[Acute poisoning with lithium carbonate in a young woman--case report].
In the clinical practice there are three types of lithium intoxication: acute poisoning in patients not previously treated with lithium, acute on chronic poisoning, i.e., an acute overdose in patients who are under lithium treatment and chronic poisoning that occurs in patients who are under lithium treatment. Threats and the clinical management in these types are different. The paper describes a case of a young woman acutely intoxicated with lithium carbonate, never treated lithium before. Plasma concentration of lithium, 15 hours after ingestion of 9.75 g lithium carbonate, was 2.56 mmol/L. Only minor clinical symptoms were observed. Calculated elimination half-life was 15-26.8 hours.


Recommended standards for modern tuberculosis laboratory services in Europe.
The principles underpinning these standards are that any tuberculosis laboratory-based diagnostic procedure should be performed by appropriately trained staff, working to standardised operating procedures in appropriately equipped and safe laboratories, against clear national and international proficiency and quality standards. Quality should be the pre-eminent criteria, not cost. The standards are technologically feasible, but initially may not be within the financial capacity of all laboratories. There is a requirement for government and international donors to adequately fund an appropriate safe infrastructure to enable staff to deliver accurate and timely results at whatever level of activity they are performing. There is a need for national reference laboratories to train a new cadre of mycobacterial laboratory experts. This will require the funding of appropriate individuals at these centres to train and assist in the implementation of good laboratory practice and evaluation to build sustainable capacity. Further operational research is needed to establish the optimal configuration of new technologies to determine isoniazid, rifampicin and second-line drug susceptibility in mycobacterial cultures and also, increasingly, directly on specimens. Improved integration of laboratory medicine as a core part of all tuberculosis programmes is needed to achieve and maximise the potential of new developments.


A Data-Driven Intelligent System for Assistive Design of Interior Environments.
This paper analyses the design of a healthy interior environment using big data intelligence. The application of big data intelligence in the design of healthy interior environments is necessary because the traditional interior design approaches consume a lot of energy and other problems. Benefited by its strong ability of computation and analytics, artificial intelligence can well improve a series of problems in the field of interior design. The proposal summarizes the sources, classifications, and expressions of behavioral data in interior spaces, carries out analysis and research on behavioral data from two aspects: display space and supermarket space, summarizes the interior methods based on behavioral data, and analyses the visualization application of behavioral data in different interior scenes, to explore the application value of behavioral data in interior design. In contrast to it is the unconscious behavioral response, the biggest characteristic of which is that it is regulated by the behavioral subject's physiological factors or habits of the behavior issuer. In this paper, we convert the layout recommendation problem of a space into a functional classification problem of segmented segments and household segments on a plane. The scene layout features are extracted by binary coding, the abstraction of the cross features between the vector segments is achieved by using a word embedding algorithm, the feature matrix is reduced in dimensionality, and finally, the segmentation network model and the layout network model are constructed, respectively, by using a bidirectional LSTM. The experiments show that the accuracy of the layout recommendation model in this paper is 98%, which can meet the demand for real-time online layouts.


Boron Deficiency in Unfertilized Cotton (Gossypium hirsutum) Ovules Grown in Vitro.
Boron deficiency and phytohormone interactions have been studied in unfertilized cotton (Gossypium hirsutum) ovules grown in vitro. Such ovules required exogenous indoleacetic acid and/or gibberellic acid for fiber elongation. Boron also was required for maintenance of fiber elongation and normal morphogenesis throughout 14 days of culture. The amount of exogenous boron necessary for maximum fiber elongation varied among experiments, presumably in relation to endogenous boron levels at anthesis. Some ovular epidermal cells distant from the liquid medium could be induced to elongate into fiber even after 6 days in boron-deficient medium in response to the later addition of boron.Boron deficiency, in the presence of exogenous indoleacetic acid, was characterized by lack of fiber development on the inundated ovular surface and reduced fiber growth on the ovular surface exposed to air. In the presence of gibberellic acid, boron deficiency was characterized by complete absence of fiber and callusing of the entire ovular surface. When both indoleacetic acid and gibberellic acid were added, the lack of boron resulted in proliferation of callus laterally and upward from the inundated epidermis, accumulation of brown pigments (presumably phenolic compounds) in the callus, and restriction of fiber to a small area of the upper ovular surface.


HPLC-DAD-ESI-MS analysis of phenolic compounds during ripening in exocarp and mesocarp of tomato fruit.
Identification of phenolic compounds was done by means of liquid chromatography (HPLC) coupled to mass spectrometry (MS) using the electrospray ionization interface (ESI). Quantification of phenolic compounds was carried out by using HPLC with diode array detector (DAD) in exocarp and mesocarp of tomato fruit at 6 different ripeness stages (mature-green, breakers, turning, pink, light-red, and red). Several phenolic compounds were identified including chlorogenic acid, caffeic acid, p-coumaric acid, ferulic acid, and rutin and some combined phenolic acids were tentatively identified, mainly glycosides, such as caffeoyl hexose I, caffeoyl hexose II, caffeoylquinic acid isomer, dicaffeoylquinic acid, p-coumaroyl hexose I, p-coumaroyl hexose II, feruloyl hexose I, feruloyl hexose II, siringyl hexose, and caffeoyl deoxyhexose hexose. Fruit exocarp had higher quantities of total soluble phenolics (TSP) compared to mesocarp. During ripening, TSP increased in both exocarp and mesocarp, mainly in exocarp. While rutin increased, chlorogenic acid decreased in both tissues: exocarp and mesocarp.


Retrospective clinicopathologic correlation of gross tumor size of hepatocellular carcinoma: implications for stereotactic body radiotherapy.
To determine the degree of correlation between radiographic size and true gross pathologic size for subjects with primary hepatocellular carcinoma (HCC). This analysis included 18 patients with 27 tumors who underwent either partial hepatectomy or orthotopic liver transplantation for HCC at the University of Colorado Hospital between 1997 and 2002. Preoperative imaging was performed using computed tomography (CT) or magnetic resonance imaging (MRI). After surgical resection the size of each tumor on gross pathologic examination was recorded. The maximal measurement in one dimension on axial imaging and pathologic examination was extracted for statistical analysis. The clinical and pathologic sizes were compared using a percent size difference (%Deltasize) as an end point for each patient. A regression analysis was applied to study the association between pathologic and clinical size. The median radiographic size was 2.90 cm (range 1.2-4.9). The median pathologic size was 2.50 cm (range 1-4.8). The radiographic size was larger than or equal to the pathologic size in 22/27 tumors (81%) and smaller in 5/27 (19%) tumors. The median %Deltasize was 17.5% (range -20-144%). Overall, the radiographic and pathologic sizes were positively correlated (r = 0.8). This correlation was not affected by choice of imaging modality (CT versus MRI, P = 0.71) or time of preoperative imaging (0-4 weeks versus 4-8 weeks before surgery, P = 0.61). Our study shows that in most instances (81%), imaging by CT or MRI overestimates true gross pathologic size of HCC. Nineteen percent of tumors appeared smaller on preoperative imaging than on the final pathologic specimen. Radiation therapy utilizing a 0.5 or 1.0 cm margin around the radiographic tumor would have encompassed the gross pathologic tumor in 93% and 100% of cases, respectively.


Preparation and Application of Phosphorylated Xylan as a Flocculant for Cationic Ethyl Violet Dye.
In this study, phosphorylated birchwood xylan was produced under alkali conditions using trisodium trimetaphosphate. Three single-factor experiments were used to explore the influences of time, temperature, and the molar ratio of trisodium trimetaphosphate to xylan on the degree of substitution (DS) and charge density of xylan. The response surface methodology was used to explore the interaction of these three factors. Phosphorylated xylan with a maximum DS of 0.79 and a charge density of -3.40 mmol/g was produced under the optimal conditions of 80 °C, 4 h, and a molar ratio of xylan/sodium trimetaphosphate (STMP) of 1/3. Fourier transform infrared (FTIR), ascorbic acid method analyses, and inductively coupled plasma⁻atomic emission spectrometer (ICP-AES) analyses confirmed that the phosphate groups were successfully attached to xylan. Thermogravimetric analysis confirmed that phosphorylated xylan was less stable than birchwood xylan. Furthermore, the phosphorylated xylan was applied as a flocculant for removing ethyl violet dye from a simulated dye solution. The results indicated that more than 95% of the dye was removed from the solution. The theoretical and experimental values of charge neutralization for the dye removal were close to one another, confirming that charge neutralization was the main mechanism for the interaction of dye and phosphorylated xylan. The impacts of salts on the flocculation efficiency of phosphorylated xylan were also analyzed.


Multiple regression of skeletal muscle tension on inositol phosphates: cross-talk between signal transduction mechanisms in burn trauma.
Skeletal muscle weakness associated with burn trauma prolongs the time of rehabilitation of burn patients. Understanding the underlying chemical changes that impact on physiological tension may provide new therapeutic options for the treatment of burn patients. This report demonstrates the novelty of applying 3-dimensional graphic capabilities, involving area and vector changes to understand variations in inositol derivatives and their co-modulating influence on physiological tension in skeletal muscle. This muscle was distant from the primary anatomical burn site. It was subjected to circulatory shock emanating from burn trauma. Burn injury was achieved by scalding of predefined areas (0, 20% and 50%) on the dorsal and ventral surfaces of mice. At day 21, tension studies via muscle twitch analyses were performed. Through multiple regression, the dependency of physiologic tension was determined with respect to three poly-inositol forms each representing independent parameters simultaneously. The contribution of each of these parameters was assigned to a three-dimensional axis. Relationships of tension on three fixed independent parameters were found only for the 20% and 50% burn groups. Vector analysis on a plane in three-dimensional space determined the relationship of tension to each of the independent parameters in 20% and 50% burn groups. No significant relationship of tension dependency on three fixed poly-inositol variables was found in the control group. Such vector analysis, using solid and differential analytical geometry, allowed for a clear visualization of the interrelationships that existed between secondary messenger systems (viz, IP3) and a resulting physiologic manifestation (viz, tension). This clear visualization allows for a greater understanding of messenger systems that may lead to more effective treatment of skeletal muscle weakness associated with the systemic effects of severe burn trauma.


T cell receptor gene in synovial tissues of rheumatoid arthritis.
Rheumatoid arthritis is a chronic and destructive autoimmune joint disease characterized by inflammation of synovial tissue of unknown aetiology. Studies on TCR genes expressed by infiltrating T cells in synovial tissues have attempted to identify mechanism and specificity of the recruitment. T cell infiltrate in rheumatoid arthritis appears to be an association of a polyclonal non specific infiltrate with dominant clones or clonotypes. T cell repertoire in synovial tissue is biased compared to peripheral blood but no TCR V gene can be identified as commonly over-used. Comparison of motifs found in the CDR3 region of dominant clones from different studies has currently failed to identified a commonly motif. The fact that a number of dominant clones or clonotypes is present in different joints and at different times of the disease suggests a selective expansion of T lymphocytes in rheumatoid arthritis synovial membrane. Further investigations are needed to characterize the specificity of these dominant clonotypes.


Pharmacokinetics of moxalactam in subjects with various degrees of renal dysfunction.
We have examined the pharmacokinetics of moxalactam (LY127935) in 36 subjects with various degrees of renal dysfunction. Creatinine clearance (Ccr)/1.73 m2 ranged from zero to 135.8 ml/min. After a 1-g administration of moxalactam intravenously, the volume of distribution was 20.6 /+- 9.5 liters (0.28 liter/kg), and the mean half-life ranged from 3.1 h for subjects with Ccr greater than 65 ml/min to 19.3 h for subjects with Ccr less than 10 ml/min. The moxalactam clearance was closely correlated to Ccr (r = 0.93, P less than 0.0001) and excretion of antibiotic was 73.6 +/- 13% in normal subjects. Renal clearance accounted for 90% of moxalactam clearance in the normal subjects. A dosage schedule for administering moxalactam to patients with various degrees of renal dysfunction is provided.


Eosinophilic Lung Disease.
Eosinophils are involved in the pathogenesis of a number of lung diseases. Recent advances in eosinophil biology have now produced clinically applicable therapies that seek to counter eosinophilia in blood and lungs. This article reviews the basic biology of eosinophils and their role in mediating T-helper 2 cell responses. The current status of anticytokine therapy for eosinophilic lung disease is discussed. A clinical approach to eosinophilic lung disease based on symptoms and radiography is generated. The clinical significance of persistent eosinophilia in lung transplant patients and patients with asthma will receive special emphasis.


Analysis and biochemistry of blood folate.
Although the analysis of low plasma concentrations of 5-methyltetrahydrofolate by several specific HPLC methods has been reported, considerably fewer routine chromatographic techniques exist for the analysis of specific folate coenzymes in the erythrocyte where a nonspecific bioassay indicates that the vitamin achieves a level 10 times higher than that in plasma. By using three separate folypolyglutamate deconjugation procedures and combining an extraction technique which adequately preserves all native folate coenzymes with an HPLC technique utilizing fluorescence, diode array, and off-line radioassay detection capable of resolving all crucial native folates in their monoglutamyl forms, we were unable to demonstrate levels of 5-methyltetrahydrofolate in whole blood hemolysate beyond what might be expected from the plasma component. While the exact nature of erythrocyte folate could not be ascertained, we provide evidence that a proportion of it may exist at the formyl level of oxidation. The complex pH and enzymatic interrelationship between folate coenzymes at the formyl oxidation level is discussed in terms of our extraction technique and findings, as well as in a broader biological context. This paper also describes a simple acid precipitation technique for measuring plasma 5-methyltetrahydrofolate, as well as providing comprehensive data on the chromatographic behavior of all the folylmonoglutamates in reversed-phase and weak anion-exchange modes, including useful spectral data for optimizing detection parameters and identifying individual coenzymes. 10-Formyltetrahydrofolate and 5-methyltetrahydrofolate are the two most important one-carbon-substituted folate coenzymes. 10-Formyltetrahydrofolate is unavailable commercially, probably due to its instability. We chart the chemical synthesis of this important coenzyme and show that it and what is thought to be 5,10-hydroxymethylenetetrahydrofolate are actually minor products compared to the parent 5,10-methenyltetrahydrofolate and the ultimate reaction product, 5-formyltetrahydrofolate. Since intraerythrocyte folate binds to a specific hemoglobin site, we ascertained the total number of binding sites on hemoglobin (Bmax) and the equilibrium dissociation constant (Kd) for 5-methyltetrahydrofolate, 5-formyltetrahydrofolate, and the antimetabolite methotrexate. Binding affinities were consistent with a low-affinity, low-capacity interaction for all three. It was demonstrated that hemoglobin has a greater affinity for 5-methyltetrahydrofolate than for the other folate derivatives (Kd = 1.2 x 10(-3) M), while rather surprisingly, methotrexate had a higher affinity for hemoglobin than did 5-formyltetrahydrofolate (Kd = 2.5 x 10(-3) and 3.7 x 10(-2) M, respectively.


Fructose 2,6-bisphosphate hydrolyzing enzymes in higher plants.
The phosphatases that hydrolyze fructose 2,6-bisphosphate in a crude spinach (Spinacia oleracea L.) leaf extract were separated by chromatography on blue Sepharose, into three fractions, referred to as phosphatases I, II, and III, which were further purified by various means. Phosphatase I hydrolyzed fructose 2,6-bisphosphate, with a K(m) value of 30 micromolar, to a mixture of fructose 2-phosphate (90%) and fructose 6-phosphate (10%). It acted on a wide range of substrates and had a maximal activity at acidic pH. Phosphatase II specifically recognized the osyl-link of phosphoric derivatives and had more affinity for the beta-anomeric form. Its apparent K(m) for fructose 2,6-bisphosphate was 30 micromolar. It most likely corresponded to the fructose-2,6-bisphosphatase described by F. D. Macdonald, Q. Chou, and B. B. Buchanan ([1987] Plant Physiol 85: 13-16). Phosphatase III copurified with phosphofructokinase 2 and corresponded to the specific, low-K(m) (24 nanomolar) fructose-2,6-bisphosphatase purified and characterized by Y. Larondelle, E. Mertens, E. Van Schaftingen, and H. G. Hers ([1986] Eur J Biochem 161: 351-357). Three similar types of phosphatases were present in a crude extract of Jerusalem artichoke (Helianthus tuberosus) tuber. The concentration of fructose 2,6-bisphosphate decreased at a maximal rate of 30 picomoles per minute and per gram of fresh tissue in slices of Jerusalem artichoke tuber, upon incubation in 50 millimolar mannose. This rate could be accounted for by the maximal extractable activity of the low-K(m) fructose-2,6-bisphosphatase. A new enzymic method for the synthesis of beta-glucose 1,6-bisphosphate from beta-glucose 1-phosphate and ATP is described.


Synthesis and Characterization of Pyrochlore-Type Praseodymium Stannate Nanoparticles: An Effective Electrocatalyst for Detection of Nitrofurazone Drug in Biological Samples.
Apart from perovskites, the development of different types of pyrochlore oxides is highly focused on various electrochemical applications in recent times. Based on this, we have synthesized pyrochlore-type praseodymium stannate nanoparticles (Pr2Sn2O7 NPs) by using a coprecipitation method and further investigated by different analytical and spectroscopic techniques such as X-ray diffraction, Raman spectroscopy, field emission-scanning electron microscopy, high resolution-transmission electron microscopy, and X-ray photoelectron spectroscopy analysis. Followed by this, we have designed a unique and novel electrochemical sensor for nitrofurazone detection, by modifying the glassy carbon electrode (GCE) with the prepared Pr2Sn2O7 NPs. For that, the electrochemical experiments were performed by using cyclic voltammetry and differential pulse voltammetry techniques. The Pr2Sn2O7 NPs modified GCE exhibits high sensitivity (2.11 μA μM-1 cm-2), selectivity, dynamic linear ranges (0.01-24 μM and 32-332 μM), and lower detection limit (4 nM). Furthermore, the Pr2Sn2O7 NPs demonstrated promising real sample analysis with good recovery results in biological samples (human urine and blood serum) which showed better results than the noble metal catalysts. Based on these results, the present work gives clear evidence that the pyrochlore oxides are highly suitable electrode materials for performing outstanding catalytic activity toward electrochemical sensors.


Monochloramination of resorcinol: mechanism and kinetic modeling.
The kinetics of monochloramination of resorcinol, 4-chlororesorcinol, and 4,6-dichlororesorcinol have been investigated over the pH range of 5-12, at 23 +/- 2 degrees C. Monochloramine solutions were prepared with ammonia-to-chlorine ratios (N/Cl) ranging from 1.08 to 31 mol/mol. Under conditions that minimize free chlorine reactions (N/Cl > 2 mol/mol), the apparent second-order rate constants of monochloramination of resorcinol compounds show a maximum at pH values between 8.6 and 10.2. The intrinsic second-order rate constants for the reaction of monochloramine with the acid-base forms of the dihydroxybenzenes (Ar(OH)(2), Ar(OH)O(-), and Ar(O(-))(2)) were calculated from the apparent second-order rate constants. The stoichiometric coefficients for the formation of 4-chlororesorcinol by monochloramination of resorcinol and 4,6-dichlororesorcinol by monochloramination of 4-chlororesorcinol were found to be equal to 0.66 +/- 0.05 and 0.25 +/- 0.02 mol/mol, respectively at pH 8.6. A kinetic model that incorporates reactions of free chlorine and monochloramine with the different acid-base forms of resorcinol compounds simulated well the initial rates of degradation of resorcinol compounds and was useful to evaluate the contribution of free chlorine reactions to the overall rates of degradation of resorcinol at low N/Cl ratios.


Hydrolysis of cellulose into glucose over carbons sulfonated at elevated temperatures.
The hydrolysis of cellulose over sulfonated carbons was promoted greatly by elevating the sulfonation temperature. With 250 degrees C-sulfonated CMK-3 as a catalyst, the cellulose was selectively hydrolyzed into glucose with the glucose yield as high as 74.5%, which is the highest level reported so far on solid acid catalysts.


Analysis of neurotrophic factors in limb and extraocular muscles of mouse model of amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is currently an incurable fatal motor neuron syndrome characterized by progressive weakness, muscle wasting and death ensuing 3-5 years after diagnosis. Neurotrophic factors (NTFs) are known to be important in both nervous system development and maintenance. However, the attempt to translate the potential of NTFs into the therapeutic options remains limited despite substantial number of approaches, which have been tested clinically. Using quantitative RT-PCR (qRT-PCR) technique, the present study investigated mRNA expression of four different NTFs: brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4/5 (NT-4) and glial cell line-derived neurotrophic factor (GDNF) in limb muscles and extraocular muscles (EOMs) from SOD1G93A transgenic mice at early and terminal stages of ALS. General morphological examination revealed that muscle fibres were well preserved in both limb muscles and EOMs in early stage ALS mice. However, in terminal ALS mice, most muscle fibres were either atrophied or hypertrophied in limb muscles but unaffected in EOMs. qRT-PCR analysis showed that in early stage ALS mice, NT-4 was significantly down-regulated in limb muscles whereas NT-3 and GDNF were markedly up-regulated in EOMs. In terminal ALS mice, only GDNF was significantly up-regulated in limb muscles. We concluded that the early down-regulation of NT-4 in limb muscles is closely associated with muscle dystrophy and dysfunction at late stage, whereas the early up-regulations of GDNF and NT-3 in EOMs are closely associated with the relatively well-preserved muscle morphology at late stage. Collectively, the data suggested that comparing NTFs expression between limb muscles and EOMs from different stages of ALS animal models is a useful method in revealing the patho-physiology and progression of ALS, and eventually rescuing motor neuron in ALS patients.


On the meaning of low-dose ACTH(1-24) tests to assess functionality of the hypothalamic-pituitary-adrenal axis.
To analyse further the ACTH(1-24) low-dose test, which is of clinical interest, we have examined the dose-response relationship between plasma ACTH(1-24) and cortisol concentrations after i.v. administration of increasing doses (1, 5 or 250 microg) of ACTH(1-24) as a bolus. In addition, we have measured plasma ACTH(1-39) and cortisol levels after an insulin tolerance test (ITT). Although there was a dose response relationship between plasma ACTH(1-24) immunoreactivity and the dose injected, cortisol peaks were comparable, but lower than those reached after an ITT. Under these experimental conditions, an increase in plasma ACTH as low as 13 pmol/l (i.e. the increase obtained with the 1 microg dose) induced a near maximal cortisol response. Following injection of 1 microg ACTH(1-24), peak ACTH values were short lasting, similar to physiological daily bursts. After injection of 5 microg ACTH(1-24), plasma ACTH concentrations were higher than those reached during an ITT, but clearly shorter lasting. Injection of 250 microg ACTH(1-24) induced strikingly supraphysiological levels of plasma ACTH. We conclude that neither regular nor low-dose ACTH tests can fully reproduce the ITT. Our observations strongly suggest that the low-dose ACTH(1-24) test (1 microg) can be useful to estimate the adrenal sensitivity under basal, physiological conditions.


Gender differences in emotion recognition: Impact of sensory modality and emotional category.
Results from studies on gender differences in emotion recognition vary, depending on the types of emotion and the sensory modalities used for stimulus presentation. This makes comparability between different studies problematic. This study investigated emotion recognition of healthy participants (N = 84; 40 males; ages 20 to 70 years), using dynamic stimuli, displayed by two genders in three different sensory modalities (auditory, visual, audio-visual) and five emotional categories. The participants were asked to categorise the stimuli on the basis of their nonverbal emotional content (happy, alluring, neutral, angry, and disgusted). Hit rates and category selection biases were analysed. Women were found to be more accurate in recognition of emotional prosody. This effect was partially mediated by hearing loss for the frequency of 8,000 Hz. Moreover, there was a gender-specific selection bias for alluring stimuli: Men, as compared to women, chose "alluring" more often when a stimulus was presented by a woman as compared to a man.


The electronic structure and bonding of AlNAl.
We have studied 16 states, 7 doublets, and 9 quartets of the AlNAl isomer mainly through multireference methods and correlation consistent basis sets. We report equilibrium geometries, energetics, and dipole moments, whereas for a number of low lying states we have constructed dissociation AlN-Al potential energy profiles. For the same states we also analyze their bonding character using valence-bond-Lewis diagrams. Our results are consistent with the limited experimental data.


Ubc9 Impairs Activation of the Brown Fat Energy Metabolism Program in Human White Adipocytes.
Insulin resistance and type 2 diabetes mellitus (T2DM) result from an inability to efficiently store and catabolize surplus energy in adipose tissue. Subcutaneous adipocytes protect against insulin resistance and T2DM by coupling differentiation with the induction of brown fat gene programs for efficient energy metabolism. Mechanisms that disrupt these programs in adipocytes are currently poorly defined, but represent therapeutic targets for the treatment of T2DM. To gain insight into these mechanisms, we performed a high-throughput microscopy screen that identified ubiquitin carrier protein 9 (Ubc9) as a negative regulator of energy storage in human sc adipocytes. Ubc9 depletion enhanced energy storage and induced the brown fat gene program in human sc adipocytes. Induction of adipocyte differentiation resulted in decreased Ubc9 expression commensurate with increased brown fat gene expression. Thiazolidinedione treatment reduced the interaction between Ubc9 and peroxisome proliferator-activated receptor (PPAR)γ, suggesting a mechanism by which Ubc9 represses PPARγ activity. In support of this hypothesis, Ubc9 overexpression remodeled energy metabolism in human sc adipocytes by selectively inhibiting brown adipocyte-specific function. Further, Ubc9 overexpression decreased uncoupling protein 1 expression by disrupting PPARγ binding at a critical uncoupling protein 1 enhancer region. Last, Ubc9 is significantly elevated in sc adipose tissue isolated from mouse models of insulin resistance as well as diabetic and insulin-resistant humans. Taken together, our findings demonstrate a critical role for Ubc9 in the regulation of sc adipocyte energy homeostasis.


Bedaquiline-Pretomanid-Linezolid Regimens for Drug-Resistant Tuberculosis.
The bedaquiline-pretomanid-linezolid regimen has been reported to have 90% efficacy against highly drug-resistant tuberculosis, but the incidence of adverse events with 1200 mg of linezolid daily has been high. The appropriate dose of linezolid and duration of treatment with this agent to minimize toxic effects while maintaining efficacy against highly drug-resistant tuberculosis are unclear. We enrolled participants with extensively drug-resistant (XDR) tuberculosis (i.e., resistant to rifampin, a fluoroquinolone, and an aminoglycoside), pre-XDR tuberculosis (i.e., resistant to rifampin and to either a fluoroquinolone or an aminoglycoside), or rifampin-resistant tuberculosis that was not responsive to treatment or for which a second-line regimen had been discontinued because of side effects. We randomly assigned the participants to receive bedaquiline for 26 weeks (200 mg daily for 8 weeks, then 100 mg daily for 18 weeks), pretomanid (200 mg daily for 26 weeks), and daily linezolid at a dose of 1200 mg for 26 weeks or 9 weeks or 600 mg for 26 weeks or 9 weeks. The primary end point in the modified intention-to-treat population was the incidence of an unfavorable outcome, defined as treatment failure or disease relapse (clinical or bacteriologic) at 26 weeks after completion of treatment. Safety was also evaluated. A total of 181 participants were enrolled, 88% of whom had XDR or pre-XDR tuberculosis. Among participants who received bedaquiline-pretomanid-linezolid with linezolid at a dose of 1200 mg for 26 weeks or 9 weeks or 600 mg for 26 weeks or 9 weeks, 93%, 89%, 91%, and 84%, respectively, had a favorable outcome; peripheral neuropathy occurred in 38%, 24%, 24%, and 13%, respectively; myelosuppression occurred in 22%, 15%, 2%, and 7%, respectively; and the linezolid dose was modified (i.e., interrupted, reduced, or discontinued) in 51%, 30%, 13%, and 13%, respectively. Optic neuropathy developed in 4 participants (9%) who had received linezolid at a dose of 1200 mg for 26 weeks; all the cases resolved. Six of the seven unfavorable microbiologic outcomes through 78 weeks of follow-up occurred in participants assigned to the 9-week linezolid groups. A total of 84 to 93% of the participants across all four bedaquiline-pretomanid-linezolid treatment groups had a favorable outcome. The overall risk-benefit ratio favored the group that received the three-drug regimen with linezolid at a dose of 600 mg for 26 weeks, with a lower incidence of adverse events reported and fewer linezolid dose modifications. (Funded by the TB Alliance and others; ZeNix ClinicalTrials.gov number, NCT03086486.).


The effectiveness of silver diamine fluoride in arresting caries.
Data sourcesPubMed, Embase, Scopus, China National Knowledge Infrastructure (CNKI), Ichushi-web, Biblioteca Virtual en Salud Espana (BVSE) and Biblioteca Virtual em Saude (BVS) databases. There were no limits on language or publication dates.Study selectionTwo reviewers selected prospective clinical studies investigating SDF treatment for caries prevention in children.Data extraction and synthesisData was abstracted independently by two reviewers and risk of bias assessed. Meta-analysis was performed on studies in which the caries-arresting rate using 38% SDF solution on primary teeth could be obtained or calculated.ResultsNineteen studies were included; 16 were conducted in the primary dentition and three in permanent dentition. Fourteen studies used 38% SDF, three 30% SDF, and two 10% SDF. Eight studies using 38% SDF contributed to a meta-analysis and the overall proportion of arrested caries was 81% (95% CI; 68-89%). Percentage reductions were also calculated for 6,12,18,24 and >30 months. Arrested carious lesions stained black but no other adverse effects were reported.ConclusionsSDF commonly used at a high concentration (38%, 44,800ppm fluoride) is effective in arresting caries among children. There is no consensus on its number and frequency of application to arrest caries. Further studies are necessary to develop evidence-based guidelines on its use in children.


Perception of Influencing Factors on Acceptance of Mobile Health Monitoring Service: A Comparison between Users and Non-users.
To improve and promote mobile health monitoring services, this study investigated the perception of various factors influencing the acceptance of services between users and non-users. This study drew 9 variables from studies related to mobile health monitoring services and the unified theory of acceptance and the use of technology model. A total of 219 samples were collected by a paper-based survey from users (n = 106) and non-users (n = 113). Analysis was carried out using a two-independent samples t-test. The findings indicate that users have a more positive perception of service benefits than non-users. Although there were difference between users and non-users, all respondents had a positive perception of the service benefits. After users used the service, they were less concerned about the risks involved with it. However, both users and non-users had a high negative perception of service risk. Users also had a more positive perception of intimacy and communication associated with the services than non-users. Both users and non-users had a high behavioral intention to use the services. Finally, this study observed that older subjects tended to recognize the higher value of the services. This study provides insights to improve and invigorate mobile health monitoring services. This study also offers insights into how to increase the number of users of mobile health monitoring services in South Korea.


Occupational medicine. An overview for physician assistants.
Occupational medicine encompasses the delivery of physical, mental, and emotional health care in the workplace. Involvement of PAs in occupational medicine escalated in 1978, as industry responded to cost-containment pressures; PAs performed annual employee physical examinations, exercise stress testing, occupational health education, and treatment of work-related injuries. Work settings initially focused on underserved areas; today they include plant sites, private industrial-medicine clinics, and corporate medical administration. Utilization continues to expand. The American Academy of Physician Assistants in Occupational Medicine--founded in 1981--develops continuing medical education programs and educates industry and the public about PAs in occupational medicine. The future of PA utilization in occupational medicine lies in cost containment.


Structure-Activity Relationship Study of Leucyl-3-epi-deoxynegamycin for Potent Premature Termination Codon Readthrough.
(+)-Negamycin, isolated from Streptomyces purpeofuscus, shows antimicrobial activity against Gram-negative bacteria and readthrough activity against nonsense mutations. Previously, we reported that two natural negamycin analogues, 5-deoxy-3-epi-negamycin and its leucine adduct, have more potent readthrough activity in eukaryocytes (COS-7 cells) than negamycin but possess no antimicrobial activity and no in vitro readthrough activity in prokaryotic systems. In the present study, on leucyl-3-epi-deoxynegamycin, a structure-activity relationship study was performed to develop more potent readthrough agents. In a cell-based readthrough assay, the derivative 13b with an o-bromobenzyl ester functions as a prodrug and exhibits a higher readthrough activity against TGA-type PTC than the aminoglycoside G418. This ester (13b) shows an in vivo readthrough activity with low toxicity, suggesting that it has the potential for treatment of hereditary diseases caused by nonsense mutations.


Maternal near miss and predictive ability of potentially life-threatening conditions at selected maternity hospitals in Latin America.
Every year millions of women around the world suffer from pregnancy, childbirth and postpartum complications. Women who survive the most serious clinical conditions are regarded as to have experienced a severe acute maternal complication called maternal near miss (MNM). Information about MNM cases may complement the data collected through the analysis of maternal death, and was proposed as a helpful tool to identify strengths and weaknesses of health systems in relation to maternal health care. The purpose of this study is to evaluate the performance of a systematized form to detect severe maternal outcomes (SMO) in 20 selected maternity hospitals from Latin America (LAC). Cross-sectional study. Data were obtained from analysis of hospital records for all women giving birth and all women who had a SMO in the selected hospitals. Univariate and multivariate adjusted logistic regression models were used to assess the predictive ability of different conditions to identify SMO cases. In parallel, external auditors were hired for reviewing and reporting the total number of discharges during the study period, in order to verify whether health professionals at health facilities identified all MNM and Potentially life-threatening condition (PLTC) cases. Twenty hospitals from twelve LAC were initially included in the study and based on the level of coverage, 11 hospitals with a total of 3,196records were included for the final analysis. The incidence of SMO and MNM outcomes was 12.9 and 12.3 per 1,000 live births, respectively. The ratio of MNM to maternal death was 19 to 1, with a mortality index of 5.1 %. Both univariate and multivariate analysis showed a good performance for a number of clinical and laboratory conditions to predict a severe maternal outcome, however, their clinical relevance remains to be confirmed. Coherence between health professionals and external auditors to identify SMO was high (around 100 %). The form tested, was well accepted by health professionals and was capable of identifying 100 % of MNM cases and more than 99 % of PLTC variables. Altered state of consciousness, oliguria, placenta accrete, pulmonary edema, and admission to Intensive Care Unit have a high (LR+ ≥80) capacity to anticipate a SMO.


Effects of exercise and caffeic acid phenethyl ester after chronic exercise rat model.
In order to understand whether exercise and caffeic acid phenethyl ester (CAPE) has an effect on obesity and weight control, we investigated the effects of CAPE, and exercise on lipid parameters (triglyceride, total cholesterol, HDL-C, LDL-C), and adipokine substances such as leptin and resistin in rats. 40 male rat were randomly assigned into 4 groups. It was determined that CAPE does not have any significant effect on these parameters but that lipid parameters and leptin values in exercise groups decreased considerably, while no significant change occurred in resistin levels. In order to understand whether diet has an effect on exercise, body weights of all animal groups in pre and post-exercise were compared. A significant weight gain was observed (p = 0.005) in all groups. This study concluded that exercise has a considerable effect on leptin and lipid parameters; however, exercise alone was not sufficient for weight control and could be effective in weight control only when accompanied by a restricted diet. Key pointsCaffeic acid phenethyl ester is not effective on weight control, lipid parameters, and adipokine substances such as leptin and resistin.Exercise can be effective in weight control only when accompanied by a restricted diet.


The Pathogenesis of African Trypanosomiasis.
African trypanosomes are bloodstream protozoan parasites that infect mammals including humans, where they cause sleeping sickness. Long-lasting infection is required to favor parasite transmission between hosts. Therefore, trypanosomes have developed strategies to continuously escape innate and adaptive responses of the immune system, while also preventing premature death of the host. The pathology linked to infection mainly results from inflammation and includes anemia and brain dysfunction in addition to loss of specificity and memory of the antibody response. The serum of humans contains an efficient trypanolytic factor, the membrane pore-forming protein apolipoprotein L1 (APOL1). In the two human-infective trypanosomes, specific parasite resistance factors inhibit APOL1 activity. In turn, many African individuals express APOL1 variants that counteract these resistance factors, enabling them to avoid sleeping sickness. However, these variants are associated with chronic kidney disease, particularly in the context of virus-induced inflammation such as coronavirus disease 2019. Vaccination perspectives are discussed.


Analytical solution of beam spread function for ocean light radiative transfer.
We develop a new method to analytically obtain the beam spread function (BSF) for light radiative transfer in oceanic environments. The BSF, which is defined as the lateral distribution of the (scalar) irradiance with increasing depth in response to a uni-directional beam emanating from a point source in an infinite ocean, must in general be obtained by solving the three-dimensional (3D) radiative transfer equation (RTE). By taking advantage of the highly forward-peaked scattering property of the ocean particles, we assume, for a narrow beam source, the dependence of radiance on polar angle and azimuthal angle is deliberately separated; only single scattering takes place in the azimuthal direction while multiple scattering still occurs in the polar direction. This assumption enables us to reduce the five-variable 3D RTE to a three-variable two-dimensional (2D) RTE. With this simplification, we apply Fourier spectral method to both spatial and angular variables so that we are able to analytically solve the 2D RTE and obtain the 2D BSF accordingly. Using the relations between 2D and 3D solutions acquired during the process of simplification, we are able to obtain the 3D BSF in explicit form. The 2D and 3D analytical solutions are validated by comparing with Monte Carlo radiative transfer simulations. The 2D analytical BSF agrees excellently with the Monte Carlo result. Despite assumptions of axial symmetry and spike-like azimuthal profile of the radiance in deriving the 3D BSF, the comparisons to numerical simulations are very satisfactory especially for limited optical depths (< O(5)) for single scattering albedo values typical in the ocean. The explicit form of the analytical BSF and the significant gain in computational efficiency (several orders higher) relative to RTE simulations make many forward and inverse problems in ocean optics practical for routine applications.


Ordinal classification in medical prognosis.
Medical prognosis is commonly expressed in terms of ordered outcome categories. This paper provides simple statistical procedures to judge whether the predictor variables reflect this natural ordering. The concept of stochastic ordering in logistic regression and discrimination models is applied to naturally ordered outcome scales in medical prognosis. The ordering stage is assessed by a data-generated choice between ordered, partially ordered, and unordered models. The ordinal structure of the outcome is particularly taken into consideration in the construction of allocation rules and in the assessment of their performance. The specialized models are compared to the unordered model with respect to the classification efficiency in a clinical prognostic study. It is concluded that our approach offers more flexibility than the widely used cumulative-odds model and more stability than the multinomial logistic model. The procedure described in this paper is strongly recommended for practical applications to support medical decision-making.


Diagnosis of Nonmigrating Metallic Foreign Bodies in the Abdomen Using Ultrasound: An Alternative Approach Using a Traditional Method.
Ingestion of foreign bodies (FBs) is a common phenomenon among young children. Plain radiography is the first step diagnostic modality to detect the radio-opaque FBs. And computed tomography has been recommended by several guidelines as useful modalities for diagnosing ingested FBs. However, there is a risk of radiation exposure, making it burdensome to use in asymptomatic patients. Ultrasound (US) is not a commonly used technique for diagnosing ingested foreign bodies. However, US can provide real-time imaging with good resolutions without radiation exposure in pediatric patients. Herein, we report two pediatric cases of metallic foreign body ingestion that were successfully diagnosed using US for localizing foreign bodies. This study indicates that US may be used as an alternative method for detecting the localization of metallic foreign bodies in the gastrointestinal tract without exposure of radiation, particularly in pediatric patients.


Design and synthesis of small molecule glycerol 3-phosphate acyltransferase inhibitors.
The incidence of obesity and other diseases associated with an increased triacylglycerol mass is growing rapidly, particularly in the United States. Glycerol 3-phosphate acyltransferase (GPAT) catalyzes the rate-limiting step of glycerolipid biosynthesis, the acylation of glycerol 3-phosphate with saturated long-chain acyl-CoAs. In an effort to produce small molecule inhibitors of this enzyme, a series of benzoic and phosphonic acids was designed and synthesized. In vitro testing of this series has led to the identification of several compounds, in particular 2-(nonylsulfonamido)benzoic acid (15g), possessing moderate GPAT inhibitory activity in an intact mitochondrial assay.


Long-term skeletal stability after maxillary advancement with distraction osteogenesis using a rigid external distraction device in cleft maxillary deformities.
Rigid external distraction is a highly effective technique for correction of maxillary hypoplasia in patients with orofacial clefts. The clinical results after correction of sagittal maxillary deformities in both the adult and pediatric age groups have been stable. The purpose of this retrospective longitudinal cephalometric study was to review the long-term stability of the repositioned maxilla in cleft patients who underwent maxillary advancement with rigid external distraction. Between April 1, 1995, and April 1, 1999, 17 consecutive patients with cleft maxillary hypoplasia underwent maxillary advancement using rigid external distraction. There were 13 male patients and four female patients, with ages ranging from 5.2 to 23.6 years (mean, 12.6 years). After a modified complete high Le Fort I osteotomy and a latency period of 3 to 5 days, patients underwent maxillary advancement with rigid external distraction until proper facial convexity and dental overjet and overbite were obtained. After active distraction, a 3- to 4-week period of rigid retention was undertaken; this was followed by removable elastic retention for 6 to 8 weeks using, during sleep time, an orthodontic protraction face mask. Cephalometric radiographs were obtained preoperatively, after distraction, at 1 year after distraction, and 2 or more years after distraction. The mean follow-up was 3.3 years (minimum, 2.1 years; maximum, 5.3 years). The following measurements were obtained in each cephalogram: three linear horizontal and two linear vertical maxillary measurements, two angular craniomaxillary measurements, and one craniomandibular measurement. Differences between the preoperative and postoperative cephalometric values were analyzed by paired t tests (p < 0.05). The cephalometric analysis demonstrated postoperatively significant advancement of the maxilla. In addition, the mandibular plane angle opened 1.2 degrees after surgery. After the 1- to 3-year follow-up period, the maxilla was stable in the sagittal plane. Minimal anteroposterior growth was observed in the maxilla compared with that exhibited in the anterior cranial base. However, there was significant vertical maxillary growth over the 3-year observation period. The mandibular plane angle tended to decrease during the follow-up period. The cephalometric data from this study support the clinical impression of maxillary stability after maxillary advancement with rigid external distraction in cleft patients. This effective and stable technique is now considered for all pediatric patients with severe cleft maxillary hypoplasia and for adolescent and adult patients with moderate to severe deformities.


Structure and occurrence of cyphonautes larvae (bryozoa, ectoprocta).
We have studied larvae of the freshwater ctenostome Hislopia malayensis with scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), and LM of serial sections. Some additional observations on larvae of M. membranacea using SEM and CLSM are also reported. The overall configuration of muscles, nerves, and cilia of the two larvae are identical. However, the larva of H. malayensis is much smaller than that of M. membranacea, which may explain most of the differences observed. Although all major nerves and muscle strands are present in H. malayensis, they are generally composed of fewer fibers. The H. malayensis larva lacks the anterior and posterior intervalve cilia. Its pyriform organ is unciliated with only a small central depression. The adhesive epithelium is not invaginated as an adhesive sac and lacks the large muscles interpreted as adhesive sac muscles in the M. membranacea larva. The velum carries two rows of ciliated cells, though the lower "row" consists of only one or two cells. Both rows of ciliated cells are innervated by nerves, which have not been detected in the M. membranacea larva. The ciliated ridge of H. malayensis lacks the frontal cilia. The planktotrophic cyphonautes larvae in a number of ctenostome clades and in the "basal" cheilostome clade Malacostega (and probably in the earliest cheilostomes) support the idea that the cyphonautes larva is the ancestral larval type of the Eurystomata. It may even represent the ancestral larval type of the bryozoans (= ectoprocts).


Drug delivery to the brain--realization by novel drug carriers.
Delivery of drugs to the brain is still a major challenge. Successful delivery across the bloodbrain barrier has only been achieved in some cases, e.g., using pro-drugs. The review describes the delivery to the brain using nanoparticulate drug carriers in combination with the novel targeting principle of "differential protein adsorption" (PathFinder technology). The PathFinder technology exploits proteins in the blood which adsorb onto the surface of intravenously injected carriers for targeting. Apolipoprotein E is the targeting moiety for the delivery of particles to the endothelials of the blood-brain barrier. To reach therapeutic drug level in the brain, nanoparticulate drug carriers with sufficiently high loading capacity are reviewed, including drug nanocrystals (nanosuspensions), lipid drug conjugate (LDC) nanoparticles and lipid nanoparticles (solid lipid nanoparticles-SLN, nanostructured lipid carriers-NLC). The features are described, including regulatory aspects and large scale production.


[Effect of pancreatin replacement on pancreatic function in the postoperative period after pancreatic surgery].
There is evidence that disturbances of exocrine function can persist for several weeks following pancreatic surgery. Active proteases in the duodenal lumen may help to recovery of exocrine function. A placebo-controlled trial of enteric-coated pancreatin (25,000 U lipase; 3 x 1 caps/day) was performed during 2 weeks following pancreatic surgery (resection and drainage operation). A total of 39 patients were randomized, 20 to pancreatin group and 19 to placebo group. The exocrine function was tested via serum and faecal elastase determinations, the amylum tolerance test (ATT) and checks on the symptoms of maldigestion. After medication for 10 days, there was evidence of the beneficial effect of pancreatin suggested by a 35% improvement in ATT, an unchanged body weight and the disappearance of symptoms of maldigestion. In the control group, abnormal ATT and symptoms of maldigestion were remained, while the body weight decreased with by 3.5 kg. In both groups, no significant change was noted in the elastase concentration. The results suggest that enteric-coated pancreatin treatment after pancreatic surgery may lead to a rapid improvement of exocrine pancreatic function, probably by reducing the cholelcystokinin response to stimulation by food and represent a new indication of the enteric-coated pancreatin medication.


Expression of macrophage migration inhibitory factor transcript and protein by first-trimester human trophoblasts.
Macrophage migration inhibitory factor (MIF) was originally identified for its capacity to inhibit the random migration of macrophages in vitro. To date, the role of MIF as a pro-inflammatory cytokine, pituitary hormone, and counter-regulator of glucocorticoid action on the immune response is commonly recognized. Although recent studies suggest an involvement of MIF in reproduction, no data exist on the expression of this cytokine in early human pregnancy. In this study, we evaluated the presence of MIF protein and mRNA in specimens of chorionic villi from first-trimester human placenta. Tissues were obtained at 6-10 wk of gestation and analyzed by Western blotting, reverse transcription-polymerase chain reaction, and immunohistochemistry. Our results demonstrate that human villous tissue is a novel site of MIF synthesis. In addition, immunohistochemical analysis identified MIF protein in the cytotrophoblasts of both the inner layer of villi and in the trophoblastic cell islands. We speculate that in view of its proinflammatory features, MIF might play a critical role in human implantation and in early embryonic development.


Interactions between charged surfaces mediated by stiff, multivalent zwitterionic polymers.
The interaction between like-charged objects in electrolyte solutions can be heavily altered by the presence of multivalent ions which possess a spatially distributed charge. In this work, we examine the influence of stiff, multivalent zwitterionic polymers on the interaction between charged surfaces using a splitting field theory previously shown to be accurate for the weak to the intermediate to the strong electrostatic coupling regimes. The theory is compared to Monte Carlo simulations and good agreement is found between both approaches. For surface separations shorter than the polymer length, the polymers are mainly oriented parallel to the surfaces, and the surface-surface interaction is repulsive. When the surface separation is comparable to the length of polymers, the polymers have two main orientations. The first corresponds to the polymers adsorbed onto the surface with their centers located near to or in contact with the surface; the second corresponds to polymers which are perpendicular to the charged surfaces, bridging both surfaces and leading to an attractive force between them. Increasing the surface charge density leads to more pronounced attraction via bridging. At surface separations greater than the polymer length, the polymers in the center of the system are still mainly perpendicular to the surfaces, due to "chaining" between zwitterions that enable them to bridge the surfaces at larger separations. This leads to an attractive interaction between the surfaces with a range significantly longer than the length of the polymers.


Species of Mediorhynchus (Acanthocephala: Gigantorhynchidae) in Australian birds with the description of Mediorhynchus colluricinclae n. sp..
Four species of Mediorhynchus are identified from Australian birds. New locality records are given for Mediorhynchus alecturae (Johnston and Mawson, 1947) Golvan, 1962 and new host and locality records for M. corcoracis Johnston and Edmonds, 1951. Mediorhychus grandis has been reported from Australian hosts, but this record could not be verified. Two females from Acanthogenys rufogularis and the anterior portion of a single female from a "gull" had characters of proboscis armature, lemnisci, and eggs that precluded them being assigned to any of the presently known species of Mediorhynchus. Mediorhynchus colluricinclae n. sp. was found in pomatostomatids from South Australian localities. A high degree of host specificity is recorded for M. corcoracis and M. colluricinclae. Selection of specific dietary items may be one filter that influences the degree of host specificity encountered.


Suicidal ideation and behaviour.
Suicide is a leading cause of death among Canadian adolescents. The present practice point provides paediatricians and child health professionals with a framework for assessing the adolescent with suicidal thoughts and/or behaviours. The epidemiological context, general considerations and practical suggestions for how to approach the suicidal adolescent are reviewed. Paediatricians can and should screen youth for mental illness and significant psychosocial stressors. Early identification and treatment of mental illness are important ways in which paediatricians can assist in self-injury prevention for adolescents who are considering suicide.


The development and in vivo evaluation of a colon drug delivery system using human volunteers.
The aim of this study was to develop a multiple-unit dosage system that released model drug into the colon, and also to evaluate the efficiency of the dosage form in human volunteers. The developed system combines pH-, time- and biodegradable polymer-based mechanisms for drug targeting to the colon. Pellet cores containing caffeine as model drug and chitosan and microcrystalline cellulose as excipients were prepared by the extrusion/spheronization method. The prepared pellets were film coated with a pH-dependent polymer, Eudragit FS 30 D. The coating total weight gain was 28.83% (w/w). Thanks to the application of an outer enteric film and the multiple unit design of the dosage form, the variability in gastric emptying was overcome, and a colon-specific targeting relied on the reproducibility of a small intestinal transit time, which was reported to be 3 ± 1 hours. A biodegradable polymer in the pellet core, chitosan, ensured the site-specific release of the model drug due to its solubility at the lower pH of the colonic region and by its biodegradability from the bacteria present. The efficiency of the system was confirmed by the in vivo testing of human saliva. The time of the first appearance of caffeine into the saliva, T(lag), was used as a parameter to estimate the disintegration time of the pellets into the gastrointestinal tract. The caffeine appeared in the saliva within 6.95 ± 1.12 hours (T(lag)) in 9 volunteers. A comparison of the reported colon arrival times indicates that the developed system is applicable to colonic drug delivery.


Magnetic resonance imaging in the management of anal fistula and anorectal sepsis.
Complex perianal disease may be extremely debilitating for the patient with significant impingement on quality of life. The accurate identification of anatomical areas of involvement and subsequent appropriate management is crucial to achieving a successful outcome when treating anorectal sepsis and anal fistulae. Magnetic resonance imaging (MRI) has become a powerful tool in the evaluation of anal anatomy. In patients with complex disease MRI is an important adjunct in delineating disease location and extent, its relationship to sphincter muscles, and in planning management. MRI also plays an important role in evaluating the response to medical and surgical therapies.


Contrast-enhanced digital holographic imaging of cellular structures by manipulating the intracellular refractive index.
The understanding of biological reactions and evaluation of the significance for living cells strongly depends on the ability to visualize and quantify these processes. Digital holographic microscopy (DHM) enables quantitative phase contrast imaging for high resolution and minimal invasive live cell analysis without the need of labeling or complex sample preparation. However, due to the rather homogeneous intracellular refractive index, the phase contrast of subcellular structures is limited and often low. We analyze the impact of the specific manipulation of the intracellular refractive index by microinjection on the DHM phase contrast. Glycerol is chosen as osmolyte, which combines high solubility in aqueous solutions and biological compatibility. We show that the intracellular injection of glycerol causes a contrast enhancement that can be explained by a decrease of the cytosolic refractive index due to a water influx. The underlying principle is proven by experiments inducing cell shrinkage and with fixated cells. The integrity of the cell membrane is considered as a prerequisite and allows a reversible cell swelling and shrinking within a certain limit. The presented approach to control the intracellular phase contrast demonstrated for the example of DHM opens prospects for applications with other quantitative phase contrast imaging methods.


The microcirculation of myocutaneous island flaps in pigs studied with radioactive blood volume tracers and microspheres of different sizes.
In order to further improve the understanding of hemodynamic changes in the immediate postoperative phase after elevation of myocutaneous flaps, regional blood flow and arteriovenous (A-V) shunting were measured in rectus abdominis island flaps in 8 pigs. Radioactive microspheres of two sizes (15 and 50 micron) were used. Approximately half (53.4 +/- 6 percent) of the 15-micron microspheres and one-fourth (24.1 +/- 6 percent) of the 50-micron microspheres entering the flap appeared in the venous outflow. Compared with the control area, A-V shunting was significantly increased in muscle and substantially more pronounced in skin. Nutritional blood flow, total blood flow, and vascular volume were increased in muscle and unchanged in skin and subcutis. The lowest tissue hematocrit of 7 +/- 1 percent was found in skin as compared with a central hematocrit of 35 +/- 2 percent. Tissue hematocrit in flap muscle was decreased to 17 +/- 2 percent when compared with control muscle (22 +/- 3 percent), and the mean transit time for blood was correspondingly decreased. Thus vasodilation provided increased perfusion through muscular capillaries and through A-V shunts. Shunting of 15-micron microspheres appeared to take place not only in skin, but also in subcutis and muscle, which challenges the widespread belief that A-V shunting does not occur in muscle.


A cheminformatics review of auxins as herbicides.
Herbicides are an important asset in ensuring food security, especially when faced with an ever-increasing demand on food production to feed the global population. The current selection of herbicides is increasingly encountering resistance in agricultural weeds they once targeted effectively. It is imperative that new compounds or more effective modes of action are discovered in order to overcome this resistance. This cheminformatics review looks at current herbicides and evaluates their physiochemical properties on a class-by-class basis. We focus in particular on the synthetic auxin herbicides, Herbicide Resistance Action Committee class O, analyzing these against herbicides more generally and for class-specific features such as mobility in plant vasculature. We summarise the physiochemical properties of all 24 compounds used commercially as auxins and relate these results to ongoing approaches to novel auxin discovery. We introduce an interactive, open source cheminformatics tool known as DataWarrior for herbicide discovery, complete with records for over 300 herbicidal compounds. We hope this tool helps researchers as part of a rational approach to not only auxin discovery but agrochemical discovery in general.


Fluorescence in situ hybridization (FISH) in the molecular cytogenetics of cancer.
In this review, we discuss the developments of fluorescence in situ hybridization (FISH) and place them in the context of their applications in cancer research. These methods are not only very useful for the causal analysis of the development and spread of certain tumors, they are also efficient tools for tumor diagnosis. Although a review of all of the literature in this field is not possible here, many of the major contributions are summarized along with recent work from our laboratory. Our group contributes to the goal of functional identification of tumor growth antagonizing genes. FISH and molecular analyses have shown that the short arm of human chromosome 3 is frequently deleted in kidney, lung, breast, uterus, testis and ovary carcinomas. Deletion-mapping studies have outlined several separate deletion prone regions in different tumors, namely 3pter-p25, p22-p21.3, p21.1-p14 and p14-p12, which may contain putative tumor suppressor genes (TSGs). Candidate suppressor genes isolated from frequently deleted regions need to be assayed for possible tumor-antagonizing ability by functional tests. We have developed a functional test system, the microcell hybrid (MCH) based "elimination test" (Et). The Et is based on the introduction of a single human chromosome into tumor cells of human or murine origin, via microcell fusion. The MCHs were analyzed by FISH painting and PCR for the elimination or retention of specific human chromosome 3 (chr. 3) regions after one or several passages in severe combined immunedeficient (SCID) mice. We have defined a common eliminated region (CER) on chr. 3p21.3. CER is approximately 1 megabase (Mb) in size. We have covered this region with PACs (bacteriophage PI based artificial chromosome) and used FISH mapping for localization and ordering PACs and cosmids on the chromosome 3 and high-resolution free chromatin/DNA fiber FISH to orient the PAC contig, to measure the lengths of PACs, and to establish their order. Activation of cellular oncogene by chromosomal tanslocation, which brings an oncogene under the influence of a highly active chromosome region, appears to play a pivotal role in the genesis of certain hematopoetic and lymphoid tumors. We have detected specific chromosomal translocations by FISH painting in mouse plamacytoma (MPC), human Burkitt lymphoma (BL) other B-cell derived tumors. We have showed in a murine sarcoma derived line (SEWA) that FISH can be also be used for detection of amplified oncogene (c-myc) and the linked locus (pvt-1). We have also applied the FISH technique for visualization of integrated and episomal Epstein-Barr virus (EBV) genomes and EBV transcripts in EBV-carrying B-cell derived human cell lines.


Prevention of trismus with different pharmacological therapies after surgical extraction of impacted mandibular third molar.
Aim To assess prevention and reduction of trismus after surgically extracted impacted mandibular third molars with individual and combined therapy with corticosteroids and anti-inflammatory analgesics. Methods The research included 60 randomly selected patients (3 groups) attended to the Dental Oral Surgery of the Public Institution Healthcare Center Zenica during the period January-December 2008. Patients of both genders, 18-45 years of age, were presented without pain and other inflammatory symptoms at the time of surgery. According to a scheme established in the research protocol, two medications were administered orally: methylprednisolone(corticosteroid) 32 mg and meloxicam (non-steroidal anti-inflammatory analgesic, NSAID) 15 mg as a single drug, or a combination of both drugs. The level of trismus is assessed on the basis of differences of preoperative and postoperative values of interincisal spaces when fully opening the mouth on the second and the seventh post-operative day. The differences between groups of patients were evaluated by means of Tukey's HSD test. Results On the second and on the seventh post-operative day significantly better results were registered in the group that received only corticosteroids and in the group that received both, corticosteroids and NSAIDs compared to the group that received only NSAIDs. A tendency of trismus reduction was present in all patient groups for the second and seventh day after surgery. Conclusion Prevention and control of postoperative trismus after surgical extraction of impacted mandibular third molars with combined therapy is effective and superior comparing to individual therapy with meloxicam-or methylprednisolone alone.


[Relation of left and right axillary temperature with Yin-Yang and its guiding action on diagnosis and treatment of acupuncture and moxibustion].
Body temperature is one of the four physical signs and clinically, the axillary temperature is the most commonly used as the index of body temperature. The study on relation of the difference of the left and right axillary temperature with constitution types and diagnosis of diseases proves that the temperature of the left and right axillary is correlated with excess and insufficiency of Yin and Yang, namely, higher left axillary temperature is recognized as Yin-deficiency and Yang-excess, and higher right axillary temperature as Yang-deficiency and Yin-excess, and this can guide clinical syndrome differentiation treatment of acupuncture and moxibustion and individual diagnostic and therapeutic program can be established based on this.


Pivotal Role of Heteroatoms in Improving the Corrosion Inhibition Ability of Thiourea Derivatives.
1,3-Diphenyl-2-thiourea (DPTU) and 1-phenyl-3-(2-pyridyl)-2-thiourea (PPTU) were selected as the researched subject for investigating the effect of heteroatoms on the low carbon steel corrosion inhibition ability. Results from the potentiodynamic polarization measurements (PPM) indicate that the addition of a nitrogen atom in the benzene ring increases the corrosion inhibition efficiency of PPTU (97.2%), being higher than that of DPTU (93.1%) at the same condition of 2.0 × 10-4 M at 30 °C. The Nyquist diagrams show that increasing the concentrations of both DPTU and PPTU will enhance the charge-transfer resistance and reduce the double-layer capacitance. The obtained data based on PPM and electrochemical impedance spectroscopy methods are in accordance to the analysis based on the scanning electrochemical microscopy images. Besides, results from quantum chemical calculations prove that the heteroatoms in the inhibitor molecules are the adsorption centers, and the benzene rings increase the electrostatic interaction between the inhibitor molecules and the steel surface. Results from Monte Carlo and molecular dynamics simulation have clarified the adsorption mechanism of DPTU and PPTU on the steel surface. Adsorption energies confirm that PPTU displays the higher inhibition ability as compared with DPTU.


Effect of folic acid supplementation on cardiovascular outcomes: a systematic review and meta-analysis.
Folic acid is widely used to lower homocysteine concentrations and prevent adverse cardiovascular outcomes. However, the effect of folic acid on cardiovascular events is not clear at the present time. We carried out a comprehensive systematic review and meta-analysis to assess the effects of folic acid supplementation on cardiovascular outcomes. We systematically searched Medline, EmBase, the Cochrane Central Register of Controlled Trials, reference lists of articles, and proceedings of major meetings for relevant literature. We included randomized placebo-controlled trials that reported on the effects of folic acid on cardiovascular events compared to placebo. Of 1594 identified studies, we included 16 trials reporting data on 44841 patients. These studies reported 8238 major cardiovascular events, 2001 strokes, 2917 myocardial infarctions, and 6314 deaths. Folic acid supplementation as compared to placebo had no effect on major cardiovascular events (RR, 0.98; 95% CI, 0.93-1.04), stroke (RR, 0.89; 95% CI,0.78-1.01), myocardial infarction (RR, 1.00; 95% CI, 0.93-1.07), or deaths from any cause (RR, 1.00;95% CI, 0.96-1.05). Moreover, folic acid as compared to placebo also had no effect on the following secondary outcomes: risk of revascularization (RR, 1.05; 95%CI, 0.95-1.16), acute coronary syndrome (RR, 1.06; 95%CI, 0.97-1.15), cancer (RR, 1.08; 95%CI, 0.98-1.21), vascular death (RR, 0.94; 95%CI,0.88-1.02), or non-vascular death (RR, 1.06; 95%CI, 0.97-1.15). Folic acid supplementation does not effect on the incidence of major cardiovascular events, stroke, myocardial infarction or all cause mortality.


Low-dose tubacin promotes BMSCs proliferation and morphological changes through the ERK pathway.
Histone deacetylase 6 (HDAC6) plays critical roles in many cellular processes related to cancer, but its epigenetic regulation in bone marrow stromal stem cells (BMSCs) remains unexplored. This study investigated the beneficial effects of Tubulin Acetylation Inducer (tubacin), a novel specific HDAC6 inhibitor, on the proliferation and migration of BMSCs. A low concentration of tubacin promoted BMSC commitment and enhanced proliferation of BMSCs. Atomic force microscopy results showed that tubacin induced morphological changes and enhanced the mechanical properties of BMSCs. Furthermore, low tubacin concentrations significantly upregulated protein expression of acetylated α-tubulin, VCAM-1, and ICAM-1, which could be suppressed by an ERK inhibitor. Protein chip analysis showed that there were significant changes in the expression levels of 49 cytokines after tubacin treatment, which participate in inflammatory responses and cell activation, proliferation, and differentiation. Our findings suggest that the protective effects of tubacin on BMSCs involve HDAC6 inhibition by activating the ERK pathway.


A Study of the Developing Paediatric Skullbase Anatomy and its Application to Endoscopic Endonasal Approaches in Children.
The sinonasal anatomy in growing children undergoes change in size along with progressive pneumatization, this is of particular significance in endoscopic endonasal surgery. We aim to measure and quantify the sinonasal dimensions in the Indian paediatric population, which are relevant to skull base surgeons. This is a retrospective radio anatomical study of sinonasal measurements and volumetric analysis of the sphenoid sinus performed on archived CT images of children less than 18 years of age. CT scan images of 110 patients (male, 68; female, 42) were included for the study. The number of patients in each age groups was as follows [0-6 years, 17; 7-9 years, 20; 10-12 years, 27; 13-15 years, 29; 16-18 years, 17]. The distance from the nares to the sphenoid and from the sphenoid to the sella was significantly greater in children of 13-15 years (69.4 ± 5.2 mm) as compared to children less than six years (62.6 ± 6.7 mm) (P < 0.003). The volume of the sphenoid in children between 0 and 6 years was 4641.4 ± 1924.7 mm3. The pneumatized sphenoid volume in the same age group was 1655 ± 1631.1 mm3. In older children between 13 and 15 years, the total volume of sphenoid sinus was 11732.8 ± 2614.4 mm3. The volume of pneumatization in the sphenoid sinus in this group was 6287.5 ± 2157.9 mm3. The total volume of the sphenoid sinus (Pearson coefficient (r) = 0.704, P < 0.001) and the volume of pneumatization of the sphenoid sinus was also seen to have a positive correlation to the age of the child (r = 0.62, P < 0.0001). The narrowest distance between both the internal carotid arteries was seen at the level of the proximal dural ring. In children less than six years of age it was 13.4 ± 2.0 mm, a significant change was seen by the age of 10-12 years where this distance was 15.6 ± 2.2 mm (P = 0.036). The sinonasal anatomy shows progressive development between the age of 6 to 15 years after which it plateaus. The pneumatization in young children may be incomplete, which necessitates drilling in the sphenoid sinus. The intercarotid distance was not seen to be a hindrance for endoscopic endonasal surgery. None of the measurements of the skull-base, made in this study appear to restrict endoscopic endonasal surgery in children. However, a meticulous preoperative assessment of the CT scan may be needed for optimal surgical outcome.


Different Types of Long-Term Milk Consumption and Mortality in Adults with Cardiovascular Disease: A Population-Based Study in 7236 Australian Adults over 8.4 Years.
Most studies disregard long-term dairy consumption behaviour and how it relates to mortality. We examined four different types of long-term milk consumption, namely whole milk, reduced fat milk, skim milk and soy milk, in relation to mortality among adults diagnosed with cardiovascular disease (CVD). A retrospective population-based study was conducted in Australia (the 45 and Up Study) linking baseline (2006-2009) and follow-up data (2012-2015) to hospitalisation and mortality data up to 30 September 2018. A total of 1,101 deaths occurred among 7236 participants with CVD over a mean follow-up of 8.4 years. Males (Hazard Ratio, HR = 0.69, 95% CI (0.54; 0.89)) and females (HR = 0.59 (0.38; 0.91)) with long-term reduced fat milk consumption had the lowest risk of mortality compared to counterparts with long-term whole milk consumption. Among participants with ischemic heart disease, males with a long-term reduced fat milk consumption had the lowest risk of mortality (HR = 0.63, 95% CI: 0.43; 0.92). We conclude that among males and females with CVD, those who often consume reduced fat milk over the long-term present with a 31-41% lower risk of mortality than those who often consume whole milk, supporting dairy advice from the Heart Foundation of replacing whole milk with reduced fat milk to achieve better health.


Smart Responsive Quercetin-Conjugated Glycol Chitosan Prodrug Micelles for Treatment of Inflammatory Bowel Diseases.
The incidence and progression of inflammatory bowel disease are closely related to oxidative stress caused by excessive production of reactive oxygen species (ROS). To develop an efficacious and safe nanotherapy against inflammatory bowel diseases (IBD), we designed a novel pH/ROS dual-responsive prodrug micelle GC-B-Que as an inflammatory-targeted drug, which was comprised by active quercetin (Que) covalently linked to biocompatible glycol chitosan (GC) by aryl boronic ester as a responsive linker. The optimized micelles exhibited well-controlled physiochemical properties and stability in a physiological environment. Time-dependent NMR spectra traced the changes in the polymer structure in the presence of H2O2, confirming the release of the drug. The in vitro drug release studies indicated a low release rate (<20 wt %) in physiological conditions, but nearly complete release (>95 wt % after 72 h incubation) in a pH 5.8 medium containing 10 μM H2O2, exhibiting a pH/ROS dual-responsive property and sustained release behavior. Importantly, the negligible drug release in a simulated gastric environment in 1 h allowed us to perform intragastric administration, which has potential to achieve the oral delivery by mature enteric-coating modification in future. Further in vivo activities and biodistribution experiments found that the GC-B-Que micelles tended to accumulate in intestinal inflammation sites and showed better therapeutic efficacy than the free drugs (quercetin and mesalazine) in a colitis mice model. Typical inflammatory cytokines including TNF-α, IL-6, and iNOS were significantly suppressed by GC-B-Que micelle treatment. Our work promoted inflammatory-targeted delivery and intestinal drug accumulation for active single drug quercetin and improved the therapeutic effect of IBD. The current study also provided an alternative strategy for designing a smart responsive nanocarrier for a catechol-based drug to better achieve the target drug delivery.


Hydrocortisone induced regional cerebral activity changes in schizophrenia: a PET scan study.
There is evidence that, even during remission, schizophrenia (SZ) patients are especially vulnerable to de-compensate under stress, and that they tend to have a high baseline serum cortisol levels. This study was undertaken to determine whether raising serum cortisol by the infusion of hydrocortisone, in the absence of additional psychological stress, would result in different cerebral activity changes in schizophrenic patients compared to normal controls (CON). We were especially interested in cerebral activity in regions such as the medial temporal lobe and hippocampus, since structural abnormalities in these brain regions were frequent in association with schizophrenia. Serum cortisol levels were raised, by infusing hydrocortisone, in 8 pairwise-matched SZ patients and 8 CONs. The associated regional cerebral activity changes were analyzed using statistical parametric mapping (SPM). There was increased regional cerebral activity in response to elevated cortisol in the left hippocampal region in the SZ group, while the controls showed evidence of decreased regional cerebral activity in the same anatomical location. For the rest of the brain regions, cerebral activity increases and decreases, in response to raised serum cortisol, in the SZ followed the same regional pattern as in the control group, but with a smaller overall magnitude of change. The blunted response in SZ was most marked in the regions that showed greatest regional cerebral activity changes in normal subjects. Patients with schizophrenia showed an abnormal increased regional cerebral activity response to cortisol infusion in the left hippocampal region, and similar but attenuated regional cerebral activity response in other regions, when compared to matched controls.


Sorting of encystation-specific cysteine protease to lysosome-like peripheral vacuoles in Giardia lamblia requires a conserved tyrosine-based motif.
Encystation-specific cysteine protease (ESCP) was the first membrane-associated protein described to be part of the lysosome-like peripheral vacuoles in the intestinal parasite Giardia lamblia. ESCP is homologous to cathepsin C enzymes of higher eukaryotes, but is distinguished from other lysosomal cysteine proteases because it possesses a transmembrane domain and a short cytoplasmic tail. Tyrosine-based motifs within tails of membrane proteins are known to participate in endosomal/lysosomal protein sorting in higher eukaryotes. In this study, we show that a YRPI motif within the ESCP cytoplasmic tail is necessary and sufficient to mediate ESCP sorting to peripheral vacuoles in Giardia. Deletion and point mutation analysis demonstrated that the tyrosine residue is critical for ESCP sorting, whereas amino acids located at the Y+1 (Arg), Y+2 (Pro), and Y+3 (Ile) positions show minimal effect. Loss of the motif resulted in surface localization, whereas addition of the motif to a variant-specific surface protein resulted in lysosomal localization. Although Giardia trophozoites lack a morphologically discernible Golgi apparatus, our findings indicate that this parasite directs proteins to the lysosomes using a conserved sorting signal similar to that used by yeast and mammalian cells. Because Giardia is one of the earliest branching protist, these results demonstrate that sorting motifs for specific protein traffic developed very early during eukaryotic evolution.


Laser dentistry in daily practice during the COVID-19 pandemic: Benefits, risks and recommendations for safe treatments.
The COVID-19 pandemic forced dental professionals to cope with an unexpected challenge and caused an abrupt cessation of conventional care practices. The high degree of contagiousness as well as the diffusion of the virus through the air and droplets via respiratory transmission placed dental professionals at top-level risk of contracting and spreading the disease. General recommendations were announced in different countries, including patient distancing, air ventilation, surface and instrument sanitization, and the wearing of suitable masks and shields. However, many dental treatments are performed using lasers, and some specific precautions must be added to conventional procedures to ensure the advantages of this technology to patients because of the particular tissue–matter interaction effects of laser wavelengths. Based on the literature, the authors evaluated all of using laser wavelengths to analyze the risk and the benefits of using lasers in daily dental practice, and to provide safety recommendations during pandemic. An unrestricted search of indexed databases was performed. Laser use effects were categorized into: 1) explosive processes that produce tissue ablation and aerosol formation; 2) thermal actions that create vaporization and smoke plume; 3) photobiomodulation of the cells; and 4) enhanced chemical activity. Knowledge of the device functions and choice of adequate parameters will reduce aerosol and plume formation, and the application of suction systems with high flow volume and good filtration close to the surgical site will avoid virus dissemination during laser use. In the categories that involve low energy, the beneficial effects of lasers are available and sometimes preferable during this pandemic because only conventional precautions are required. Lasers maintain the potential to add benefits to dental practice even in the COVID-19 era, but it is necessary to know how lasers work to utilize these advantages. The great potential of laser light, with undiscovered limits, may provide a different path to face the severe health challenges of this pandemic.


A novel CT acquisition and analysis technique for breathing motion modeling.
To report on a novel technique for providing artifact-free quantitative four-dimensional computed tomography (4DCT) image datasets for breathing motion modeling. Commercial clinical 4DCT methods have difficulty managing irregular breathing. The resulting images contain motion-induced artifacts that can distort structures and inaccurately characterize breathing motion. We have developed a novel scanning and analysis method for motion-correlated CT that utilizes standard repeated fast helical acquisitions, a simultaneous breathing surrogate measurement, deformable image registration, and a published breathing motion model. The motion model differs from the CT-measured motion by an average of 0.65 mm, indicating the precision of the motion model. The integral of the divergence of one of the motion model parameters is predicted to be a constant 1.11 and is found in this case to be 1.09, indicating the accuracy of the motion model. The proposed technique shows promise for providing motion-artifact free images at user-selected breathing phases, accurate Hounsfield units, and noise characteristics similar to non-4D CT techniques, at a patient dose similar to or less than current 4DCT techniques.


Synthesis of multifunctional PAMAM-aminoglycoside conjugates with enhanced transfection efficiency.
The development of multifunctional vectors for efficient and safe gene delivery is one of the major challenges for scientists working in the gene therapy field. In this context, we have designed a novel type of aminoglycoside-rich dendrimers with a defined structure based on polyamidoamine (PAMAM) in order to develop efficient, nontoxic gene delivery vehicles. Three different conjugates, i.e., PAMAM G4-neamine, -paromomycin, and -neomycin, were synthesized and characterized by nuclear magnetic resonance (NMR) and MALDI analysis. The conjugates were found to self-assemble electrostatically with plasmid DNA, and unlike neamine conjugate, each at its optimum showed increased gene delivery potency compared to PAMAM G4 dendrimer in three different cell lines, along with negligible cytotoxicity. These results all disclosed aminoglycosides as suitable functionalities for tailoring safe and efficient multifunctional gene delivery vectors.


Innovative Opportunities for Nurse Practitioner Education Uncovered by the Pandemic.
The coronavirus disease 2019 pandemic resulted in the abrupt withdrawal of clinical sites for nurse practitioner (NP) students during the Spring semester of 2020. This situation necessitated the identification of innovative clinical opportunities to ensure advanced practice nursing students met course objectives and program requirements. This article describes innovative clinical opportunities that met the needs of the community, including those impacted by the pandemic, and enabled NP students' progression toward completing clinical requirements. Participation in these unique opportunities provided more than 130 NP students with meaningful clinical experiences to increase competence in the care of vulnerable populations and communities during a public health crisis. Experiences supported competency development in the areas of leadership, clinical management, population health and infection control, policy and advocacy, informatics, telehealth, and ethical considerations while providing essential services to the community. These innovative clinical opportunities may be useful for graduate clinical programs worldwide. [J Nurs Educ. 2022;61(3):153-155.].


Nonlinear Finite Element Analysis of γ-Graphyne Structures under Shearing.
In this study, a nonlinear, spring-based finite element approach is employed in order to predict the nonlinear mechanical response of graphyne structures under shear loading. Based on Morse potential functions, suitable nonlinear spring finite elements are formulated simulating the interatomic interactions of different graphyne types. Specifically, the four well-known types of γ-graphyne, i.e., graphyne-1 also known as graphyne, graphyne-2 also known as graphdiyne, graphyne-3, and graphyne-4 rectangular sheets are numerically investigated applying appropriate boundary conditions representing shear load. The obtained finite element analysis results are employed to calculate the in-plane shear stress-strain behaviour, as well as the corresponding mechanical properties as shear modulus and shear strength. Comparisons of the present graphyne shearing response predictions with other corresponding estimations are performed to validate the present research results.


The role of GM-CSF in enhancing immunotherapy of cancer.
Evaluation of: Kanerva A, Nokisalmi P, Diaconu I et al. Antiviral and anti-tumor T-cell immunity in patients treated with GM-CSF coding oncolytic adenovirus. Clin. Cancer Res. 19(10), 2734-2744 (2013). The field of oncolytic viral therapy has been reinvigorated recently with publication of clinical data from two leading vectors, one based on HSV and one on Vaccinia, both of which express GM-CSF. Part of the reason for the improved clinical results with these vectors appears to be the enhanced immunotherapeutic mechanism of tumor destruction mediated by GM-CSF expression itself. The article by Kanerva et al. extends this work to describe early clinical use of an oncolytic adenovirus expressing GM-CSF, although the data are too preliminary to describe significant therapeutic benefits of GM-CSF expression in this backbone. However, the description of enhanced antitumor immunity in those patients that developed greater antiviral immunity after treatment provides a potent demonstration of the immunotherapeutic potential of epitope spreading after treatment with oncolytic viral therapies.


Uterine Clear Cell Carcinoma of Postmenopausal Woman: A Case Report.
Endometrial cancer is the most common gynecologic malignancy in developed countries. Clear cell carcinoma typically occurs in the ovaries, and very rarely occurs in the endometrium; it accounts for less than 3% of all endometrial cancers. It is presumed that clear cell carcinomas are of Müllerian duct origin, and an association with exposure to diethylstilbestrol (DES) or other nonsteroidal follicle stimulating hormones has been described. We report a case of a postmenopausal woman who presented with vaginal bleeding without a specific medical history. Under the impression of an endometrial mass, we performed a laparoscopic operation. Pathologic results showed clear cell carcinoma of the endometrium. Depth of invasion was 0.2 cm out of a 0.5 cm total thickness, and the rectal shelf mass was clear cell carcinoma. We report the case with a brief review of the relevant literature.


Backbone and ILV methyl resonance assignments of E. coli thymidylate synthase bound to cofactor and a nucleotide analogue.
Thymidylate synthase (TSase) is a 62 kDa homodimeric enzyme required for de novo synthesis of thymidine monophosphate in most organisms. This makes the enzyme an excellent target for anticancer and microbial antibiotic drugs. In addition, TSase has been shown to exhibit negative cooperativity and half-the-sites reactivity. For these collective reasons, TSase is widely studied, and much is known about its kinetics and structure as it progresses through a multi-step catalytic cycle. Recently, nuclear magnetic resonance spin relaxation has been instrumental in demonstrating the critical role of dynamics in enzyme function in small model systems. These studies raise questions about how dynamics affect function in larger enzymes with more complex reaction coordinates. TSase is an ideal candidate given its size, oligomeric state, cooperativity, and status as a drug target. Here, as a pre-requisite to spin relaxation studies, we present the backbone and ILV methyl resonance assignments of TSase from Escherichia coli bound to a substrate analogue and cofactor.


Bioassay for determining sensitivity to sulfosulfuron on seven plant species.
This study presents a bioassay procedure, based on the root and shoot growth parameters, for the determination of the herbicide sulfosulfuron (1-(4,6 dimethoxypyrimidin-2-yl)-3-(2-ethylsulfonylimidazo[1,2-a]pyridin-3-ylsulfonil)urea) sensitivity on seven vegetal species. Plant response to sulfosulfuron was calculated with the equations fitted to the root growth data as a function of the logarithm of the herbicide concentration by non-linear regression and was used to calculate the doses for 10, 30 and 50% inhibition of root growth (EC10, EC30 and EC50). The results indicate that the phytotoxic effect of sulfosulfuron in all the species assayed followed the order: flax > maize > onion > vetch > lepidium sativum > tomato > barley. These species showed phytotoxicity at low levels of sulfosulfuron and flax appeared to be the most susceptible species to sulfosulfuron (0.001 mg/L).


[Perioperative managment of laparoscopic sleeve gastrectomy].
To summarize the surgical technique and perioperative management of laparoscopic sleeve gastrectomy (LSG). A total of 57 morbid obesity patients undergoing LSG surgery from May 2010 to December 2012 were enrolled in the study, whose clinical data in perioperative period were analyzed retrospectively. These patients had more than 1 year of follow-up. All the patients received preoperative preparation and postoperative management, and postoperative excess weight loss(EWL%) and improvement of preoperative complications was evaluated. All the cases completed the operation under laparoscopy, except 1 case because of the abdominal extensive adhesion. The average operation time was(102.0±15.2) min and the mean intraoperative blood loss (132.3±45.6) ml. Of 2 postoperative hemorrhage patients, 1 case received conservative treatment, and another one underwent laparoscopic exploration. The EWL% at 3 months, 6 months and 1 year after procedure was (54.9±13.8)%, (79.0±23.6)% and (106.9±25.1)% respectively. The preoperative complications were improved in some degree. There were no operative death, and anastomotic leak, anastomotic stenosis, or surgical site infection occurred. LSG is a safe and effective surgical technique, whose safety and efficacy may be increased by improving the perioperative management.