Mir363-3p attenuates post-stroke depressive-like behaviors in middle-aged female rats.
Women are more likely to develop Post Stroke Depression (PSD) than men and generally do not respond well to anti-depressants with age. This study investigated the effect of microRNA mir363-3p treatment on PSD using a physiologically-relevant animal model. Our previous work showed that mir363-3p treatment, delivered post-stroke, effectively reduces infarct volume in the acute phase of stroke in middle-aged females but not males. Middle-aged female Sprague Dawley rats were tested for baseline sensory motor function and depressive-like behaviors, and then subjected to ischemic stroke via middle cerebral artery occlusion (MCAo) or sham surgery. Animals received either control oligos (MCAo+scrambled, Sham+scrambled) or mir363-3p (MCAo+mir363-3p, Sham+mir363-3p) treatment 4 h later. Sensory motor function and depressive-like behaviors were reassessed up to 100 d after stroke, and circulating levels of IL-6, TNF-alpha and Brain-Derived Neurotrophic Factor (BDNF) were quantified at regular intervals. Prior to termination, Fluorogold was injected into the striatum to assess meso-striatal projections. MCAo+scrambled animals had impaired sensorimotor performance in the acute phase (5 days) of stroke and developed anhedonia, decreased sociability and increased helplessness in the chronic phase. MCAo+mir363-3p animals showed significantly less sensory motor impairment and fewer depressive-like behaviors. IL-6 and TNF-alpha were elevated transiently at 4 weeks after MCAo in both groups. BDNF levels decreased progressively after stroke in the MCAo+scrambled group, and this was attenuated in the mir363-3p group. The number of retrogradely-labeled SNc and VTA cells was reduced in the ischemic hemisphere of the MCAo+scrambled group. In contrast, there was no interhemispheric difference in the number of retrogradely-labeled SNc and VTA cells of MCAo+mir363-3p treated animals. Our results support a therapeutic role for mir363-3p for long-term stroke disability.


Collagen Sequence Analysis Reveals Evolutionary History of Extinct West Indies Nesophontes (Island-Shrews).
Ancient biomolecule analyses are proving increasingly useful in the study of evolutionary patterns, including extinct organisms. Proteomic sequencing techniques complement genomic approaches, having the potential to examine lineages further back in time than achievable using ancient DNA, given the less stringent preservation requirements. In this study, we demonstrate the ability to use collagen sequence analyses via proteomics to assist species delimitation as a foundation for informing evolutionary patterns. We uncover biogeographic information of an enigmatic and recently extinct lineage of Nesophontes across their range on the Caribbean islands. First, evolutionary relationships reconstructed from collagen sequences reaffirm the affinity of Nesophontes and Solenodon as sister taxa within Solenodonota. This relationship helps lay the foundation for testing geographical isolation hypotheses across islands within the Greater Antilles, including movement from Cuba toward Hispaniola. Second, our results are consistent with Cuba having just two species of Nesophontes (N. micrus and N. major) that exhibit intrapopulation morphological variation. Finally, analysis of the recently described species from the Cayman Islands (N. hemicingulus) indicates that it is a closer relative to N. major rather than N. micrus as previously speculated. This proteomic sequencing improves our understanding of the origin, evolution, and distribution of this extinct mammal lineage, particularly with respect to the approximate timing of speciation. Such knowledge is vital for this biodiversity hotspot, where the magnitude of recent extinctions may obscure true estimates of species richness in the past.


Protective Effects of Acupuncture Against Gentamicin-Induced Ototoxicity in Rats: Possible Role of Neurotrophin-3.
BACKGROUND The aim of this study was to investigate the protective effects of acupuncture against gentamicin-induced ototoxicity and explore the possible protective role of neurotrophin-3 (NT-3). MATERIAL AND METHODS Twenty-four rats were divided randomly into 4 groups: control group, gentamicin group, neitinggong group, and tinggong group. Rats in the gentamicin, neitinggong, and tinggong groups received intraperitoneal injection of gentamicin (100 mg/kg) for 14 consecutive days. Rats in the neitinggong and tinggong groups further received acupuncture at neitinggong or tinggong acupoints once every 2 days for 20 days. Rats in the control group received intraperitoneal injection of saline. Auditory brainstem response (ABR) was tested in all rats on the day before treatment (day 0), and again on day 14 and day 20 to determine the average threshold value of ABR for each treatment group. The expression of NT-3 in the cochlear nucleus and the inferior colliculus nucleus were detected by immunohistochemical staining. RESULTS The average threshold value of ABR was significantly higher in the gentamicin group as compared with that of the control group on day 14 (P<0.05). On day 20, the average threshold values of ABR in the neitinggong and tinggong groups were significantly lower than that of the gentamicin group (P<0.05). No statistically significant differences in NT-3 expression in the cochlear nucleus were observed among the groups (P>0.05). However, the expression of NT-3 in the inferior colliculus nucleus in both the neitinggong and tinggong groups was significantly higher than that of the gentamicin group (P<0.01). CONCLUSIONS A decrease in NT-3 expression in the inferior colliculus nucleus may contribute to gentamicin-induced ototoxicity in rats. Acupuncture at neitinggong or tinggong acupoints effectively improved hearing, which was attributed partially to the rescue of NT-3 expression in the inferior colliculus nucleus. Therefore, preserving NT-3 expression in the auditory system may be a viable strategy to counteract gentamicin-induced ototoxicity.


Determination of rutin in cigarette tobacco, filters, mainstream smoke and burned ash of different branded cigarettes by high performance liquid chromatography.
Tobacco consists of at least 3,800 chemical constituents. Among them, rutin is an important polyphenolic secondary metabolite in tobacco, which has positive actions such as antiallergic, anti-inflammatory and vasoactive, antitumor, antibacterial, antiviral and anti-protozoal properties. A high performance liquid chromatography method was used to analyze rutin in tobacco and filters, mainstream smoke, and burned ash of ten varieties of cigarettes made in China. The chromatographic analysis was performed on a Hypersil ODS2 column with a gradient elution of acetonitrile and water at a flow rate of 1.0 mL/min. Detection was carried out at 350 nm using a photodiode array detector. The calibration curves for the determination of analytes showed good linearity over the investigated ranges (R2 > 0.9998). Precision and reproducibility were evaluated by six replicated analyses, and the R.S.D. values were less than 0.59% and 1.53%. The recoveries were between 98.47 and 100.84%. Under the optimized conditions, namely 45 mL/g of solvent to solid ratio, 30 min of extraction time and 200 W of ultrasound power, the concentrations of rutin in tobacco and filter, mainstream smoke, burned ash of different brands cigarettes were 10.20-63.98, 0.10-0.32, 0.06-0.16 and 0 μg/per cigarette, respectively.


Novel control motif cluster in the IgH delta-gamma 3 interval exhibits B cell-specific enhancer function in early development.
The majority of the human Ig heavy chain (IgH) constant (C) region locus has been cloned and mapped. An exception is the region between C delta and C gamma 3, which is unstable and may be a recombination hot spot. We isolated a pBAC clone (pHuIgH3'delta-gamma 3) that established a 52-kb distance between C delta and C gamma 3. Sequence analysis identified a high number of repeat elements, explaining the instability of the region, and an unusually large accumulation of transcription factor-binding motifs, for both lymphocyte-specific and ubiquitous transcription activators (IKAROS, E47, Oct-1, USF, Myc/Max), and for factors that may repress transcription (Delta EF1, Gfi-1, E4BP4, C/EBP beta). Functional analysis in reporter gene assays revealed the importance of the C delta-C gamma 3 interval in lymphocyte differentiation and identified independent regions capable of either enhancement or silencing of reporter gene expression and interaction with the IgH intron enhancer E mu. In transgenic mice, carrying a construct that links the beta-globin reporter to the novel delta-gamma 3 intron enhancer (E delta-gamma 3), transgene transcription is exclusively found in bone marrow B cells from the early stage when IgH rearrangement is initiated up to the successful completion of H and L locus recombination, resulting in Ab expression. These findings suggest that the C delta-C gamma 3 interval exerts regulatory control on Ig gene activation and expression during early lymphoid development.


Paradoxical effects of pyrazinoate and nicotinate on urate transport in dog renal microvillus membranes.
The effects of pyrazinoate and nicotinate on urate transport in microvillus membrane vesicles isolated from canine renal cortex were evaluated. An outwardly directed gradient of pyrazinoate stimulated uphill urate accumulation, suggesting urate-pyrazinoate exchange. An inside-alkaline pH gradient stimulated uphill pyrazinoate accumulation, which suggested pyrazinoate-OH- exchange. Pyrazinoate-OH- exchange and urate-OH- exchange were similarly sensitive to inhibitors, implying that both processes occur via the same transport system. In addition, an inward Na+ gradient stimulated uphill pyrazinoate accumulation, suggesting Na+-pyrazinoate cotransport. Inhibitor studies demonstrated that Na+-pyrazinoate cotransport takes place via the same pathway that mediates Na+-lactate cotransport in these membrane vesicles. Previously we found that urate does not share this Na+-dependent cotransport pathway. Nicotinate inhibited transport of pyrazinoate by the anion exchange pathway and the Na+ cotransport pathway, suggesting that it is a substrate for both transport systems. Finally, in the presence of an inward Na+ gradient, low doses of pyrazinoate or nicotinate stimulated urate uptake, and higher doses of pyrazinoate or nicotinate inhibited urate accumulation, thereby mimicking in vitro the paradoxical effects of drugs on renal urate excretion that have been observed in vivo. These findings indicate that the paradoxical effect of uricosuric drugs at low doses to cause urate retention may result at least in part from stimulation of urate reabsorption across the luminal membrane of the proximal tubular cell.


Minimally Invasive Incision and Drainage Technique in the Treatment of Simple Subcutaneous Abscess in Adults.
A minimally invasive (MI) approach using small incisions and vessel loops for drainage of simple perianal abscesses has been described in the pediatric population with decreased postoperative pain and comparable results to the traditional incision and drainage (I&D). The hypothesis was MI I&D will yield similar outcomes in adults. Patients who underwent I&D of perianal abscesses at an urban hospital from January 2008 to December 2015 were identified by Current Procedural Terminology code. Patients below 18 years of age, with inflammatory bowel diseases, or fistulae were excluded. Recurrences, readmissions, operative time, length of stay, complications, and costs were compared. There were 47 traditional and 96 MI I&D with no significant differences in demographics, average body mass index, and abscess size. No significant differences were noted in recurrences, readmissions, length of stay, operative time, or costs (P > 0.05). Postoperative complications occurred more frequently in the traditional group (P < 0.01) with a lower rate of follow-up (P < 0.05). MI I&D for simple anal abscesses in adults is associated with better compliance and fewer complications than the traditional approach. Although further studies are needed to determine if MI I&D confers superiority, this approach should be considered as first-line treatment for uncomplicated perirectal abscesses in adults.


Evaluation of Fracture Strength after Repair of Cervical External Resorption Cavities with Different Materials.
The aim was to evaluate the stress distributions on dentin and repair materials caused by static force applied to teeth, with cervical external root resorption (CER) after repair with different materials using finite element analysis. This study was performed with the 3-dimensional finite element analysis method. Access cavity, root canal cavity dimensions, and supporting tissues other than cementum were modeled in the maxillary central tooth. The CER cavity was created on the labial side of the tooth model. The coronal side of the resorption cavity was restored with composite, and the radicular side with different materials (MTA, Biodentine, BioAggregate, calcium-enriched cement [CEM], glass ionomer cement [GIC], and resin-modified glass ionomer cement [RMGIC]). A static force of 300 N was applied to the palatal surface of the crown at an angle of 135° to the long axis of the tooth. The stress distributions in dentin and repair materials were analyzed. The highest stress in dentin was seen in the fFigmodel with unrepaired CER. In the models repaired with MTA, GIC, and RMGIC, von Mises stress values in dentin were greater than for repairs with Biodentine, BioAggregate, and CEM materials. The von Mises stress on the repair materials applied to the root were highest for the BioAggregate material. This was followed by CEM, Biodentine, MTA, RMGIC, and GIC materials, respectively. The repair of CER in the tooth significantly decreased the stress values in dentin. Biodentine, BioAggregate, and CEM absorbed more force and caused less stress to be transmitted to dentin compared to MTA, GIC, and RMGIC.


Non-Equilibrium Thermodynamics View on Kinetics of Autocatalytic Reactions-Two Illustrative Examples.
Autocatalytic reactions are in certain contrast with the linear algebra of reaction stoichiometry, on which rate equations respecting the permanence of atoms are constructed. These mathematical models of chemical reactions are called conservative. Using a non-equilibrium thermodynamics-based theory of chemical kinetics, it is shown how to introduce autocatalytic step into such (conservative) rate equation properly. Further, rate equations based on chemical potentials or affinities are derived, and conditions for the consistency of rate equations with the entropic inequality (the second law of thermodynamics) are illustrated. The theory illustrated here can be viewed as a tool for verifying and generalizing traditional mass-action kinetics by means of modern non-equilibrium thermodynamics, which is able to deal also with such rather problematic cases.


Cigarette smoking and metallothionein expression in invasive breast carcinomas.
Studies indicate that smoking is significantly related to breast cancer mortality. One hypothesis is that this association is due to the elevated expression of proteins associated with resistance to cancer therapies. The metallothioneins (MTs) are a family of proteins that appear to play a role in conferring resistance to certain cancer therapies. This study was carried out to assess whether smoking was associated with MT expression in breast carcinomas. Archival breast tissues with accompanying clinical and epidemiological information were collected from three different cancer centers for 123 women diagnosed with invasive breast cancer. MT expression was assessed using immunohistochemical procedures and semi-quantified using an immunoreactivity score that was obtained by multiplying the percentage of MT-positive tumor cells by MT staining intensity. The results showed that 27.6% of the women were current smokers. Among women whose tissues were collected at the cancer center where enrolled women had primarily early stage, low grade breast cancer, smokers had increased odds, although not significantly, of having a MT-positive tumor compared to non-smokers, independent of cancer stage. This association was not observed among the women whose tissues were collected from the other cancer centers. These findings suggest that among specific groups of women, smoking at the time of breast cancer diagnosis may be associated with an increase in breast tissue MT.


Immunotherapy for Guillain-Barré syndrome: a systematic review.
Guillain-Barré syndrome (GBS) is an acute inflammatory disorder of the peripheral nervous system thought to be due to autoimmunity for which immunotherapy is usually prescribed. To provide the best evidence on which to base clinical practice, we systematically reviewed the results of randomized trials of immunotherapy for GBS. We searched the Cochrane Library, MEDLINE and EMBASE in July 2006 and used the methods of the Cochrane Neuromuscular Disease Group to extract and synthesize data. Almost all trials used a 7-point disability grade scale. In four trials with altogether 585 severely affected adult participants, those treated with plasma exchange (PE) improved significantly more on this scale 4 weeks after randomization than those who did not, weighted mean difference (WMD) -0.89 (95% confidence interval (CI) -1.14 to -0.63). In five trials with altogether 582 participants, the improvement on the disability grade scale with intravenous immunoglobulin (IVIg) was very similar to that with PE, WMD -0.02 (95% CI -0.25 to 0.20). There was also no significant difference between IVIg and PE for any of the other outcome measures. In one trial with 148 participants, following PE with IVIg did not produce significant extra benefit. Limited evidence from three open trials in children suggested that IVIg hastens recovery compared with supportive care alone. Corticosteroids were compared with placebo or supportive treatment in six trials with altogether 587 participants. There was significant heterogeneity in the analysis of these trials which could be accounted for by analysing separately four small trials of oral corticosteroids with altogether 120 participants, in which there was significantly less improvement after 4 weeks with corticosteroids than without, WMD -0.82 (95% CI -0.17 to -1.47), and two large trials of intravenous methylprednisolone with altogether 467 participants, in which there was no significant difference between corticosteroids and placebo WMD -0.17 (95% CI 0.06 to -0.39). None of the treatments significantly reduced mortality. Since approximately 20% of patients die or have persistent disability despite immunotherapy, more research is needed to identify better treatment regimens and new therapeutic strategies.


Use of beryllium-7 to document soil redistribution following forest harvest operations.
Rapid and reliable methods for documenting soil erosion associated with forest harvest operations are needed to support the development of best management practices for soil and water conservation. To address this need, the potential for using 7Be measurements to estimate patterns and amounts of soil redistribution associated with individual post-harvest events was explored. The 7Be technique, which was originally developed for use on agricultural land, was employed to estimate soil redistribution associated with a period of heavy rainfall within a harvested forest area located in the Lake Region of Chile (39 degrees 44'7'' S, 73 degrees 10'39'' W; 22% slope; and mean annual rainfall 2300 mm yr(-1)). The results provided by the 7Be technique were validated against direct measurements of soil gain or loss during the same period obtained using erosion pins. The information produced by the two approaches was similar. The results of this study demonstrate the potential for using 7Be measurements to document event-based erosion in recently harvested forest areas.


Recent progress in MoS2 nanostructures for biomedical applications: Experimental and computational approach.
In the category of 2D materials, MoS2 a transition metal dichalcogenide, is a novel and intriguing class of materials with interesting physicochemical properties, explored in applications ranging from cutting-edge optoelectronic to the frontiers of biomedical and biotechnology. MoS2 nanostructures an alternative to heavy toxic metals exhibit biocompatibility, low toxicity and high stability, and high binding affinity to biomolecules. MoS2 nanostructures provide a lot of opportunities for the advancement of novel biosensing, nanodrug delivery system, electrochemical detection, bioimaging, and photothermal therapy. Much efforts have been made in recent years to improve their physiochemical properties by developing a better synthesis approach, surface functionalization, and biocompatibility for their safe use in the advancement of biomedical applications. The understanding of parameters involved during the development of nanostructures for their safe utilization in biomedical applications has been discussed. Computational studies are included in this article to understand better the properties of MoS2 and the mechanism involved in their interaction with biomolecules. As a result, we anticipate that this combined experimental and computational studies of MoS2 will inspire the development of nanostructures with smart drug delivery systems, and add value to the understanding of two-dimensional smart nano-carriers.


Influence of image acquisition parameters on CT artifacts and polyp depiction in spiral CT colonography: in vitro evaluation.
To quantify the effects of spiral computed tomographic (CT) acquisition parameters on the magnitude of three-dimensional (3D) rippling artifacts and polyp depiction. An in vitro colon phantom was constructed with air-filled acrylic cylinders that contained synthetic polyps of 3-13 mm. The phantom was submerged in fluid and positioned at four angles of inclination relative to the z axis. Image data were acquired at collimation and pitch combinations of 3 mm and 1.67 and 5 mm and 1.6, respectively. Rippling artifacts were quantified by measuring the longitudinal variation of in-plane phantom edge width, and the influence of these artifacts on the depiction of pedunculated and sessile polyps was assessed qualitatively. The in-plane magnitude of the rippling artifact was a function of the angle of inclination relative to the longitudinal axis and the table increment. The through-plane periodicity of the artifact was equal to one-half the table increment. The table increment and angle of inclination of the surface of the object relative to the z axis determine the periodicity and magnitude of the rippling artifact at 3D spiral CT colonography. Although the depiction of small pedunculated polyps was not compromised, some sessile polyps were degraded by the artifact.


Effects of exposure to selective serotonin reuptake inhibitors during pregnancy on serotonergic symptoms in newborns and cord blood monoamine and prolactin concentrations.
Selective serotonin reuptake inhibitors (SSRIs) have gained wide acceptance in the treatment of mental disorders in pregnant women, but there seems to be an increased risk for neonatal adaptation problems after exposure to SSRIs in late pregnancy. We aimed to investigate the perinatal sequelae of infants exposed to SSRIs during their fetal life and the relationship of these symptoms to the cord blood monoamine and prolactin concentrations. We conducted a prospective, controlled, follow-up study with 20 mothers taking 20 to 40 mg/d of either citalopram or fluoxetine for depression (n = 10) or panic disorder (n = 10) and their infants and 20 matched controls not receiving psychotropic medication for confounding obstetric characteristics. Maternal cord blood and infant citalopram, fluoxetine, and norfluoxetine, cord blood monoamine and metabolite, and prolactin concentrations were measured. The newborns underwent standard clinical examination and specific assessment of serotonergic symptoms during the first 4 days of life and at the ages of 2 weeks and 2 months. There was a statistically significant (P =.008, V = 15, n = 20 for both groups), 4-fold difference in the serotonergic symptom score during the first 4 days of life between the SSRI group and the control group. The SSRI-exposed infants had significantly lower cord blood 5-hydroxyindoleacetic acid (5-HIAA) concentrations (P =.02, t31 = 2.57) compared with the control group. A significant inverse correlation (rs = -0.66, P =.007, n = 15) was seen between the serotonergic symptom score and the umbilical vein 5-HIAA concentrations in the SSRI-exposed but not the control infants. Infants exposed to SSRIs during late pregnancy are at increased risk for serotonergic central nervous system adverse effects, and the severity of these symptoms is significantly related to cord blood 5-HIAA levels.


Radiorespirometric studies in genus Neisserai. I. The catabolism of glucose.
The catabolism of glucose in selected Neisseria species was studied by radiorespirometry. The Entner-Doudoroff and pentose phosphate pathways were operating in all species, the greater part of the substrate being routed through the former, somewhat dependent on the medium used. Acetate was oxidized via the tricarboxylic acid cycle. In all species, a fraction of the triose was recycled through fructose phosphates to glucose 6-phosphate. Phosphate inhibited the oxidation of acetate. In media devoid of phosphate and sodium (N. meningitidis and N. gonorrhoeae) or of phosphate and potassium (other saccharolytic Neisseria), the conversion of triose to pyruvate was inhibited. In these media the catabolism of glucose proceeded slowly, and no substrate was used for biosynthetic purposes. The results point to a difference in the regulation of glucose metabolism in pathogenic and non-pathogenic Neisseria.


A key ecological trait drove the evolution of biparental care and monogamy in an amphibian.
Linking specific ecological factors to the evolution of parental care pattern and mating system is a difficult task of key importance. We provide evidence from comparative analyses that an ecological factor (breeding pool size) is associated with the evolution of parental care across all frogs. We further show that the most intensive form of parental care (trophic egg feeding) evolved in concert with the use of small pools for tadpole deposition and that egg feeding was associated with the evolution of biparental care. Previous research on two Peruvian poison frogs (Ranitomeya imitator and Ranitomeya variabilis) revealed similar life histories, with the exception of breeding pool size. This key ecological difference led to divergence in parental care patterns and mating systems. We present ecological field experiments that demonstrate that biparental care is essential to tadpole survival in small (but not large) pools. Field observations demonstrate social monogamy in R. imitator, the species that uses small pools. Molecular analyses demonstrate genetic monogamy in R. imitator, the first example of genetic monogamy in an amphibian. In total, this evidence constitutes the most complete documentation to date that a single ecological factor drove the evolution of biparental care and genetic and social monogamy in an animal.


Polymerization-induced epitaxy: scanning tunneling microscopy of a hydrogen-bonded sheet of polyamide on graphite.
A molecularly thin film of a two-dimensional polymer network formed by hydrogen bonding was synthesized and investigated with scanning tunneling microscopy. Poly(in-caprolactam) (nylon 6) was epitaxially grown on the basal plane of graphite and an ultrathin film of the polymer was obtained after the bulk materials had been washed away with solvents. The polymer chain has a planar, all-trans conformation and adjacent chains run in the antiparallel direction. This produces complete pairing of hydrogen bonding groups, with each amide group lying on a straight line perpendicular to the polymer backbone. This hydrogen-bonded sheet is oriented so that each polymer backbone lies in the (1010) direction on the graphite hexagonal lattice, as opposed to the (1120) direction taken by other paraffinic molecules studied so far. This experiment shows that hydrogen bonding can be used to control the orientation of macromolecules in two dimensions.


Dental health and cognitive impairment in an English national survey population.
To investigate the association between dental health and cognitive impairment and to examine the extent to which dental status accounts for the association between cognitive impairment and low body mass index (BMI) in a national survey sample. A secondary analysis of data from the Health Survey for England 2000. A nationally representative cross-sectional population survey. Two thousand four hundred sixty-three adults aged 65 and older living in private households and 1,569 adults aged 65 and older living in care homes. Data collected by interview (self-reported or by proxy) included age, sex, level of education, disability, BMI, dental status, and cognitive function (Abbreviated Mental Test Score). Less than half of the community sample (40.4%) and 67.9% of the care home sample were edentulous; lack of teeth was significantly associated with cognitive impairment (odds ratio=3.59, 95% confidence interval=2.36-5.47). This association remained strong after adjustment for other covariates only in the community sample. Cognitive impairment was associated with lower BMI in both samples, but dental status did not explain this. Poor dentition is associated with cognitive impairment. Nutritional status in people with cognitive impairment is recognized to be at risk. Although dental health did not account for the association between cognitive impairment and low BMI in this sample, other possible nutritional consequences require further evaluation.


Technical note: High-throughput method for antifungal activity screening in a cheese-mimicking model.
In this study, we developed a high-throughput antifungal activity screening method using a cheese-mimicking matrix distributed in 24-well plates. This method allowed rapid screening of a large variety of antifungal agent candidates: bacterial fermented ingredients, bacterial isolates, and preservatives. Using the proposed method, we characterized the antifungal activity of 44 lactic acid bacteria (LAB) fermented milk-based ingredients and 23 LAB isolates used as protective cultures against 4 fungal targets (Mucor racemosus, Penicillium commune, Galactomyces geotrichum, and Yarrowia lipolytica). We also used this method to determine the minimum inhibitory concentration of a preservative, natamycin, against 9 fungal targets. The results underlined the strain-dependency of LAB antifungal activity, the strong effect of fermentation substrate on this activity, and the effect of the screening medium on natamycin minimum inhibitory concentration. Our method could achieved a screening rate of 1,600 assays per week and can be implemented to evaluate antifungal activity of microorganisms, fermentation products, or purified compounds compatible with dairy technology.


In vitro activity of the new triazole voriconazole (UK-109,496) against opportunistic filamentous and dimorphic fungi and common and emerging yeast pathogens.
The in vitro antifungal activity of a new triazole derivative, voriconazole, was compared with those of itraconazole and amphotericin B against 67 isolates of Aspergillus flavus, Aspergillus fumigatus, Bipolaris spp., Fusarium oxysporum, Fusarium solani, Pseudallescheria boydii, Rhizopus arrhizus, Blastomyces dermatitidis, Histoplasma capsulatum, and Sporothrix schenckii. The in vitro activities of voriconazole were also compared with those of amphotericin B, fluconazole, and itraconazole against 189 isolates of emerging and common yeast pathogens of Blastoschizomyces capitatus, Candida (13 species), Cryptococcus neoformans, Hansenula anomala, Rhodotorula rubra, Saccharomyces cerevisiae, Sporobolomyces salmonicolor, and Trichosporon beigelii. MICs were determined according to a procedure under evaluation by the National Committee for Clinical Laboratory Standards (NCCLS) for broth microdilution testing of filamentous fungi and by the NCCLS M27-A broth microdilution method for yeasts. The in vitro activities of voriconazole were similar to or better than those of itraconazole and amphotericin B against Aspergillus spp., Fusarium spp., and P. boydii as well as against B. dermatitidis and H. capsulatum. The activities of voriconazole were also comparable to or better than those of amphotericin B, fluconazole, and itraconazole against most species of yeasts tested. Exceptions were certain isolates of R. rubra and S. salmonicolor. These results suggest that voriconazole has a wide spectrum of activity in vitro; its effectiveness in the treatment of human mycoses is under evaluation in clinical trials.


Optimizing the implementation of practice improvement modules in training: lessons from educators.
The American Board of Internal Medicine approved the use of Practice Improvement Modules (PIMs) to help training programs teach and assess practice-based learning and improvement (PBLI) and systems-based practice (SBP). We surveyed individuals who ordered a PIM in a residency or fellowship training program between June 2006 and August 2009. The 43 programs that volunteered to participate completed a 30-minute anonymous online survey. Program directors or associate program directors led the PIM process in 30 programs (70%). Trainees' degrees of involvement in PIMs were highly variable between programs, and several respondents felt that trainees were either not sufficiently engaged or not engaged with enough consistency. The most common activity for trainee involvement was data collection through patient surveys or chart review, although only 17 programs (40%) provided protected time for this activity. Few trainees participated in higher level activities such as data analysis or identification for areas of improvement or were given leadership roles; yet most respondents reported that completing the PIM helped trainees learn basic principles of QI and develop competence in PBLI and SBP and that PIM completion improved the program's ability to develop QI initiatives and resulted in program or institutional improvements, including sustainable improvement in patient care. Most respondents reported that the outcome warranted the effort to complete PIMs. PIMs may be a valuable but underused educational experience for trainees as well as training programs. Focusing on particular themes and facets of PIMs may facilitate implementation.


[Treatment of benign tumors in thoracic spinal canal by modified replanting posterior ligament complex applying piezoelectric osteotomy].
To investigate the feasibility and effectiveness of modified replanting posterior ligament complex (PLC) applying piezoelectric osteotomy in the treatment of primary benign tumors in thoracic spinal canal. The clinical data of 38 patients with primary benign tumors in thoracic spinal canal between March 2014 and March 2016 were retrospectively analyzed. There were 16 males and 22 females, aged from 21 to 72 years (mean, 47.1 years). The disease duration ranged from 6 to 57 months (mean, 32.6 months). Pathological examination showed 24 cases of schwannoma, 6 cases of meningioma, 4 cases of ependymoma, 2 cases of lipoma, and 2 cases of dermoid cyst. The lesions located in 18 cases of single segment, 15 cases of double segments, and 5 cases of three segments. The length of the tumors ranged from 0.7 to 6.5 cm. There were boundaries between the tumors and the spinal cord, cauda equina, and nerve roots. The preoperative Japanese Orthopaedic Association (JOA) score was 12.2±2.3 and the thoracic Cobb angle was (11.7±2.7)°. Modified PLC replantation and microsurgical resection were performed with piezoelectric osteotomy. Continuity of uniside supraspinal and interspinous ligaments were preserved during the operation. The PLC was exposed laterally. After removing the tumors under the microscope, the pedicled PLC was replanted in situ and fixed with bilateral micro-reconstruction titanium plate. X-ray film, CT, and MRI examinations were performed to observe spinal stability, spinal canal plasty, and tumor resection after operation. The effectiveness was evaluated by JOA score. The operation time was 56-142 minutes (mean, 77.1 minutes). The intraoperative blood loss was 110-370 mL (mean, 217.2 mL). The tumors were removed completely and the incisions healed well. Three cases complicated with cerebrospinal fluid leakage, and there was no complications such as spinal cord injury and infection. All the 38 patients were followed up 24-28 months (mean, 27.2 months). There was no internal fixation loosening, malposition, or other related complications. At last follow-up, X-ray films showed no sign of kyphosis and instability. CT showed no displacement of vertebral lamina and reduction of secondary spinal canal volume, and vertebral lamina healed well. MRI showed no recurrence of tumors. At last follow-up, the thoracic Cobb angle was (12.3±4.1)°, showing no significant difference when compared with preoperative value ( t=0.753, P=0.456). JOA score increased to 23.7±3.8, showing significant difference when compared with preoperative value ( t=15.960, P=0.000). Among them, 14 cases were excellent, 18 were good, 6 were fair, and the excellent and good rate was 84.2%. Modified replanting PLC applying piezoelectric osteotomy and micro-reconstruction with titanium plate for the primary benign tumors in thoracic spinal canal can reconstruct the anatomy of the spinal canal, enable patients to recover daily activities quickly. It is an effective and safe treatment.


HIV-1 Nef Changes the Proteome of T Cells Extracellular Vesicles Depleting IFITMs and Other Antiviral Factors.
Extracellular vesicles (EVs) are biomolecule carriers for intercellular communication in health and disease. Nef is a HIV virulence factor that is released from cells within EVs and is present in plasma EVs of HIV-1 infected individuals. We performed a quantitative proteomic analysis to fully characterize the Nef-induced changes in protein composition of T cell-derived EVs and identify novel host targets of HIV. Several proteins with well-described roles in infection or not previously associated with HIV pathogenesis were specifically modulated by Nef in EVs. Among the downregulated proteins are the interferon-induced transmembrane 1, 2, and 3 (IFITM1-3) proteins, broad-spectrum antiviral factors known to be cell-to-cell transferable by EVs. We demonstrate that Nef depletes IFITM1-3 from EVs by excluding these proteins from the plasma membrane and lipid rafts, which are sites of EVs biogenesis in T cells. Our data establish Nef as a modulator of EVs' global protein content and as an HIV factor that antagonizes IFITMs.


Relationship Between Polypharmacy and Quality of Life Among People in 24 Countries Living With HIV.
People living with HIV (PLHIV) have greater risk of having multiple health conditions. We measured the relationship between increased medication and overall quality of life among PLHIV from 24 countries. We analyzed data for 2,112 adult PLHIV on antiretroviral therapy (ART) in 24 countries who completed the 2019 Positive Perspectives survey. Polypharmacy was defined as taking 5 or more pills a day or currently taking medications for 5 or more conditions. Outcomes were self-rated overall health, treatment satisfaction, and self-reported virologic control. New treatment concerns were issues not prioritized at ART initiation but now deemed paramount. Data were analyzed with descriptive and multivariable statistics. Overall prevalence of polypharmacy was 42.1%. People reporting polypharmacy had significantly poorer health outcomes independent of existing comorbidities; their odds of treatment satisfaction, optimal overall health, and virologic control were lower by 27.0% (adjusted odds ratio [AOR] = 0.73; 95% CI, 0.59-0.91), 36.0% (AOR = 0.64; 95% CI, 0.53-0.78), and 46.0% (AOR = 0.54, 95% CI, 0.42-0.70), respectively, compared with those without polypharmacy (all P < .05). Most PLHIV (56.6%) were concerned about taking more medicines as they age, and 73.1% were interested in ARTs with fewer medicines. Top reasons for switching ART among those who had ever switched (n = 1,550) were to reduce severity and frequency of side effects (45.3%), number of pills (35.0%), or number of medicines (26.8%). People reporting polypharmacy had significantly higher odds of having new concerns relative to when they initiated ART, regarding risks of drug-drug interactions (AOR = 1.32; 95% CI, 1.02-1.71) and side effects (AOR = 1.31; 95% CI, 1.02-1.68). Polypharmacy was associated with poorer health-related outcomes among PLHIV. Many PLHIV expressed concerns about side effects of ART. Clinicians should carefully consider patient preferences, comorbidities, and drug profiles when prescribing ART.


Use of selective serotonin reuptake inhibitors during pregnancy and risk of major and cardiovascular malformations: an update.
General consensus exists about the need to avoid drug intake as much as possible during pregnancy due to the lack of thorough evidence about the safety of pharmacologic treatments during gestation for both mothers and fetuses. In this respect, the overall safety profile of selective serotonin reuptake inhibitors (SSRIs) in pregnancy remains unclear. This article reviews current evidence about the safety of each SSRI during pregnancy in order to describe their specific teratogenic potential, with a particular focus on major and cardiovascular malformations, and to verify whether such toxicity can be considered as a class effect. The literature review included controlled studies and meta-analyses (retrieved using PsychINFO, EMBASE, and Medline from January 1966 to May 2010) from which the risk of major and/or cardiovascular malformations associated with a specific SSRI (ie, fluoxetine, paroxetine, sertraline, citalopram, escitalopram, and fluvoxamine) could be estimated. Although there is evidence to support the association between birth defects and first-trimester exposure to paroxetine, findings from the studies reviewed suggest a teratogenic potential of the whole SSRI class, consistent with preclinical evidence. These teratogenic effects are mainly in the heart region, and they are often described as septal defects. It may be suggested that the higher frequency of teratogenic effects reported for paroxetine might depend on specific pharmacologic features of this drug compared with other SSRIs, although it is difficult to test this hypothesis. It is noteworthy that current evidence on SSRI teratogenicity stems from studies affected by several methodological weaknesses (ie, lack of investigations using control groups of untreated depressed mothers, confounding by indication, and recall bias). Accordingly, we are not yet able to rule out the possibility that positive associations, as determined in some studies, result from analyses of poor quality.


Correlation of cerebral hemodynamic changes during mental activity and recovery after stroke.
To investigate the correlation between changes in cerebral functional activity during mental engagement and the potential for neurologic recovery after stroke. Transcranial Doppler ultrasonography (TCD) makes it possible to detect the dynamic adjustment of cerebral perfusion related to functional neuronal changes. TCD monitoring of flow velocity changes in the middle cerebral artery of 29 ischemic stroke patients was performed during an object recognition task. The study took place within 4 weeks from stroke onset. Based on recovery occurring after 2 months, the patients were divided into four groups depending on the side of hemispheric lesion and the presence or absence of neurologic recovery. Ten healthy subjects served as control subjects. During the recognition task, control subjects showed a bilateral increase in flow velocity with respect to the rest phase (right side, 7.02 +/- 1.3%; left side, 6.65 +/- 1. 1%), with no side-to-side difference. In patients who experienced recovery, a similar pattern of bilateral activation was observed, irrespective of the side of the lesion. Conversely, in patients with no recovery, the increase of flow velocity was significantly higher on the side contralateral to the brain lesion (p < 0.0001) with respect to the lesion side. Performance during the recognition task was comparable in the four groups of patients. These findings suggest that satisfactory recovery from a neurologic deficit requires the persistence of functional activity in the damaged hemisphere despite the presence of an anatomic lesion. The possibility of obtaining early prognostic indications with TCD may be relevant for an early selection of patients with the best probability of benefiting from rehabilitation therapy.


Treatment of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue with fludarabine: effect on tumor microenvironment.
Gastric Helicobacter pylori (HP) positive extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) develops during chronic antigenic stimulation with specific T-cell help. Chemotherapy that acts both on the malignant B-cells and on T-cells in the microenvironment, i.e. nucleoside analogs, might therefore be an attractive treatment. In 14 patients with gastric MALT lymphoma treated with fludarabine, alterations in T-cell subsets were studied in subsequent peripheral blood samples and in gastric biopsies. Treatment with fludarabine resulted in a steep decrease in T-cell subsets in peripheral blood samples. By contrast no decrease in T-cell populations was observed in subsequent gastric biopsy samples and a moderate increase was observed in relative infiltration with CD3 +, CD4 + and CD8 + cells. In addition an increase in density of FOXP3 + cells (i.e. Tregs) was seen (p = 0.047). These alterations in different T-cell subsets were not observed in gastric biopsy samples of patients treated with HP-eradication only.


Quantification of motion artifact rejection due to active electrodes and driven-right-leg circuit in spike detection algorithms.
Identification of spikes in the electroencephalogram (EEG) plays an important role during the diagnosis of neurological disorders such as epilepsy. Automatic spike detection (ASD) is attractive because it reduces the diagnostic time and improves objectivity of the scoring. Unfortunately, automatic detection is sometimes confounded by artifacts, particularly motion artifacts which can be frequent in ambulatory recording, in the ICU, when recording from restless patients or children, etc. EEG systems have recently been improved by using active electrodes and driven-right-leg circuits (DRL) to reduce motion artifacts. However, the performances of ASD algorithms, both with unimproved and improved EEG systems, are difficult to quantify in patients because of poor reproducibility of the results. In this paper, a test set-up was used to evaluate the performance of active electrodes and DRL and assess if they can be complemented or substituted by a spike detection algorithm in avoiding motion artifact. Results show that motion artifacts can largely degrade spike detection when a traditional EEG system is used, whereas an EEG fitted with active electrodes and a DRL allows high quality detection. When using a traditional EEG, the choice of a spike detection algorithm has a large influence on detection quality.


Oxytocin mitigates peripheral nerve damage via Nrf2 and irisin pathway.
Peripheral nerve injuries present challenges in achieving full functional restoration, necessitating effective therapeutic strategies. Oxytocin, known for its neuroprotective and anti-inflammatory properties, has shown potential in nerve recovery. This study aims to elucidate the role of oxytocin in nerve recovery via the nuclear factor erythroid 2-related factor 2 (Nrf2) and irisin pathways. Adult male Wistar rats (n=30) were subjected to surgical dissection of sciatic nerves and divided into Control, Surgery and Saline Group, and Surgery and Oxytocin (OT) group. Electromyographic (EMG) recordings, inclined plane tests, and histological assessments were conducted to evaluate nerve function, and Nerve growth factor (NGF) immunoexpression and axonal parameters were measured. Plasma irisin levels, nerve NGF, and Nrf2 levels were quantified. The Surgery and Saline Group exhibited impaired EMG latency, amplitude, and inclined plane score compared to Controls, while the Surgery and OT Group demonstrated improved outcomes. Histomorphometric analysis revealed increased NGF immunoexpression, axon number, diameter, and reduced fibrosis in the Surgery and OT Group. Plasma irisin levels were higher following oxytocin administration. Additionally, nerve NGF and Nrf2 levels were elevated in the Surgery and OT Group. OT administration mitigated nerve injury effects, promoting functional and histological improvements. Elevated NGF and Nrf2 levels, along with increased irisin, indicated the potential interplay of these pathways in enhancing nerve recovery. The results align with OT's neuroprotective and anti-inflammatory roles, suggesting its potential as a therapeutic intervention for nerve injuries. OT's positive impact on nerve recovery is associated with its modulation of Nrf2 and irisin pathways, which collectively enhance antioxidant defense and neurotrophic support and mitigate inflammation. These findings underline OT's potential as a therapeutic agent to enhance nerve regeneration and recovery. Further research is needed to elucidate the intricate molecular mechanisms and potential clinical applications of OT in nerve injury management.


Proximal bicarbonate reabsorption during Ringer and albumin infusions in the rat.
Several studies have clearly shown that extracellular volume expansion is associated with suppression of whole kidney bicarbonate reabsorption, although little is known concerning the single nephron correlates of this response. More recently, attention has also been focussed on bicarbonate transport in attempts to identify a possible role for this ion in enhancing the rate of net fluid efflux by proximal tubules. To further explore proximal tubular bicarbonate handling in the rat, we carried out recollection micropuncture studies to assess the effects of infusions of modified Ringer or salt-poor hyperoncotic human albumin. With stable levels of arterial PCO2, plasma [HCO3-] or plasma [K+], marked suppression of fractional HCO3- reabsorption occurred: during Ringer infusion fractional reabsorption fell by 31% (P less than 0.001) while during albumin infusion a decrease of 20% (P less than 0.001) was observed. Despite this, absolute net HCO3- reabsorptive rates did not change significantly. Simple and partial correlation analysis of single tubular responses revealed strong linkage effects between changes in absolute net reabsorptive rates for HCO3- and H2O in both types of infusion; the partial r was 0.91 (P less than 0.001) and 0.94 (P less than 0.001) during Ringer and albumin infusions, respectively. We conclude that under these free-flow conditions, Ringer and albumin infusions do not suppress absolute net HCO3- reabsorption by proximal tubules, and that strongly linked changes in absolute HCO3- and H2O fluxes are characteristic of both protocols.


A Description of COVID-19-Directed Therapy in Children Admitted to US Intensive Care Units 2020.
It is unclear how acute coronavirus disease 2019 (COVID-19)-directed therapies are used in children with life-threatening COVID-19 in US hospitals. We described characteristics of children hospitalized in the intensive care unit or step-down unit (ICU/SDU) who received COVID-19-directed therapies and the specific therapies administered. Between March 15, 2020 and December 27, 2020, children <18 years of age in the ICU/SDU with acute COVID-19 at 48 pediatric hospitals in the United States were identified. Demographics, laboratory values, and clinical course were compared in children who did and did not receive COVID-19-directed therapies. Trends in COVID-19-directed therapies over time were evaluated. Of 424 children in the ICU/SDU, 235 (55%) received COVID-19-directed therapies. Children who received COVID-19-directed therapies were older than those who did not receive COVID-19-directed therapies (13.3 [5.6-16.2] vs 9.8 [0.65-15.9] years), more had underlying medical conditions (188 [80%] vs 104 [55%]; difference = 25% [95% CI: 16% to 34%]), more received respiratory support (206 [88%] vs 71 [38%]; difference = 50% [95% CI: 34% to 56%]), and more died (8 [3.4%] vs 0). Of the 235 children receiving COVID-19-directed therapies, 172 (73%) received systemic steroids and 150 (64%) received remdesivir, with rising remdesivir use over the study period (14% in March/April to 57% November/December). Despite the lack of pediatric data evaluating treatments for COVID-19 in critically ill children, more than half of children requiring intensive or high acuity care received COVID-19-directed therapies.


Synthesis of heterocyclic compounds through palladium-catalyzed C-H cyclization processes.
Herein, we describe our development of synthetic methods for heterocyclic compounds based on the palladium-catalyzed carbon-hydrogen bond (C-H) functionalization/intramolecular carbon-heteroatom (nitrogen or sulfur) bond formation process. By this C-H cyclization method, we efficiently prepared various N-heterocycles, including indazoles, indoles, and 2-quinolinones, as well as S-heterocycles such as benzothiazoles and benzo[b]thiophenes. Yields are typically good to high and good functional-group tolerance is observed for each process, thereby indicating that the method provides a novel, highly applicable synthetic route to the abovementioned biologically important heterocyclic frameworks. As an application of this approach, an auto-tandem-type, one-pot process involving the oxidative Heck reaction and subsequent C-H cyclization using cinnamamides and arylboronic acids as starting materials in the presence of a palladium catalyst was also developed for the rapid construction of the 2-quinolinone nucleus.


Safety and Effectiveness of Oral Nutraceuticals for Treating Acne: A Systematic Review.
Patients with acne are interested in nutraceuticals as a potential treatment option. However, there is uncertainty regarding the efficacy and safety of these products. To evaluate the evidence for oral nutraceuticals in the treatment of acne. The PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science databases were searched from inception through January 30, 2023, to identify randomized clinical trials evaluating oral nutraceutical interventions (ie, vitamins and minerals, botanical extracts, prebiotics, and probiotics) in individuals with acne. Clinician-reported outcomes (eg, investigator global assessment, lesion counts), patient-reported outcomes (eg, quality of life), and adverse events were extracted from the included studies. The quality of evidence was assessed using the Cochrane Risk of Bias checklist tool for randomized clinical trials. Based on the Risk of Bias tool, articles were converted to Agency for Healthcare Research and Quality standards of good, fair, or poor quality. A total of 2582 abstracts were identified in the database search, 42 of which met inclusion criteria (a total of 3346 participants). Studies of fair or good quality showed the potential benefit of vitamins B5 and D, botanical extracts (green tea), probiotics, and ω-3 fatty acids in the treatment of acne. These interventions were most frequently associated with decreased lesion counts or improved investigator global assessment scores. Adverse effects were rare for most of the therapies evaluated, but gastrointestinal tract adverse effects were reported for zinc therapy. This systematic review suggests a possible role for nutraceutical supplements in the treatment of acne. Physicians should be prepared to discuss the evidence regarding the potential role of nutraceuticals with patients. Many studies were of small size, and future research should focus on larger randomized clinical trials to assess the utility of nutraceuticals in the treatment of acne.


Measurement of fruit and vegetable consumption with diet questionnaires and implications for analyses and interpretation.
Measurement error can have an important impact on the estimation of the true relation between diet and disease. The authors examined the performance of models regressing plasma vitamin C level on fruit and vegetable consumption and the effect of categorization of fruit and vegetable consumption on the association with plasma vitamin C. They used diet information reported by 4,487 participants in the Norfolk, United Kingdom, portion of the European Prospective Investigation into Cancer and Nutrition by means of a 7-day diet diary and a food frequency questionnaire (FFQ) (1993-1998). The authors found substantial differences in mean fruit and vegetable consumption assessed by the two diet instruments. Consumption estimated with the FFQ was about twice as high as that obtained with the 7-day diary, and the ranking of individuals according to estimates of fruit and vegetable consumption from the 7-day diary and the FFQ differed substantially. When fruit and vegetable consumption were categorized into quintiles, the two questionnaires produced similar associations of relative intake with plasma vitamin C, but estimation of the association of absolute intake with plasma vitamin C differed.


Endemic paragonimiasis in Africa.
Human paragonimiasis has been recorded in 4 West African countries but there is clear evidence of endemicity only in certain parts of Nigeria and Cameroon. In Nigeria, the dominant parasite species is Paragonimus uterobilateralis, while in Cameroon it is P. africanus. Both the fresh water crab Sudanonautes africanus and the land crab S. aubryi are proved vectors in Nigeria. Epidemiological studies using Paragonimus skin tests suggest an infection rate of between 5% and 10% in some endemic areas. African paragonimiasis, like its Asian counterpart, responds well to treatment with bithionol.


[Anisakidosis of the colon as a cause of acute abdomen].
We report a case of acute abdomen caused by the invasion of the ascending colon by larvae of Anisakis simplex in a 57 year-old-woman whose initial symptoms were colic abdominal pain, diarrhea and fever. The diagnosis was done by the histological study of the surgical specimen in which two parasites were morphologically identified in the submucosa. Although a causal relationship of the disease with the ingestion of crude fish could not be established initially, there were antecedents of ingestion of anchovy in vinegar (Engraulis encrasicholus) and dyspeptic symptoms for several months.


Seasonal ingestion of anthropogenic debris in an urban population of gulls.
Gulls are generalist seabirds, increasingly drawn to urban environments where many species take advantage of abundant food sources, such as landfill sites. Despite this, data on items ingested at these locations, including human refuse, is limited. Here we investigate ingestion of prey and anthropogenic debris items in boluses (regurgitated pellets) from Pacific Gulls (Larus pacificus). A total of 374 boluses were collected between 2018 and 2020 in Tasmania. Debris was present in 92.51% of boluses (n = 346), with plastic (86.63%, n = 324) and glass (64.71%, n = 242) being the most prominent types. An abundance of intact, household items (e.g., dental floss, food wrappers) suggest the gulls regularly feed at landfill sites. In addition, the boluses are deposited at a roosting site located within an important wetland, thus we propose that the gulls may be functioning as a previously unrecognised vector of anthropogenic debris from urban centres to aquatic environments.


Abnormal development of the hippocampal dentate gyrus in mice lacking the CXCR4 chemokine receptor.
We investigated the role of the CXCR4 chemokine receptor in development of the mouse hippocampus. CXCR4 mRNA is expressed at sites of neuronal and progenitor cell migration in the hippocampus at late embryonic and early postnatal ages. mRNA for stromal cell-derived factor 1 (SDF-1), the only known ligand for the CXCR4 receptor, is expressed close to these migration sites, in the meninges investing the hippocampal primordium and the primordium itself. In mice engineered to lack the CXCR4 receptor, the morphology of the hippocampal dentate gyrus (DG) is dramatically altered. Gene expression markers for DG granule neurons and bromodeoxyuridine labeling of dividing cells revealed an underlying defect in the stream of postmitotic cells and secondary dentate progenitor cells that migrate toward and form the DG. In the absence of CXCR4, the number of dividing cells in the migratory stream and in the DG itself is reduced, and neurons appear to differentiate prematurely before reaching their target. Our findings indicate a role for the SDF-1/CXCR4 chemokine signaling system in DG morphogenesis. Finally, the DG is unusual as a site of adult neurogenesis. We find that both CXCR4 and SDF-1 are expressed in the adult DG, suggesting an ongoing role in DG morphogenesis.


Exemestane and Its Active Metabolite 17-Hydroexemestane Induce UDP-Glucuronosyltransferase (UGT) 2B17 Expression in Breast Cancer Cells.
Exemestane (EXE) is an aromatase inhibitor indicated for endocrine therapy of breast cancer in postmenopausal women. The primary active metabolite of EXE, 17-hydroexemestane (17-HE), is inactivated via glucuronidation, mainly by UDP-glucuronosyltransferase 2B17 (UGT2B17). UGT2B17 also has a primary role in inactivation of endogenous androgens testosterone and dihydrotestosterone and may play an important role in regulation of breast and prostate tumor intracrinology. We recently reported that UGT2B17 could be induced by both estrogenic and androgenic ligands in breast cancer cells via binding of the estrogen receptor α (ERα) or the androgen receptor (AR) to a complex regulatory unit in the proximal UGT2B17 promoter. In this study we show that both EXE and 17-HE increase UGT2B17 mRNA levels in breast cancer MCF-7 and MDA-MB-453 cells, and increase glucuronidation of UGT2B17 substrates, including 17-HE and androsterone. Using antagonists of ERα and AR as well as inhibition mediated by small interfering RNA (siRNA) we demonstrate that EXE and 17-HE induce UGT2B17 expression primarily via the AR. This result is consistent with previous reports that 17-HE can act as an AR ligand. In vitro studies suggest that multiple steroid-responsive DNA elements within the proximal promoter are involved in the response to 17-HE-liganded AR. The up-regulation of UGT2B17 by EXE and 17-HE in breast cancer cells might enhance the local metabolism of 17-HE as well as that of endogenous androgens, hence impacting potentially on treatment outcomes.


Associations of the objective built environment along the route to school with children's modes of commuting: A multilevel modelling analysis (the SLIC study).
As active commuting levels continue to decline among primary schoolchildren, evidence about which built environmental characteristics influence walking or cycling to school remains inconclusive and is strongly context-dependent. This study aimed to identify the objective built environmental drivers of, and barriers to, active commuting to school for a multi-ethnic sample of 1,889 healthy primary schoolchildren (aged 5-11) in London, UK. Using cross-sectional multilevel ordered logistic regression modelling, supported by the spatial exploration of built environmental characteristics through cartography, the objective built environment was shown to be strongly implicated in children's commuting behaviour. In line with earlier research, proximity to school emerged as the prime variable associated with the choice for active commuting. However, other elements of the urban form were also significantly associated with children's use of active or passive modes of transport. High levels of accidents, crime and air pollution along the route to school were independently correlated with a lower likelihood of children walking or cycling to school. Higher average and minimum walkability and higher average densities of convenience stores along the way were independently linked to higher odds of active commuting. The significance of the relations for crime, air pollution and walkability disappeared in the fully-adjusted model including all built environmental variables. In contrast, relationships with proximity, traffic danger and the food environment were maintained in this comprehensive model. Black children, pupils with obesity, younger participants and those from high socioeconomic families were less likely to actively commute to school. There is thus a particular need to ensure that roads with high volumes of actively commuting children are kept safe and clean, and children's exposure to unhealthy food options along the way is limited. Moreover, as short commuting distances are strongly correlated with walking or cycling, providing high-quality education near residential areas might incite active transport to school.


Downregulation of HS6ST2 Inhibits Cervical Cancer Cell Migration and Invasion in Vivo and in Vitro.
Emerging evidence indicates the importance of heparan sulfate 6-O-sulfotransferase 2 (HS6ST2) in a number of developmental processes. Little is known regarding its biological function in regulating cervical cancer (CC) progression. In this study, we aim to explore the role of HS6ST2 in CC progression. The transcriptome sequencing data of CC tissues from three databases, GSE64217, GSE138080, and GSE63514, was examined for genes with significant changes. The expression profile for HS6ST2 within CC tissue was then assessed through fluorescence quantitative PCR and immunohistochemistry and compared to data from patients with clinicopathological features. A multivariate survival analysis was performed using the COX regression. The real-time quantitative PCR assessed the HS6ST2 expression profile within CC cellular cultures. The results of knocking down HS6ST2, considering the proliferative activity and invasiveness of CC cultures in vitro, were detected through cell viability assay, clonogenic assessment, tumorsphere formation analysis, 3D invasion experiment and transwell assay. The impact of HS6ST2 knockdown in CC proliferation was also evaluated in vivo using a nude mice model. HS6ST2 was severely upregulated within CC tissues across the three explored databases (GSE64217, GSE138080, and GSE63514). Fluorescent quantitative PCR and immunohistochemistry experiments identified HS6ST2 as highly upregulated within patients CC tissues. Survival analysis taking into account the parameters of lymph node metastasis, Federation of Gynecology and Obstetrics (FIGO) stage, depth of invasion, pathological grade, and HS6ST2 expression level demonstrated that individuals with downregulated HS6ST2 exhibited considerably extended progression-free survival (PFS) and overall survival (OS) in comparison to upregulated HS6ST2 cases. According to the findings of COX univariate analysis, the parameters lymph node metastasis, FIGO stage, depth of invasion, pathological grade, and HS6ST2 expression level, all showed a statistically significant correlation with effect upon prognosis of CC patients. The FIGO stage, depth of invasion and expression level of HS6ST2 were identified as independent risk variables influencing CC case prognosis within subsequent COX multivariate analysis. Cell function experiments proved that HS6ST2 knockdown can considerably diminish the proliferative potential, stemness and invasive traits of CC cells. Tumor formation experiments in nude mice in vivo demonstrated that knocking down HS6ST2 can significantly thwart CC cellular proliferative properties within animal models. The clinicopathological features and the survival time of the patients significantly correlate with the level of HS6ST2 expression in CC tissue samples.


Accuracy of a vertical jump contact mat for determining jump height and flight time.
Several devices are available to measure vertical jump (VJ) height based on flight time, VJ reach height, or ground reaction forces. The purpose of this study was to determine the accuracy of a VJ mat for measuring flight time and VJ height compared with a VJ tester or a force plate. Seventeen men and 18 women (X ± SD; age = 20.9 ± 0.7 years, height = 176.1 ± 0.9 cm, weight = 72.6 ± 13.5 kg) served as subjects. Subjects performed counter-movement vertical jumps while standing on both a force plate (1,000 Hz) and a VJ mat. A Vertec VJ tester was used to measure jump reach. Compared with the force plate, the VJ mat reported greater VJ height (VJ mat = 0.50 ± 0.12 m, force plate = 0.34 ± 0.10 m) and flight time (VJ mat = 0.629 ± 0.078 seconds, force plate = 0.524 ± 0.077 seconds). Comparison of VJ heights from the VJ mat and the Vertec revealed no significant differences (Vertec = 0.48 ± 0.11 m). Regression analyses indicated strong relationships between testing methods and suggested that high VJ performances may be underestimated with the VJ mat. This particular VJ mat compared favorably with the Vertec but not the force plate. It seems that the different flight times derived from the VJ mat may permit the VJ mat to be in closer agreement with VJ heights from the Vertec. Also, the VJ mat may not be an appropriate tool for assessing high VJ performances (i.e., ≥0.70 m; ≈28 inches). Practitioners and researchers using similar VJ mats may not obtain accurate flight times and may underestimate high performers.


Improving patient safety during insertion of peripheral venous catheters: an observational intervention study.
Peripheral venous catheters are frequently used in hospitalized patients but increase the risk of nosocomial bloodstream infection. Evidence-based guidelines describe specific steps that are known to reduce infection risk. However, the degree of guideline implementation in clinical practice is not known. The aim of this study was to determine the use of specific steps for insertion of peripheral venous catheters in clinical practice and to implement a multimodal intervention aimed at improving both compliance and the optimum order of the steps. The study was conducted at University Hospital Hamburg. An optimum procedure for inserting a peripheral venous catheter was defined based on three evidence-based guidelines (WHO, CDC, RKI) including five steps with 1A or 1B level of evidence: hand disinfection before patient contact, skin antisepsis of the puncture site, no palpation of treated puncture site, hand disinfection before aseptic procedure, and sterile dressing on the puncture site. A research nurse observed and recorded procedures for peripheral venous catheter insertion for healthcare workers in four different departments (endoscopy, central emergency admissions, pediatrics, and dermatology). A multimodal intervention with 5 elements was established (teaching session, dummy training, e-learning tool, tablet and poster, and direct feedback), followed by a second observation period. During the last observation week, participants evaluated the intervention. In the control period, 207 insertions were observed, and 202 in the intervention period. Compliance improved significantly for four of five steps (e.g., from 11.6% to 57.9% for hand disinfection before patient contact; p<0.001, chi-square test). Compliance with skin antisepsis of the puncture site was high before and after intervention (99.5% before and 99.0% after). Performance of specific steps in the correct order also improved (e.g., from 7.7% to 68.6% when three of five steps were done; p<0.001). The intervention was described as helpful by 46.8% of the participants, as neutral by 46.8%, and as disruptive by 6.4%. A multimodal strategy to improve both compliance with safety steps for peripheral venous catheter insertion and performance of an optimum procedure was effective and was regarded helpful by healthcare workers.


Performances and limits of a parallel oscillator for electrochemical quartz crystal microbalances.
This paper describes a driving circuit for an electrochemical quartz crystal microbalance (EQCM) adapted to a wide range of applications. The oscillator is a Miller-type parallel oscillator using an operational transconductance amplifier (OTA). A theoretical study of the oscillating circuit led to the analytical expression of the microbalance frequency as well as to an overestimation of the error on the mass measurement. The reliability of the EQCM was then experimentally verified through electrochemical copper deposition and dissolution. The limit of operation of the EQCM was also investigated, both analytically and experimentally. This work shows that parallel oscillators using few electronic components allow a very reliable EQCM to be obtained for mass measurements on metallic films, even if they are highly damped.


Determinants of postnatal care utilization in Tigray, Northern Ethiopia: A community based cross-sectional study.
Globally, 289,000 women die from complications related to pregnancy, childbirth, or the postnatal period every year. Two-thirds of all maternal deaths occur during the first six weeks following birth and more than two thirds of newborn deaths occur during the first week of life, These statistics underscore the importance of postnatal care, an often neglected service according to the World Health Organization (WHO). The purpose of this study was to assess the factors associated with postnatal service utilization in the Tigray region of Ethiopia. The study was a community-based, cross-sectional study. A multi-stage sampling method was used to select study districts randomly from the entire region. A total of 1,690 participants were selected using systematic random sampling. Participants were 18-49 years old, had given birth within the last six months, and were residents of the district for at least six months. Using SPSS version 20 means, frequencies, and percentages were calculated for the sub-group of participants who did attend postnatal care. Barriers to non-attendance of postatal care were analyzed using descriptive statistics. Bivariate analysis was undertaken to assess the association between demographic, obstetric, and knowledge regarding PNC and attendance at antenatal care. Variables with a P value, <0.05 were included in the multivariate logistic regression analysis to identify the determinant factors of postnatal care utilization. Of the women surveyed, 132 (8%) obtained postnatal care. Women who did not receive postnatal care reported lack of awareness of the services (n = 1110, 73.3%). Most mothers who received postnatal care reported that they were aware of the service prior to the birth of their child (n = 101, 76.5%). Women were more likely to receive postnatal services if they lived in an urban area (odds ratio 1.96, 95% confidence interval 1.07, 3.59), had greater than a secondary education (OR 3.60, 95% CI 1.32,9.83), delivered by cesarean section (OR 2.88 95% CI 1.32,6.29), had four or more antenatal visits (OR 4.84, 95% CI 1.57,14.9), or had a planned pregnancy (OR 6.47, 95% CI 2.04,20.5). Postnatal care service utilization is very low in Tigray region. Interventions targeted at increasing women's awareness of the importance of postnatal services and improving accessibility, particularly in rural areas, is needed.


Two cases of long-lasting, sub-microscopic Plasmodium malariae infections in adults from coastal Tanzania.
Malaria is endemic in Tanzania with majority of clinical cases caused by Plasmodium falciparum. Additionally, Plasmodium malariae and Plasmodium ovale spp. are also present and clinical manifestations caused by these infections are not well described. Clinical episodes caused by P. malariae infections are often characterized by a relatively mild illness with a low number of parasites, which can persist for long periods. In this report, two cases of P. malariae infections that were identified during a clinical trial evaluating the P. falciparum malaria vaccine candidate, PfSPZ Vaccine are described. The two participants were followed up and monitored for clinical and laboratory parameters to assess vaccine safety providing the opportunity to study clinical manifestations of P. malariae over 4 months. Two young, healthy Tanzanian men infected with low density asexual blood stage P. malariae diagnosed by quantitative polymerase chain reaction (qPCR) are described. Retrospective analysis of collected and stored blood samples revealed that the two volunteers had constant asexual blood stage parasitaemia for more than 4 months. During the 132 days of infection, the volunteers' vital signs, body temperature and serum biochemistry all remained within normal ranges. Haematological abnormalities, which were transiently outside normal ranges, were regarded as not clinically significant. During this time period, four consecutive evaluations of blood samples by thick blood smear microscopy conducted by an experienced microscopist were all negative, indicating the presence of low-density sub-microscopic infections. The two cases of P. malariae infections presented here confirm the ability of this Plasmodium species to persist at low density in the human host for extended time periods without causing clinical symptoms. The presented data also demonstrate that clinical study sites in malaria endemic regions need to have a strong malaria diagnostic infrastructure, including the ability of capturing sub-microscopic parasitaemia and differentiation of Plasmodium species. Trial registration ClinicalTrials.gov: NCT02613520, https://clinicaltrials.gov/ct2/show/NCT02613520 , Registered: November 24th 2015, Enrolment of the first participant to the trial: December 15th 2015, Trial was registered before the first participant was enrolled.


Altered receptor specificity of coxsackievirus B3 after growth in rhabdomyosarcoma cells.
Serial "blind" passages in human rhabdomyosarcoma (RD) cells of prototype viruses from each of the six immunotypes of the group B coxsackieviruses (CB) resulted in the isolation of intratypic variants of CB1, CB3, CB5, and CB6. Each variant virus strain acquired the capacity to agglutinate human erythrocytes and produce small plaques on HeLa cells, although their serological specificity remained unchanged. An alteration in VP1 mobility in sodium dodecyl sulfate-polyacrylamide gel electrophoresis was noted for CB3-RD. The CB3-RD variant was plaque purified on RD cells and studied for receptor interactions on both HeLa and RD cells. An attachment restriction appeared to exist for prototype CB3 on RD cells, whereas CB3-RD attached well to both cells. In attachment interference assays, HeLa cells saturated with CB3-RD blocked the attachment of CB3. In contrast, saturation of cells with CB1 (which shares a common receptor with parental CB3) failed to block the attachment of CB3-RD. This unidirectional receptor blockade suggested that a second site for the attachment of virions to receptors was acquired by the CB3-RD variant. Thus, more than one virus receptor specificity may be operative in the selection of host range virus mutants. The implications of this phenomenon as they may relate to pathogenesis are discussed.


Expression of Lamp-1 and Lamp-2 and their interactions with galectin-3 in human tumor cells.
Lysosomal-membrane-associated glycoproteins (Lamps) 1 and 2 are rarely found on the plasma membranes of normal cells. There is evidence suggesting an increase in their cell-surface expression in tumor cells, with some data indicating that the adhesion of some cancer cells to the extracellular matrix is partly mediated by interactions between Lamps and E-selectin and between Lamps and galectins (endogenous-galactoside-binding lectins). The present study examined the expression of Lamp-1 and Lamp-2 and their interactions with galectin-3 in different human tumor cell lines. Indirect immunofluorescence staining revealed accumulation of Lamp molecules at the edges of A2058 human metastasizing melanoma cells suggesting that these glycoproteins could participate in cell adhesion. Flow cytometry showed the presence of cell-surface Lamps in A2058, HT1080 (human fibrosarcoma) and CaCo-2 (human colon-adenocarcinoma) cells. Treatment with 2 mM sodium butyrate for 24 and 48 hr resulted in a significant increase in Lamps surface expression. A strong binding of A2058 to recombinant galectin-3 was detected by FACS. The application of 2 and 5 mM butyrate for the same incubation period enhanced galectin-3 binding to Lamps-expressing cells. Our results support the idea that Lamps may be considered a new family of adhesive glycoproteins participating in the complex process of tumor invasion and metastasis.


Design of fuzzy systems using neurofuzzy networks.
This paper introduces a systematic approach for fuzzy system design based on a class of neural fuzzy networks built upon a general neuron model. The network structure is such that it encodes the knowledge learned in the form of if-then fuzzy rules and processes data following fuzzy reasoning principles. The technique provides a mechanism to obtain rules covering the whole input/output space as well as the membership functions (including their shapes) for each input variable. Such characteristics are of utmost importance in fuzzy systems design and application. In addition, after learning, it is very simple to extract fuzzy rules in the linguistic form. The network has universal approximation capability, a property very useful in, e.g., modeling and control applications. Here we focus on function approximation problems as a vehicle to illustrate its usefulness and to evaluate its performance. Comparisons with alternative approaches are also included. Both, nonnoisy and noisy data have been studied and considered in the computational experiments. The neural fuzzy network developed here and, consequently, the underlying approach, has shown to provide good results from the accuracy, complexity, and system design points of view.


Recent advances in endovascular techniques for management of acute nonvariceal upper gastrointestinal bleeding.
Over the past two decades, transcatheter arterial embolization has become the first-line therapy for the management of upper gastrointestinal bleeding that is refractory to endoscopic hemostasis. Advances in catheter-based techniques and newer embolic agents, as well as recognition of the effectiveness of minimally invasive treatment options, have expanded the role of interventional radiology in the management of hemorrhage for a variety of indications, such as peptic ulcer bleeding, malignant disease, hemorrhagic Dieulafoy lesions and iatrogenic or trauma bleeding. Transcatheter interventions include the following: selective embolization of the feeding artery, sandwich coil occlusion of the gastroduodenal artery, blind or empiric embolization of the supposed bleeding vessel based on endoscopic findings and coil pseudoaneurysm or aneurysm embolization by three-dimensional sac packing with preservation of the parent artery. Transcatheter embolization is a fast, safe and effective, minimally invasive alternative to surgery when endoscopic treatment fails to control bleeding from the upper gastrointestinal tract. This article reviews the various transcatheter endovascular techniques and devices that are used in a variety of clinical scenarios for the management of hemorrhagic gastrointestinal emergencies.


NK/T cell non-Hodgkin lymphoma in a HIV-positive patient.
NK/T lymphomas have rarely been reported in HIV/AIDS patients. Here we report a case of a 37-year-old woman, with AIDS and a recent diagnosis of Kaposi sarcoma in a mesenteric lymph node, who presented with extra-ocular nerve palsies and gastrointestinal bleeding. A small intestine resection specimen revealed an extra-nodal NK/T cell lymphoma, nasal type. The unique presentation of this rare and aggressive lymphoma in the setting of AIDS and Kaposi sarcoma underscores the importance of maintaining a broad differential diagnosis when evaluating a malignant neoplasm from a HIV-positive patient.


Emotional stimuli capture spatial attention but do not modulate spatial memory.
There is evidence that emotional stimuli capture spatial attention and that visual memory is enhanced for emotional content. Here we examine the relationship between emotional content of stimuli and interactions with spatial memory. To assess spatial memory, a modified version of the Corsi Blocks Task (CBT), utilising emotional stimuli, was employed. In the CBT a series of spatial positions are highlighted and the participant has to repeat these in the order in which they were produced. Results showed that presenting more meaningful stimuli, such as emotional faces (e.g. angry or happy) at the spatial locations in the CBT did not enhance spatial memory span relative to the presentation of neutral stimuli (e.g. neutral faces) or non-image stimuli signified by a change in the luminance of the blocks. In addition, saccadic eye movements performed during retention disrupted spatial memory for all items. This occurred irrespective of whether the item to be remembered was a face, a luminance-defined stimulus or whether the face carried emotional significance. The results were not related to the visibility of the test stimuli as participants recognised the emotion displayed by the faces significantly above chance and rated emotional faces as being more arousing than neutral faces. Changes in the type of emotional stimulus (e.g. fearful faces, emotional schematic faces, spiders or flowers) or encoding (short vs. long) duration did not alter the pattern of results. These findings demonstrate an important dissociation between spatial capture and memory. Although emotional content can modulate orienting behaviour, it appears to be of limited effect on spatial memory.


Overexpression screen in Drosophila identifies neuronal roles of GSK-3 beta/shaggy as a regulator of AP-1-dependent developmental plasticity.
AP-1, an immediate-early transcription factor comprising heterodimers of the Fos and Jun proteins, has been shown in several animal models, including Drosophila, to control neuronal development and plasticity. In spite of this important role, very little is known about additional proteins that regulate, cooperate with, or are downstream targets of AP-1 in neurons. Here, we outline results from an overexpression/misexpression screen in Drosophila to identify potential regulators of AP-1 function at third instar larval neuromuscular junction (NMJ) synapses. First, we utilize >4000 enhancer and promoter (EP) and EPgy2 lines to screen a large subset of Drosophila genes for their ability to modify an AP-1-dependent eye-growth phenotype. Of 303 initially identified genes, we use a set of selection criteria to arrive at 25 prioritized genes from the resulting collection of putative interactors. Of these, perturbations in 13 genes result in synaptic phenotypes. Finally, we show that one candidate, the GSK-3beta-kinase homolog, shaggy, negatively influences AP-1-dependent synaptic growth, by modulating the Jun-N-terminal kinase pathway, and also regulates presynaptic neurotransmitter release at the larval neuromuscular junction. Other candidates identified in this screen provide a useful starting point to investigate genes that interact with AP-1 in vivo to regulate neuronal development and plasticity.


Malignant haemangioendothelioma of bone in a HbSC disease patient--a case report.
We report here a 35-year-old man with sickle cell disease (SCD), who presented in 1989 with pain in the (R) hip of 7 years duration and swelling of the (R) calf of 3 months duration. Clinical examination revealed a hard tender mass in the (R) calf. Histology of the (R) calf mass revealed haemangioendothelioma (HE), similar to the histology of the (R) iliac bone mass obtained in another institution previously. He was treated with external radiotherapy with the 1.25 megavoltage beam to antero-posterior fields of the (R) hemipelvis and (R) calf, with good response. Chemotherapy was subsequently administered using 6 cycles of VAC regime. The patient remained in remission for 12 months. In 1991 he had lymphoedema of (R) lower limb and received further radiotherapy and chemotherapy after an isotope bone scan had revealed disease activity in the (R) hemipelvis, (R) femur and (L) upper tibia. He responded again with complete regression of the lymphoedema and remained well until April 1993 when the lymphoedema recurred. He died while being evaluated for further treatment. Although there is no evidence to suggest that SCD confers any protection from development of neoplasms, the co-existence of SCD with a neoplasm is not common. We consider the occurrence of HE of bone, a rare malignancy, in a HbSC patient worthy of reporting.


[Hepatorenal correlations in patients with pulmonary tuberculosis in the presence of viral hepatitis B markers and organic chlorine pesticides: radionuclide studies].
Excretory hepatic function (EHF) and effective renal plasma flow (ERPF) were studied in 115 patients with pulmonary tuberculosis by the data of radionuclide studies. The patients were divided into 2 groups: Group 1 included 89 patients whose blood samples showed viral hepatitis B markers (VHBM) and organic chlorine pesticides (OCP) and Group 1 comprised 26 patients without VHBM and OCP. More than 50% of the examinees were found to have impairments in both EHF and ERPF. In some of them, these disorders progressed during treatment. There was a correlation between these parameters, which makes it necessary to search for new pathogenetic exposures in order to improve hepatic and renal functions in patients with blood VHBM and OCP.


Emergence of molecular recognition phenomena in a simple model of imprinted porous materials.
Polymerization in the presence of templates, followed by their consequent removal, leads to structures with cavities capable of molecular recognition. This molecular imprinting technology has been employed to create porous polymers with tailored selectivity for adsorption, chromatographic separations, sensing, and other applications. Performance of these materials crucially depends on the availability of highly selective binding sites. This parameter is a function of a large number of processing conditions and is difficult to control. Furthermore, the nature of molecular recognition processes in these materials is poorly understood to allow a more systematic design. In this work we propose a simple model of molecularly imprinted polymers mimicking the actual process of their formation. We demonstrate that a range of molecular recognition effects emerge in this model and that they are consistent with the experimental observations. The model also provides a wealth of information on how binding sites form and function in the imprinted structures. It demonstrates the capability to assess the role of various processing conditions in the final properties of imprinted materials, and therefore it can be used to provide some qualitative insights on the optimal values of processing parameters.


A multicenter, randomized, double-blind, placebo-controlled trial to test efficacy and safety of magnetic resonance imaging-based thrombolysis in wake-up stroke (WAKE-UP).
In about 20% of acute ischemic stroke patients stroke occurs during sleep. These patients are generally excluded from intravenous thrombolysis. MRI can identify patients within the time-window for thrombolysis (≤4·5 h from symptom onset) by a mismatch between the acute ischemic lesion visible on diffusion weighted imaging (DWI) but not visible on fluid-attenuated inversion recovery (FLAIR) imaging. The study aims to test the efficacy and safety of MRI-guided thrombolysis with tissue plasminogen activator (rtPA) in ischemic stroke patients with unknown time of symptom onset, e.g., waking up with stroke symptoms. We hypothesize that stroke patients with unknown time of symptom onset with a DWI-FLAIR-mismatch pattern on MRI will have improved outcome when treated with rtPA compared to placebo. WAKE-UP is an investigator initiated, European, multicentre, randomized, double-blind, placebo-controlled clinical trial. Patients with unknown time of symptom onset who fulfil clinical inclusion criteria (disabling neurological deficit, no contraindications against thrombolysis) will be studied by MRI. Patients with MRI findings of a DWI-FLAIR-mismatch will be randomised to either treatment with rtPA or placebo. The primary efficacy endpoint will be favourable outcome defined by modified Rankin Scale 0-1 at day 90. The primary safety outcome measures will be mortality and death or dependency defined by modified Rankin Scale 4-6 at 90 days. If positive, WAKE-UP is expected to change clinical practice making effective and safe treatment available for a large group of acute stroke patients currently excluded from specific acute therapy.


Curcumin induces EGFR degradation in lung adenocarcinoma and modulates p38 activation in intestine: the versatile adjuvant for gefitinib therapy.
Non-small cell lung cancer (NSCLC) patients with L858R or exon 19 deletion mutations in epidermal growth factor receptor (EGFR) have good responses to the tyrosine kinase inhibitor (TKI), gefitinib. However, patients with wild-type EGFR and acquired mutation in EGFR T790M are resistant to gefitinib treatment. Here, we showed that curcumin can improve the efficiency of gefitinib in the resistant NSCLC cells both in vitro and in vivo models. After screening 598 herbal and natural compounds, we found curcumin could inhibit cell proliferation in different gefitinib-resistant NSCLC cell lines; concentration-dependently down-regulate EGFR phosphorylation through promoting EGFR degradation in NSCLC cell lines with wild-type EGFR or T790M EGFR. In addition, the anti-tumor activity of gefitinib was potentiated via curcumin through blocking EGFR activation and inducing apoptosis in gefitinib-resistant NSCLC cell lines; also the combined treatment with curcumin and gefitinib exhibited significant inhibition in the CL1-5, A549 and H1975 xenografts tumor growth in SCID mice through reducing EGFR, c-MET, cyclin D1 expression, and inducing apoptosis activation through caspases-8, 9 and PARP. Interestingly, we observed that the combined treatment group represented better survival rate and less intestinal mucosal damage compare to gefitinib-alone therapy. We showed that curcumin attenuated the gefitinib-induced cell proliferation inhibition and apoptosis through altering p38 mitogen-activated protein kinase (MAPK) activation in intestinal epithelia cell. Curcumin potentiates antitumor activity of gefitinib in cell lines and xenograft mice model of NSCLC through inhibition of proliferation, EGFR phosphorylation, and induction EGFR ubiquitination and apoptosis. In addition, curcumin attenuates gefitinib-induced gastrointestinal adverse effects via altering p38 activation. These findings provide a novel treatment strategy that curcumin as an adjuvant to increase the spectrum of the usage of gefitinib and overcome the gefitinib inefficiency in NSCLC patients.


Chest Radiological Findings of Patients With Severe H1N1 Pneumonia Requiring Intensive Care.
A new strain of human influenza A (H1N1) virus originated from Mexico in 2009 and spread to more than 190 countries and territories. The World Health Organization (WHO) declared it a level 6 (highest level) pandemic. In August 2010, WHO announced that the H1N1 2009 influenza virus had moved into the postpandemic period. The WHO also declared that this flu strain is expected to continue to circulate as a seasonal virus "for some years to come." The objective of this study is to describe the chest radiographic and computed tomography (CT) findings of patients with severe H1N1 pneumonia admitted to the intensive care unit (ICU) during the 2009 pandemic. Patients with severe H1N1 pneumonia requiring ICU admission have extensive radiographic and CT abnormalities. Eighteen patients, aged 23 to 62 (mean 41), admitted to the ICU at UCLA-Olive View Medical Center with a primary diagnosis of pandemic H1N1 infection, confirmed either via rapid influenza detection test or by real-time reverse transcriptase polymerase chain reaction assay, formed the study population. All patients had chest x-ray (CXR) within 24 hours of admission and 5 patients had CT examinations. In this retrospective study, images were evaluated for the pattern (ground-glass opacities, consolidation, reticular opacities, and nodular opacities), distribution (unilateral/bilateral, upper/middle/lower lung zone, and central/peripheral/peribronchovascular), and extent (focal/multifocal/diffuse; number of lung zones) of abnormalities. All (100%) patients had abnormal CXR and CT studies. The predominant radiographic findings were ground-glass opacities (16 of 18; 89%), consolidation (16 of 18; 89%), and reticular opacities (6 of 18, 33%). The radiographic abnormalities were bilateral in 17 (94%) patients; involved lower lung distribution in 18 (100%) patients, and mid and lower lung distribution in 16 (89%) patients. Radiographic abnormalities were peribronchovascular in 11 (61%) patients and multifocal in 10 (56%). Sixteen (89%) patients had extensive abnormalities involving 3 or more lung zones. The patients requiring mechanical ventilation had a higher incidence of bilateral, diffuse consolidation in a peribronchovascular distribution on chest radiographs. The predominant CT abnormalities were consolidation (5 of 5; 100%), ground-glass opacities (5 of 5; 100%), and nodular opacities (3 of 5, 60%). The CT findings were peribronchovascular and multifocal in 4 (80%) patients and extensive and bilateral in all (100%) patients. Patients with H1N1 pneumonia admitted to the ICU had bilateral, extensive CXR, and CT abnormalities. Consolidations and ground-glass opacities were the most common imaging findings, predominantly affecting mid and lower lung zones. Imaging abnormalities were peribronchovascular and multifocal in a majority of patients.