b) the difficulty of establishing boundaries between species and varieties, and (c) Macleay's method of variation. Darwin's interest in the last of these left a mark on his discussion of taxonomic methodology in the Origin.


The predictive value of biochemical markers of bone turnover for bone mineral density in postmenopausal Japanese women.
To examine the predictive value of biochemical markers of bone turnover for bone loss pre- and postmenopausally, we measured two markers of bone formation, bone-specific alkaline phosphatase (BALP) and intact osteocalcin (OC); four markers of bone resorption, urinary cross-linked N-telopeptides of type I collagen (NTx), type I collagen C-telopeptide breakdown products (CTx), hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP); serum OC N-terminal (OC-N); and two serum cytokines, soluble interleukin-6 receptor (sIL-6R) and IL-1r antagonist at baseline and 1 year, as well as lumbar spine bone mineral density (BMD) at baseline and 1, 2, 3, 4, and 5 years after trial in 82 premenopausal (44.8 +/- 5.4 years old) and 325 postmenopausal (60.2 +/- 6.1 years old) healthy Japanese women. In premenopausal women, stratification of the baseline value of each biochemical marker into quartiles did not cause any significant difference in the change in BMD. Stratification of the NTx baseline value in postmenopausal women showed significant differences in rate of bone loss to the first year among those subjects with each quartile (Q1 [0.28 +/- 0.28%], Q2 [-0.32 +/- 0.34%], Q3 [-1.50 +/- 0.31%], and Q4 [-2.43 +/- 0.35%]) except for the difference between Q1 and Q2. The predictive value of NTx for BMD was greater in early postmenopausal women within 5 years after menopause than in late postmenopausal women with more than 5 years since menopause (YSM). Quartile analysis of the other biochemical markers and serum cytokines did not show any significant capacity for differentiating between bone loss rates. Moreover, when the changes in the lumbar spine BMD to the second and third years were stratified into quartiles by the baseline NTx, the ratios of bone loss to the second and the third years were significantly higher in those women with higher NTx (Q4; -3.15 +/- 0.56% and -4.06 +/- 0.57%, respectively) than in those with lower NTx (Q1; -0.74 +/- 0.44% and -1.03 +/- 0.51%, respectively). In conclusion, baseline urinary NTx was the most sensitive predictor of bone loss in the lumbar spine after 1, 2, and 3 years. Markers of bone resorption can be used clinically to predict future BMD in postmenopausal women.


Ecological Covariates of Subtle and Blatant Heterosexist Discrimination Among LGBQ College Students.
Sexual minority college students report experiencing interpersonal heterosexism, ranging from subtle insults to blatant physical violence. Such negative experiences can complicate developmental tasks common to adolescence and emerging adulthood. Studies examining the nature of heterosexism on college campuses have focused on blatant manifestations, yet subtle forms are more prevalent. Guided by ecological theory, we investigate the microsystem (e.g., perceived social support from friends, ambient heterosexism on campus), mesosystem (e.g., interaction between social support and ambient heterosexism), and macrosystem level (e.g., knowledge of gay-straight alliances on campus) covariates of interpersonal microaggressions, avoidance behaviors, verbal threats, and physical threats. Participants consisted of 530 self-identified LGBQ college students from 37 states. Regression results suggest that at the microsystem level, ambient heterosexism was positively associated with interpersonal microaggressions, avoidance behaviors, and verbal threats. At the mesosystem level, perceptions of LGBQ student support within one's institution moderated the effects of ambient heterosexism on three types of interpersonal heterosexism. At the macrosystem level, students who reported knowing that their campus had a sexual-orientation inclusive anti-discrimination policy reported encountering fewer verbal threats. Directions for future research and implications for campus programming are discussed.


Microbial Diversity of Fermented Greek Table Olives of Halkidiki and Konservolia Varieties from Different Regions as Revealed by Metagenomic Analysis.
Current information from conventional microbiological methods on the microbial diversity of table olives is insufficient. Next-generation sequencing (NGS) technologies allow comprehensive analysis of their microbial community, providing microbial identity of table olive varieties and their designation of origin. The purpose of this study was to evaluate the bacterial and yeast diversity of fermented olives of two main Greek varieties collected from different regions-green olives, cv. Halkidiki, from Kavala and Halkidiki and black olives, cv. Konservolia, from Magnesia and Fthiotida-via conventional microbiological methods and NGS. Total viable counts (TVC), lactic acid bacteria (LAB), yeast and molds, and Enterobacteriaceae were enumerated. Microbial genomic DNA was directly extracted from the olives' surface and subjected to NGS for the identification of bacteria and yeast communities. Lactobacillaceae was the most abundant family in all samples. In relation to yeast diversity, Phaffomycetaceae was the most abundant yeast family in Konservolia olives from the Magnesia region, while Pichiaceae dominated the yeast microbiota in Konservolia olives from Fthiotida and in Halkidiki olives from both regions. Further analysis of the data employing multivariate analysis allowed for the first time the discrimination of cv. Konservolia and cv. Halkidiki table olives according to their geographical origin.


Investigating the eco-efficiency of China's textile industry based on a firm-level analysis.
Industrial eco-efficiency has been an invaluable measurement for the relationship between production activities and environmental depletion, which is important to investigate when aiming for sustainable development. For the textile industry, however, limited rigorous studies have comprehensively evaluated the eco-efficiency from a firm-level perspective, and research on multi-level comparisons of the sub-sectors has also been lacking. Given the differences in environmental impacts due to the selection of various raw materials and unstandardized production processes in the textile industry, we focused on three sub-sectors, i.e., the cotton, chemical fibers textile sector (CCTS), the non-cotton textile sector (NCTS), and the printing and dyeing sector (PDS). By applying the slacks-based measure (SBM) model based on the principle of the data envelopment analysis (DEA), i.e., the SBM-DEA model, the eco-efficiency of China's textile industry was measured at the firm level from 2001 to 2011 using a large sample dataset. We then further analyzed the factors affecting eco-efficiency using the Tobit regression model. An empirical analysis showed an upward trend of eco-efficiency over time in the eastern, central, and western regions of China with great disparities for the three sub-sectors. Analyses of the typical provinces in the eastern region all showed increasing trends in eco-efficiency, with Shandong Province consistently performing the best. We also found that large-scale firms had the highest annual average eco-efficiency than that of small- and medium-scale firms. For the influencing factors on the eco-efficiency, our results indicated that the economic scale and export delivery value both had a significant positive correlation with the eco-efficiency, while foreign direct investment and environmental regulation were both significantly negative for the eco-efficiency in all three sub-sectors. These findings provide valuable insights into helping the textile industry address high-quality green development and sustainability.


Congenital subclavian-superior vena cava arteriovenous fistula with initial stenosis in an adult: a case report.
A subclavian-superior vena cava arteriovenous fistula is usually acquired and secondary to trauma or operations, while congenital causes are very rare. A congenital arteriovenous fistula leads to congestive heart failure soon after birth and is typically diagnosed in early infancy. We present an unusual case of a 21-year-old female suffering from new-onset heart failure at 20 years old who was diagnosed with a congenital arteriovenous fistula from the right subclavian artery to the superior vena cava (RSA-to-SVC) with stenosis at the proximal initial site of the fistula. The patient successfully underwent transcatheter occlusion for the fistula and had a significant improvement in symptoms at the 3-month follow-up. An RSA-to-SVC fistula is a very rare congenital disorder that can lead to shunt-related heart failure. If there is an indication for closure, as with the patient presented, percutaneous device closure can be considered a reasonable option.


MALAT1-mediated EZH2 Recruitment to the GFER Promoter Region Curbs Normal Hepatocyte Proliferation in Acute Liver Injury.
The goal of this study was to investigate the mechanism by which the long noncoding RNA MALAT1 inhibited hepatocyte proliferation in acute liver injury (ALI). Lipopolysaccharide (LPS) was used to induce an ALI cellular model in HL7702 cells, in which lentivirus vectors containing MALAT1/EZH2/GFER overexpression or knockdown were introduced. A series of experiments were performed to determine their roles in liver injury, oxidative stress injury, and cell biological processes. The interaction of MALAT1 with EZH2 and enrichment of EZH2 and H3K27me3 in the GFER promoter region were identified. Rats were treated with MALAT1 knockdown or GFER overexpression before LPS induction to verify the results derived from the in vitro assay. MALAT1 levels were elevated and GFER levels were reduced in ALI patients and the LPS-induced cell model. MALAT1 knockdown or GFER overexpression suppressed cell apoptosis and oxidative stress injury induced cell proliferation, and reduced ALI. Functionally, MALAT1 interacted directly with EZH2 and increased the enrichment of EZH2 and H3K27me3 in the GFER promoter region to reduce GFER expression. Moreover, MALAT1/EZH2/GFER was activated the AMPK/mTOR signaling pathway. Our study highlighted the inhibitory role of reduced MALAT1 in ALI through the modulation of EZH2-mediated GFER.


Coronary reperfusion studies with pro-urokinase in acute myocardial infarction: evidence for synergism of low dose urokinase.
Pro-urokinase is a single chain precursor of two chain urokinase, which has been shown to induce fibrin-selective plasminogen activation. In the present study, thrombolytic efficacy of 9 million U of glycosylated pro-urokinase administered intravenously was compared with that of a combined regimen utilizing 4.5 million U of pro-urokinase and 0.2 million U of urokinase. Seventy-five patients with a first myocardial infarction were randomized to receive high dose pro-urokinase (n = 40, group A) or the combination therapy (n = 35, group B). Reperfusion of the infarct-related artery was assessed by repeat coronary angiography. Thrombolysis in Myocardial Infarction trial (TIMI) grade II or III reperfusion was achieved in 73% of group A patients compared with 66% of group B patients (p = NS). A trend toward faster reopening of the infarct-related artery was observed in patients in group B. Coronary artery reocclusion occurred in 5 (10%) of 49 patients in whom angiography was repeated within 36 h after the start of therapy. Clot-selective thrombolysis was indicated by a minimal fibrinogen decline (15% and 13%, respectively, in groups A and B). Alpha 2-antiplasmin levels, however, decreased more rapidly in patients in group B (p less than 0.05). This finding and the equivalent reperfusion rate in the combined treatment group strongly suggest synergistic interaction between these two thrombolytic agents. In summary, the high incidence of reperfusion, the low rate of early reocclusion and the paucity of side effects, particularly with regard to bleeding complications, indicate that pro-urokinase possesses the characteristics of an ideal thrombolytic agent.


2011 Focused Update of 2009 American Society of Clinical Oncology Clinical Practice Guideline Update on Chemotherapy for Stage IV Non-Small-Cell Lung Cancer.
ASCO produced the 2011 Focused Update based on phase III randomized clinical trials published on maintenance chemotherapy, addressing one question from the 2009 Guideline Update on chemotherapy for stage IV NSCLC: what is the optimal duration of first-line chemotherapy for stage IV NSCLC?


Observer agreement on the Dejour trochlear dysplasia classification: a comparison of true lateral radiographs and axial magnetic resonance images.
Trochlear dysplasia is known to be an important cause of patellofemoral instability. D. Dejour's radiographic and magnetic resonance imaging (MRI) classifications are widely used in clinical practice and in the orthopaedic literature to assess the severity of trochlear dysplasia. The indication for deepening trochleoplasty to treat trochlear dysplasia is also mainly based on the severity of trochlear dysplasia according to Dejour's criteria. To our knowledge, there is no study evaluating the efficacy of the Dejour classification. The aim of this study was to assess the intraobserver and interobserver agreements of the radiographic and MRI-based classification as described by Dejour. Cohort study (diagnosis); Level of evidence, 2. From 50 patients, 50 lateral radiographs as well as 50 MRI scans were read twice independently within 4 weeks by 4 surgeons (2 senior and 2 junior examiners). Analysis was made according to Dejour's 4 grades of radiological criteria of trochlear dysplasia as well as differentiating between 2 grades: low-grade (type A) and high-grade trochlear dysplasia (types B-D). The 4-grade analysis showed fair intraobserver and interobserver agreements (24%-78%), while the 2-grade analysis showed good to excellent agreement (56%-96%). The best overall agreement was found for the 2-grade analysis on MRI scans (62%-96%). The lateral radiographs tended to underestimate the severity of trochlear dysplasia compared with axial MRI. D. Dejour's classification is valid for typing trochlear dysplasia and is particularly useful in separating low-grade from high-grade dysplasia.


Use of autologous Tenon's capsule and scleral patch grafts for repair of excessively draining fistulas with leaking filtering blebs.
To report the use of autologous Tenon's and partial-thickness scleral tissues for patch graft revisions of excessively draining fistulas associated with leaking filtering blebs. Appropriate sized pieces of autologous Tenon's tissue and partial-thickness scleral tissue were dissected near the surgical sites and used as patch grafts to effectively repair excessively draining fistulas with leaking filtering blebs. Both Tenon's and partial-thickness scleral patch grafts were useful in adequately closing the excessively draining fistulas. Autologous Tenon's and scleral tissue patch grafts appear to be safe and effective for the repair of excessively draining fistulas, and are useful when patch grafts are unexpectedly needed.


Inhibitory effect of N-adamantyl-3,4-dihydroxybenzamide on melanogenesis in melan-a cells and brown guinea pigs.
To find novel depigmenting agents, a new synthetic compound, N-adamantyl-3,4-dihydroxybenzamide (NADB) was produced and the effects on melanogenesis were investigated. Our results showed that NADB reduced melanin synthesis in a dose-dependent manner in melan-a cells. Tyrosinase activity was also reduced by NADB treatment in melan-a cells. However, NADB did not inhibit tyrosinase activity directly in a cell-free system. Treatment of melan-a cells with NADB caused a marked decrease in protein and mRNA levels of tyrosinase along with tyrosinase-related protein 1 and dopachrome tautomerase. To determine whether NADB reduces skin pigmentation, the dorsal skin of brown guinea pigs was shaved and irradiated with UV for 3 weeks using a solar simulator. Then NADB (2 or 1% in propylene glycol:ethanol:water = 5:3:2) was applied topically twice daily for 4 weeks. Visual inspection and Fontana-Masson staining both demonstrated that NADB resulted in lower skin pigmentation and total epidermal melanin in comparison to vehicle-treated areas. These findings suggest that NADB is useful in the treatment of hyperpigmentation.


Syphilis is back: presentation of three cases at the ENT department.
Syphilis is a sexually-transmitted disease caused by the spirochete Treponema pallidum, and is transmitted either through sexual contact or vertically across the placenta. Rates of infection were at a low point in the early 1990s. Since then, increasing numbers of new cases of infections have been observed in all Western countries. Presentation of three patients with syphilis who presented within a short period of time in an ENT outpatient clinic. One must be aware of the increasing incidence of syphilis, even in head and neck disciplines. Typical symptoms of an early infection are an ulcerous lesion in the mouth, with or without cervical lymphadenopathy. The main therapy is high doses of penicillin G administered intramuscularly. Other simultaneous sexually-transmitted diseases, especially HIV infection, must be excluded. Unnoticed and untreated patients may develop late and life-threatening complications.


Copper nanoparticles induce the formation of fatty liver in Takifugu fasciatus triggered by the PERK-EIF2α- SREBP-1c pathway.
Copper nanoparticles (CuNPs), a new pollutant in water environments, were widely used in various industrial and commercial applications. This study indicated that the presence of CuNPs exposure under environmental related concentration is an inducing factor that contributes to the fatty liver formation in Takifugu fasciatus. Furthermore, we explored the fatty liver formation mechanism. The results shown, (1) the cloned genes related to endoplasmic reticulum stress (ERS) (GRP78, IRE-1α, PERK, and ATF-6α) were highly expressed in the liver of T. fasciatus. (2) after 30-days exposure, CuNPs accumulated in the endoplasmic reticulum of liver and induced the appearance of ERS, then activated unfolded protein response (UPR) signaling pathway. Furthermore, the SREBP-1c pathway that plays a key role in lipid synthesis was activated. (3) by using 4-PBA and GSK inhibitors to respectively stimulate ERS and PKR-like ER kinase (PERK) through in vitro experiments, we confirmed that CuNPs induced the fatty liver formation in T. fasciatus triggered by the PERK-EIF2α pathway by activating the SREBP-1c pathway to promote fatty liver formation. This study provides a new perspective for identifying the pathogens of fatty liver formation, and adds to the knowledge of the ecological safety data service of CuNPs in water.


Publisher Correction: Quantum coherence of multiple excitons governs absorption cross-sections of PbS/CdS core/shell nanocrystals.
The original version of this Article contained an error in the seventh sentence of the second paragraph of the 'TA amplitudes for double pump-pulse excitation" section of the Results, which incorrectly read 'The absorption cross-sections of the transitions from the single exciton state to the biexciton and triexciton states are denoted by σ' and σ'', respectively.' The correct version states 'σ''' in place of 'σ'''.The ninth and tenth sentences of the same paragraph originally incorrectly read 'The most important issue of this work is to clarify whether the multiple exciton absorption cross-sections σ' and σ'' are equal to σ or not. The black dotted curves in Fig. 3b, c show the predicted results of the TA amplitudes by assuming identical cross-sections, i.e., σ = σ ' = σ'' = .' The correct version states 'σ' and σ'' are equal" instead of 'σ' and σ'' are equal' and 'σ = σ' = σ''' in place of 'σ = σ ' = σ'' = '.This has been corrected in both the PDF and HTML versions of the Article.


Postural effects of the scaled display of visual foot center of pressure feedback under different somatosensory conditions at the foot and the ankle.
To assess the effects of the scaled display of visual foot center of pressure (COP) feedback on upright postural control under different somatosensory conditions at the foot and the ankle. Before and after intervention trials. University medical bioengineering laboratory. Young healthy adults (N=8; mean age, 23+/-2.5 y; mean body weight, 76.8+/-11.2 kg; mean height, 179.8+/-6.8 cm). Participants were asked to stand upright, as immobile as possible, in 3 visual conditions: a stationary cross feedback (SC-FB) condition and 2 different foot COP feedback (COP-FB) conditions involving increasing scale displays of 2:1 (COP-FB2) and of 10:1 (COP-FB10). These latter conditions correspond to the ratio between the COP displacement on the screen and the actual COP displacement measured by the force platform. This postural task was executed on 2 (firm, foam) support surface conditions. In the foam condition, a 2-cm thick foam support surface was placed under the participants' feet to alter the quality and/or quantity of somatosensory information at the foot and the ankle. COP displacements were recorded using a force platform. In the firm support surface condition, no significant difference was observed between the COP-FB2 and the SC-FB conditions, whereas the COP-FB10 condition yielded decreased COP displacements relative to the SC-FB condition. In the foam support surface condition, both the COP-FB2 and the COP-FB10 conditions yielded decreased COP displacements relative to the SC-FB condition, with a greater stabilizing effect in the COP-FB10 than COP-FB2 condition. The postural effects of the scale display of visual COP feedback differed depending on the somatosensory conditions at the foot and the ankle. These findings suggest that increased reliance on augmented sensory information for controlling upright posture in conditions of altered somatosensory input from the foot and ankle could have implications in clinical and rehabilitative areas.


Risk of urinary tract infection following vaginal delivery: a comparison between intermittent and indwelling bladder catheterization.
The primary objective of the study was to determine the risk of postpartum urinary tract infection (UTI) in women exposed to intermittent versus indwelling catheterization in labor. The secondary objective was to identify risk factors for development of postpartum UTI. A case-control study was conducted between 1 January 2013 and 31 December 2016. Cases were defined as patients who were diagnosed with UTI and controls were not diagnosed with UTI. Obstetrical, infectious, and catheterization variables were collected. Univariate and multivariate analyses were performed. A total of 26,517 full-term vaginal deliveries occurred during the study period with a rate of postpartum UTI of 0.7%. There were 166 cases and 695 controls included in the analysis. There was no significant difference in the rate of UTI between patients who underwent indwelling versus intermittent (reference) catheterization (OR 1.05, 95% CI: 0.67-1.64, p = .826). On multivariate analysis, significant risk factors for UTI included the relationship between use of catheterization and duration of labor (p = .026) and history of UTI during the pregnancy (p < .001). In this study, there was no difference in the rate of postpartum UTI based on catheterization method. Further studies are needed to determine the optimal method of catheterization during labor and to enable providers to implement quality improvement strategies aimed at decreasing the risk of infection.


Determination of formaldehyde in beverages using microwave-assisted derivatization and ionic liquid-based dispersive liquid-liquid microextraction followed by high-performance liquid chromatography.
A simple method based on simultaneous microwave-assisted derivatization and ionic liquid-based dispersive liquid-liquid microextraction (IL-based DLLME) is proposed for the derivatization, extraction and preconcentration of formaldehyde in beverage samples prior to the determination by high-performance liquid chromatography (HPLC). Formaldehyde was in situ derivatized with 2,4-dinitrophenylhydrazine (DNPH) and simultaneously extracted and preconcentrated by using microwave-assisted derivatization and IL-based DLLME in a single step. Several experimental parameters, including type and volume of extraction solvent, type and volume of disperser, microwave power and irradiation time, volume of DNPH, pH of sample solution, and ionic strength were evaluated. When the microwave power was 120 W, formaldehyde could be derivatized and extracted simultaneously only within 90 s. Under optimal experimental conditions, good linearity was observed in the range of 0.5-50 ng/mL with the correlation coefficient of 0.9965, and the limit of detection was 0.12 ng/mL. The proposed method was applied to the analysis of different beverage samples, and the recoveries of formaldehyde obtained were in the range of 84.9-95.1% with the relative standard deviations lower than 8.4%. The results showed that the proposed method was a rapid, convenient and feasible method for the determination of formaldehyde in beverage samples.


Effectiveness of three types of lumbar orthosis for restricting extension motion.
Spinal orthoses are implemented to restrict lumbar motion. Several studies have compared the effectiveness of various types of lumbar orthoses on restricting motion, but none have compared the effect of different back supports on restricting extension. This study sought to evaluate the effectiveness of three types of lumbar orthosis in regard to their ability to restrict motion during extension. Range of motion was quantified using the Spinal Mouse system to measure flexion and extension, and the load distribution of the back support was measured using a pressure sensor. Ten subjects (8 men, 2 women) were assessed under the following five experimental conditions: custom-made stay (CMS), aluminum stay (AS), plastic stay (PS), corset only, and no brace. None of the stays changed the flexion angle, and none of the supports prevented flexion bending. The mean extension angle after immobilization with the CMS, AS, PS, corset only, and no brace was 27.5° ± 8.5°, 33.4° ± 11.0°, 34.3° ± 9.4°, 37.8° ± 10.7°, and 42.6° ± 10.5°, respectively. The load in the CMS was concentrated at the vertical ends of the stay, with a mean load of 11.5 ± 2.4 N at the top and 8.9 ± 2.4 N at the bottom. The loads at the top and bottom of the support were 7.2 ± 4.3 and 5.3 ± 3.1 N with the AS and 5.8 ± 2.3 and 4.4 ± 1.7 N with the PS, respectively. All supports allowed similar flexion motion. Although the CMS, AS, and PS all restricted extension compared with no brace, the CMS was the most effective for restricting trunk extension motion.


Methods to study primary cilia and autophagy in the brain.
Autophagy is an intracellular catabolic pathway that allows proteins, organelles, and pathogens to be recycled. Thus, it is crucial to maintain cell homeostasis, especially important in post-mitotic cells as neurons that cannot dilute cellular damage through mitosis. In the last decade, autophagy has been connected to the primary cilium (PC), a small organelle that acts as a sensory hub and is present in most cell types, including astrocytes and neurons. In this chapter, we briefly describe the state-of-the-art of the interplay between autophagy, PC, and its implications for the brain, in healthy and pathophysiological conditions. Deregulations in autophagy can be monitored by numerous assays, both in vivo and in vitro, and so do changes in PC length/number. Here, we relate a practical and user-friendly description of immunofluorescence methods to study autophagy and PC changes in brain slices, including the tissue preparation, confocal microscopy, image analysis, and deconvolution process.


Distinct subsets of CD1d-restricted T cells recognize self-antigens loaded in different cellular compartments.
Although recent studies have indicated that the major histocompatibility complex-like, beta2-microglobulin-associated CD1 molecules might function to present a novel chemical class of antigens, lipids and glycolipids, to alpha/beta T cells, little is known about the T cell subsets that interact with CD1. A subset of CD1d-autoreactive, natural killer (NK)1.1 receptor-expressing alpha/beta T cells has recently been identified. These cells, which include both CD4(-)CD8(-) and CD4(+) T cells, preferentially use an invariant Valpha14-Jalpha281 T cell receptor (TCR) alpha chain paired with a Vbeta8 TCR beta chain in mice, or the homologous Valpha24-JalphaQ/Vbeta11 in humans. This cell subset can explosively release key cytokines such as interleukin (IL)-4 and interferon (IFN)-gamma upon TCR engagement and may regulate a variety of infectious and autoimmune conditions. Here, we report the existence of a second subset of CD1d-restricted CD4(+) T cells that do not express the NK1.1 receptor or the Valpha14 TCR. Like the Valpha14(+) NK1.1(+) T cells, these T cells exhibit a high frequency of autoreactivity to CD1d, use a restricted albeit distinct set of TCR gene families, and contribute to the early burst of IL-4 and IFN-gamma induced by intravenous injection of anti-CD3. However, the Valpha14(+) NK1.1(+) and Valpha14(-) NK1.1(-) T cells differ markedly in their requirements for self-antigen presentation. Antigen presentation to the Valpha14(+) NK1.1(+) cells requires endosomal targeting of CD1d through a tail-encoded tyrosine-based motif, whereas antigen presentation to the Valpha14(-) NK1.1(-) cells does not. These experiments suggest the existence of two phenotypically different subsets of CD1d-restricted T cells that survey self-antigens loaded in distinct cellular compartments.


Aspiration pneumonia and complications of inhalation of smoke and toxic gases.
Pulmonary aspiration of oral, esophageal, or gastric content poses a significant hazard to animals. Aspiration of acidic, alkaline, or ingesta-containing gastric contents can cause serious morbidity and mortality. Clinicians must be aware of conditions and clinical situations in which there is increased risk of aspiration. The most important aspect of the mitigation of the pneumonic complications of aspiration is prevention.


MicroRNA-205-5p: A potential therapeutic target for influenza A.
We are committed to finding host targets for influenza A therapeutics. The nucleoprotein (NP) plays an important role in influenza A virus replication and is an indispensable part of viral transcription and replication. Exploring endogenous substances that can modulate NP is critical for finding host targets. MicroRNAs (miRNAs, miR) are a novel class of powerful, endogenous gene expression regulators. Herein, we used miRanda to analyse the base complementarity between the NP gene and the 14 host miRNAs reported previously by us. MiRanda predicted that miR-431-5p, miR-744-3p and miR-205-5p could complement the NP gene. To understand the effect of these miRNAs on NP expression, we co-transfected 293 T cells with NP gene sequence containing above miRNAs binding site or full sequence of NP gene (transfected into pmirGlo or pcDNA3.1 vectors, respectively), and mimics of miR-205-5p, miR-431-5p and miR-744-3p. Dual luciferase reporter gene or Western blotting assays confirmed that miR-205-5p and miR-431-5p inhibit NP expression by binding with the miRNA binding site of NP gene. Further, we infected Mouse Lung Epithelial (MLE-12) cells overexpressing miR-205-5p and miR-431-5p with influenza A virus and performed Western blotting to examine NP expression. We found that NP expression was significantly reduced in MLE-12 cells overexpressing miR-205-5p during influenza A infection. The miR-205-5p overexpression-induced inhibition of influenza A replication could be attributed to the inhibition of NP expression. Further, we administered oseltamivir and Jinchai Antiviral Capsules (JC, an anti-influenza Chinese medicine) to influenza A virus-infected MLE-12 cells and mice. We found that miR-205-5p was significantly decreased increased in infected cells and lung tissues, and oseltamivir and JC could up-regulate miR-205-5p. In conclusion, we provide new evidence that miR-205-5p plays a role in regulating viral NP protein expression in combating influenza A and may be a potential target for influenza A therapy.


Cytokeratin distribution and expression during the maturation of mouse germinal vesicle oocytes after vitrification.
Cytokeratin (CK) is a type of the cytoskeleton that increases cell stabilization during oocyte maturation. This study was conducted to investigate the effect of vitrification on the distribution and expression of CK during mouse oocyte maturation. Germinal vesicle (GV) oocytes were randomly allocated into three groups: (1) untreated (fresh), (2) exposed to vitrification solution (VS) without being plunged into liquid nitrogen (CPA exposure), or (3) vitrified using the open-pulled straw (OPS) method (vitrification). The oocytes were then incubated for 0 h, 6h (metaphase I (MI) stage), and 10h (metaphase II (MII) stage). The CK distribution in the oocytes at the GV, MI, and MII stages was observed by immunofluorescence, and the expression at the MII stage oocytes derived from vitrified GV oocytes was detected by Western blotting. The CK distribution in the GV oocytes (88.5%) displayed a cortical pattern in the fresh group, whereas a granular pattern was mainly found at the MI (86.7%) and MII (93.5%) stages. In the CPA exposure group, 90.3% of the GV oocytes were observed to display the cortical pattern, and 69.2% of the MI oocytes and 92.9% of the MII oocytes showed the granular pattern. In the vitrification group, most oocytes (GV, 88.9%; MI, 100%; MII, 93.3%) exhibited the cortical pattern. The CK fluorescence intensities of the MII stage oocytes in both the fresh (59.27) and CPA exposure (60.05) group were significantly higher than that of the vitrification (26.53) group (p<0.05). Western blotting showed that the CK expression in the MII oocytes derived from vitrified GV oocytes was significantly lower (p<0.05) than in the control. In conclusion, OPS vitrification affects the normal CK distribution pattern during oocyte maturation and results in decreased CK expression in MII oocytes derived from vitrified GV oocytes.


Assessment of bone formation capacity using in vivo transplantation assays: procedure and tissue analysis.
In vivo assessment of bone formation (osteogenesis) potential by isolated cells is an important method for analysis of cells and factors control ling bone formation. Currently, cell implantation mixed with hydroxyapa-tite/tricalcium phosphate in an open system (subcutaneous implantation) in immunodeficient mice is the standard method for in vivo assessment of bone formation capacity of a particular cell type. The method is easy to perform and provides reproducible results. Assessment of the donor origin of tissue formation is possible, especially in the case of human-to-mouse transplanta tion, by employing human specific antibodies or in situ hybridization using human specific Alu-repeat probes. Recently, several methods have been developed to quantitate the newly formed bone using histomorphometric methods or using non-invasive imaging methods. This chapter describes the use of in vivo transplantation methods in testing bone formationpotential of human mesenchymal stem cells.


Involvement of plasma membrane-located calmodulin in the response decay of cyclic nucleotide-gated cation channel of cultured carrot cells.
Increase in cytoplasmic cyclic AMP concentration stimulates Ca2+ influx through the cyclic AMP-gated cation channel in the plasma membrane of cultured carrot cells. However, the Ca2+ current terminated after a few minutes even in the presence of high concentrations of cyclic AMP indicating that hydrolysis of the nucleotide is not responsible for stop of the Ca2+ influx. Cyclic AMP evoked discharge of Ca2+ from inside-out sealed vesicles of carrot plasma membrane, and it was strongly inhibited when the suspension of the vesicles was supplemented with 1 microM of free Ca2+, while Ca2+ lower than 0.1 microM did not affect the Ca(2+)-release. The Ca2+ flux across plasma membrane was restored from this Ca(2+)-induced inhibition by the addition of calmodulin inhibitors or anti-calmodulin. These results suggest that Ca2+ influx initiated by the increase in intracellular cAMP in cultured carrot cells is terminated when the cytosolic Ca2+ concentration reaches the excitatory level in the cells, and calmodulin located in the plasma membrane plays an important role in the response decay of the cyclic nucleotide-gated Ca2+ channel.


Demographics and replantation.
We reviewed demographic data on 761 patients who had one or more amputated parts replanted at Duke University Medical Center between 1972 and 1984 to learn more about the population that sustained amputation and replantation. Ninety-four percent were from North Carolina and its border states. Persons between ages 21 and 30 years were the most frequently injured. Eighty-five percent of patients were men. Seventy-eight percent of amputations occurred between 6:00 AM and 6:00 PM. No significant difference in the number of replantations was noted at various months of the year. Fifty-eight percent of amputations were job related, and laceration was the most frequent type of amputation. Time between injury and operation averaged 5 hours 50 minutes. Average operating time was 6 1/2 hours. Thumbs were replanted most frequently, the index and small finger least frequently. Length of hospital stay averaged 9 days. Time out of work averaged 3 months. This data suggest that efforts directed toward employee education, safety, and prevention of injury on the job have the potential of decreasing the largest single cause of amputations in the upper extremities of patients in our area of the United States.


Morphological and biological characterization of two mesenchymal murine tumors and the modulation of their growth parameters by n-3 and n-6 polyunsaturated fatty acids.
Certain tumor growth parameters (GP) of two mesenchymal transplantable tumors maintained on C57BL/6J mice were characterized. Considering that many experimental, clinical and epidemiologic data have indicated that n-3 and n-6 essential fatty acids are nutrients which may delay the development as well as improve the course of cancer, GPs were evaluated on hosts fed on a semisynthetic formula containing 5% of corn oil (CO) or cod liver oil (CLO) and stock diet (C group). Although survival and latency time of tumor-bearing mice were shortened, other GP as percentage of successful implants were improved by both oils in sarcoma-bearing hosts, suggesting that n-3 and n-6 fatty acids might play a modulating role for the development of these tumors.


In vivo EPR measurement of glutathione in tumor-bearing mice using improved disulfide biradical probe.
Disulfide nitroxide biradicals, DNB, have been used for glutathione, GSH, measurements by X-band electron paramagnetic resonance, EPR, in various cells and tissues. In the present paper, the postulated potential use of DNB for EPR detection of GSH in vivo was explored. Isotopic substitution in the structure of the DNB was performed for the enhancement of its EPR spectral properties. (15)N substitution in the NO fragment of the DNB decreased the number of EPR spectral lines and resulted in an approximately two-fold increase in the signal-to-noise ratio, SNR. An additional two-fold increase in the SNR was achieved by substitution of the hydrogen atoms with deuterium resulting in narrowing the EPR lines from 1.35 G to 0.95 G. The spectral changes of DNB upon reaction with GSH and cysteine were studied in vitro in a wide range of pHs at room temperature and "body" temperature, 37 degrees C, and the corresponding bimolecular rate constants were calculated. In in vivo experiments the kinetics of the L-band EPR spectral changes after injection of DNB into ovarian xenograft tumors grown in nude mice were measured by L-band EPR spectroscopy, and analyzed in terms of the two main contributing reactions, splitting of the disulfide bond and reduction of the NO fragment. The initial exponential increase of the "monoradical" peak intensity has been used for the calculation of the GSH concentration using the value of the observed rate constant for the reaction of DNB with GSH, k(obs) (pH 7.1, 37 degrees C)=2.6 M(-1)s(-1). The concentrations of GSH in cisplatin-resistant and cisplatin-sensitive tumors were found to be 3.3 mM and 1.8 mM, respectively, in quantitative agreement with the in vitro data.


Descending serotonergic, peptidergic and cholinergic pathways from the raphe nuclei: a multiple transmitter complex.
The localization of serotonergic, various peptidergic and possibly cholinergic neurons in the medullary raphe nuclei that project to the lumbosacral spinal cord have been studied using a retrograde transport method combined with immunocytochemical and histochemical techniques. Spinally projecting neurons stained for serotonin-like, substance P-like, enkephalin-like and thyrotropin-releasing hormone-like immunoreactivity and for the histochemical marker acetylcholinesterase were all observed in each of the raphe nuclei of the medulla, as well as in the adjacent ventrolateral reticular formation. The similar distributions of the descending serotonergic and peptidergic neurons in the raphe nuclei as well as quantitative data on their relative numbers suggest that a large fraction of raphe-spinal neurons contain serotonin co-existing with one or more peptides in the same cell.


Role of intraoperative feeding jejunostomy in esophageal cancer surgery.
Feeding jejunostomy was routinely placed during esophagectomy to ensure postoperative enteral feeding. Improved anastomosis technique and early oral feeding strategy after esophagectomy has led to question the need for the routine placement of feeding jejunostomy. The aim of this study is to evaluate role of feeding jejunostomy during Ivor Lewis operation. We retrospectively reviewed 414 patients who underwent the Ivor Lewis operations from January 2015 to December 2018. 61 patients (14.7%) received jejunostomy insertion. The most common indication for jejunostomy was neoadjuvant concurrent chemoradiation therapy (CCRT). 48 patients (79%) had jejunostomy removed within 60 days after the surgery and the longest duration of jejunostomy inserted state was 121 days. About two-third of the patients with jejunostomy had never prescribed with an enteral feeding product. Among 353 patients without intraoperative feeding jejunostomy, 11(3.1%) received delayed jejunostomy insertion. Graft-related problems (6 patients), cancer progression (3 patients), acute lung injury (1 patient), and swallowing difficulty (1 patient) were reasons for delayed feeding jejunostomy insertion. Complication rate was relatively high as 24 patients (33.3%) out of 72 patients with jejunostomy insertion had complications and 7 patients (9.7%) visited ER more than twice with jejunostomy-related complications. Only 3.6% patients who underwent the Ivor Lewis operation during 4-year span had anastomosis leakage. Although one-third of the patients with jejunostomy were benefited with alternative method of feeding after discharge, high complication rate regarding jejunostomy should be also considered. We believe feeding jejunostomy should not be applied routinely with prophylactic measures and should be reserved to very carefully selected patients with multiple high-risk factors.


Holding the line on hepatic fat.
When chronically elevated, insulin increases hepatic lipogenesis and VLDL synthesis. However, the hormone reduces liver lipids when acutely elevated. Work in this issue of Cell Metabolism (Najjar at al., 2005) suggests a new mechanism for the inhibition of the rate-limiting enzyme in liver, fatty acid synthase.


DNA ploidy measurement and human papillomavirus in abnormal cervical cytology.
To compare the efficacy of high-risk human papillomavirus (HR-HPV) and DNA image cytometry (DNA-ICM) status for identifying high-grade cervical intraepithelial neoplasia or worse (≥CIN2). This cross-sectional study was performed in women undergoing follow-up procedure after a previous abnormal cervical cytology. Cervical cells were collected for HPV detection and DNA ploidy measurement. Biopsy samples were taken for histological confirmation. Sensitivity and specificity values for ≥CIN2 detection with HR-HPV and DNA-ICM were determined. HR-HPV was present in 74.5% of the women. The most frequent HPV infection was HPV 16, followed by HPV 31, 33 and 58. Aneuploidy was observed in 60.6% of all cases. Referral cytology revealed 78.0% sensitivity and 68.6% specificity for detecting a ≥CIN2 lesion. The HR-HPV test alone showed 92.7% sensitivity, albeit it was not statistically different from DNA-ICM (88.1%, P > .05). Positivity for HPV or DNA-ICM resulted in 100% sensitivity. Higher specificity was observed for the combination of HR-HPV and DNA-ICM (88.6%), with no difference from DNA-ICM alone (85.7%, P > .05). DNA-ICM or HR-HPV positivity identified all cases of ≥CIN2 in women undergoing follow-up procedure after a previous abnormal cervical cytology. Routine cervical cancer screening could be improved by the incorporation of DNA-ICM as a complementary method to primary screening to identify which women need closer follow-up.


A comparison of the cellular toxicity of exhausts from cars driven on present and future fuels.
A cellular test system (brown-fat-cell-test) (BFC-test) has been used to evaluate the toxicity of the particulate phase of exhaust emission from vehicles fuelled with gasoline and alcohol-mixed fuels. The results were evaluated by an analysis of variance with multiple contrasts. The exhaust extracts from cars driven on commercially available gasoline were found to be significantly more toxic to the cellular oxygen consumption than a similar extract of exhausts from cars driven on alcohol-mixed fuels. The lowest toxicity was found with extracts from catalyst processed exhausts.


Cyclophosphamide-containing regimen (TCD) is superior to melphalan-containing regimen (MPT) in elderly multiple myeloma patients with renal impairment.
Renal impairment (RI) is a frequent complication with higher incidence of infections and an important prognostic factor for survival. Melphalan clearance is renal function dependent whereas cyclophosphamide is renal function independent. We investigated which combination regimen should be selected between melphalan-combining regimen (MPT) or cyclophosphamide-combining regimen (TCD) in elderly multiple myeloma (MM) patients with RI. Between 2005 and 2009, 157 newly diagnosed MM patients with RI were included comparing MPT with TCD therapy as initial treatment. Seventy-four patients were given MPT regimen, and 83 patients were given TCD regimen. Baseline characteristics were similar between the MPT and TCD groups. Analysis of different cutoff levels between 25% and 75% quartiles using log-rank test determined that glomerular filtration rate (GFR), 40 ml/min/1.73 m(2) as the cutoff point, yielded the highest difference in event-free survival (EFS) and overall survival (OS). The MPT subgroup with low GFR (GFR <40 ml/min/1.73 m(2)) had poorer response rates than others. The incidence of neutropenia and infection with febrile neutropenia were higher in the MPT subgroup with low GFR than the others (p = 0.016, p < 0.001). Furthermore, mortality due to the infection was higher in the MPT subgroup with low GFR than the others (p < 0.001). EFS was lower in the MPT subgroup with low GFR than the others (p < 0.001). OS was lower in the MPT subgroup with low GFR than the others (p < 0.001). In newly diagnosed elderly MM patients with RI, TCD regimen would be an effective and tolerable treatment option due to the combination of cyclophosphamide independent to renal function and dexamethasone effective for RI.


The late consequences of anthracycline treatment on left ventricular function after treatment for childhood cancer.
The purpose of this study was to determine the incidence of changes in left ventricular function in patients in long-term remission after treatment with anthracyclines for a childhood malignancy. The authors examined 155 patients in disease remission who underwent treatment protocols utilising anthracyclines in childhood. The group comprised 90 males and 65 females aged 15+/-4.9 years (range 5-29 years, median 15 years). The age at the time of diagnosis and start of treatment was 8.6+/-4.9 years (range 1-18 years, median 8 years). The time of follow-up was 7.3+/-4 years (range 1-21 years, median 6.3 years). The patients were given a cumulative dose of doxorubicin or daunorubicin of 250+/-131 mg/m2 (range 50-1200 mg/m2, median 240 mg/m2). The values of ejection fraction below 55% and fractional shortening below 30% assessed by means of echocardiography were considered as pathological. The control group consisted of 41 volunteers. Pathological values of fractional shortening were found in 12 patients (8%). Only one patient (0.64%) showed the development of heart failure due to cardiomyopathy. The group of the patients after chemotherapy revealed significantly worse values of left ventricular endsystolic wall stress, mean velocity of circumferential fibre shortening, Tei index, and isovolumic relaxation period in comparison with the control group. We found a correlation between the given cumulative dose of anthracyclines and indicators of systolic function of the left ventricle, but not a relation to the time indicators (age at diagnosis, time of follow-up). in the mean period of 6 years after chemotherapy, subclinical cardiotoxicity was found in 11 patients (7%) and cardiomyopathy with heart failure in one patient. Further indicators of subclinical damage are elevation of afterload (end-systolic stress), impaired relaxation and increased value of the Doppler index of global left ventricular function. Further monitoring and evaluation of the relevant subclinical abnormalities over a longer period of time are needed.


Objective Measurement of Cosmetic Outcomes of Breast Conserving Therapy Using BCCT.core.
The purpose of this study is to evaluate objective cosmetic outcomes and factors related to breast-conserving therapy (BCT) using the BCCT.core software. Fifty-one patients who received BCT with informed consent were evaluated using the BCCT.core software. Patients were divided into two groups based on the BCCT score: excellent or good (n=42) vs. fair or poor (n=9). Analysis of clinical factors was performed to determine factors affecting cosmetic outcomes. The objective cosmetic outcome of BCT measured using the BCCT.core software was excellent in 10% of patients, good in 72%, and fair in 18%. None of the patients were classified as poor outcome. Tumor characteristics, systemic adjuvant therapy (chemotherapy and hormonal therapy), and radiation dose or energy of electron boost did not show correlation with the score measured by the BCCT.core program (p > 0.05). In univariate analysis, maximum dose within the breast (Dmax), width of tangential field, and excised tumor volume were smaller in patients with excellent or good by the BCCT.core compared to those with fair or poor (Dmax, 110.2 ± 1.5% vs. 111.6 ± 1.7%, p=0.019; width of tangential field, 8.0 ± 1.1 cm vs. 8.6 ± 0.7 cm, p=0.034; excised tumor volume, 64.0 ± 35.8 cm(3) vs. 95.3 ± 54.4 cm(3), p=0.067). In multivariate analysis, only Dmax was a significant factor for breast cosmetic outcome with a risk ratio of 1.697 (95% confidence interval, 1.006 to 2.863; p=0.047). Objective measurement of cosmetic outcome of BCT using the BCCT.core software was feasible. The cosmetic outcome of BCT may be affected by the maximum dose within the breast.


[Acute injuries to peripheral nerves. 1. Diagnosis and principles for therapy].
A simple scheme for the identification of the most frequent lesions of single peripheral nerves is given. The scheme is based on a few--mostly two--characteristic features of each lesion. The significance of the degree of the nerve lesion for the choice of therapy is stressed.


The Effect of Attention on Auditory Processing in Adults on the Autism Spectrum.
This study examined the effect of attention on auditory processing in autistic individuals. Electroencephalography data were recorded during two attention conditions (passive and active) from 24 autistic adults and 24 neurotypical controls, ages 17-30 years. The passive condition involved only listening to the clicks and the active condition involved a button press following single clicks in a modified paired-click paradigm. Participants completed the Adolescent/Adult Sensory Profile and the Social Responsiveness Scale 2. The autistic group showed delayed N1 latencies and reduced evoked and phase-locked gamma power compared to neurotypical peers across both clicks and conditions. Longer N1 latencies and reduced gamma synchronization predicted greater social and sensory symptoms. Directing attention to auditory stimuli may be associated with more typical neural auditory processing in autism.


[Demand-oriented Cognitive-behavioural Intervention for Couples with Infertility (FERTIFIT): A Pilot Study about Development, Feasibility and Acceptance].
The worldwide prevalence for infertility varies between 4-17%, and in western countries about one out of seven couples with child wish is affected. The experience of infertility is associated with a risk for psychological and dyadic distress, which is characterized by partners influencing each other mutually in their individual condition. Nevertheless, there is a gap in psychotherapy supplies for couples suffering from infertility. This pilot study introduces a feasible, demand-oriented and cognitive behavioural couple therapy concept for couples with infertility. It was designed to foster dyadic coping of typical infertility-related problems and thereby to prevent increasing distress. 21 heterosexual couples attended this study in a within-subjects wait list control group design. Depending to the couple's demand, the intervention included 5-10 couple therapy sessions. Psychological and infertility-related distress, couple relationship quality and the application of individual and dyadic resources were assessed by questionnaires at four time points (M1=pre wait control phase, M2=pre intervention, M3=post intervention, M4=post catamnesis). Women reported improved psychological and infertility-related distress, and applied more resources fostering subjective well-being, active coping and emotion regulation. Over the course of the intervention, men reported having experienced more helpful support, and women and men applied more dyadic coping strategies. In the evaluation, women and men reported high satisfaction with the intervention in general and with the support provided. The findings point toward good feasibility and acceptance of this intervention in clinical psychotherapy practice and provide preliminary evidence for possible intended effects. Due to the study's design and limitations, however, the effects cannot be distinctly attributed to the intervention. The strength of the presented study lies in the introduction of a demand-oriented couple therapy concept that is feasible and well employable in clinical practice. A subsequent larger-scale clinical trial with a randomized-controlled study design is necessary to examine and verify the effects.


A 5' tRNA-Ala-derived small RNA regulates anti-fungal defense in plants.
Apart from their primordial role in protein synthesis, tRNAs can be cleaved to produce tRNA-derived small RNAs (tsRNAs). The biological functions of tsRNAs in plants remain largely unknown. In this study, we developed RtcB ligation-based small RNA (sRNA) sequencing, a method that captures and distinguishes between 3'-2',3'-cyclic-phosphate (cP)/phosphate (P)-terminated sRNAs and 3'-OH-terminated sRNAs, and profiled 5' tsRNAs and 5' tRNA halves in Arabidopsis thaliana. We found that Arabidopsis 5' tsRNAs and 5' tRNA halves predominantly contain a cP at the 3' end and require S-like RNase 1 (RNS1) and RNS3 for their production. One of the most abundant 5' tsRNAs, 5' tsR-Ala, by associating with AGO1, negatively regulates Cytochrome P450 71A13 (CYP71A13) expression and camalexin biosynthesis to repress anti-fungal defense. Interestingly, 5' tsR-Ala is downregulated upon fungal infection. Our study provides a global view of 5' tsRNAs and 5' tRNA halves in Arabidopsis and unravels an important role of a 5' tsRNA in regulating anti-fungal defense.


Study design: the basics.
In biomedical research, meaningful conclusions can only be drawn based on data collected from a valid scientific design using appropriate statistical methods. Therefore, the selection of an appropriate study design is important in order to provide an unbiased and scientific evaluation of the research questions. In this chapter, the different kinds of experimental studies commonly used in biology and medicine are introduced. A brief survey of basic experimental study designs, randomization, blinding, possible biases, issues in data analysis, and interpretation of the study results are mainly provided.


Surgical management of Crohn's disease in children.
One of the most common beliefs in the management of Crohn's disease is that surgery should be considered only as a last resort. Surgery is often considered by patients and gastroenterologists to represent a "failure." However, the role of surgery in the care of patients with Crohn's disease has increasingly become a collaborative effort, with surgeons involved in many aspects of the management of these patients. This is particularly true in pediatric patients, as issues of growth and development may involve surgical intervention at earlier stages than might be required in older patients. In fact, surgical interventions may be indicated at any stage of the disease process. For example, early examination under anesthesia with abscess drainage and delineation of fistula tracts has proven very useful in patients with complex perineal disease. Surgery may contribute to the medical management of the disease by way of providing chronic enteral or parenteral access for nutritional interventions such as elemental feedings and total parenteral nutrition. Finally, surgical treatment of intra-abdominal complications including fistulas, phlegmon, and bowel strictures may have a dramatic impact on patient symptoms and side effects. Although bowel resection carries the long-term risk of short bowel syndrome should future resections be required, the improvements in medical therapy continue to reduce the risk of recurrent disease, making surgical resection more palatable. Surgical treatment of complicated disease offers significant potential to limit toxic medical therapy and improve quality of life. In addition, application of minimally invasive techniques can minimize the impact of insults to body image in this vulnerable patient population as well as speed recovery. Future interventions may be facilitated by reducing adhesion formation through the use of minimally invasive techniques. The dynamic nature of growth and development in the pediatric population presents unique complications from medical therapies that are different from those seen in adults. Criteria for surgical intervention must be interpreted in light of the specific challenges facing the pediatric population as frequently pointed out in the oft-quoted maxim, "children are not small adults!"


Gregarines from darkling beetles of the Atacama Desert, Atacamagregarina paposa gen. et sp. nov. from Scotobius and Xiphocephalus ovatus sp. nov. from Psectrascelis (Coleoptera, Tenebrionidae).
Gregarine apicomplexans, a group of single celled organisms, inhabit the extracellular spaces of most invertebrate species. The nature of the gregarine-host interactions is not yet fully resolved, mutualistic, commensal and parasitic life forms have been recorded. In the extreme arid environment of the Atacama Desert, only a few groups of invertebrates hosting gregarines such as darkling beetles (Tenebrionidae) were able to adapt, providing an unparalleled opportunity to study co-evolutionary diversification. Here, we describe one novel gregarine genus comprising one species, Atacamagregarina paposa gen. et sp. nov., and a new species, Xiphocephalus ovatus sp. nov. (Apicomplexa: Eugregarinoridea, Stylocephalidae), found in the tenebrionid beetle genera Scotobius (Tenebrioninae, Scotobiini) and Psectrascelis intricaticollis ovata (Pimeliinae, Nycteliini), respectively. In the phylogenetic analysis based on SSU rDNA, Atacamgregarina paposa representing the new genus is basal, forming a separate clade with terrestrial gregarines specific for North American darkling beetles.


Designing Bio-Inspired Wet Adhesives through Tunable Molecular Interactions.
Marine organisms, such as mussels and sandcastle worms, can master rapid and robust adhesion in turbulent seawater, becoming leading archetypes for the design of underwater adhesives. The adhesive proteins secreted by the organisms are rich in catecholic amino acids along with ionic and amphiphilic moieties, which mediate the adaptive adhesion mainly through catechol chemistry and coacervation process. Catechol allows a broad range of molecular interactions both at the adhesive-substrate interface and within the adhesive matrix, while coacervation promotes the delivery and surface spreading of the adhesive proteins. These natural design principles have been translated to synthetic systems toward the development of biomimetic adhesives with water-resist adhesion and cohesion. This review provides an overview of the recent progress in bio-inspired wet adhesives, focusing on two aspects: (1) the elucidation of the versatile molecular interactions (e.g., electrostatic interactions, metal coordination, hydrogen bonding, and cation-π/anion-π interactions) used by natural adhesives, mainly through nanomechanical characterizations; and (2) the rational designs of wet adhesives based on these biomimetic strategies, which involve catechol-functionalized, coacervation-induced, and hydrogen bond-based approaches. The emerging applications (e.g., tissue glues, surgical implants, electrode binders) of the developed biomimetic adhesives in biomedical, energy, and environmental fields are also discussed, with future research directions proposed.


Overexpression of SOX9 in mouse embryonic stem cells directs the immediate chondrogenic commitment.
Mouse embryonic stem (mES) cells are capable of undergoing chondrogenesis in vitro. To enhance this process, the human SOX9 (hSOX9) cDNA was delivered into mES cells and the clones overexpressing hSOX9 (denoted as mES-hSOX9 cells) were verified by Western blot analysis. The transcripts of collagen IIA (a juvenile form), aggrecan and Pax1 were expressed in mES-hSOX9 cells grown on feeder layers, suggesting the immediate effect of exogenous SOX9 on chondrogenesis. However, SOX9 overexpression did not affect the cell cycle distribution in undifferentiated mES cells. Upon differentiation, collagen IIB (an adult form) was detected in day 3 immature embryoid bodies. In addition, the overexpression of exogenous SOX9 significantly induced transcriptional activity driven by SOX9 binding site. Taken together, we for the first time demonstrated that constitutive overexpression of exogenous SOX9 in undifferentiated mES cells might have dual potentials to induce both chondrogenic commitment and growth capacity in the undifferentiated status.


Acetylcholinesterase Inhibitors and Drugs Acting on Muscarinic Receptors- Potential Crosstalk of Cholinergic Mechanisms During Pharmacological Treatment.
Pharmaceuticals with targets in the cholinergic transmission have been used for decades and are still fundamental treatments in many diseases and conditions today. Both the transmission and the effects of the somatomotoric and the parasympathetic nervous systems may be targeted by such treatments. Irrespective of the knowledge that the effects of neuronal signalling in the nervous systems may include a number of different receptor subtypes of both the nicotinic and the muscarinic receptors, this complexity is generally overlooked when assessing the mechanisms of action of pharmaceuticals. We have search of bibliographic databases for peer-reviewed research literature focused on the cholinergic system. Also, we have taken advantage of our expertise in this field to deduce the conclusions of this study. Presently, the life cycle of acetylcholine, muscarinic receptors and their effects are reviewed in the major organ systems of the body. Neuronal and non-neuronal sources of acetylcholine are elucidated. Examples of pharmaceuticals, in particular cholinesterase inhibitors, affecting these systems are discussed. The review focuses on salivary glands, the respiratory tract and the lower urinary tract, since the complexity of the interplay of different muscarinic receptor subtypes is of significance for physiological, pharmacological and toxicological effects in these organs. Most pharmaceuticals targeting muscarinic receptors are employed at such large doses that no selectivity can be expected. However, some differences in the adverse effect profile of muscarinic antagonists may still be explained by the variation of expression of muscarinic receptor subtypes in different organs. However, a complex pattern of interactions between muscarinic receptor subtypes occurs and needs to be considered when searching for selective pharmaceuticals. In the development of new entities for the treatment of for instance pesticide intoxication, the muscarinic receptor selectivity needs to be considered. Reactivators generally have a muscarinic M2 receptor acting profile. Such a blockade may engrave the situation since it may enlarge the effect of the muscarinic M3 receptor effect. This may explain why respiratory arrest is the major cause for deaths by esterase blocking.


Transdermal Administration of Anti-inflammatory Medications in Sports Injuries: Use of Iontophoresis and Phonophoresis to Enhance Delivery.
Transdermal delivery of anti-inflammatory medications, both nonsteroidal and corticosteroids, has enjoyed at least a decade of success in Canada and the US. Iontophoresis and phonophoresis offer substantial benefits for the transdermal delivery of these medications and can be valuable additions to existing treatment modalities for minor sports-related injuries. Included with this article is historical and explanatory information about iontophoresis and phonophoresis, as well as formulations and case reports related to the treatment of sports-related injuries. The article emphasizes the importance of a compounding pharmacist's involvement in developing a successful treatment plan.