Continuous-scale-invariant pattern recognition with adaptive-wavelet-matched filters.
We designed and implemented a composite-wavelet-matched filter that is invariant to continuous-scale changes of the input and is useful for correlation-based pattern recognition of objects whose size is not known exactly. We optimize the adaptive wavelet to extract sparse image features and use the scale-space analysis to determine the wavelet scale for the scale invariance. Experimental results obtained by use of a programmable optical correlator with three liquid-crystal spatial light modulators are demonstrated.


Mitogen-activated protein kinase stimulation by a tyrosine kinase-negative epidermal growth factor receptor.
Mutation of the epidermal growth factor receptor (EGF-R) within the ATP binding subdomain results in a receptor that lacks tyrosine kinase activity and is defective in signal transduction. However, this kinase-negative EGF-R is able to activate MAP kinase (Campos-Gonzalez, R., and Glenny, J. R. (1992) J. Biol. Chem. 267, 14535-14538). This observation suggests that signal initiation by the EGF-R can occur by a mechanism that is independent of the receptor tyrosine kinase activity. Here, we report that the kinase-negative EGF-R is phosphorylated on tyrosine in EGF-treated cells. The mechanism of tyrosine phosphorylation can be accounted for by the action of EGF to stimulate a protein kinase activity that is associated with the kinase-negative EGF-R. This protein kinase activity is not intrinsic to the receptor and can be separated from the EGF-R by incubation with 0.5 M NaCl. MAP kinase activation by the kinase-negative EGF-R may therefore occur by a mechanism that requires a receptor-associated tyrosine kinase. Thus, it is unnecessary to propose a novel kinase-independent mechanism of signal initiation to account for MAP kinase activation by the kinase-negative EGF-R.


Utilizing next-generation sequencing to resolve the backbone of the Core Goodeniaceae and inform future taxonomic and floral form studies.
Though considerable progress has been made in inferring phylogenetic relationships of many plant lineages, deep unresolved nodes remain a common problem that can impact downstream efforts, including taxonomic decision-making and character reconstruction. The Core Goodeniaceae is a group affected by this issue: data from the plastid regions trnL-trnF and matK have been insufficient to generate adequate support at key nodes along the backbone of the phylogeny. We performed genome skimming for 24 taxa representing major clades within Core Goodeniaceae. The plastome coding regions (CDS) and nuclear ribosomal repeats (NRR) were assembled and complemented with additional accessions sequenced for nuclear G3PDH and plastid trnL-trnF and matk. The CDS, NRR, and G3PDH alignments were analyzed independently and topology tests were used to detect the alignments' ability to reject alternative topologies. The CDS, NRR, and G3PDH alignments independently supported a Brunonia (Scaevola s.l. (Coopernookia (Goodenia s.l.))) backbone topology, but within Goodenia s.l., the strongly-supported plastome topology (Goodenia A (Goodenia B (Velleia+Goodenia C))) contrasts with the poorly supported nuclear topology ((Goodenia A+Goodenia B) (Velleia+Goodenia C)). A fully resolved and maximally supported topology for Core Goodeniaceae was recovered from the plastome CDS, and there is excellent support for most of the major clades and relationships among them in all alignments. The composition of these seven major clades renders many of the current taxonomic divisions non-monophyletic, prompting us to suggest that Goodenia may be split into several segregate genera.


Dorsal raphe nucleus acetylcholine-mediated neurotransmission modulates post-ictal antinociception: The role of muscarinic and nicotinic cholinergic receptors.
The dorsal raphe nucleus (DRN) is a key structure of the endogenous pain inhibitory system. Although the DRN is rich in serotoninergic neurons, cholinergic neurons are also found in that nucleus. Both ictal and inter-ictal states are followed by post-ictal analgesia. The present study investigated the role of cholinergic mechanisms in postictal antinociceptive processes using microinjections of atropine and mecamylamine, muscarinic and nicotinic cholinergic receptor antagonists, respectively, in the DRN of rats. Intraperitoneal injection of pentylenetetrazole (PTZ) (at 64mg/kg) caused tonic and tonic-clonic seizures. The convulsive motor reactions were followed by an increase in pain thresholds, a phenomenon known as post-ictal analgesia. Pre-treatment of the DRN with atropine or mecamylamine at 1µg, 3µg and 5µg/0.2µL decreased the post-ictal antinociceptive phenomenon. The present results showed that the post-ictal analgesia was mediated by muscarinic and nicotinic cholinergic receptors in the DRN, a structure crucially involved in the neural network that organises post-ictal hypoalgesia.


Dental curriculum reform in India: Undergraduate students' awareness and perception on the newly proposed choice based credit system.
Dental education plays a crucial role in producing competent dental professionals who can cater to the diverse needs of patients. This study aimed to assess the awareness and perception of the newly proposed Choice Based Credit System (CBCS) by the Dental Council of India (DCI) among dental undergraduate students in Belagavi City, India. The study adopted a cross-sectional design and was conducted among undergraduates and interns of two dental colleges in Belagavi, India. A pilot study was conducted, which was followed by sample size estimation. A total 480 participants were recruited by simple random sampling technique. The questionnaire used was self-administered and comprising 23 close-ended questions in English, for which the Cronbach's alpha coefficient was found to be 0.85, with an 84% score for face validity and a content validity ratio of 0.78. The mean awareness and perception scores were highest among interns, while it was lowest among the first years. Majority of the study participants (62.7%) were unaware of this new curriculum whereas almost half (49%) of them found it to be student-friendly. A positive correlation was seen between the perception and awareness scores (r = +0.270, P ≤ 0.001). The findings of this study reveal that a significant proportion of dental undergraduates lacked awareness regarding the implementation of the new curriculum, however they had a positive outlook towards it. The adoption of this model appears to be a promising initiative towards enhancing the quality of dental education at a national level.


Short-term results of percutaneous treatment of acetabular fractures: functional outcomes, radiographic assessment and complications.
Our purpose was to assess functional outcomes, radiographic characteristics and complications in patients who underwent fixation of acetabular fracture using percutaneous means only. This was a retrospective cohort study of adult patients with an acetabular fracture admitted to a level 1 trauma centre and treated with closed reduction and percutaneous fixation. Nineteen patients were identified, and mechanism of injury, radiologic classification of fracture, complications and functional outcomes were analysed. Outcome measurements included Patient Reported Outcomes Measurement Information System (PROMIS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, which are validated patient questionnaires assessing functional outcome. They are scored as a point range on a per-question basis, with a combined range possibility of 0-96 for WOMAC and 5-75 for PROMIS. Nineteen patients over a two year period were reviewed. Fracture displacement improved following surgery from a mean 7.3 mm (range 0-33 mm) to 2.6 mm (range 0-12 mm). Complications included one post-operative death from non-ST-segment elevation myocardial infarction, sciatic nerve injury, malpositioned screw and deep infection. There were no vascular injuries, pulmonary emboli or deep venous thromboses. Of the 19 patients eligible for the study, seven completed both PROMIS mobility and WOMAC osteoarthritis questionnaires at a mean follow-up of 572 days (1.57 years), with a range of 435-862 days. The average WOMAC score was 7.4 (range 0-30) and mean PROMIS score 66.4 (range 50-75). Functional outcomes in this study are comparable with other published studies and support percutaneous management of acetabular fractures as an effective alternative to open reduction and internal fixation.


Total laparoscopic aortobifemoral bypass: short- and middle-term results.
We describe early and mid-term results of total laparoscopic aortofemoral bypass (TLAFB). TLAFB was performed in 150 cases of severe aortoiliac occlusive disease. Aortic approaches included transperitoneal left retrocolic (n = 86), left retrorenal (n = 51), and direct (n = 4); the retroperitoneoscopic approach was used in nine cases. The procedure was totally laparoscopic in 145 patients (96.6%). Median operative and clamping times were 260 (120-450) and 81 (36-190) min, respectively. Thirty-day mortality was 2.7%. Nonlethal systemic, local vascular, and local nonvascular complications occurred in 21 (14.3%), seven (4.8%), and two (1.3%) patients, respectively. Median return to general diet and ambulation were, respectively, days 2 and 3. Median hospital stay was 7 days. Follow-up was 25.2 +/- 17.6 months (range 1-60) with 3-year primary and secondary actuarial patency rates of 93% and 95.6%, respectively. TLAFB gives early and mid-term patency rates comparable to open direct repair. Laparoscopy allows faster recovery and reduces operative trauma.


Anatomic study of the lateral femoral cutaneous nerve with respect to the ilioinguinal surgical dissection.
To report on the anatomic variations of the lateral femoral cutaneous nerve with respect to the ilioinguinal surgical dissection. Cadaveric anatomic study. Sixty-eight ilioinguinal dissections performed in fifty cadavers. The lateral femoral cutaneous nerve was identified, and certain location variables were recorded. The distance in millimeters from the medial edge of the anterior superior iliac spine (ASIS), whether the nerve was lateral or medial to the ASIS, and the layer in which the nerve crossed the dissection. In seven dissections, the nerve was twenty-one to twenty-five millimeters medial to the ASIS; in ten dissections, the nerve was twenty-six to thirty millimeters from the ASIS; and in fourteen dissections, the nerve was more than thirty millimeters medial to the superior border of the ASIS. The average medial distance from the ASIS was 20.4 millimeters, with a range of three to forty-six millimeters. In no specimen did the nerve pass lateral to the ASIS. The lateral femoral cutaneous nerve was found to lie anterior to the iliopsoas muscle in all specimens. The course of the lateral femoral cutaneous nerve is highly variable; the nerve was most commonly found at ten to fifteen millimeters from the ASIS and as far medially as forty-six millimeters. When using the illioinguinal surgical approach, if the lateral femoral cutaneous nerve is not encountered immediately adjacent to the ASIS, dissection up to five centimeters medial to the ASIS may be necessary to locate the nerve.


Cytochalasin B inhibition of endothelial proliferation at wound edges in vitro.
Cytochalasin B prevents both migration and wound-associated replication when applied to wounded monolayers of bovine endothelium in tissue culture. The normal low background rate of replication in undisturbed areas of the cultures is not inhibited by cytochalasin B. These results suggest that some form of movement may be required for initiation of wound-associated replication by endothelial cells.


Genome-wide identification and characterization of the heavy metal ATPase (HMA) gene family in Medicago truncatula under copper stress.
In nature, the normal growth, development, and quality of plants are significantly affected by many abiotic stresses, such as drought, salinity, low temperature, and heavy metals. Among heavy metals, copper is an essential element for plant growth and development but also has a toxic effect on plants when its concentration is excessive. Therefore, plants have evolved a complex regulatory network to regulate the balance of copper ions in cells. Heavy metal ATPases (HMAs), which transport heavy metals to intracellular compartments or detoxify heavy metals present at excessive concentrations, have been extensively studied in model plant species. However, no comprehensive and systematic surveys of members of the HMA gene family have been conducted in the model legume species Medicago truncatula. Here, nine putative MtHMAs were identified in the M. truncatula genome. These MtHMAs were phylogenetically divided into two distinct groups. The members in each group had a relatively conserved gene structure and motif composition. The number of introns in the MtHMAs varied from 5 to 16, with the majority of these genes containing 8 introns. The expression patterns showed that MtHMAs exhibit preferential or distinct expression patterns among different tissues. Finally, the expression patterns of the members of this gene family were verified in the leaves and roots of plants under Cu stress. Our findings will be valuable for the functional investigation and application of members of this gene family in M. truncatula and other related legume species.


Adhesion of spider cribellate silk enhanced in high humidity by mechanical plasticization of the underlying fiber.
The disruptive nature of water presents a significant challenge when designing synthetic adhesives that maintain functionality in wet conditions. However, many animal adhesives can withstand high humidity or underwater conditions, and some are even enhanced by them. An understudied mechanism in such systems is the influence of material plasticization by water to induce adhesive work through deformation. Cribellate silk is a dry adhesive used by particular spiders to capture moving prey. It presents as a candidate for testing the water plasticization model as it can remain functional at high humidity despite lacking an aqueous component. We performed herein tensile and adhesion tests on cribellate threads from the spider, Hickmania troglodytes; a spider that lives within wet cave environments. We found that the work of adhesion of its cribellate threads increased as the axial fibre deformed during pull-off experiments. This effect was enhanced when the silk was wetted and as spider body size increased. Dry threads on the other hand were stiff with low adhesion. We rationalized our experiments by a series of scaling law models. We concluded that these cribellate threads operate best when the nanofibrils and axial fibers both contribute to adhesion. Design of future synthetic materials could draw inspiration from how water facilitates, rather than diminishes, cribellate silk adhesion.


Diet quality and cognition among older adults from the NuAge study.
A healthy diet may prevent cognitive decline either directly, or by decreasing risk of nutrition-related chronic diseases associated with cognitive decline. This study examined the relationships between diet quality (DQ) and cognition for over 3 years among 1488 older adults (52.6% female) from the NuAge study, aged 67 to 84 years at recruitment. Cognition was assessed at four annual visits using the modified mini-mental status examination (3MS); rate of cognitive decline was computed for each participant over the 3 years of follow-up using mixed model analyses and the individual-specific number of months between 3MS assessments. Dietary data were collected at recruitment using a validated 78-item, semi-quantitative food frequency questionnaire (FFQ). DQ was characterized as the Canadian Healthy Eating Index (C-HEI), a 9-component global DQ index (maximum score=100) computed from the FFQ output. Other variables were collected by questionnaire or direct measurement. Multivariate analyses were carried out to assess the association of DQ controlled for confounders on cognition. Total C-HEI was better in females (78.7±9.1 vs 75.7±9.4, p<.0001) as were C-HEI component subscores. Males, the less educated, smokers, those with poor social engagement, symptoms of depression, a higher waist:hip ratio and who reported financial insecurity had a poor quality diet that could contribute to chronic diseases associated with cognition. Along with functional autonomy, most of these variables emerged as covariates of baseline 3MS and predictors of cognitive decline. While certain C-HEI subscores and total C-HEI were positive univariate correlates of 3MS at recruitment, total DQ was not associated with cognition in multivariate analyses, either at baseline or over 3 years of follow-up. DQ was not independently associated with cognition. However, the study demonstrates relationships between diet quality and risk factors for chronic diseases associated with cognition. Consequently, older adults might benefit from a healthy diet to decrease risk of nutrition-related chronic diseases established as risk factors for cognitive decline. Further work in diverse older populations, use of dietary data collected earlier in life, finer cognitive measures and longer follow-up are necessary to better elucidate relationships between diet quality, chronic diseases and cognition.


Biochemical changes related to aging in the senescence-accelerated mouse.
Several biochemical parameters reflecting the degree of senescence were compared between senile-prone (P) and resistant (R) strains of male senescence-accelerated mouse (SAM) at 11 to 12 months of age. Plasma testosterone in SAM-P amounted to half the concentration in SAM-R. In the liver and brain of SAM-P, the content of malondialdehyde (MDA) and the activity of monoamine oxidase B (MAO-B) were significantly higher than those in SAM-R. Moreover, large amounts of fluorescent lipofuscin were detected in the SAM-P liver. Compared with SAM-R, both membrane and cytosolic fractions from the SAM-P liver contained small amounts of protein and showed less activity of superoxide dismutase (SOD). The present findings suggest that the male SAM-P rapidly acquires biochemical changes which are considered to be part of the normal aging process.


A MAP Kinase pathway in Caenorhabditis elegans is required for defense against infection by opportunistic Proteus species.
Caenorhabditis elegans innate immunity requires a conserved mitogen activated protein kinase (MAPK) pathway that regulates the basal and pathogen-induced expression of immune effectors. Being in the group of opportunistic pathogens, Proteus spp. cause large number of nosocomial infections. Since, Proteus spp. do not cause death in wild type C. elegans, to understand the role and contribution of MAP Kinase pathway, the mutants (sek-1 and pmk-1) of this pathway were employed. Physiological experiments revealed that the Proteus spp. were able to kill MAP Kinase pathway mutant's C. elegans significantly. To understand the involvement of innate immune pathways specific players at the mRNA level, the regulation of few candidate antimicrobial genes were kinetically investigated during Proteus spp. infections. Real-time PCR analysis indicated a regulation of few candidate immune regulatory genes (F08G5.6, lys-7, nlp-29, ATF-7 and daf-16) during the course of Proteus spp. infections. In addition, the lipopolysaccharides (LPS) isolated from Proteus mirabilis upon exposure to mutant C. elegans showed modifications at their functional regions suggesting that the pathogen modifies its internal machinery according to the specific host for effective pathogenesis.


catena-Poly[[bis-(1H-indole-5-carboxyl-ato-κ2 O,O')zinc(II)]-μ-4,4'-azobi-pyridine-κ2 N 1:N 1'].
The asymmetric unit of the title coordination polymer [Zn(C9H6NO2)2(C10H8N4)] n , consists of one ZnII cation, one bidentate 1H-indole-5-carboxyl-ate (I5C) anion and half of a 4,4'-azobi-pyridine (Abpy) neutral ligand. In the coordination polyhedron, the ZnII ion adopts a distorted octa-hedral geometry. The coordination polymer is stabilized by a combination of N-H⋯O and C-H⋯π inter-actions, which leads to the formation of wave-like two-dimensional coordination polymeric layers.


Urban retail location: Insights from percolation theory and spatial interaction modeling.
Characterising road networks has been the focus of a large body of research due to it being the main driver of activities in an urban ecosystem and the structuring factor in the dynamics of the city. One of these activities, and one with the largest economical impact in a city, is retail dynamics and its evolution. Therefore, the mathematical modeling of the location of retail activities and of the emergence of clustering in retail centers has as well generated a large number of works. Despite these two interwoven components strongly depending on one another and their fundamental importance in understanding cities, little work has been done in order to compare their local and global properties. Here we compare the road network's hierarchical structure, unveiled through a percolation analysis of the network, with the retail location distribution defined by exploiting a gravity-based retail model. We interpret the great agreement in the city's organizations as it emerges from both methodologies as new evidence of the interdependence of these two crucial dimensions of a city's life.


Asexual blood stage vaccines: from merozoites to peptides.
Asexual blood stage proliferation is responsible for the morbidity and mortality associated with malaria infection in man. These developmental stages are therefore obvious targets for the development of malaria vaccines. Several asexual blood stage components have been identified as potential candidates for the development of vaccines and some of them have been shown, following immunization, to induce at least partial protection in a variety of Plasmodium-host combinations. Studies on defined parasite components and on synthetic peptides derived from them have revealed new insights at the molecular level into parasite mechanisms involved in propagation and survival in the infected host, and into the interaction between parasite components and the host immune system. Practical application of these findings is likely to provide the basis for the design of more appropriate antigens for the development of vaccines.


[What become the decisions of limitation of treatments after discharge from the paediatric intensive care unit?].
The fact that some children may survive despite a decision of limitation of treatments (DLT) is taken in Paediatric Intensive Care Unit (PICU) is a recent data. Although the French-speaking Group of Paediatric Intensive and Emergency Care (GFRUP) has published guidelines for limitation of treatments in PICU, outcome of these surviving children has not yet been studied. To evaluate transmission of data concerning DLT in PICU toward teams in charge of children after the PICU stay and to evaluate perennility of these decisions. Cohort study in children for whom DLT was discussed and who were discharged from PICU between 2002 and 2006. The study included an analysis of the medical files and discussions with the physicians in charge of children at the time of the study, including their responses to standardised scenarios concerning the outcome of their patients. Among the 96 children for whom DLT was discussed in PICU, 37 were discharged toward another unit. Only 1 discharge letter mentioned the DLT. At the time of the study, the Pediatric Overall Performance Category (POPC) score had increased in 16 children and was stable in 12. All the 6 children with a worsening POPC score died, without PICU readmission. The physicians in charge of children after the PICU stay did not remember any DLT. For 18 children (including 8 with previous DLT) PICU readmission would be proposed in case of life-threatening event. Their median POPC score at the time of study was lower than that of other children (3 versus 4; p=0.001). This study shows a lack of DLT data transmission, which is in contradiction with the GFRUP's guidelines. Correction of this lack is essential to improve cooperation between units in charge of these children.


Mechanism of action of fire ant (Solenopsis) venoms. I. Lytic release of histamine from mast cells.
The mechanism of histamine release from rat mast cells by whole venom from Solenopsis geminata and S. invicta or by 2-methyl-6-undecylpiperidine HCl (C11) was investigated. Histamine release stimulated by one or more of these agents (1) occurred in normal and metabolically inactivated cells, (2) had a biphasic time course in normal and inactivated cells, (3) was temperature dependent and did not occur at 0 degrees C, (4) was accompanied by concomitant cytoplasmic enzyme release, (5) was accomplished by substantial cell swelling, and (6) was correlated with a loss of cell refractility in phase contrast microscopy. These results indicate that C11 causes initial permeability changes in the plasma membrane followed by lytic release of histamine and other cell components. The nonspecific nature of this action of the dialkylpiperidine component of the venoms provides the fire ants with a defense of general applicability.


Characterisation of brain D2 dopamine receptors solubilised by lysophosphatidylcholine.
Brain D2 dopamine receptors have been solubilised using lysophosphatidylcholine. The inclusion of proteinase inhibitors during solubilisation enables a preparation to be obtained containing a high proportion of solubilised D2 receptors with pharmacological properties similar to those of membrane-bound D2 receptors.


Pharmacodynamics of doxacurium during cardiac surgery with hypothermic cardiopulmonary bypass.
To determine the characteristics of neuromuscular block produced by two and three times the 95% effective dose (ED95) of doxacurium in patients undergoing coronary artery surgery with hypothermic cardiopulmonary bypass. In a prospective non randomized study, ten patients received doxacurium 0.05 mg.kg-1 (Group 1) and ten others received 0.075 mg.kg-1 (Group 2) with midazolam and sufentanil. The mechanomyographic response of the adductor pollicis muscle after supramaximal train-of-four (TOF) stimulation of the ulnar nerve was recorded intraoperatively and postoperatively. Additional doxacurium (10% of the initial dose) was administered until sternal closure whenever the first twitch (T1) had recovered to 25% of control. The onset time (time to maximal T1 depression) of doxacurium was 390 +/- 148 sec in Group 1 and 370 +/- 74 sec in Group 2 (P = 0.71). The clinical duration of neuromuscular block (time to 25% T1 recovery) was 165 +/- 90 min in Group 1 and 258 +/- 86 in Group 2 (P = 0.03). On arrival to recovery room the mean T1 was 57 +/- 23% in Group 1 and 24 +/- 21% in Group 2 (P = 0.003); the mean T4/T1 ratio was 0.25 +/- 0.15 for five patients of Group 1 with four responses to TOF stimulation and 0.10 for the only patient of Group 2 with four twitches. In contrast with findings in patients without cardiac disease, this study shows comparable onset times of doxacurium with doses of two and three times ED95. The clinical duration of doxacurium is 60 to 100% longer than previously reported in noncardiac surgery.


The role of the VPS4A-exosome pathway in the intrinsic egress route of a DNA-binding anticancer drug.
This study investigates the subcellular pharmacokinetics of drug efflux in cancer cells and explores the role of the multivesicular body (MVB) in facilitating efflux of doxorubicin, a widely used DNA-targeting anticancer agent, from the nucleus. Human erythroleukemic K562 cells were pulsed with doxorubicin and then chased in drug-free media to allow for efflux. Microscopy and biochemical techniques were used to visualize the subcellular localization of the drug and measure drug content and distribution during the efflux period. To explore the role of the MVB in doxorubicin efflux, K562 cells were transfected with dominant negative mutant forms of VPS4a-GFP chimeras. Although the intracellular concentration of drug exceeds the extracellular concentration, nuclear efflux of doxorubicin occurs in living cells at a faster rate than doxorubicin unbinding from isolated nuclei into drug-free buffer. In cells expressing dominant negative VPS4a, doxorubicin accumulates in VPS4a-positive vesicles and drug sequestration is inhibited, directly implicating the MVB pathway in the egress route of doxorubicin in this cell type. Cellular membranes are a component of the doxorubicin efflux mechanism in K562 cells. Dominant-negative GFP chimeric mutants can be used to elucidate the role of specific membrane trafficking pathways in subcellular drug transport routes.


Ornithine decarboxylase activity in Barrett's esophagus: a potential marker for dysplasia.
Ornithine decarboxylase activity is known to be increased in certain premalignant conditions. We determined the activity of this enzyme in mucosal biopsy specimens from 15 patients with Barrett's esophagus. Ornithine decarboxylase was greater in Barrett's mucosa than in squamous esophageal or gastric mucosa. In Barrett's mucosa from 4 patients with dysplasia, the enzyme activity was greater than in 11 patients without dysplasia (1.6 +/- 0.35 vs. 0.19 +/- 0.08 U/mg protein; p less than 0.005). Increased ornithine decarboxylase activity in biopsy specimens of Barrett's mucosa may represent a marker for dysplasia.


Association of Cardiac Galectin-3 Expression, Myocarditis, and Fibrosis in Chronic Chagas Disease Cardiomyopathy.
Chronic Chagas disease cardiomyopathy, caused by Trypanosoma cruzi infection, is a major cause of heart failure in Latin America. Galectin-3 (Gal-3) has been linked to cardiac remodeling and poor prognosis in heart failure of different etiologies. Herein, we investigated the involvement of Gal-3 in the disease pathogenesis and its role as a target for disease intervention. Gal-3 expression in mouse hearts was evaluated during T. cruzi infection by confocal microscopy and flow cytometry analysis, showing a high expression in macrophages, T cells, and fibroblasts. In vitro studies using Gal-3 knockdown in cardiac fibroblasts demonstrated that Gal-3 regulates cell survival, proliferation, and type I collagen synthesis. In vivo blockade of Gal-3 with N-acetyl-d-lactosamine in T. cruzi-infected mice led to a significant reduction of cardiac fibrosis and inflammation in the heart. Moreover, a modulation in the expression of proinflammatory genes in the heart was observed. Finally, histological analysis in human heart samples obtained from subjects with Chagas disease who underwent heart transplantation showed the expression of Gal-3 in areas of inflammation, similar to the mouse model. Our results indicate that Gal-3 plays a role in the pathogenesis of experimental chronic Chagas disease, favoring inflammation and fibrogenesis. Moreover, by demonstrating Gal-3 expression in human hearts, our finding reinforces that this protein could be a novel target for drug development for Chagas cardiomyopathy.


Distribution of kisspeptin system and its relation with gonadotropin-releasing hormone in the hypothalamus of the South American plains vizcacha, Lagostomus maximus.
Kisspeptin (KISS), a key hormone involved in the regulation of the hypothalamic-pituitary-ovarian (HPO) axis, has been localized in the anteroventral periventricular (AVPV) nucleus and the neighboring rostral periventricular nucleus (PeVN), and in the arcuate (ARC) nucleus of the mammalian hypothalamus. In the ARC, the KISS neurons that co-express neurokinin B (NKB) and dynorphin A (Dyn) are named KNDy cells. The South American plains vizcacha is a rodent with peculiar reproductive traits. Around mid-pregnancy, vizcacha shows the reactivation of its HPO axis with the pulsatile release of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH), an essential event for the success of gestation. Considering the role of KISS system in GnRH modulation, the aim of this work was to study their neuroanatomical distribution in adult vizcachas. AVPV showed sexual dimorphism with a significant smaller area in males (t-Test, p < 0.05), and KISS immunoreactivity was detected in somas and varicosities homogenously distributed in the AVPV with a concordant sex-related expression pattern. NKB and Dyn expression was also observed in cytoplasm of neurons scattered in the AVPV. Three subpopulations of neurons were detected in the AVPV: neurons expressing Dyn and NKB (DyNK cells), neurons expressing KISS and NKB (KiNK cells), and single NKB expressing neurons. Strikingly, KISS and Dyn were always expressed in different cells. In addition, in the ARC nucleus, KNDy cells were detected. On the other hand, KISS and GnRH expression was detected in different subpopulations of neurons, GnRH cells showed KISS receptor (KISSR or GPR-54) expression, and KISS immunoreactive afferent contacts were detected making close appositions onto somas and dendrites of GnRH cells. These results show similarities and differences between the KISS system in the hypothalamus of the vizcacha and other mammals, and constitute crucial observations about KISS and GnRH relation. Considering the peculiarity of HPO axis regulation in this species, the present work provides a neuroanatomical framework for the further elucidation of molecular mechanisms underlying GnRH expression and secretion.


An approach to the determination of endotoxin in anesthetics and antibiotics: use of an ultrafiltration system and enzymatic LAL reaction.
An ultrafiltration system is used to obtain an endotoxin-free buffer for the LAL test. The procedure is combined with a kinetic LAL reaction of high sensitivity. This approach allows for the easy determination of endotoxin levels in parenterals with LAL-interfering substances, reducing the maximum valid dilution necessary for use in product development.


Effect of prophylactic vitamin C administration on the efficiency of florfenicol or sulfadiazine-trimethoprim antimicrobial therapy in chickens with staphylococcal arthritis.
Septic arthritis (SA) in chickens shows improper response to antibacterial therapy. This study evaluates the effect of prophylactic vitamin C administration on the efficiency of sulfadiazine-trimethoprim (SDT) or florfenicol (FF) in broilers with experimental SA. Broilers (210) were randomly allocated into 7 equal groups: (I) negative control (NC) (normal birds); (II) positive control (PC) arthritic birds by injection of Staphylococcus aureus in tibiotarsal joint at the age of 35 days; (III) vehicle control (injected with sterile medium); (IV) arthritic FF-treated (20 mg/kg/day); (V) arthritic vitamin C + FF-treated (as above + vitamin C at 15 g/100L of D.W. from day 25 of age); (VI) arthritic SDT-treated (35 mg/kg/day); (VII) arthritic vitamin C + SDT-treated. Antibacterial therapy started at day 39 of age and lasted for 5 days. Samplings were performed at the age of 44 and 54 days. A long lasting SA with severe fibrinoheterophilic synovitis and reduced body weights developed in PC broilers as compared to NC group (p < 0.05). Oxidative stress was present at sampling 1. Arthritis was not reflected in IL-6 levels of synovial fluid of PC group. None of the antibacterials resulted in completely successful treatment. Vitamin C did not appreciably improve lameness and arthritis scores, although it decreased lipid peroxidation and improved weights of FF treated-arthritic birds. For SDT-treated birds, vitamin C only ameliorated histopathological changes. In conclusion, except for improving body weight in FF-treated birds, prophylactic administration of vitamin C is not associated with improvements in clinical outcome of antimicrobial therapy of broilers with SA, although it ameliorates oxidative stress and some histopathological changes.


V region T cell receptor repertoire in Parkinson's disease.
Restricted usage of V alpha and beta genes has been found in several diseases, which exert autoreactive T cells. So far no information on T cell receptor (TCR) usage in degenerative diseases is available. Since T cells may be involved in pathogenesis of Parkinson's disease, the analysis of the TCR repertoire is of importance. We have tested the frequency of 6 V beta-subtypes and the most common V alpha-subfamily on peripheral blood lymphocytes in 21 PD patients and 20 controls, separately on CD4+ and CD8+ T cells. For our study Diversi--T, the first available Mab set specific for TCR V regions, was used. As a results, no significant differences were found with one exception, i.e., lower frequency of V beta 8(a) expression on CD8+ T cells in PD patients than in controls. The failure of preferential usage or lack of usage of the tested V-chain alleles by CD4+ T cells argues against an involvement of helper T cells in PD induction.


The complete mitochondrial genomes and phylogenetic analysis of two Nycteribiidae bat flies (Diptera: Hippoboscoidea).
We sequenced the complete mitochondrial genomes of two bat fly species within the Nycteribiidae (Diptera: Hippoboscoidea) - Dipseliopoda setosa (Cyclopodiinae) and Basilia ansifera (Nycteribiinae). Both mitogenomes were complete and contained 13 protein-coding genes, 22 tRNAs, and two rRNAs. Relative to the inferred ancestral gene order of dipteran mitochondrial genomes, no rearrangements were identified in either species. There were large differences in size between the two genomes, with D. setosa having a larger genome (19,164 bp) than B. ansifera (16,964 bp); both species had larger genomes than two previously published Streblidae bat fly species (e.g., Paradyschiria parvula and Paratrichobius longicrus). The increased genome sizes were due to expansions in the control region and the non-coding region downstream of the light-strand origin of replication. Additional differences between the two mitogenomes included a significantly longer cox3 gene in B. ansifera and a longer nad1 gene in D. setosa. Interestingly, both genomes also had the lowest GC content (D. setosa - 15.9%; B. ansifera - 17.0%) of any available Hippoboscoidea mitochondrial genome (18.8-23.9%). These mitogenomes represent the first sequences from species within the bat fly family Nycteribiidae. The sequence data here will provide a foundation for continued studies of genome evolution more generally within obligate blood-feeding ectoparasites, and specifically for the bat flies as vectors of significant 'bat-associated' viruses and microorganisms.


Identification of a novel WT1-derived peptide which induces human leucocyte antigen-A24-restricted anti-leukaemia cytotoxic T lymphocytes.
We previously reported the establishment of a Wilms' tumour (WT)1-derived peptide (CMTWNQMNL)-specific and human leucocyte antigen (HLA)-A24-restricted anti-leukaemia cytotoxic T lymphocyte (CTL) line, TAK-1. In this study, we have established a novel WT1-derived peptide (RWPSCQKKF)-specific CD8+ CTL line, designated NIM-1. NIM-1 lysed HLA-A24-positive leukaemia cells, but not HLA-A24-negative leukaemia cells or normal cells. The effects of TAK-1 and NIM-1 on cytotoxicity against leukaemia cells were not synergistic, suggesting that recognition of a single epitope on the tumour-specific antigen by CTLs is sufficient to exert maximal cytotoxic activity against tumour cells.


Foot function and strength of patients with diabetes grouped by ulcer risk classification (IWGDF).
The stratification system from the International Working Group on the Diabetic Foot (IWGDF) was used to classify the participants as to the ulcer risk. However, it is not yet known what the classification groups' individual deficits are regarding sensitivity, function, and musculoskeletal properties and mechanics. This makes it difficult to design proper ulcer prevention strategies for patients. Thus, this study aimed to investigate the foot function, foot strength and health of people with diabetes mellitus (DM)-with or without DPN-while considering the different ulcer risk classifications determined by the IWGDF. The subject pool comprised 72 people with DM, with and without DPN. The patients were divided into three groups: Group 0 (G0), which comprised diabetic patients without DPN; Group 1 (G1), which comprised patients with DPN; and Group 2 (G2), which comprised patients with DPN who had foot deformities. The health and foot function of the subjects' feet were assessed using a foot health status questionnaire (FHSQ-BR) that investigated four domains: foot pain, foot function, footwear, and general foot health. The patients' foot strength was evaluated using the maximum force under each subject's hallux and toes on a pressure platform (emed q-100, Novel, Munich, Germany). Moderate differences were found between G0 and G1 and G2 for the foot pain, foot function, general foot health, and footwear. There was also a small but significant difference between G0 and G2 in regards to hallux strength. Foot health, foot function and strength levels of people with DM and DPN classified by the ulcer risk are different and this must be taken into account when evaluating and developing treatment strategies for these patients.


Gallic acid: molecular rival of cancer.
Gallic acid, a predominant polyphenol, has been shown to inhibit carcinogenesis in animal models and in vitro cancerous cell lines. The inhibitory effect of gallic acid on cancer cell growth is mediated via the modulation of genes which encodes for cell cycle, metastasis, angiogenesis and apoptosis. Gallic acid inhibits activation of NF-κB and Akt signaling pathways along with the activity of COX, ribonucleotide reductase and GSH. Moreover, gallic acid activates ATM kinase signaling pathways to prevent the processes of carcinogenesis. The data so far available, both from in vivo and in vitro studies, indicate that this dietary polyphenol could be promising agent in the field of cancer chemoprevention.


Treatment of Cancer-related-Fatigue in Acute Hematological Malignancies: Results of a Feasibility Study of using Cognitive Behavioral Therapy.
Despite cancer related fatigue (CRF) being the most common, and debilitating symptom in patients with recently diagnosed acute hematological malignancies (HM), there are limited effective treatments for CRF in HM. The aim of this study was to determine the feasibility of cognitive behavioral therapy (CBT) for CRF in HM. In this preliminary longitudinal prospective study, HM patients diagnosed a median of one month previously with moderate to severe fatigue were enrolled. Patients received CBT in seven weekly sessions for eight weeks. Change in Functional Assessment of Cancer Illness Therapy (FACIT) - Fatigue (primary), FACT-G, Pittsburg Sleep Quality Index (PSQI), Hospital Anxiety Depression Scale (HADS), M.D. Anderson Symptom Inventory - Acute Myeloid Leukemia (MDASI-AML/MDS), and Herth Hope Index (HHI) were analyzed. Twenty-seven of 36 (75 %) patients were evaluable. Adherence and satisfaction rates to the CBT intervention were 78.6% (95% CI 67.2%, 89.9%), and 92% (95% CI 76.7%, 98.3%) respectively. The median age 66, 64% female, the most common HM was AML (60%), median FACIT-F was 27. The mean (SD) improvement at end eight weeks for FACIT-F was 5.5(13.6), Cohen δ 0.4, P=0.046; and for PSQI total was 2.9 (3), Cohen δ -1, P=0.006. We also found significant improvement in HADS anxiety -2.7(4.5), P=0.049, MDASI Sleep -1.8(3.0), P=0.022, MDASI mean module symptom severity -0.7(1.6), P=0.006. However, no significant improvements were found in FACT-G, HHI, and HADS-depression scores. The use of CBT was feasible with improvement of CRF, sleep quality, and anxiety scores in HM. Randomized controlled trials are justified.


Changes at an activated sludge sewage treatment plant alter the numbers of airborne aerobic microorganisms.
In 1976, the activated sludge sewage treatment plant in Edmonton, Canada, was surveyed to determine the numbers of culturable airborne microorganisms. Many changes have been made at the plant to reduce odors and improve treatment efficiency, so in 2004 another survey was done to determine if these changes had reduced the bioaerosols. Covering the grit tanks and primary settling tanks greatly reduced the numbers of airborne microbes. Changing the design and operation of indoor automated sampling taps and sinks also reduced bioaerosols. The secondary was expanded and converted from a conventional activated sludge process using coarse bubble aeration to a biological nutrient removal system using fine bubble aeration. Although the surface area of the secondary more than doubled, the average number of airborne microorganisms in this part of the plant in 2004 was about 1% of that in 1976.


Inter-rater and intra-rater reliability of finger goniometry measured from screenshots taken via video consultation.
The purpose of this study was to assess the intra- and inter-rater reliability of using screenshots and handheld manual goniometers to assess range of finger movements during video consultations. Twenty-seven hand therapists measured finger joint angles from four different screenshots using two different goniometers. Results were compared within and between participants using the intraclass correlation coefficient (ICC). The ICC grading for both intra- and inter-rater reliability was moderate to excellent for all joints and both goniometers. Clinicians can measure finger joint angles from a screenshot with good reliability. The protocol used in this study can be used in remote video consultations as a no-cost substitute for in-person goniometry.Level of evidence: II.


Toward in vivo detection of hydrogen peroxide with ultrasound molecular imaging.
We present a new class of ultrasound molecular imaging agents that extend upon the design of micromotors that are designed to move through fluids by catalyzing hydrogen peroxide (H₂O₂) and propelling forward by escaping oxygen microbubbles. Micromotor converters require 62 mm of H₂O₂ to move - 1000-fold higher than is expected in vivo. Here, we aim to prove that ultrasound can detect the expelled microbubbles, to determine the minimum H₂O₂ concentration needed for microbubble detection, explore alternate designs to detect the H₂O₂ produced by activated neutrophils and perform preliminary in vivo testing. Oxygen microbubbles were detected by ultrasound at 2.5 mm H₂O₂. Best results were achieved with a 400-500 nm spherical design with alternating surface coatings of catalase and PSS over a silica core. The lowest detection limit of 10-100 μm was achieved when assays were done in plasma. Using this design, we detected the H₂O₂ produced by freshly isolated PMA-activated neutrophils allowing their distinction from naïve neutrophils. Finally, we were also able to show that direct injection of these nanospheres into an abscess in vivo enhanced ultrasound signal only when they contained catalase, and only when injected into an abscess, likely because of the elevated levels of H₂O₂ produced by inflammatory mediators.


PTBP1 acts as a dominant repressor of the aberrant tissue-specific splicing of ISCU in hereditary myopathy with lactic acidosis.
Hereditary myopathy with lactic acidosis (HML) is an autosomal recessive disease caused by an intron mutation in the iron-sulfur cluster assembly (ISCU) gene. The mutation results in aberrant splicing, where part of the intron is retained in the final mRNA transcript, giving rise to a truncated nonfunctional ISCU protein. Using an ISCU mini-gene system, we have previously shown that PTBP1 can act as a repressor of the mis-splicing of ISCU, where overexpression of PTBP1 resulted in a decrease of the incorrect splicing. In this study, we wanted to, in more detail, analyze the role of PTBP1 in the regulation of endogenous ISCU mis-splicing. Overexpression and knockdown of PTBP1 was performed in myoblasts from two HML patients and a healthy control. Quantification of ISCU mis-splicing was done by qRTPCR. Biotinylated ISCU RNA, representing wildtype and mutant intron sequence, was used in a pull-down assay with nuclear extracts from myoblasts. Levels of PTBP1 in human cell lines and mice tissues were analyzed by qRTPCR and western blot. PTBP1 overexpression in HML patient myoblasts resulted in a substantial decrease of ISCU mis-splicing while knockdown of PTBP1 resulted in a drastic increase. The effect could be observed in both patient and control myoblasts. We could also show that PTBP1 interacts with both the mutant and wild-type ISCU intron sequence, but with a higher affinity to the mutant sequence. Furthermore, low levels of PTBP1 among examined mouse tissues correlated with high levels of incorrect splicing of ISCU. Our results show that PTBP1 acts as a dominant repressor of ISCU mis-splicing. We also show an inverse correlation between the levels of PTBP1 and ISCU mis-splicing, suggesting that the high level of mis-splicing in the skeletal muscle is primarily due to the low levels of PTBP1.


Conformationally restricted anti-plasmodial chalcones.
Chalcones can exist as Z- or E-isomers and it is generally anticipated that both isomers are equipotent. In order to determine the active isomer of anti-plasmodial chalcones a series of analogues locked in the Z- or the E-form were prepared and evaluated for their anti-plasmodial activity. It was shown that the Z-locked analogue was nearly inactive, whereas the E-locked analogues were equipotent to the parent chalcones, indicating that the E-isomer is the active conformation.


Evaluation of synthetic isoflavones on cell proliferation, estrogen receptor binding affinity, and apoptosis in human breast cancer cells.
Natural isoflavones have demonstrated numerous pharmacological activities in breast cancer cells, including antiproliferative activities and binding affinities for estrogen receptors (ERs). Chemical modifications on the isoflavone ring system have been prepared and explored for the development of new therapeutics for hormone-dependent breast cancer. The antiproliferative actions of the synthesized isoflavones on MCF-7 and MDA-MB-231 breast cancer cells were examined, as well as cytotoxicity, interaction with estrogen receptors, and proapoptotic activity. The compounds were screened in the absence and in the presence of estradiol to evaluate whether or not estradiol could rescue cell proliferation on MCF-7 cells. Several compounds were able to inhibit cell proliferation in a dose-dependent manner, and compounds containing the bulky 7-phenylmethoxy substituent resulted in cell toxicity not only in MCF-7 cells but also in MDA-MB-231 cells. Selected synthetic isoflavones were able to bind to estrogen receptor with low affinity. Apoptotic pathways were also activated by these compounds in breast cancer cells. The majority of the compounds can bind to both ERs with low affinity, and their effects on hormone-independent breast cancer cells suggest that their ability to inhibit cell growth in breast cancer cells is not exclusively mediated by ERs. Thus, the synthetic trisubstituted isoflavones act on multiple signaling pathways leading to activation of mechanisms of cell-death and ultimately affecting breast cancer cell survival.


Towards identification of the scale insects (Hemiptera: Coccomorpha) of continental Africa: 2. Checklists and keys to six archaeococcoid families.
Scale insects (Hemiptera: Sternorrhyncha: Coccomorpha) feed on plant sap; some are damaging pests in agriculture and forestry. However, the scale insects found in continental Africa have not been extensively studied and the available means of identification are incomplete. This synoptic work, the second in this series, covers the six archaeococcoid scale insect families found in continental Africa: Kuwaniidae, Margarodidae, Matsucoccidae, Monophlebidae, Ortheziidae and Putoidae. The work provides identification keys to a total of 29 genera and 137 species, and a checklist for each family. Pseudaspidoproctus zimmermanni (Newstead) (Monophlebidae) is transferred to Aspidoproctus, as Aspidoproctus zimmermanni (Newstead), comb. n. Praelongorthezia praelonga (Douglas) (Ortheziidae) is recorded from Gambia for the first time.


Role of mTOR in the degradation of IRS-1: regulation of PP2A activity.
We have investigated the role of PI 3-kinase and mTOR in the degradation of IRS-1 induced by insulin. Inhibition of mTOR with rapamycin resulted in approximately 50% inhibition of the insulin-induced degradation of IRS-1. In contrast, inhibition of PI-3 kinase, an upstream activator of mTOR, leads to a complete block of the insulin-induced degradation. Inhibition of either PI-3 kinase or mTOR prevented the mobility shift in IRS-1 in response to insulin, a shift that is caused by Ser/Thr phosphorylation. These results indicate that insulin stimulates PI 3-kinase-mediated degradation of IRS-1 via both mTOR-dependent and -independent pathways. Platelet-derived growth factor (PDGF) stimulation leads to a lower level of degradation, but significant phosphorylation of IRS-1. Both the degradation and phosphorylation of IRS-1 in response to PDGF are completely inhibited by rapamycin, suggesting that PDGF stimulates IRS-1 degradation principally via the mTOR-dependent pathway. Inhibition of the serine/threonine phosphatase PP2A with okadaic acid also induced the phosphorylation and degradation of IRS-1. IRS-1 phosphorylation and degradation in response to okadaic acid were not inhibited by rapamycin, suggesting that the action of mTOR in the degradation of IRS-1 results from inhibition of PP2A. Consistent with this, treatment of cells with rapamycin stimulated PP2A activity. While the role of mTOR in the phosphorylation of IRS-1 appears to proceed primarily through the regulation of PP2A, we also provide evidence that the regulation of p70S6 kinase phosphorylation requires the direct activity of mTOR.


Indoleamine 2,3 dioxygenase contributes to transferable tolerance in rat red blood cell inducible model of experimental autoimmune haemolytic anaemia.
Autoimmune haemolytic anaemia (AIHA) is caused by autoantibodies against red blood cell (RBC) surface antigens that render RBC susceptible to Fc-mediated phagocytosis and complement-mediated lysis. Experimental AIHA can be induced by injection of rat RBC to naive mice, but a lymphocyte-mediated regulatory mechanism eventually suppresses the production of autoantibodies specific for mouse RBC. Critically, this tolerogenic response can be transferred to naive mice by splenocytes from the rat RBC-immunized mouse. Here we investigate whether indoleamine 2,3 dioxygenase (IDO) or the initiators of IDO cascade, including the cytotoxic T lymphocyte antigen (CTLA)-4 receptor and its soluble isoform, contribute to this tolerogenic mechanism. Splenocytes from experimental AIHA mice were transferred adoptively to naive mice under the cover of anti-CTLA-4, anti-soluble CTLA-4 antibodies or IDO inhibitor 1-methyl tryptophan (1-MT). Recipient mice were immunized with rat RBC and levels of antibody against self-RBC and rat-RBC were monitored. Our results indicate that transfer of tolerance to naive recipients is dependent upon IDO-mediated immunosuppression, as mice receiving previously tolerized splenocytes under the cover of 1-MT were refractory to tolerance and developed haemolytic disease upon further challenge with rat RBC. Initiators of IDO activity, CTLA-4 or soluble CTLA-4 did not mediate this tolerogenic process but, on their blockade, boosted antigen-specific effector immune responses.


Vasorelaxation to capsaicin and its effects on calcium influx in arteries.
Capsaicin, an activator of the transient potential vanilloid receptor type 1 (TRPV1), is a commonly used pharmacological tool for desensitising sensory nerves. Capsaicin can induce vasorelaxation of isolated blood vessels by activating perivascular TRPV1 receptors, causing the release of vasoactive neuropeptides. This study attempted to characterise the vascular effects of capsaicin in the rat isolated aorta and porcine coronary arteries. Capsaicin elicited concentration-dependent vasorelaxation of both rat aortae and porcine coronary arteries. Capsaicin-induced vasorelaxation of rat aorta was unaffected by a chronic pre-treatment of vessels with capsaicin. Moreover, relaxation was insensitive to the presence of capsazepine, a competitive TRPV1 antagonist, in both the rat aorta and porcine coronary artery. It was hypothesised that capsaicin may be inhibiting calcium influx into smooth muscle cells. Indeed, in vessels incubated in a Ca²⁺-free high-k⁺ buffer, the presence of 30 μM capsaicin significantly inhibited the contractile response to the re-introduction of Ca²⁺. In porcine coronary arteries 100 μM capsaicin completely abolished the contractile response to the re-introduction of Ca²⁺. In addition, capsaicin also abolished the concentration-dependent contraction of porcine coronary arteries induced by the L-type calcium activator Bay-K 8644. Therefore, we suggest that capsaicin causes vascular responses in arteries through the inhibition of L-type Ca²⁺ channels. In summary,we have identified a potential mechanism underlying TRPV1-independent capsaicin-induced vasorelaxation. Our results also question the use of chronic capsaicin pre-treatment in experimental pharmacology in order to elucidate the role of sensory nerves in vascular responses.


The compensatory reserve index predicts recurrent shock in patients with severe dengue.
Dengue shock syndrome (DSS) is one of the major clinical phenotypes of severe dengue. It is defined by significant plasma leak, leading to intravascular volume depletion and eventually cardiovascular collapse. The compensatory reserve Index (CRI) is a new physiological parameter, derived from feature analysis of the pulse arterial waveform that tracks real-time changes in central volume. We investigated the utility of CRI to predict recurrent shock in severe dengue patients admitted to the ICU. We performed a prospective observational study in the pediatric and adult intensive care units at the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. Patients were monitored with hourly clinical parameters and vital signs, in addition to continuous recording of the arterial waveform using pulse oximetry. The waveform data was wirelessly transmitted to a laptop where it was synchronized with the patient's clinical data. One hundred three patients with suspected severe dengue were recruited to this study. Sixty-three patients had the minimum required dataset for analysis. Median age was 11 years (IQR 8-14 years). CRI had a negative correlation with heart rate and moderate negative association with blood pressure. CRI was found to predict recurrent shock within 12 h of being measured (OR 2.24, 95% CI 1.54-3.26), P < 0.001). The median duration from CRI measurement to the first recurrent shock was 5.4 h (IQR 2.9-6.8). A CRI cutoff of 0.4 provided the best combination of sensitivity and specificity for predicting recurrent shock (0.66 [95% CI 0.47-0.85] and 0.86 [95% CI 0.80-0.92] respectively). CRI is a useful non-invasive method for monitoring intravascular volume status in patients with severe dengue.


Cellular pharmacology of chloroquinoxaline sulfonamide and a related compound in murine B16 melanoma cells.
Chloroquinoxaline sulfonamide (CQS), a chlorinated derivative of sulfaquinoxaline (SQ), inhibited proliferation of murine B16 melanoma cells, but only when relatively high drug concentrations (1 mM) were used. The inhibition of cell growth by CQS was at least partially reversible by incubation in drug-free medium. Incubation of melanoma cells with CQS was associated with an arrest of the cell cycle in G0/G1 as measured by flow cytometry. The drug slightly decreased uptake of radiolabeled deoxyuridine and thymidine after 24- and 48-hr incubation periods but increased nucleoside incorporation at 72 hr. No evidence of intercalation with DNA was found. Because SQ previously was reported to inhibit an aspect of folate metabolism, we investigated the possibility that CQS limits tumor cell growth by altering folate homeostasis. This appears unlikely, however, in view of the following observations: (1) the cytotoxic effects of CQS could not be reversed by folinic acid; (2) deoxyuridine suppression of thymidine incorporation was not affected by CQS treatment; (3) CQS did not inhibit dihydrofolate reductase from mammalian or bacterial sources; and (4) CQS toxicity in mice was not reduced by folinic acid. Experiments performed with analogues modified in the quinoxaline and para-amino phenyl functions indicated that tumor cell inhibition did not require preservation of the conventional sulfonamide structure.


Solid-State [4+4] Cycloaddition and Cycloreversion with Use of Unpaired Hydrogen-Bond Donors to Achieve Solvatomorphism and Stabilization.
The crystal structure of a commercially available anthracene derivative, anthracene-9-thiocarboxamide, is reported here for the first time. The compound undergoes a [4+4] cycloaddition in the solid state to afford facile synthesis of the cycloadduct (CA). The cycloaddition is also reversible in the solid state using heat or mechanical force. Due to the presence of unpaired, strong hydrogen-bond donor atoms on the CA, significant solvatomorphism is achieved, and components of the solvatomorphs self-assemble into four different classes of supramolecular structures. The CA readily crystallizes with a variety of structurally-diverse solvents including those containing oxygen-, nitrogen-, or pi-acceptors. Some of the solvents the CA crystallized with include thiophene, benzene, and the three xylene isomers; thus, the CA was employed in industrially-relevant solvent separation. However, in competition studies, the CA did not exhibit selectivity. Lastly, it is demonstrated that the CA crystallizes with vinyl-containing monomers and is currently the only compound that crystallizes with both widely used monomers 4-vinylpyridine and styrene. Solid-state complexation of the CA with the monomers affords over a 50 °C increase in the monomer's thermal stabilities. The strategy of designing molecules with unused donors can be applied to achieve separations or volatile liquid stabilization.


COVID infection in 4 steps: Thermodynamic considerations reveal how viral mucosal diffusion, target receptor affinity and furin cleavage act in concert to drive the nature and degree of infection in human COVID-19 disease.
We have developed a mechanistic model of SARS-CoV-2 and SARS-CoV infection, exploring the relationship between the viral diffusion in the mucosa and viral affinity for the angiotensin converting enzyme 2 (ACE2) target. Utilising the structural similarity of SARS-CoV and SARS-CoV-2 and a shared viral target receptor (ACE2), but a dramatic difference in upper or lower respiratory tract infectivity, we were able to generate insights into the linkage of mucosal diffusion and target receptor affinity in determining the pathophysiological pathways of these two viruses. Our analysis reveals that for SARS-CoV-2 the higher affinity of ACE2 binding, the faster and more complete the mucosal diffusion in its transport from the upper airway to the region of the ACE2 target on the epithelium. This diffusional process is essential for the presentation of this virus to the furin catalysed highly efficient entry and infection process in the upper respiratory tract epithelial cells. A failure of SARS-CoV to follow this path is associated with lower respiratory tract infection and decreased infectivity. Thus, our analysis supports the view that through tropism SARS-CoV-2 has evolved a highly efficient membrane entry process that can act in concert with a high binding affinity of this virus and its variants for its ACE2 which in turn promotes enhanced movement of the virus from airway to epithelium. In this way ongoing mutations yielding higher affinities of SARS-CoV-2 for the ACE2 target becomes the basis for higher upper respiratory tract infectivity and greater viral spread. It is concluded that SARS-CoV-2 is constrained in the extent of its activities by the fundamental laws of physics and thermodynamics. Laws that describe diffusion and molecular binding. Moreover it can be speculated that the very earliest contact of this virus with the human mucosa defines the pathogenesis of this infection.


Tamavidin 2-REV: an engineered tamavidin with reversible biotin-binding capability.
A biotin-binding protein with reversible biotin-binding capability is of great technical value in the affinity purification of biotinylated biomolecules. Although several proteins, chemically or genetically modified from avidin or streptavidin, with reversible biotin-binding have been reported, they have been problematic in one way or another. Tamavidin 2 is a fungal protein similar to avidin and streptavidin in biotin-binding. Here, a mutein, tamavidin 2-REV, was engineered from tamavidin 2 by replacing the serine at position 36 (S36) with alanine. S36 is thought to form a hydrogen bond with biotin in tamavidin 2/biotin complexes and two hydrogen bonds with V38 within the protein. Tamavidin 2-REV bound to biotin-agarose and was eluted with excess free biotin at a neutral pH. In addition, the model substrate biotinylated bovine serum albumin was efficiently purified from a crude extract from Escherichia coli by means of single-step affinity chromatography with tamavidin 2-REV-immobilized resin. Tamavidin 2-REV thus demonstrated reversible biotin-binding capability. The Kd value of tamavidin 2-REV to biotin was 2.8-4.4×10(-7)M.Tamavidin 2-REV retained other convenient characteristics of tamavidin 2, such as high-level expression in E. coli, resistance to proteases, and a neutral isoelectric point, demonstrating that tamavidin 2-REV is a powerful tool for the purification of biotinylated biomolecules.


A national census of medicines use: a 24-hour snapshot of Australians aged 50 years and older.
To explore the current use of conventional and complementary medicines in Australians aged ≥ 50 years. Cross-sectional postal survey sent to a random sample of 4500 Australians aged ≥ 50 years between June 2009 and February 2010. Prevalence of medicines use, reasons for medicines use and sources of medicines. Response rate was 37.3%. Medicines use was very common; 87.1% of participants took one or more medicines and 43.3% took five or more in the previous 24 hours. Complementary medicines were used by 46.3% of participants, 87.4% of whom used both conventional and complementary medicines. The most commonly used medicines were antihypertensive agents (43.2% of participants), natural marine and animal products including fish oil and glucosamine (32.4%) and lipid-lowering agents (30.4%). Doctors recommended 79.3% of all medicines and 93.0% of conventional medicines. Pharmacists commonly recommended occasional medicines (ie, as needed), while friends, family and media most often influenced use of complementary medicines. The use of multiple medicines is common and higher than reported in the 1995 National Health Survey. Today, much medicines use is to prevent future disease by influencing risk factors. High levels of polypharmacy highlight the need to support the safe and effective use of medicines in the community. Although doctors recommend or prescribe most medicines, self-directed medication use is common. This highlights the need for consumer access to accurate information and strategies to improve health literacy about medicines.


Epidermal growth factor-independent transformation of Ba/F3 cells with cancer-derived epidermal growth factor receptor mutants induces gefitinib-sensitive cell cycle progression.
Epidermal growth factor receptor (EGFR) plays critical roles in many biological processes and in tumorigenesis. Here, we show that two mutated EGFRs found in lung and other malignancies, EGFR-G719S and EGFR-L858R, could transform Ba/F3 cells to interleukin-3 (IL-3)-independent growth, in a ligand-independent manner, an activity associated with the transforming function of other mutated tyrosine kinases. The mutated receptors are autophosphorylated in the absence of IL-3 without EGF stimulation, and their expression led to the constitutive activation of signal transducers and activators of transcription 5, extracellular signal-regulated kinase 1/2 (ERK1/2), ERK5, and AKT. In wild-type EGFR-expressing Ba/F3 cells, the major EGF-mediated signaling pathways were still intact. Gefitinib inhibited the growth of mutant EGFR-transformed Ba/F3 cells. Strikingly, the gefitinib sensitivity of cells expressing the L858R mutant was significantly greater than that of cells expressing the G719S mutant form, suggesting that distinct EGFR mutations may be differentially sensitive to small-molecule inhibitors. Furthermore, our data showed an antiproliferative effect of gefitinib on the EGFR-transformed Ba/F3 cells. Our results provide a model system to study the function of mutated EGFR and the differential effects of pharmacologic EGFR inhibition on the distinct mutant forms of this tyrosine kinase.


The effect of surface texture on the kinetic friction of a nanowire on a substrate.
The friction between Al2O3 nanowires and silicon substrates of different surface textures was characterised by use of optical manipulation. It was found that surface textures had significant effect on both the friction and the effective contact area between a nanowire and a substrate. A genetic algorithm was developed to determine the effective contact area between the nanowire and the textured substrate. The frictional force was found to be nearly proportional to the effective contact area, regardless of width, depth, spacing and orientation of the surface textures. Interlocking caused by textured grooves was not observed in this study.


Evidence of possible association of nephrolithiasis and nephroptosis.
Two separate populations, one consisting of 100 patients with renal stones and one consisting of 81 patients with nephroptosis were examined to determine whether an association may exist between excessive renal mobility and renal stone formation. The statistical analysis of the data suggests a direct relationship between nephroptosis and the occurrence of renal stones.


Microwave assisted biocidal extraction is an alternative method to measure microbial biomass of carbon from cultivated and non-cultivated soils.
Developing simple and cost-effective methods for soil microbial biomass carbon (MBC) measurement eases routine laboratory analysis and enables large numbers of soil samples to be measured in a relatively short period of time. Thus, the objective of this study was to develop a microwave-assisted biocidal-extraction (MWE) method which does not employ CHCl3 as biocide and K2SO4 as C-extractor, to estimate MBC. First, the microorganisms of soil samples are killed using microwave (MW) irradiation at energy level of 800 J g-1 soil as biocide followed by microwave irradiation extraction (MWE) at 562 W (120 J g-1 soil for 1 min), using deionized water as solvent. Microbial biomass of carbon from two contrasting soils microwaved with 80, 100, and 140 J g-1 soil did not differ from those obtained by using the chloroform fumigation-extraction (CFE) method with 0.5 mol L-1 K2SO4 as extractant. To evaluate the robustness of the MWE method, twenty-six soil samples, from cultivated and non-cultivated areas, with clay contents from 70-690 g kg-1, organic carbon from 5.52 to 50.82 g C kg-1 and pH values from 3.9 to 6.8 were analyzed for MBC using MWE and CFE methods. There was a linear regression (MW = - 17.87 + 0.92*K2SO4; R2 = 0.705; p < 0.001) between MWE and CFE. The biocidal microwave-assisted extraction method using 120 J g-1 soil for 1 min is a cleaner method for evaluating MBC, because it does not require chloroform, potassium sulfate salt and takes a shorter time to extract a set of soil samples.


In-depth proteomic analysis of a mollusc shell: acid-soluble and acid-insoluble matrix of the limpet Lottia gigantea.
Invertebrate biominerals are characterized by their extraordinary functionality and physical properties, such as strength, stiffness and toughness that by far exceed those of the pure mineral component of such composites. This is attributed to the organic matrix, secreted by specialized cells, which pervades and envelops the mineral crystals. Despite the obvious importance of the protein fraction of the organic matrix, only few in-depth proteomic studies have been performed due to the lack of comprehensive protein sequence databases. The recent public release of the gastropod Lottia gigantea genome sequence and the associated protein sequence database provides for the first time the opportunity to do a state-of-the-art proteomic in-depth analysis of the organic matrix of a mollusc shell. Using three different sodium hypochlorite washing protocols before shell demineralization, a total of 569 proteins were identified in Lottia gigantea shell matrix. Of these, 311 were assembled in a consensus proteome comprising identifications contained in all proteomes irrespective of shell cleaning procedure. Some of these proteins were similar in amino acid sequence, amino acid composition, or domain structure to proteins identified previously in different bivalve or gastropod shells, such as BMSP, dermatopontin, nacrein, perlustrin, perlucin, or Pif. In addition there were dozens of previously uncharacterized proteins, many containing repeated short linear motifs or homorepeats. Such proteins may play a role in shell matrix construction or control of mineralization processes. The organic matrix of Lottia gigantea shells is a complex mixture of proteins comprising possible homologs of some previously characterized mollusc shell proteins, but also many novel proteins with a possible function in biomineralization as framework building blocks or as regulatory components. We hope that this data set, the most comprehensive available at present, will provide a platform for the further exploration of biomineralization processes in molluscs.


Aspects of cognitive performance relating to Theory of Mind (ToM) among people diagnosed with Post-Traumatic Stress Disorder (PTSD) [Retraction].
[This retracts the article DOI: 10.2147/NDT.S214595.].


Effects of dithiocarb and (+)-cyanidanol-3 on the hepatotoxicity and metabolism of vinylidene chloride in rats.
The acute hepatotoxic effects of vinylidene chloride (VDC) were evidenced by measurement of the increase in the serum levels of the aminotransferase (GPT) and sorbitol dehydrogenase (SDH), hepatic glutathione (GSH) depletion and histological examinations in rats. The hepatoprotective agents dithiocarb and (+)-cyanidanol-3 proved well able to antagonize these toxic effects of VDC. While dithiocarb inhibited the in vivo metabolism of VDC in a closed exposure system, (+)-cyanidanol-3 had no influence at all. These findings substantiate the role of the microsomal monooxygenase system in the metabolism and hepatotoxicity of VDC. The mechanisms by which dithiocarb and (+)-cyanidanol-3 act as antihepatotoxic agents are different: the inhibition of the metabolic activation by dithiocarb and free radical-scavenging by (+)-cyanidanol-3.


Engineering Escherichia coli for efficient and economic production of C-glycosylflavonoids by deleting YhhW and regulating pH.
C-glycosylflavonoids have a number of pharmacological activities. An efficient method for the preparation of C-glycosylflavonoids is through metabolic engineering. Thus, it is important to prevent the degradation of C-glycosylflavonoids for producing C-glycosylflavonoids in the recombinant strain. In this study, two critical factors for the degradation of C-glycosylflavonoids were clarified. The quercetinase (YhhW) gene from Escherichia coli BL21(DE3) was expressed, purified, and characterized. YhhW effectively degraded quercetin 8-C-glucoside, orientin, and isoorientin, while the degradation of vitexin and isovitexin was not significant. Zn2+ can significantly reduce the degradation of C-glycosylflavonoids by inhibiting the activity of YhhW. pH was another key factor causing the degradation of C-glycosylflavonoids, and C-glycosylflavonoids were significantly degraded with pH exceeding 7.5 in vitro or in vivo. On this basis, two strategies, deleting YhhW gene from the genome of E. coli and regulating pH during the bioconversion, were developed to relieve the degradation of C-glycosylflavonoids. Finally, the total degradation rates for orientin and quercetin 8-C-glucoside decreased from 100 to 28% and 65% to 18%, respectively. The maximum yield of orientin reached 3353 mg/L with luteolin as substrate, and the maximum yield of quercetin 8-C-glucoside reached 2236 mg/L with quercetin as substrate. Therefore, the method described herein for relieving the degradation of C-glycosylflavonoids may be widely used for the biosynthesis of C-glycosylflavonoids in recombinant strains.


How do we measure a residual tumor size in histopathology (the gold standard) after neoadjuvant chemotherapy?
Accurate reporting of the residual tumor size by pathologists after neoadjuvant chemotherapy is an important component of a breast cancer. Recent literature reported comparisons regarding the accuracy of clinical and radiological residual tumor size findings using the histopathology as a "gold standard". However, the histopathological methods of measuring the residual tumor size are not standardized. Most pathologists use the tumor size measured by the gross examination. We collected 32 patient samples and compared the residual tumor size by gross and microscopic pathologic examinations. Using microscopic tumor size as the gold standard, our study showed gross tumor size is overestimated in 25%, underestimated in 56% and correlated to the final microscopic tumor size in 19% of the cases after neoadjuvant chemotherapy. Determining accurate residual tumor size to estimate pathologic response to chemotherapy is essential. We attempted to provide guidelines for pathology reporting post-neoadjuvant chemotherapy on breast cancers.


The immunolocalisation of VEGF in the articular cartilage of sheep mandibular condyles.
Vascular endothelial growth factor (VEGF) has recently been found to be essential for hypertrophic chondrocyte apoptosis and angiogenesis at the growth plate of long bones, indicating a central role in endochondral ossification. VEGF has more recently, also been shown to be expressed in articular cartilage chondrocytes in human osteoarthritic and rheumatoarthritic joints but not healthy adult joints. To investigate the role of VEGF in the fibrocartilage of the temporomandibular joint, this study aimed to document the presence and distribution of VEGF in the condylar articular cartilage of sheep temporomandibular joints. Mandibular condyles of the temporomandibular joints of five 18-month old Wether sheep were fixed, decalcified, paraffin embedded and sectioned. The sections were analyzed using immunohistochemistry for VEGF. VEGF was found to be localised predominantly to the proliferative and maturing layers of chondrocytes in the condylar fibrocartilage of the temporomandibular joints. Articular cartilage is an avascular and alymphatic tissue. As such, the localisation of VEGF to the articular cartilage of normal temporomandibular joint condyles suggests a role for VEGF other than angiogenesis. VEGF is shown here for the first time to be present in mandibular condylar cartilage, leading us to propose a possible role in non-angiogenic extracellular matrix remodeling.


Phase I study of tauromustine administered in a weekly schedule.
Tauromustine was administered orally in weekly doses with interindividual dose escalation to patients with disseminated malignant melanoma. The dose in the first cohort of 6 patients was 20 mg/m2/week. The dose escalation was 5 mg/m2/week. The limit of tolerance was 55 mg/m2/week. 99 patients completed at least 8 weeks of treatment and eight dose levels were evaluated for toxicity. Reversible thrombocytopenia, and to a lesser degree leukopenia, were dose limiting. From a starting dose of 40 mg/m2/week, the long-term tolerated dose was 35 mg/m2/week, thus achieving a considerable increase of dose intensity without a significant increase of toxicity by employing this weekly schedule of tauromustine.


Ecological risk assessments and context-dependence analysis of heavy metal contamination in the sediments of mangrove swamp in Leizhou Peninsula, China.
Sediments in eight types of mangroves were sampled in the Leizhou Peninsula. Heavy metals were analyzed to investigate the effects on metal distribution of mangrove communities, to evaluate contamination levels, identify sources and relationships between the two. Results showed that mangrove communities have effects on most heavy metal distributions in sediments, especially in the sediment with shrub communities of Aegiceras corniculatum where the contents of many metals are highest. As, Cr and Ni were identified as metal pollutants of primary concern, while Cd was of no concern. Zn, Pb, As mainly originated from anthropogenic source while the other metals are geogenic. Heavy metal distributions were affected by the independent and joint effects of landscape and sediment context; landscape context explains more variations in heavy metals than does sediment physicochemical variables. Total sulfur, total phosphorus and total potassium in sediment, and the existence of paddy field and forest land within 2000m around the sampling sites are significant variables also.


Use of an Interferon Gamma Release Assay (IGRA) to test T-cell responsiveness to soluble Leishmania infantum antigen in whole blood of dogs from endemic areas.
Interferon-Gamma (IFN-γ) Release Assays (IGRAs) are easy tests that allow rapid screening of primed memory T-cells immunity in response to antigen. The aim of this study was to use IGRA to assess IFN-γ release in response to Soluble Leishmania infantum antigen (SLA) in whole blood of dogs living in endemic area of visceral leishmaniasis and to interpret IGRA results according to clinical examination, specific anti-Leishmania humoral response and presence of L. infantum DNA in blood. The study was carried out on 56 dogs living in greater Tunis area. Physical examination, quantitative serology and PCR on blood were used to characterize dogs' status in relation to Leishmania infection and disease. IGRA consisted on testing by ELISA for IFN-γ-secretion in whole blood after a 20-h challenge with SLA. PBS and Phytohemagglutinin (PHA) stimulations were used as controls. Four groups of dogs were characterized: 31 were negative by both serology and PCR, two had doubtful serology, 10 presented no to mild clinical signs but low antibodies levels and 13 were affected by Canine Leishmaniasis (CanL). In seronegative dogs, IGRA was little contributory in 4 puppies (age <6months) and 5 old dogs (median age=72months, IQR: 45-84 months) that didn't respond to PHA stimulation, IGRA was negative in 19 and positive in three animals with lymph node enlargement. In dogs with doubtful serology, IGRA was positive in one dog and negative in the other. In infected dogs with no to mild clinical signs, one dog exhibited high level of IFN-γ in absence of antigenic stimulation and all the other were positive by IGRA. CanL dogs showed variable IGRA results. Negative IGRAs (n=4) were shown in animals with the highest parasitic burden whereas positive IGRAs (n=5) were shown in dogs with negative PCR or low parasitic load. The 4 remaining dogs either didn't respond to PHA (n=2) or showed non-specific secretion in PBS tube (n=2). The results of this study showed that IGRA is a useful new tool that can assess exposure to Leishmania in dogs with no to mild clinical signs in endemic area. Further comparative investigations using assays exploring cellular immunity are needed to determine its accuracy.


ViscY nuclear magnetic resonance experiments for in situ chemical reaction monitoring under spin diffusion conditions.
Viscosity-enhanced spectroscopY (ViscY) offers a new way to analyze complex mixtures of time-varying composition. This communication reports the use of the viscous binary solvent DMSO-d6/water to induce NMR spin diffusion for in situ chemical reaction monitoring and real-time characterization of a 3-substituted 4-hydroxycoumarin derivative and its side-product.


Preclinical Development and Validation of Translational Temperature Sensitive Iodized Oil Emulsion Mediated Transcatheter Arterial Chemo-Immuno-Embolization for the Treatment of Hepatocellular Carcinoma.
Herein a practical strategy for augmenting immune activation in transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) is presented. Pluronic F127 (PF127) is incorporated with Lipiodol (LPD) to achieve safe and effective delivery of therapeutic agents during transcatheter intra-arterial (IA) local delivery. Enhanced emulsion stability, IA infusion, embolic effect, safety, pharmacokinetics, and tumor response of Doxorubicin loaded PF127-LPD (Dox-PF127-LPD) for TACE in both in vitro and in vivo preclinical VX2 liver cancer rabbit model and N1S1 HCC rat model are demonstrated. Then, transcatheter arterial chemo-immuno-embolization (TACIE) combining TACE and local delivery of immune adjuvant (TLR9 agonist CpG oligodeoxynucleotide) is successfully performed using CpG-loaded Dox-PF127-LPD. Concurrent and safe local delivery of CpG and TACE during TACIE demonstrate leveraged TACE-induced immunogenic tumor microenvironment and augment systemic anti-tumor immunity in syngeneic N1S1 HCC rat model. Finally, the broad utility and enhanced therapeutic efficacy of TACIE are validated in the diethylnitrosamine-induced rat HCC model. TACIE using clinically established protocols and materials shall be a convenient and powerful therapeutic approach that can be translated to patients with HCC. The robust anti-cancer immunity and tumor regression of TACIE, along with its favorable safety profile, indicate its potential as a novel localized combination immunotherapy for HCC treatment.


Mangrove succession enriches the sediment microbial community in South China.
Sediment microorganisms help create and maintain mangrove ecosystems. Although the changes in vegetation during mangrove forest succession have been well studied, the changes in the sediment microbial community during mangrove succession are poorly understood. To investigate the changes in the sediment microbial community during succession of mangroves at Zhanjiang, South China, we used phospholipid fatty acid (PLFA) analysis and the following chronosequence from primary to climax community: unvegetated shoal; Avicennia marina community; Aegiceras corniculatum community; and Bruguiera gymnorrhiza + Rhizophora stylosa community. The PLFA concentrations of all sediment microbial groups (total microorganisms, fungi, gram-positive bacteria, gram-negative bacteria, and actinomycetes) increased significantly with each stage of mangrove succession. Microbial PLFA concentrations in the sediment were significantly lower in the wet season than in the dry season. Regression and ordination analyses indicated that the changes in the microbial community with mangrove succession were mainly associated with properties of the aboveground vegetation (mainly plant height) and the sediment (mainly sediment organic matter and total nitrogen). The changes in the sediment microbial community can probably be explained by increases in nutrients and microhabitat heterogeneity during mangrove succession.


Impact of FDG PET-CT imaging on the decision making in the biologic suspicion of ovarian carcinoma recurrence.
The aim of this prospective study was to evaluate the impact of integrated PET-CT on treatment management in ovarian carcinoma recurrence suspicion because of increased CA-125. Twenty-nine patients (mean age=61 years), initially treated for ovarian carcinoma (FIGO stage I n=2, stage II n=3, stage III n=21 and stage IV n=3), presenting with increased CA-125 (mean=160 IU/ml, range 33-1930), underwent subsequently a CT and a PET-CT scans. The recurrence was acknowledged by the referring physicians for all patients. The impact of PET-CT on patient's management was evaluated by comparing the therapeutic decision mentioned respectively on the pre and post PET-CT questionnaires filled in by the oncologists. The CT scan was positive in 22/29 patients (76%) and negative in 7/29 patients (24%). The PET-CT scan was positive in 27/29 patients (93%) and negative in 2/29 (7%) patients. Five out of the seven patients with a negative CT scan had a positive PET-CT scan. In comparison to CT scan alone, the PET-CT scan modified the disease distribution for 16 patients (55%; p<0.001) in the following ways: more advanced disease (n=11), more limited disease (n=4), and different localizations (n=1). The assessment of pre and post PET-CT questionnaires showed a statistically significant change in the decision making for 10 patients (34%, p<0.0001). This questionnaire-based study showed that PET-CT imaging allows a better restaging than CT and induces a change in clinical management in over one third of patients with suspected ovarian carcinoma recurrence on increased CA-125.


Amyloid-β peptide-induced extracellular S100A9 depletion is associated with decrease of antimicrobial peptide activity in human THP-1 monocytes.
S100A9 protein (myeloid-related protein MRP14, also referred to as calgranulin B) is a reliable marker of inflammation, an important proinflammatory factor of innate immunity and acts as an additional antimicrobial peptide in the innate immune system. Evidence indicates that S100A9 contributes to Alzheimer's disease (AD) pathology, although the precise mechanisms are not clear. We were interested to study the mechanisms of S100A9 release upon Aβ1-42 stimulation, the potential roles of extracellular S100A9 depletion in Aβ-induced cytotoxicity, and the interaction with innate immune response in THP-1 monocytic cells that have been challenged with mostly Aβ1-42 monomers instead of oligomers. We used protein preparation, Ca(2+) influx fluorescence imaging, MTT assay, siRNA knockdown, colony forming units (CFUs) assay and western blotting techniques to perform our study. Aβ1-42 monomers elicited a marked decrease of S100A9 release into the cell culture supernatant in a dose-dependent manner in human THP-1 monocytes. This reduction of S100A9 release was accompanied by an increase of intracellular Ca(2+) level. Aβ1-42-mediated decrease of S100A9 release was not associated with Aβ1-42-induced cytotoxicity as measured by MTT reduction assay. This observation was confirmed with the recombinant S100A9, which had little effect on Aβ1-42-induced cytotoxicity. Moreover, depletion of S100A9 with siRNA did not significantly evoke the cell toxicity. On the other hand, Aβ1-42-induced extracellular S100A9 depletion resulted in decreased antimicrobial activity of the culture supernatant after Aβ1-42 stimulation. Immunodepletion of S100A9 with anti-S100A9 also decreased the antimicrobial peptide activity of the vehicle treated culture supernatant. Consistently, the recombinant S100A9 clearly elicited the antimicrobial peptide activity in vitro, confirming the observed antimicrobial activity of S100A9 in the culture supernatant. Collectively, our findings suggest that the mostly monomeric form of Aβ1-42 negatively regulates the innate immune system by down-regulating the secretion of S100A9, which is likely a main mediator of antimicrobial activity in the conditioned media of human THP-1 monocytes.


Ultrasound Irradiation Assisted Synthesis of Luminescent Nano Amide-Functionalized Metal-Organic Frameworks; Application Toward Phenol Derivatives Sensing.
Two nano amide-functionalized metal-organic frameworks (MOFs) with molecular formula [Co(oba) (bpta)]·(DMF)2 TMU-50 and [Co2(oba)2 (bpfn)]·(DMF)2.5 TMU-51 obtained under ultrasonic method without any surfactants. The only difference between the two selected amide functionalized pillar ligands, N,N'-bis(4-pyridinyl)-terephthalamide (bpta), and N,N'-bis-(4-pyridylformamide)-1,5-naphthalenediamine (bpfn), is related to the naphthyl group, which led to the different luminescence properties of the nano frameworks. In this study, the special ability of the luminescent nano MOFs were investigated to sensitize nitroaromatic compounds. Due to its unique and porous framework, Nano TMU-50 shows a good sensitivity towards nitro phenol by strong fluorescence emission with a detection limit of 2 × 10-3 mM-1. Both nano MOF structures were characterized via many analyses such as powder X-ray diffraction, Field Emission Scanning Electron Microscopy (FE-SEM), elemental analysis, and FTIR spectroscopy. Moreover, the effect of a number of important parameters including initial reagent concentrations, power of ultrasound, time on morphology, and size of nano structures were examined. According to the fluorescence titration results, the activated nano-TMU-50 detected NP selectively with a quick response.


L-Histidinol inhibits specifically and reversibly protein and ribosomal RNA synthesis in mouse L cells.
The addition of the histidine analogue L-histidinol to mouse L cells in suspension culture results in an abrupt inhibition of protein and ribosomal RNA synthesis with relatively little effect on messenger RNA production. Messenger RNA synthesized in the presence of L-histidinol associates with ribosomal subunits to form initiation complexes whose ability to commence elongation appears impaired. As a result of this mode of action, L-histidinol treatment results in a dramatic reduction of polyribosomes and a concomitant accumulation of 80 S ribosomes. The inhibition of both protein and ribosomal RNA synthesis mediated by L-histidinol is rapidly reversed by the addition of L-histidine to treated cultures.


Different haematopoietic growth factors have different capacity in overcoming the in vitro interferon gamma-induced suppression of bone marrow progenitor cells.
Interferon gamma (IFN gamma) inhibits haematopoiesis in vitro and an in vivo role in bone marrow suppression has been implied from clinical studies. We investigated the capacity of three recombinant (r), human (h), haematopoietic growth factors to overcome the in vitro IFN gamma inhibition of bone marrow progenitor cells in a methylcellulose culture system. Granulocyte macrophage-colony stimulating factor (GM-CSF) partially reversed IFN gamma-induced suppression of granulocyte-macrophage colony formation, by increasing colony forming units-granulocyte macrophage (CFU-GM) in a proportion ranging from 54-101%. Interleukin-3 (IL-3) and granulocyte-colony stimulating factor (G-CSF) were much less effective. For erythropoiesis, IL-3 was much more effective and partially reversed IFN gamma-mediated inhibition by increasing burst forming units-erythroid (BFU-E) in a proportion ranging from 52-138%. GM-CSF and G-CSF had no significant effect on IFN gamma-induced suppression of BFU-E. In conclusion, haematopoietic growth factors have different capacity to overcome IFN gamma-induced suppression of marrow progenitor cells in vitro. The findings may have therapeutic implications, as combinations of growth factors may be more effective in treating bone marrow failure syndromes.


Analysis of Commitment Point Attainment in Algae Dividing by Multiple Fission.
This work represents a detailed guide for commitment point analysis in microalgae dividing by multiple fission. The method is based on allowing the committed cells to divide in favorable conditions in the dark. This protocol offers a strategy to monitor cell cycle progression, both in control cultures and cultures treated with compounds affecting cell cycle length and/or progression. As the variety of such compounds is wide, our aim was to make the protocol easily modifiable to various research aims. The technique is easy to follow, low-cost, does not require any special equipment and offers reliable results in a reasonable time. The protocol offers step-by-step instructions, explains the theory behind these steps and offers solutions to some of the problems that may arise during the procedure.


A Pilot Randomized Trial of Heart Rate Monitoring Using Conventional Versus a New Electrocardiogram Algorithm during Neonatal Resuscitation at Birth.
Current guidelines support the use of a cardiac monitor during neonatal resuscitation. Infants born preterm randomized to a novel electrocardiogram algorithm displayed a heart rate sooner than the conventional electrocardiogram algorithm. Although resuscitation outcomes were not different, the availability of an earlier heart rate may benefit neonatal providers during high-risk resuscitations. TRIAL REGISTRATION: ClinicalTrials.govNCT04587934.


Highly stretchable, self-healing, and degradable ionic conductive cellulose hydrogel for human motion monitoring.
Self-healing biomass-based conductive hydrogels are applied as flexible strain sensors for wearable devices and human movement monitoring. Cellulose is the most abundant biomass-based materials and exhibits excellent toughness, dispersion and degradability. In this paper, nanocellulose crystals (NCCs) prepared from sisal, used as reinforcing fillers were coated with tannic acid (TA) to prepare inexpensive bio-nanocomposite hydrogels that also included polyvinyl alcohol, okra polysaccharide (OP), and borax. These hydrogels exhibit excellent self-healing and mechanical properties with the maximum elongation, toughness, and self-healing efficiency (9 min) of 1426.2 %, 264.4 kJ/m3, and 62.1 %, respectively. A fabricated hydrogel strain sensor was successfully used to detect and monitor various human movements such as wrist bending, elbow bending, and slight changes in facial expression. In addition, this sensor possessed excellent durability and good working stability after repeated circulation. The nanocomposite hydrogel synthesized in this work utilized natural polysaccharide to manufacture flexible functional materials with good application prospects in the field of flexible sensors.