Multiple synaptic and membrane sites of anesthetic action in the CA1 region of rat hippocampal slices.
Anesthesia is produced by a depression of central nervous system function, however, the sites and mechanisms of action underlying this depression remain poorly defined. The present study compared and contrasted effects produced by five general anesthetics on synaptic circuitry in the CA1 region of hippocampal slices. At clinically relevant and equi-effective concentrations, presynaptic and postsynaptic anesthetic actions were evident at glutamate-mediated excitatory synapses and at GABA-mediated inhibitory synapses. In addition, depressant effects on membrane excitability were observed for CA1 neuron discharge in response to direct current depolarization. Combined actions at several of these sites contributed to CA1 circuit depression, but the relative degree of effect at each site was different for each anesthetic studied. For example, most of propofol's depressant effect (> 70 %) was reversed with a GABA antagonist, but only a minor portion of isoflurane's depression was reversed (< 20 %). Differences were also apparent on glutamate synapses-pentobarbital depressed transmission by > 50 %, but thiopental by only < 25 %. These results, in as much as they may be relevant to anesthesia, indicate that general anesthetics act at several discrete sites, supporting a multi-site, agent specific theory for anesthetic actions. No single effect site (e.g. GABA synapses) or mechanism of action (e.g. depressed membrane excitability) could account for all of the effects produced for any anesthetic studied.


[Effect of the level and extent of a brain stem lesion on central hemodynamics in patients with an arterial aneurysm in the acute stage of a subarachnoid hemorrhage].
Using the dye-dilution method (indigo carmine), the authors studied the central hemodynamics in 46 people, including 36 patients with arterial aneurysms in the acute period of subarachnoidal hemorrhage and 10 healthy subjects (a control group). Hyperkinetic, hypokinetic and normokinetic types of the central hemodynamics were specified. The hyperkinetic type was characteristic of patients in a satisfactory state and with injuries at the hypothalamo-diencephalic level. The hypokinetic type is characteristic of grave and very grave patients with injuries at the mesencephalodienchephalic and mesencephalo-bulbar levels and with severe damage to the brain stem.


Weakly Supervised Learning of Placental Ultrasound Images with Residual Networks.
Accurate classification and localization of anatomical structures in images is a precursor for fully automatic image-based diagnosis of placental abnormalities. For placental ultrasound images, typically acquired in clinical screening and risk assessment clinics, these structures can have quite indistinct boundaries and low contrast, and image-level interpretation is a challenging and time-consuming task even for experienced clinicians. In this paper, we propose an automatic classification model for anatomy recognition in placental ultrasound images. We employ deep residual networks to effectively learn discriminative features in an end-to-end fashion. Experimental results on a large placental ultra-sound image database (10,808 distinct 2D image patches from 60 placental ultrasound volumes) demonstrate that the proposed network architecture design achieves a very high recognition accuracy (0.086 top-1 error rate) and provides good localization for complex anatomical structures around the placenta in a weakly supervised fashion. To our knowledge this is the first successful demonstration of multi-structure detection in placental ultrasound images.


Dependence of nodal sodium channel clustering on paranodal axoglial contact in the developing CNS.
Na(+) channel clustering at nodes of Ranvier in the developing rat optic nerve was analyzed to determine mechanisms of localization, including the possible requirement for glial contact in vivo. Immunofluorescence labeling for myelin-associated glycoprotein and for the protein Caspr, a component of axoglial junctions, indicated that oligodendrocytes were present, and paranodal structures formed, as early as postnatal day 7 (P7). However, the first Na(+) channel clusters were not seen until P9. Most of these were broad, and all were excluded from paranodal regions of axoglial contact. The number of detected Na(+) channel clusters increased rapidly from P12 to P22. During this same period, conduction velocity increased sharply, and Na(+) channel clusters became much more focal. To test further whether oligodendrocyte contact directly influences Na(+) channel distributions, nodes of Ranvier in the hypomyelinating mouse Shiverer were examined. This mutant has oligodendrocyte-ensheathed axons but lacks compact myelin and normal axoglial junctions. During development Na(+) channel clusters in Shiverer mice were reduced in numbers and were in aberrant locations. The subcellular location of Caspr was disrupted, and nerve conduction properties remained immature. These results indicate that in vivo, Na(+) channel clustering at nodes depends not only on the presence of oligodendrocytes but also on specific axoglial contact at paranodal junctions. In rats, ankyrin-3/G, a cytoskeletal protein implicated in Na(+) channel clustering, was detected before Na(+) channel immunoreactivity but extended into paranodes in non-nodal distributions. In Shiverer, ankyrin-3/G labeling was abnormal, suggesting that its localization also depends on axoglial contact.


[Orphan drugs].
Diseases lacking in satisfactory therapies, named orphans (over 60% of the known), raise the problem of the availability of new drugs to be discovered and evaluated on toxicological and clinical bases. The estimated cost for the full development of a drug makes it not profitable (and therefore orphan drug) in the case of rare diseases and the typical diseases of developing countries. The USA with the Orphan Drug Act have faced the former, whereas WHO with the "Tropical Diseases Research" programme has faced the latter. Uncommon formulations and dosages of known substances and products no longer marketed as non-profitable are considered orphans drugs as well.


Role of s-p orbital mixing in the bonding and properties of second-period diatomic molecules.
Qualitative molecular orbital theory is widely used as a conceptual tool to understand chemical bonding. Symmetry-allowed orbital mixing between atomic or fragment orbitals of different energies can greatly complicate such qualitative interpretations of chemical bonding. We use high-level Amsterdam Density Functional calculations to examine the issue of whether orbital mixing for some familiar second-row homonuclear and heteronuclear diatomic molecules results in net bonding or antibonding character for a given molecular orbital. Our results support the use of slopes of molecular orbital energy versus bond distance plots (designated radial orbital-energy slope: ROS) as the most useful criterion for making this determination. Calculated atomic charges and frontier orbital properties of these molecules allow their acid-base chemistry, including their reactivities as ligands in coordination chemistry, to be better understood within the context of the Klopman interpretation of hard and soft acid-base theory. Such an approach can be extended to any molecular species.


Delta-24-RGD combined with radiotherapy exerts a potent antitumor effect in diffuse intrinsic pontine glioma and pediatric high grade glioma models.
Pediatric high grade gliomas (pHGG), including diffuse intrinsic pontine gliomas (DIPGs), are aggressive tumors with a dismal outcome. Radiotherapy (RT) is part of the standard of care of these tumors; however, radiotherapy only leads to a transient clinical improvement. Delta-24-RGD is a genetically engineered tumor-selective adenovirus that has shown safety and clinical efficacy in adults with recurrent gliomas. In this work, we evaluated the feasibility, safety and therapeutic efficacy of Delta-24-RGD in combination with radiotherapy in pHGGs and DIPGs models. Our results showed that the combination of Delta-24-RGD with radiotherapy was feasible and resulted in a synergistic anti-glioma effect in vitro and in vivo in pHGG and DIPG models. Interestingly, Delta-24-RGD treatment led to the downregulation of relevant DNA damage repair proteins, further sensitizing tumors cells to the effect of radiotherapy. Additionally, Delta-24-RGD/radiotherapy treatment significantly increased the trafficking of immune cells (CD3, CD4+ and CD8+) to the tumor niche compared with single treatments. In summary, administration of the Delta-24-RGD/radiotherapy combination to pHGG and DIPG models is safe and significantly increases the overall survival of mice bearing these tumors. Our data offer a rationale for the combination Delta-24-RGD/radiotherapy as a therapeutic option for children with these tumors. SIGNIFICANCE: Delta-24-RGD/radiotherapy administration is safe and significantly increases the survival of treated mice. These positive data underscore the urge to translate this approach to the clinical treatment of children with pHGG and DIPGs.


Slow oscillatory changes of DPOAE magnitude and phase after exposure to intense low-frequency sounds.
Sensitive sound detection within the mammalian cochlea is performed by hair cells surrounded by cochlear fluids. Maintenance of cochlear fluid homeostasis and tight regulation of intracellular conditions in hair cells are crucial for the auditory transduction process but can be impaired by intense sound stimulation. After a short, intense low-frequency sound, the cochlea shows the previously described "bounce phenomenon," which manifests itself as slow oscillatory changes of hearing thresholds and otoacoustic emissions. In this study, distortion product otoacoustic emissions (DPOAEs) were recorded after Mongolian gerbils were exposed to intense low-frequency sounds (200 Hz, 100 dB SPL) with different exposure times up to 1 h. After all sound exposure durations, a certain percentage of recordings (up to 80% after 1.5-min-long exposure) showed oscillatory DPOAE changes, similar to the bounce phenomenon in humans. Changes were quite uniform with respect to size and time course, and they were independent from sound exposure duration. Changes showed states of hypo- and hyperactivity with either state preceding the other. The direction of changes was suggested to depend on the static position of the cochlear operating point. As assessed with DPOAEs, no indication for a permanent damage after several or long exposure times was detected. We propose that sensitivity changes occur due to alterations of the mechanoelectrical transduction process of outer hair cells. Those alterations could be induced by different challenged homeostatic processes with slow electromotility of outer hair cells being the most plausible source of the bounce phenomenon. NEW & NOTEWORTHY Low-frequency, high-intensity sound can cause slowly cycling activity changes in the mammalian cochlea. We examined the effect of low-frequency sound duration on the degree of these alterations. We found that cochlear changes showed a stereotypical biphasic pattern independent of sound exposure duration, but the probability that significant changes occurred decreased with increasing sound duration. Despite exposure durations of up to 1 h, no permanent or transient impairments of the cochlea were detected.


'Pulse oral' versus intravenous calcitriol therapy in chronic hemodialysis patients. A prospective and randomized study.
The aim of this prospective and randomized study was to compare the efficacy, side effects, and costs of 'pulse oral' versus intravenous calcitriol in the treatment of secondary hyperparathyroidism in hemodialysis (HD) patients. A total of 20 patients were randomized to receive over a 4-month period pulse orally administered calcitriol (pulse oral group; n = 10) or intravenous calcitriol (intravenous group; n = 10). All patients used standard dialysate calcium (1.75 mmol/l) throughout the study period. In accordance with the study design calcium dialysate concentrations were reduced when this was necessary to avoid hypercalcemic crises. The patients were stratified into two subgroups according to their initial serum PTH levels: patients with mild or moderate degree of hyperparathyroidism (17 patients) and patients with severe hyperparathyroidism (3 patients). Intravenous and pulse oral cacitriol did not significantly reduce serum PTH concentrations in patients with severe hyperparathyroidism (1,157 +/- 156 vs. 807 +/- 228 pg/ml [corrected], p = 0.09). Intermittent calcitriol, administered by intravenous or oral route, significantly reduced serum PTH levels (326 +/- 119 vs. 109 +/- 79 pg/ml [corrected], p = 0.0001) in patients with mild or moderate hyperparathyroidism. In patients with mild or moderate hyperparathyroidism, intravenous calcitriol significantly reduced PTH concentrations at the end of the 1st month, before the increase of serum ionized calcium levels, whereas 'pulse oral' calcitriol significantly suppressed parathyroid activity at the end of the 2nd month. Calcium dialysate concentration was reduced in 9 out of 10 (90%) patients of the pulse oral group and in all patients (10/10) of intravenous group. The incidence of hypercalcemic crises was 24% (39/160) in the pulse oral group and 14% (27/160) in the intravenous group. Analysis of costs showed that intravenous calcitriol was more expensive compared to pulse oral calcitriol. These data indicate that intermittent intensive calcitriol therapy, regardless of the route of administration, is effective in suppressing parathyroid activity in HD patients with mild or moderate hyperparathyroidism. In contrast, intermittent calcitriol therapy has a limited ability to achieve sustained serum PTH reductions in HD patients with severe hyperparathyroidism. Intravenous calcitriol was more expensive than pulse oral calcitriol, and we recommend the use of pulse oral calcitriol in HD patients with mild or moderate secondary hyperparathyroidism.


Three-year prospective multicenter study evaluating marginal bone levels and soft tissue health around a one-piece implant system.
The aim of this clinical investigation was to evaluate marginal bone remodeling and soft tissue health surrounding a novel one-piece implant system over a 3-year study period. Subjects missing at least one tooth in either arch were consecutively enrolled in this open prospective 3-year investigation. Five clinics were invited to participate. Strict inclusion and exclusion criteria were used. Marginal bone levels were evaluated using radiographs taken at implant insertion, 6 months, and annually thereafter. Plaque and bleeding indices were recorded at 3 and 6 months and 1 and 3 years following implant insertion. The shapes of papillae were evaluated at implant insertion with the provisional restoration in place, at the insertion of the definitive restoration, and at the 3-year follow-up, using Jemt's papilla index. Life tables and the Mann-Whitney U test were used for statistical analyses. Fifty-six patients were restored with a total of 82 one-piece implants; 47 patients attended the 3-year appointment. One implant had to be removed 1 month postinsertion, giving a cumulative survival rate of 98.8% for the 3-year study period. Most bone resorption (mean, 1.19 ± 1.38 mm; n = 61) occurred during the first year of function, while there was minimal change in mean marginal bone levels between 1 and 3 years (-0.07 ± 1.07 mm; n = 58). Normal peri-implant mucosa was registered for more than 81% of the sites, and no visible plaque was registered for more than 54% of the sites. This prospective 3-year multicenter study showed stable marginal bone levels, good soft tissue health, and a high implant survival rate, supporting the hypothesis that the presented one-piece implant system has the capacity to maintain both hard and soft tissues after the first year of initial bone remodeling.


Case report: overnight hospital stay for minimally invasive bilateral total hip arthroplasty.
Bilateral total hip arthroplasty was performed on a 58-year-old man. He was successfully discharged home from hospital the following morning, 23 hours post surgery. A direct anterior, minimally invasive approach was used which avoided detachment of hip musculature. Preoperative assessment was carried out, with early multidisciplinary team input. Modified anaesthetic techniques with an ambulatory pain pump were employed. Follow-up in the community was carried out by an outreach team. All these factors were important in a successful early supported discharge. We believe this to be the first such case reported.


Long-lasting and context-specific freezing preference is acquired after spaced repeated presentations of a danger stimulus in the crab Chasmagnathus.
A visual danger stimulus elicits an escape response in the crab Chasmagnathus that declines after repeated presentations. Previous results report that such waning may be retained as context-signal memory (CSM) or signal memory (SM): CSM is long lasting, associative, and produced by spaced training, while SM is an intermediate memory, nonassociative, and produced by massed training. The performances of both spaced and massed trained crabs are here examined, using video analysis to determine topographic changes in the behavioral response during and after training. During spaced training, escape vanishes and is mainly replaced by freezing, while during massed training, escape decreases over trials without being replaced by any defensive response. After 24 h, the marked proclivity to freezing persists in spaced trained crabs, while a high level of escaping is shown by massed trained crabs. The long-lasting freezing preference of spaced trained crabs proves to be context-specific and apparent from the very first presentation of the danger stimulus at testing, though freezing is not triggered by the sole exposure to the context. We conclude (a) that freezing preference is the acquired response of the CSM process; (b) that CSM can be properly categorized as an instance of contextual conditioning and SM of classical habituation; (c) that CSM and SM are not two phases of a memory processing but two distinctly types of memory; and (d) that therefore, the temporal distribution of training trials has a drastic effect on crab's memory, more dramatic than that previously described. The possibility that massed and spaced presentations of the same stimulus may represent two different stimulus types is discussed.


Evaluation of CNS Depressant Activity of Different Plant parts of Nyctanthes arbortristis Linn.
The present study was carried out with the water-soluble portion of the ethanol extracts of flowers, barks, seeds and leaves of Nyctanthes arbortristis Linn. to confirm their CNS depressant activity. The ethanol extracts of the plant parts were obtained by soxhlet extraction. After performing the gross behavioral study, the CNS depressant activity was evaluated by observing the prolongation of sleeping time induced by pentobarbital sodium in mice. Attempts have been made to explore the possible mechanism behind this activity by determining their effect on brain monoamine neurotransmitters like dopamine and serotonin. The gross behavioral study showed that ethanol extracts of the leaves, flowers and seeds possess significant CNS depressant activity. The leaves, flowers, seeds and barks (600 mg/kg) showed significant and dose-dependent prolongation of onset and duration of sleep and so found to cause decrease dopamine and increase serotonin level. From which it can be concluded that the CNS depressant activity of the ethanol extracts of seeds, leaves and flowers may be due to the decrease in dopamine and increase in serotonin level.


[Postural crush syndrome].
The clinic of such injuries is characterized by marked local manifestations (solid progressive edema of the injured limb leading frequently to decompensated ischemia) and a high incidence of acute renal insufficiency. Hemostatic disorders are manifested in hyperkalemia, hyponatremia, hypocalcemia, cell-extracell transfer of electrolytes, metabolic disorders in the myocardium, as evidenced by EEG findings. It is the authors' opinion that therapeutic measures should be aimed at liquidation of the progressive edema (hypothermia, fasciotomy), prevention of acute renal insufficiency and correction of metabolic disorders.


Association of BP variability with mortality among African Americans with CKD.
Increased systolic BP visit-to-visit variability (SBV) may be associated with higher overall mortality and cardiovascular events. However, few studies have examined these associations in patients with CKD, and the relation of SBV with CKD progression and ESRD has not been shown. This study analyzed the association of SBV with overall mortality, cardiovascular mortality, cardiovascular events, and renal events among individuals enrolled in the African American Study of Kidney Disease (AASK) trial. This was a prospective observational study of 908 participants during the trial phase of the AASK study, with at least 1 year of BP measurements available and followed for 3-6.4 years. SBV was calculated as the SD of the systolic pressure from five visits occurring 3-12 months after randomization. The association of SBV with risk of overall mortality, cardiovascular mortality, a composite of fatal and nonfatal cardiovascular events, and a composite of renal events was assessed using proportional hazards regression and adjusting for multiple potential confounders. Greater SBV was associated with higher overall mortality. The adjusted hazard ratio (95% confidence interval) was 2.82 (1.14-6.95) comparing the highest with lowest tertile of SBV. A similar comparison revealed that greater SBV was also associated with cardiovascular mortality (adjusted hazard ratio, 4.91; 1.12-21.50). SBV was associated with both the cardiovascular renal composite endpoints in unadjusted but not adjusted analyses. In African Americans with CKD, SBV is strongly and independently associated with overall and cardiovascular mortality.


Caveolin, caveolae, and endothelial cell function.
Caveolae are 50- to 100-nm cell-surface plasma membrane invaginations observed in terminally differentiated cells. They are particularly abundant in endothelial cells, where they are believed to play a major role in the regulation of endothelial vesicular trafficking and signal transduction. The use of caveolin-1-deficient mice has provided many new insights into the roles of caveolae and caveolin-1 in the regulation of endothelial cell function. These novel findings suggest an important role for caveolin-1 in the pathogenesis of cancer, atherosclerosis, and vascular disease.


Connecticut competency-based point of dispensing worker training needs assessment.
In April 2006, Connecticut conducted an exercise that tested its ability to receive and dispense antibiotics from the Strategic National Stockpile. In conjunction with the exercise, a competency-based assessment was performed to determine the training needs of point of dispensing (POD) workers. POD core competencies were developed by adapting existing preparedness materials. They were used to assess the training needs of more than 250 people who staffed a POD during the exercise. The assessment measured their confidence in their ability to perform 17 competency-based tasks. The vast majority needed training on 5 or fewer tasks, suggesting that they were fairly well trained. Pharmacists were particularly likely to need training on at least 5 tasks. Given their role in a POD operation, they should be a focus of further training. Almost one third of participants needed additional training on at least 1 of the 3 basic POD Incident Command System tasks. Additional training is also needed on competencies concerning POD safety and security, liability protections, and family preparedness. POD workers who are concerned about these matters may be less willing or able to staff a POD. People who participated in training both before and on the day of the exercise were best prepared to staff the POD, indicating that both types of training have value. When compared with the competencies, POD workers possessed many of the necessary skills to staff a POD; however, training with emphasis on areas of weakness revealed by the assessment could improve willingness to report for duty and performance.


[Characteristics of hospital admissions in the Unified National Health System for osteoporotic hip fracture in elderly people in Brazil, 2006-2008].
Osteoporosis is a multifactorial syndrome of the skeletal system, and hip fracture is the most serious consequence for the elderly, due to the high mortality and cost. This article describes osteoporotic hip fractures in Brazilian elderly in 2006-2008. Secondary data were obtained from the Authorization Forms for Hospital Admissions (AIH) and allowed the creation of indicators for hip fracture in elders. The proportion of elderly patients hospitalized for hip fractures in the Unified National Health System was 1%. The percentages of hospital admissions and deaths were higher in females, and increased with age. Hip fractures accounted for approximately 2% of health care expenditures for persons 60 years or older. Length of hospital stay ranged from one to seven days, 50.1% occurred in charity hospitals, and 42.7% occurred outside the county of residence. The findings emphasize the need for greater attention to osteoporosis and show the relevance of costs in hospital admissions for elderly with osteoporotic hip fractures. Understanding such hospitalizations can contribute to the formulation of health policies to address this issue.


Blocking epithelial-to-mesenchymal transition in glioblastoma with a sextet of repurposed drugs: the EIS regimen.
This paper outlines a treatment protocol to run alongside of standard current treatment of glioblastoma- resection, temozolomide and radiation. The epithelial to mesenchymal transition (EMT) inhibiting sextet, EIS Regimen, uses the ancillary attributes of six older medicines to impede EMT during glioblastoma. EMT is an actively motile, therapy-resisting, low proliferation, transient state that is an integral feature of cancers' lethality generally and of glioblastoma specifically. It is believed to be during the EMT state that glioblastoma's centrifugal migration occurs. EMT is also a feature of untreated glioblastoma but is enhanced by chemotherapy, by radiation and by surgical trauma. EIS Regimen uses the antifungal drug itraconazole to block Hedgehog signaling, the antidiabetes drug metformin to block AMP kinase (AMPK), the analgesic drug naproxen to block Rac1, the anti-fibrosis drug pirfenidone to block transforming growth factor-beta (TGF-beta), the psychiatric drug quetiapine to block receptor activator NFkB ligand (RANKL) and the antibiotic rifampin to block Wnt- all by their previously established ancillary attributes. All these systems have been identified as triggers of EMT and worthy targets to inhibit. The EIS Regimen drugs have a good safety profile when used individually. They are not expected to have any new side effects when combined. Further studies of the EIS Regimen are needed.


[Characteristics of the value-based attitude of medical workers to healthy lifestyle].
Reduction in the medical labor reserve leads to economic losses, therefore, the issue related to medical personnel health improvement is relevant at all management levels in healthcare. The article presents results of the survey of doctors in Moscow, reflecting their own attitude to a healthy lifestyle and related self-preserving behavior patterns. The searches focused on the analysis of activities of medical workers related to health improvement and promotion and analysis of psychosocial attitudes of medical workers. The article presents results of the survey of doctors of different specialty providing primary health care at Moscow polyclinics. The survey used Health-Promoting Lifestyle Profile, HPLP-II. HPLP-II is actively used by both foreign and Russian scientists. It has been validated on the Russian sample. Respondents give their responses scoring the degree of their agreement with an item by the following blocks (health responsibility, physical activity, spiritual growth, nutrition, interpersonal relations and stress management). Using this questionnaire, the authors have evaluated healthy lifestyle of medical workers as a multicomponent structure for better understanding of major priorities in self-preservation behavior of physicians. Based on the survey results, the authors have ranked the scales to identify priority factors affecting the formation of the value-based attitude to healthy lifestyle by medical workers.


Improving parental emotion socialization in military families: Results of a randomized controlled trial.
Prior research indicates that children of deployed parents are at risk for emotional problems, suggesting the utility of preventive efforts for military families. Effective parental socialization of children's emotions is protective for children's development, and parental experiential avoidance may impede parental emotion socialization, yet intervention studies in this area are lacking. This study examined the impact of a parenting program, After Deployment Adaptive Parenting Tools (ADAPT), on parental emotion socialization postintervention (6 months postbaseline) and whether intervention effects were moderated by parental experiential avoidance. The sample included 336 families (294 fathers and 313 mothers) with at least 1 deployed parent and a focal child aged 4-12. Families were randomized into either ADAPT (a 14-week group-based intervention) or control group. Self-reported data on parental emotion socialization and experiential avoidance were analyzed using structural equation modeling. Results showed that mothers who were assigned to the intervention had significant improved supportive emotion socialization and reduced nonsupportive emotion socialization at postintervention compared with controls. Mothers with higher levels of experiential avoidance assigned to the intervention group had higher levels of supportive emotion socialization at postintervention. No significant intervention effects were found in fathers. This study provides support for the effects of the ADAPT program on maternal emotion socialization at 6-month postbaseline, and the role of experiential avoidance as a moderator. We discuss findings in relation to the different parental roles that mothers and fathers play in postdeployed families, as well as implications for personalized intervention programming. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Moving target tracking using symbolic registration.
This correspondence describes a moving target tracking (MTT) algorithm that performs image registration and motion analysis between pairs of images from a passive sensor. Unlike previously reported moving target indicators that operate at the signal level, the registration and motion analysis in the MTT is totally performed at a symbolic level. The operation of the MTT is demonstrated by simulation results obtained from applications of the algorithm to infrared images.


Self-Forming 3D Core-Shell Ceramic Nanostructures for Halogen-Free Flame Retardant Materials.
The synthesis of aluminum phosphates-based composites has been widely studied during the past decade because of the promising industrial application of these materials. Here we show a simple one-pot heterogeneous precipitation approach to fabricate a sepiolite-phosphate (SepP) composite with adequate control of the size and dispersion of the phosphate nanoparticles. This coupling between aluminum phosphate and sepiolite nanofibers results in the development of a novel three-dimensional rigid supported phosphate structure, which is generated during the thermal treatment. According to our results, this phenomenon can be explained by a migration-coalescence mechanism of phosphate nanoparticles over the sepiolite support, assisted by a liquid phase. It is worth pointing out that this stimulant behavior observed here could have potential technological applications such as halogen-free flame retardant materials.


Study of haemolytic activity of some Campylobacter spp. on blood agar plates.
A total of 152 strains of Campylobacter jejuni, C. coli, C. laridis and C. fetus subsp. fetus were tested for haemolysis on blood agar plates. Distinct haemolysis was detected in 92.3% (96/104) of strains of C. jejuni and 21.7% (5/23) of strains of C. coli on sheep blood heart infusion agar after incubation for 4 d microaerobically at 42 degrees C. Haemolysis was also detected on horse blood heart infusion agar. Haemolysis was not detected at 37 degrees C except with one of 50 strains of C. jejuni tested at this temperature, which was weakly positive. Campylobacter laridis was not haemolytic; C. fetus subsp. fetus, which does not grow at 42 degrees C, showed no haemolysis at 37 degrees C. Blood agar (Oxoid, BA Base No. 2) was not suitable for testing for haemolysis by these organisms. A microaerobic gas mixture containing hydrogen is better than that containing nitrogen because the medium has a brighter colour, making haemolysis easier to detect. There was no synergistic haemolysis with Staphylococcus aureus or Streptococcus agalactiae. The plate haemolysis test as described here may aid differentiation within the thermophilic campylobacters.


Resveratrol inhibits KSHV reactivation by lowering the levels of cellular EGR-1.
In the field of herpesvirus research, the exact molecular mechanism by which such viruses reactivate from latency remains elusive. Kaposi's sarcoma-associated herpesvirus (KSHV) primarily exists in a latent state, while only 1-3% of cells support lytic infection at any specific time. KSHV reactivation from latency is an exceedingly intricate process mediated by the integration of viral and cellular factors. Previously, our lab has described early growth response-1 (Egr-1) as an essential component for the KSHV reactivation process via its ability to mediate transcription of KSHV ORF50, the gene encoding for replication and transcription activator (RTA), a viral component known to control the switch from latent to lytic infection. In here, electrophoretic mobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP) experiments revealed that Egr-1 binds KSHV ORF50 promoter (ORF50P) in at least two different GC-rich binding domains. Expression profiles of cellular egr-1 and KSHV-encoded ORF50 follow a similar pattern during de novo KSHV infection. Over-expressing Egr-1, a signaling component downstream of Raf>MEK>ERK1/2, in KSHV-infected cells activates KSHV lytic replication. Through performing more physiologically relevant experiments, we analyzed the effect of a dietary supplement containing resveratrol on KSHV-infected cells. Our results, for the first time, demonstrate resveratrol to act in lowering ERK1/2 activity and expression of Egr-1 in KSHV-infected cells, resulting in the suppression of virus reactivation from latency. Taken together, these findings will undoubtedly contribute to future studies on not only combating KSHV related disease conditions, but also on other herpesviruses-induced pathogenesis.


Targeting tumor vasculature with an oncolytic virus.
Oncolytic viruses (OVs) have been engineered or selected for cancer cell-specific infection however, we have found that following intravenous administration of vesicular stomatitis virus (VSV), tumor cell killing rapidly extends far beyond the initial sites of infection. We show here for the first time that VSV directly infects and destroys tumor vasculature in vivo but leaves normal vasculature intact. Three-dimensional (3D) reconstruction of infected tumors revealed that the majority of the tumor mass lacks significant blood flow in contrast to uninfected tumors, which exhibit relatively uniform perfusion. VSV replication in tumor neovasculature and spread within the tumor mass, initiates an inflammatory reaction including a neutrophil-dependent initiation of microclots within tumor blood vessels. Within 6 hours of intravenous administration of VSV and continuing for at least 24 hours, we observed the initiation of blood clots within the tumor vasculature whereas normal vasculature remained clot free. Blocking blood clot formation with thrombin inhibitors prevented tumor vascular collapse. Our results demonstrate that the therapeutic activity of an OV can go far beyond simple infection and lysis of malignant cells.


Around Semipalatinsk nuclear test site: progress of dose estimations relevant to the consequences of nuclear tests (a summary of 3rd Dosimetry Workshop on the Semipalatinsk nuclear test site area, RIRBM, Hiroshima University, Hiroshima, 9-11 of March, 2005).
The paper is an analytical overview of the main results presented at the 3rd Dosimetry Workshop in Hiroshima(9-11 of March 2005), where different aspects of the dose reconstruction around the Semipalatinsk nuclear test site(SNTS) were discussed and summarized. The results of the international intercomparison of the retrospective luminescence dosimetry(RLD) method for Dolon' village(Kazakhstan) were presented at the Workshop and good concurrence between dose estimations by different laboratories from 6 countries (Japan, Russia, USA, Germany, Finland and UK) was pointed out. The accumulated dose values in brick for a common depth of 10mm depth obtained independently by all participating laboratories were in good agreement for all four brick samples from Dolon' village, Kazakhstan, with the average value of the local gamma dose due to fallout (near the sampling locations) being about 220 mGy(background dose has been subtracted).Furthermore, using a conversion factor of about 2 to obtain the free-in-air dose, a value of local dose approximately 440 mGy is obtained, which supports the results of external dose calculations for Dolon': recently published soil contamination data, archive information and new models were used for refining dose calculations and the external dose in air for Dolon village was estimated to be about 500 mGy. The results of electron spin resonance(ESR) dosimetry with tooth enamel have demonstrated the notable progress in application of ESR dosimetry to the problems of dose reconstruction around the Semipalatinsk nuclear test site. At the present moment, dose estimates by the ESR method have become more consistent with calculated values and with retrospective luminescence dosimetry data, but differences between ESR dose estimates and RLD/calculation data were noted. For example mean ESR dose for eligible tooth samples from Dolon' village was estimated to be about 140 mGy(above background dose), which is less than dose values obtained by RLD and calculations. A possible explanation of the differences between ESR and RLD/calculations doses is the following: for interpretation of ESR data the "shielding and behaviour" factors for investigated persons should be taken into account. The "upper level" of the combination of "shielding and behaviour" factors of dose reduction for inhabitants of Dolon' village of about 0.28 was obtained by comparing the individual ESR tooth enamel dose estimates with the calculated mean dose for this settlement. The biological dosimetry data related to the settlements near SNTS were presented at the Workshop. A higher incidence of unstable chromosome aberrations, micronucleus in lymphocytes, nuclear abnormalities of thyroid follicular cells, T-cell receptor mutations in peripheral blood were found for exposed areas (Dolon', Sarjal) in comparison with unexposed ones(Kokpekty). The significant greater frequency of stable translocations (results of analyses of chromosome aberrations in lymphocytes by the FISH technique) was demonstrated for Dolon' village in comparison with Chekoman(unexposed village). The elevated level of stable translocations in Dolon' corresponds to a dose of about 180 mSv, which is close to the results of ESR dosimetry for this village. The importance of investigating specific morphological types of thyroid nodules for thyroid dosimetry studies was pointed out. In general the 3rd Dosimetry Workshop has demonstrated remarkable progress in developing an international level of common approaches for retrospective dose estimations around the SNTS and in understanding the tasks for the future joint work in this direction. In the framework of a special session the problems of developing a database and registry in order to support epidemiological studies around SNTS were discussed. The results of investigation of psychological consequences of nuclear tests, which are expressed in the form of verbal behaviour, were presented at this session as well.


3DGAUnet: 3D Generative Adversarial Networks with a 3D U-Net Based Generator to Achieve the Accurate and Effective Synthesis of Clinical Tumor Image Data for Pancreatic Cancer.
Pancreatic ductal adenocarcinoma (PDAC) presents a critical global health challenge, and early detection is crucial for improving the 5-year survival rate. Recent medical imaging and computational algorithm advances offer potential solutions for early diagnosis. Deep learning, particularly in the form of convolutional neural networks (CNNs), has demonstrated success in medical image analysis tasks, including classification and segmentation. However, the limited availability of clinical data for training purposes continues to represent a significant obstacle. Data augmentation, generative adversarial networks (GANs), and cross-validation are potential techniques to address this limitation and improve model performance, but effective solutions are still rare for 3D PDAC, where the contrast is especially poor, owing to the high heterogeneity in both tumor and background tissues. In this study, we developed a new GAN-based model, named 3DGAUnet, for generating realistic 3D CT images of PDAC tumors and pancreatic tissue, which can generate the inter-slice connection data that the existing 2D CT image synthesis models lack. The transition to 3D models allowed the preservation of contextual information from adjacent slices, improving efficiency and accuracy, especially for the poor-contrast challenging case of PDAC. PDAC's challenging characteristics, such as an iso-attenuating or hypodense appearance and lack of well-defined margins, make tumor shape and texture learning challenging. To overcome these challenges and improve the performance of 3D GAN models, our innovation was to develop a 3D U-Net architecture for the generator, to improve shape and texture learning for PDAC tumors and pancreatic tissue. Thorough examination and validation across many datasets were conducted on the developed 3D GAN model, to ascertain the efficacy and applicability of the model in clinical contexts. Our approach offers a promising path for tackling the urgent requirement for creative and synergistic methods to combat PDAC. The development of this GAN-based model has the potential to alleviate data scarcity issues, elevate the quality of synthesized data, and thereby facilitate the progression of deep learning models, to enhance the accuracy and early detection of PDAC tumors, which could profoundly impact patient outcomes. Furthermore, the model has the potential to be adapted to other types of solid tumors, hence making significant contributions to the field of medical imaging in terms of image processing models.


The resistance of Pseudomonas aeruginosa strains to fluoroquinolone group of antibiotics.
Fluoroquinolones are antibiotics that are very effective against many gram negative microorganisms, including P. aeruginosa. However, resistance to these antibiotics has been reported in recent years as well. In this study, the sensitivity of 136 P. aeruginosa strains, isolated from various clinical materials, to fluoroquinolones has been investigated. The lowest resistance rate was in ciprofloxacin with 12.5%. The resistance rates of the others were as follows: norfloxacin 14.7%, levofloxacin 16.9%, ofloxacin 19.9% and pefloxacin 28.7%. The 88.2% of the resistant strains to all fluoroquinolones were originated from intensive care unit.


Immunohistochemical expression of vascular endothelial growth factor (VEGF) and p53 in breast lesions.
Vascular endothelial growth factor (VEGF) is a leading factor for tumour angiogenesis and p53 protein is the product of a tumor suppressor gene. The main aim of the study was to assess the association of p53 protein with VEGF expression in breast carcinoma. This was a retrospective study involving 66 invasive breast carcinomas, 66 normal breast tissues and 55 cases of usual ductal hyperplasia (UDH), obtained from the histopathology records. The paraffin blocks were cut and processed by immunohistochemical technique using a monoclonal VEGF and a monoclonal p53 antibody. VEGF positive staining was detected in 12 (18.2%) of the 66 cases of breast carcinoma and only 1 (1.8%) of UDH cases (p=0.004). Expression of p53 was positive in 33 (50%) of the 66 cases of carcinoma; whereas 8 cases of UDH (14.5%) were p53 protein positive (p<0.001). There was statistically significant associations between p53 expression and tumour size (p=0.018) and lymph node status (p=0.046). The VEGF and p53 expressions were negative in all normal breast tissues analyzed. Ten (83.3%) of 33 invasive carcinoma with p53 protein positive were VEGF positive, whereas 2 of 33 patients did not have p53 expression and were VEGF positive (p=0.011). The expression of p53 in invasive breast carcinoma had a significant correlation with the tumour size and lymph node metastasis. The evaluation of VEGF expression together with p53 protein may aid clinicians in effective management.


Prognostic value of computer-quantitated exercise thallium imaging early after percutaneous transluminal coronary angioplasty.
To develop an approach to predicting adverse events after percutaneous transluminal coronary angioplasty (PTCA), 50 patients had thallium-201 exercise testing within 1 month after successful single vessel coronary angioplasty and were followed up for a mean of 18 months. Adverse events were: 1) clinical events consisting of recurrent angina (17 patients) and myocardial infarction (1 patient); 2) treatment events consisting of repeat coronary angioplasty (10 patients) and coronary bypass surgery (1 patient); and 3) restenosis, defined as a greater than 30% increase in luminal stenosis (15 of 38 recatheterized patients). There were no deaths. Of the clinical, exercise, angiographic and thallium scan variables analyzed by stepwise logistic regression, postangioplasty gradient greater than 20 mm Hg predicted clinical events and treatment events, and the number of segments with slower thallium clearance predicted clinical events, treatment events and restenosis. Using Cox Hazards model regression of survival without events, the number of transient qualitative thallium defects also predicted clinical events and restenosis. At 1 year after angioplasty, 24% of patients with these variables had restenosis compared with only 6% of those without these variables and 36% of patients with these variables had a clinical or treatment event compared with 8% of patients without these variables. Three measures of the adequacy of myocardial perfusion (post-angioplasty gradient, reduced thallium clearance and transient thallium defects) were additive predictors of adverse events after coronary angioplasty with the relative risk being approximately four times greater in patients with these variables than in those without. Such adverse events, therefore, are usually a consequence of inadequate revascularization.


Dietary influences on chronic obstructive lung disease and asthma: a review of the epidemiological evidence.
The epidemiological evidence for a relationship between diet and indicators of asthma and chronic obstructive pulmonary disease (COPD) is evaluated. The review focuses on the intake of Na, n-3 fatty acids, and antioxidant vitamins as well as fruit and vegetables. Experimental studies suggest that a high-Na diet has a small adverse effect on airway reactivity in asthma patients. However, observational studies provide no clear evidence that high Na intake has adverse effects on airway reactivity or asthma symptoms in open populations. n-3 Polyunsaturated fatty acids, which are present in fish oils, are metabolized into less broncho-constricting and inflammatory mediators than n-6 polyunsaturated fatty acids. Studies in the general adult population suggest that a high fish intake has a beneficial effect on lung function, but the relationship with respiratory symptoms and clinically-manifest asthma or COPD is less evident. Also, experimental studies in asthma patients have not demonstrated an improvement in asthma severity after supplementations with fish oil. Several studies showed a beneficial association between fruit and vegetable intake and lung function, but the relationship with respiratory symptoms and the clinically-manifest disease was less convincing. A similar pattern was found for vitamin C in relation to indicators of asthma and COPD, but there are still conflicting results with respect to vitamin E and beta-carotene. In conclusion, the epidemiological evidence for a beneficial effect on indicators of asthma and COPD of eating fish, fruit and vegetables is increasing. However, the effectiveness of dietary supplementation in open-population samples is often not demonstrated. Several unresolved questions are raised, which should be addressed in future studies on the relationship between diet and respiratory disease.


Tansy ragwort poisoning in a horse in southern Ontario.
Bizarre behavior, apparent lameness, and colic were noticed in 1 of 3 horses on a pasture overgrown by weeds during a drought. Liver failure and hepatoencephalopathy were diagnosed, caused by pyrrolizidine alkaloid toxicosis associated with consumption of tansy ragwort. The horse made a full recovery when removed from the pasture.


Calcium and acute renal failure.
Tubular cell calcium concentration and content rise following acute renal injury induced by ischemic and toxic insults. Since calcium plays a critical role in many cell functions and the proximal tubule appears to be a major site of injury in acute renal failure, it is possible that cell calcium overload plays a direct role in the pathogenesis of acute renal failure. Tubular cell calcium overload has been associated with altered function at the level of the plasma membrane, mitochondria, endoplasmic reticulum and cytoskeleton. While there is evidence to support a role for calcium in acute renal injury, the importance of cell calcium overload needs to be further explored. Furthermore, alterations in extracellular calcium and mineral metabolism may be involved in some aspects of acute renal failure and recovery. Calcium channel blockers and other interventions designed to modulate calcium changes may have a role in the treatment of acute renal failure.


Purification and characterization of a fibrinolytic enzyme from Streptomyces sp. XZNUM 00004.
A fibrinolytic enzyme (SFE1) from Streptomyces sp. XZNUM 00004 was purified to electrophoretic homogeneity with the methods including ammonium sulfate precipitation, polyacrylamide gel, DEAE-Sepharose Fast Flow anion exchange and gel-filtration chromatography. The molecular weight of SFE1 was estimated to be 20 kDa by SDS-PAGE, fibrin zymography, and gel filtration chromatography. The isoelectric point was 4.9. K (m) and V (max) values were 0.96 mg/ml and 181.8 unit/ml, respectively. It was very stable at pH 5.0-8.0 and below 65 °C. The optimum pH for enzyme activity was 7.8. The optimum temperature was 35 °C. The fibrinolytic activity of SFE1 was enhanced by Na(+), K(+), Mn(2+), Mg(2+), Zn(2+) and Co(2+). Conversely, Cu(2+) showed strong inhibition. Furthermore, the fibrinolytic activity was strongly inhibited by PMSF, and partly inhibited by EDTA and EGTA. SFE1 rapidly hydrolyzed the Aα-chain of fibrinogen, followed by the Bβ-chain and finally the γ-chain. The first 15 amino acids of the N-terminal sequence were APITLSQGHVDVVDI. Additionally, SFE1 directly digested fibrin and not by plasminogen activators in vitro. SFE1 can be further developed as a potential candidate for thrombolytic therapy.


Familial Mediterranean fever in children: a single centre experience in Jordan.
Familial Mediterranean fever is quite prevalent among Arabs. We reviewed the files of 56 patients diagnosed with familial Mediterranean fever and followed up at King Hussein Medical Centre in Jordan over 4 years for their clinical profile, course, genotype, treatment and complications. There were 30 males and 26 females with a mean age at onset of 5.2 years. Abdominal pain (79%) was the commonest manifestation, followed by arthritis (13%) and chest pain (4%). Family history was positive in 50% of patients. Regarding treatment, 97% of patients responded well to colchicine, and amyloidosis was not documented in any patients after 5 years follow-up. The commonest genotype was M694 (64%), followed by heterozygous M694V-V726A (23%) and E148Q (8%).


Hyperoxia and lack of ascorbic acid deplete tetrahydrobiopterin without affecting NO generation in endothelial cells.
Nitric oxide (NO) may protect against gas bubble formation and risk of decompression sickness. We have previously shown that the crucial co-factor tetrahydrobiopterin (BH4) is oxidized in a dose-dependent manner when exposed to hyperoxia similar to diving conditions but with minor effects on the NO production by nitric oxide synthase. By manipulating the intracellular redox state, we further investigated the relationship between BH4 levels and production of NO in human endothelial cells (HUVECs). HUVECs were cultured with and without ascorbic acid (AA) and the glutathione (GSH) synthesis inhibitor buthionine sulfoximine, prior to hyperoxic exposure. The levels of biopterins and GSH were determined in cell lysates while the production of NO was determined in intact cells. Omitting AA resulted in a 91% decrease in BH4 levels (0.49 ± 0.08 to 0.04 ± 0.01 pmol/10⁶ cells, p⟨0.001) at 20 kPa oxygen (O2), and 88% decrease (0.24 ± 0.03 to 0.03 ± 0.01 pmol/10⁶ cells, p=0.01) after exposure to 60 kPa O2. The NO generation was decreased by 23% (74.5 ± 2.2 to 57.3 ± 5.6 pmol/min/mg protein, p⟨0.001) at 20 kPa O2, but no significant change was observed at 60 kPa O2. GSH depletion had no effects on the NO generation. No correlation was found between NO generation and the corresponding intracellular BH4 concentration (p=0.675, r=-0.055) or the BH4 to BH2 ratio (p=0.983, r=0.003), determined across 18 in vitro experiments. Decreased BH4 in HUVECs, due to hyperoxia or lack of ascorbic acid, does not imply corresponding decreases in NO generation.


Premature senescence activation in DLD-1 colorectal cancer cells through adjuvant therapy to induce a miRNA profile modulating cellular death.
Cancer, and particularly colon cancer, is associated with an increasing number of cases resistant to chemotherapy. One approach to overcome this, and to improve the prognosis and outcome of patients, is the use of adjuvant therapy alongside the standard chemotherapy regiment. In the present study, the effect of deuterium-depleted water (DDW) as a potential modulator of adjuvant therapy on DLD-1 colorectal cancer models was assessed. A number of functionality assays were performed, including MTT, apoptosis and autophagy, and mitochondrial activity and senescence assays, in addition to assessing the capacity to modify the pattern of released miRNA via microarray technology. No significant effect on cell viability was identified, but an increase in mitochondrial activity and a weak pro-apoptotic effect were observed in the treated DLD-1 cells cultured in DDW-prepared medium compared with those grown in standard conditions (SC). Furthermore, the findings revealed the capacity of DDW medium to promote senescence to a higher degree compared with SC. The exosome-released miRNA pattern was significantly modified for the cells maintained in DDW compared with those maintained in SC. These findings suggest that DDW may serve as an adjuvant treatment; however, a better understanding of the underlying molecular mechanism of action will be useful for developing novel and efficient therapeutic strategies, in which the transcriptomic pattern serves an important role.


A novel cricket morph has diverged in song and wing morphology across island populations.
Divergence of sexual signals between populations can lead to speciation, yet opportunities to study the immediate aftermath of novel signal evolution are rare. The recent emergence and spread of a new mating song, purring, in Hawaiian populations of the Pacific field cricket (Teleogryllus oceanicus) allows us to investigate population divergence soon after the origin of a new signal. Male crickets produce songs with specialized wing structures to attract mates from afar (calling) and entice them to mate when found (courtship). However, in Hawaii, these songs also attract an eavesdropping parasitoid fly (Ormia ochracea) that kills singing males. The novel purring song, produced with heavily modified wing morphology, attracts female crickets but not the parasitoid fly, acting as a solution to this conflict between natural and sexual selection. We've recently observed increasing numbers of purring males across Hawaii. In this integrative field study, we investigated the distribution of purring and the proportion of purring males relative to other morphs in six populations on four islands and compared a suite of phenotypic traits (wing morphology, calling song and courtship song) that make up this novel signal across populations of purring males. We show that purring is found in varying proportions across five, and is locally dominant in four, Hawaiian populations. We also show that calling songs, courtship songs and wing morphology of purring males differ geographically. Our findings demonstrate the rapid pace of evolution in island populations and provide insights into the emergence and divergence of new sexual signals over time.


Trans-Pacific RAD-Seq population genomics confirms introgressive hybridization in Eastern Pacific Pocillopora corals.
Discrepancies between morphology-based taxonomy and phylogenetic systematics are common in Scleractinian corals. In Pocillopora corals, nine recently identified genetic lineages disagree fundamentally with the 17 recognized Pocillopora species, including 5 major Indo-Pacific reef-builders. Pocillopora corals hybridize in the Tropical Eastern Pacific, so it is possible that some of the disagreement between the genetics and taxonomy may be due to introgressive hybridization. Here we used 6769 genome-wide SNPs from Restriction-site Associated DNA Sequencing (RAD-Seq) to conduct phylogenomic comparisons among three common, Indo-Pacific Pocillopora species - P. damicornis, P. eydouxi and P. elegans - within and between populations in the Tropical Eastern Pacific (TEP) and the Central Pacific. Genome-wide RAD-Seq comparisons of Central and TEP Pocillopora confirm that the morphospecies P. damicornis, P. eydouxi and P. elegans are not monophyletic, but instead fall into three distinct genetic groups. However, hybrid samples shared fixed alleles with their respective parental species and, even without strict monophyly, P. damicornis share a common set of 33 species-specific alleles across the Pacific. RAD-Seq data confirm the pattern of one-way introgressive hybridization among TEP Pocillopora, suggesting that introgression may play a role in generating shared, polyphyletic lineages among currently recognized Pocillopora species. Levels of population differentiation within genetic lineages indicate significantly higher levels of population differentiation in the Tropical Eastern Pacific than in the Central West Pacific.


Interventions for necrotizing soft tissue infections in adults.
Necrotizing soft tissue infections (NSTIs) are severe and rapidly spreading soft tissue infections of the subcutaneous tissue, fascia, or muscle, which are mostly caused by bacteria. Associated rates of mortality and morbidity are high, with the former estimated at around 23%, and disability, sequelae, and limb loss occurring in 15% of patients. Standard management includes intravenous empiric antimicrobial therapy, early surgical debridement of necrotic tissues, intensive care support, and adjuvant therapies such as intravenous immunoglobulin (IVIG). To assess the effects of medical and surgical treatments for necrotizing soft tissue infections (NSTIs) in adults in hospital settings. We searched the following databases up to April 2018: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers, pharmaceutical company trial results databases, and the US Food and Drug Administration and the European Medicines Agency websites. We checked the reference lists of included studies and reviews for further references to relevant randomised controlled trials (RCTs). RCTs conducted in hospital settings, that evaluated any medical or surgical treatment for adults with NSTI were eligible for inclusion. Eligible medical treatments included 1) comparisons between different antimicrobials or with placebo; 2) adjuvant therapies such as intravenous immunoglobulin (IGIV) therapy compared with placebo; no treatment; or other adjuvant therapies. Eligible surgical treatments included surgical debridement compared with amputation, immediate versus delayed intervention, or comparisons of number of interventions.RCTs of hyperbaric oxygen (HBO) therapy for NSTI were ineligible because HBO is the focus of another Cochrane Review. We used standard methodological procedures expected by Cochrane. The primary outcome measures were 1) mortality within 30 days, and 2) proportion of participants who experience a serious adverse event. Secondary outcomes were 1) survival time, and 2) assessment of long-term morbidity. We used GRADE to assess the quality of the evidence for each outcome. We included three trials randomising 197 participants (62% men) who had a mean age of 55 years. One trial compared two antibiotic treatments, and two trials compared adjuvant therapies with placebo. In all trials, participants concomitantly received standard interventions, such as intravenous empiric antimicrobial therapy, surgical debridement of necrotic tissues, intensive care support, and adjuvant therapies. All trials were at risk of attrition bias and one trial was not blinded.Moxifloxacin versus amoxicillin-clavulanate One trial included 54 participants who had a NSTI; it compared a third-generation quinolone, moxifloxacin, at a dose of 400 mg given once daily, against a penicillin, amoxicillin-clavulanate, at a dose of 3 g given three times daily for at least three days, followed by 1.5 g three times daily. Duration of treatment varied from 7 to 21 days. We are uncertain of the effects of these treatments on mortality within 30 days (risk ratio (RR) 3.00, 95% confidence interval (CI) 0.39 to 23.07) and serious adverse events at 28 days (RR 0.63, 95% CI 0.30 to 1.31) because the quality of the evidence is very low.AB103 versus placebo One trial of 43 randomised participants compared two doses, 0.5 mg/kg and 0.25 mg/kg, of an adjuvant drug, a CD28 antagonist receptor (AB103), with placebo. Treatment was given via infusion pump for 10 minutes before, after, or during surgery within six hours after the diagnosis of NSTI. We are uncertain of the effects of AB103 on mortality rate within 30 days (RR of 0.34, 95% CI 0.05 to 2.16) and serious adverse events measured at 28 days (RR 1.49, 95% CI 0.52 to 4.27) because the quality of the evidence is very low.Intravenous immunoglobulin (IVIG) versus placebo One trial of 100 randomised participants assessed IVIG as an adjuvant drug, given at a dose of 25 g/day, compared with placebo, given for three consecutive days. There may be no clear difference between IVIG and placebo in terms of mortality within 30 days (RR 1.17, 95% CI 0.42 to 3.23) (low-certainty evidence), nor serious adverse events experienced in the intensive care unit (ICU) (RR 0.73 CI 95% 0.32 to 1.65) (low-certainty evidence).Serious adverse events were only described in one RCT (the IVIG versus placebo trial) and included acute kidney injury, allergic reactions, aseptic meningitis syndrome, haemolytic anaemia, thrombi, and transmissible agents.Only one trial reported assessment of long-term morbidity, but the outcome was not defined in the way we prespecified in our protocol. The trial used the Short Form Health Survey (SF36). Data on survival time were provided upon request for the trials comparing amoxicillin-clavulanate versus moxifloxacin and IVIG versus placebo. However, even with data provided, it was not possible to perform survival analysis. We found very little evidence on the effects of medical and surgical treatments for NSTI. We cannot draw conclusions regarding the relative effects of any of the interventions on 30-day mortality or serious adverse events due to the very low quality of the evidence.The quality of the evidence is limited by the very small number of trials, the small sample sizes, and the risks of bias in the included trials. It is important for future trials to clearly define their inclusion criteria, which will help with the applicability of future trial results to a real-life population.Management of NSTI participants (critically-ill participants) is complex, involving multiple interventions; thus, observational studies and prospective registries might be a better foundation for future research, which should assess empiric antimicrobial therapy, as well as surgical debridement, along with the placebo-controlled comparison of adjuvant therapy. Key outcomes to assess include mortality (in the acute phase of the condition) and long-term functional outcomes, e.g. quality of life (in the chronic phase).


Prediction of chronic kidney disease progression using recurrent neural network and electronic health records.
Chronic kidney disease (CKD) is a progressive loss in kidney function. Early detection of patients who will progress to late-stage CKD is of paramount importance for patient care. To address this, we develop a pipeline to process longitudinal electronic heath records (EHRs) and construct recurrent neural network (RNN) models to predict CKD progression from stages II/III to stages IV/V. The RNN model generates predictions based on time-series records of patients, including repeated lab tests and other clinical variables. Our investigation reveals that using a single variable, the recorded estimated glomerular filtration rate (eGFR) over time, the RNN model achieves an average area under the receiver operating characteristic curve (AUROC) of 0.957 for predicting future CKD progression. When additional clinical variables, such as demographics, vital information, lab test results, and health behaviors, are incorporated, the average AUROC increases to 0.967. In both scenarios, the standard deviation of the AUROC across cross-validation trials is less than 0.01, indicating a stable and high prediction accuracy. Our analysis results demonstrate the proposed RNN model outperforms existing standard approaches, including static and dynamic Cox proportional hazards models, random forest, and LightGBM. The utilization of the RNN model and the time-series data of previous eGFR measurements underscores its potential as a straightforward and effective tool for assessing the clinical risk of CKD patients concerning their disease progression.


The dark side of SOX2: cancer - a comprehensive overview.
The pluripotency-associated transcription factor SOX2 is essential during mammalian embryogenesis and later in life, but SOX2 expression can also be highly detrimental. Over the past 10 years, SOX2 has been shown to be expressed in at least 25 different cancers. This review provides a comprehensive overview of the roles of SOX2 in cancer and focuses on two broad topics. The first delves into the expression and function of SOX2 in cancer focusing on the connection between SOX2 levels and tumor grade as well as patient survival. As part of this discussion, we address the developing connection between SOX2 expression and tumor drug resistance. We also call attention to an under-appreciated property of SOX2, its levels in actively proliferating tumor cells appear to be optimized to maximize tumor growth - too little or too much SOX2 dramatically alters tumor growth. The second topic of this review focuses on the exquisite array of molecular mechanisms that control the expression and transcriptional activity of SOX2. In addition to its complex regulation at the transcriptional level, SOX2 expression and activity are controlled carefully by microRNAs, long non-coding RNAs, and post-translational modifications. In the Conclusion and Future Perspectives section, we point out that there are still important unanswered questions. Addressing these questions is expected to lead to new insights into the functions of SOX2 in cancer, which will help design novels strategies for more effectively treating some of the most deadly cancers.


Mechanistic study of malononitrileamide FK778 in cardiac transplantation and CMV infection in rats.
FK778 is a malononitrilamide, a class of immune suppressive compounds with antiviral features and experimental activity in chronic rejection, a potentially interesting combination for organ transplantation. The goal of this project was to study the tolerability, immune suppressive efficacy, and anti-cytomegalovirus (CMV) activity of FK778 and to assess the in vivo relevance of its previously described inhibition of de novo pyrimidine synthesis. Heart transplants were performed in rats (Brown Norway [BN] to Lewis) and treated with varying doses of FK778 or leflunomide for 28 days. At 28 days, at the time of rejection or at the death of the animal, the allograft and other vital organs were obtained for study by light microscopy and immunohistochemistry. In separate experiments, Lewis rats were given sublethal irradiation, inoculated with rat CMV (Maastricht strain), and treated with varying doses of FK778 and leflunomide. In both the transplant and CMV studies, IP uridine was given at 250 mg/kg to cohorts or animals receiving FK778 and leflunomide. FK778 controls acute rejection and inhibits CMV replication at 20 mg/kg but is toxic at 25 mg/kg. Toxicity is manifested as anemia, changes in hepatic and intestinal histology, and mortality. The toxicity but not the immune suppressive or antiviral efficacy, is reduced significantly by exogenous uridine administration. FK778 has both immune suppressive and antiviral activities, neither of which is entirely dependent on inhibition of pyrimidine synthesis. These, and other published observations, suggest that the antiviral activity and a considerable part of the efficacy of the malononitrilamide family of drugs is attributable to activities other than drug induced pyrimidine deficiency.


Kinetic modelling of β-cell metabolism reveals control points in the insulin-regulating pyruvate cycling pathways.
Insulin, a key hormone in the regulation of glucose homoeostasis, is secreted by pancreatic β-cells in response to elevated glucose levels. Insulin is released in a biphasic manner in response to glucose metabolism in β-cells. The first phase of insulin secretion is triggered by an increase in the ATP:ADP ratio; the second phase occurs in response to both a rise in ATP:ADP and other key metabolic signals, including a rise in the NADPH:NADP+ ratio. Experimental evidence indicates that pyruvate-cycling pathways play an important role in the elevation of the NADPH:NADP+ ratio in response to glucose. The authors developed a kinetic model for the tricarboxylic acid cycle and pyruvate cycling pathways. The authors successfully validated the model against experimental observations and performed a sensitivity analysis to identify key regulatory interactions in the system. The model predicts that the dicarboxylate carrier and the pyruvate transporter are the most important regulators of pyruvate cycling and NADPH production. In contrast, the analysis showed that variation in the pyruvate carboxylase flux was compensated by a response in the activity of mitochondrial isocitrate dehydrogenase (ICDm ) resulting in minimal effect on overall pyruvate cycling flux. The model predictions suggest starting points for further experimental investigation, as well as potential drug targets for the treatment of type 2 diabetes.


Why socio-political borders and boundaries matter in conservation.
Acting to demarcate the spatial limits of decision-making processes, socio-political boundaries are an inevitable part of a human-dominated world. Rarely coincident with ecological boundaries, and thus having no ecological functional role by themselves, they nevertheless impose substantial costs on biodiversity and ecosystem conservation by fragmenting ownership, governance, and management. Where boundaries are in place, a lack of coordination on either side of a boundary affects the efficiency and efficacy of ecosystem management. We suggest four research pathways which will enhance our ability to address the adverse effects of socio-political borders on conservation: (i) scale-matching, (ii) quantification of the mutual economic benefits of conservation across boundaries, (iii) determining transboundary societal values, and (iv) acknowledging the importance of stakeholder behaviour and incentives.


Semi-2DCAE: a semi-supervision 2D-CNN AutoEncoder model for feature representation and classification of encrypted traffic.
Traffic classification is essential in network-related areas such as network management, monitoring, and security. As the proportion of encrypted internet traffic rises, the accuracy of port-based and DPI-based traffic classification methods has declined. The methods based on machine learning and deep learning have effectively improved the accuracy of traffic classification, but they still suffer from inadequate extraction of traffic structure features and poor feature representativeness. This article proposes a model called Semi-supervision 2-Dimensional Convolution AutoEncoder (Semi-2DCAE). The model extracts the spatial structure features in the original network traffic by 2-dimensional convolution neural network (2D-CNN) and uses the autoencoder structure to downscale the data so that different traffic features are represented as spectral lines in different intervals of a one-dimensional standard coordinate system, which we call FlowSpectrum. In this article, the PRuLe activation function is added to the model to ensure the stability of the training process. We use the ISCX-VPN2016 dataset to test the classification effect of FlowSpectrum model. The experimental results show that the proposed model can characterize the encrypted traffic features in a one-dimensional coordinate system and classify Non-VPN encrypted traffic with an accuracy of up to 99.2%, which is about 7% better than the state-of-the-art solution, and VPN encrypted traffic with an accuracy of 98.3%, which is about 2% better than the state-of-the-art solution.


[Arthroscopic capsular shrinkage for posterosuperior internal impingement of the shoulder].
We evaluated clinical and radiological findings and functional results following arthroscopic capsular shrinkage in patients with internal impingement of the shoulder. The study included four patients (2 females, 2 males; mean age 27.5 years; range 25 to 32 years) who underwent arthroscopic capsular shrinkage between 1997 and 2001. Three patients were overhead athletes (2 volleyball, 1 water polo player), the fourth was a clerk. All the patients suffered from shoulder pain upon abduction and external rotation and all received a preoperative unsuccessful rehabilitation for at least three months (range 3 to 10 months). Following arthroscopic examination of the glenohumeral joint, anterior joint capsule was shrunk using a radiofrequency probe. A specific rehabilitation program was applied postoperatively. The mean follow-up was 3.5 years (range 2 to 6 years). The Neer test was positive in all cases, and the relocation test in 3 cases, preoperatively. Magnetic resonance imaging showed contact between the glenoid rim and the greater tuberosity in three cases, degeneration in the rotator cuff in two cases, a partial tear in one patient, and a subchondral cyst in another. Arthroscopic examination revealed glenoid-rotator cuff contact in all cases and degeneration in the contact areas. Drive-through sign was positive in all cases. Kissing lesion was present in one case. No SLAP lesion was identified. The patients' complaints disappeared and the three athletes were able to resume their professional sporting activities. Arthroscopic shrinkage of the stretched anterior capsule proved successful throughout a follow-up period of at least two years.


Isoflavones in Animals: Metabolism and Effects in Livestock and Occurrence in Feed.
Soybeans are a common ingredient of animal feed. They contain isoflavones, which are known to act as phytoestrogens in animals. Isoflavones were described to have beneficial effects on farm animals. However, there are also reports of negative outcomes after the consumption of isoflavones. This review summarizes the current knowledge of metabolization of isoflavones (including the influence of the microbiome, phase I and phase II metabolism), as well as the distribution of isoflavones and their metabolites in tissues. Furthermore, published studies on effects of isoflavones in livestock species (pigs, poultry, ruminants, fish) are reviewed. Moreover, published studies on occurrence of isoflavones in feed materials and co-occurrence with zearalenone are presented and are supplemented with our own survey data.


A Gradient in Synaptic Strength and Plasticity among Motoneurons Provides a Peripheral Mechanism for Locomotor Control.
The recruitment of motoneurons during force generation follows a general pattern that has been confirmed across diverse species [1-3]. Motoneurons are recruited systematically according to synaptic inputs and intrinsic cellular properties and corresponding to movements of different intensities. However, much less is known about the output properties of individual motoneurons and how they affect the translation of motoneuron recruitment to the strength of muscle contractions. In larval zebrafish, spinal motoneurons are recruited in a topographic gradient according to their input resistance (Rin) at different swimming strengths and speeds. Whereas dorsal, lower-Rin primary motoneurons (PMns) are only activated during behaviors that involve strong and fast body bends, more ventral, higher-Rin secondary motoneurons (SMns) are recruited during weaker and slower movements [4-6]. Here we perform in vivo paired recordings between identified spinal motoneurons and skeletal muscle cells in larval zebrafish. We characterize individual motoneuron outputs to single muscle cells and show that the strength and reliability of motoneuron outputs are inversely correlated with motoneuron Rin. During repetitive high-frequency motoneuron drive, PMn synapses undergo depression, whereas SMn synapses potentiate. We monitor muscle cell contractions elicited by single motoneurons and show that the pattern of motoneuron output strength and plasticity observed in electrophysiological recordings is reflected in muscle shortening. Our findings indicate a link between the recruitment pattern and output properties of spinal motoneurons that can together generate appropriate intensities for muscle contractions. We demonstrate that motoneuron output properties provide an additional peripheral mechanism for graded locomotor control at the neuromuscular junction.


The larynx of roaring and non-roaring cats.
Dissections were made of the larynges of 14 species of the cat family, with representative specimens from all genera. It was found that the vocal folds of the larynx of genus Panthera (with the exception of the snow leopard) form the basic structure of a sound generator well-designed to produce a high acoustical energy. Combined with an efficient sound radiator (vocal tract) that can be adjusted in length, a Panthera can use its vocal instrument literally to blow its own horn with a 'roar'. Also, it is proposed that laryngeal morphology can be used as an anatomical character in mammalian taxonomy.


Outcomes in thread lift for face and neck: A study performed with Silhouette Soft and Promo Happy Lift double needle, innovative and classic techniques.
Increased demand for rejuvenation of the aging face has led to the evolution of various plastic surgery techniques. This study was conducted to evaluate the surgical efficacy and outcomes of the absorbable suture suspension system related to eyebrow, midface, mandibular, and neck lifting. In this prospective review chart clinical study, a total of 193 patients were included in the study from January 2016 to May 2017. All participants underwent thread lifting using the Proma Happy Lift double needle and Silhouette Soft threads. The patients were followed up for first week and first, third, and sixth month after lifting surgery. Outcomes were assessed by two surgeons and patients based on the GAIS score. A total of 193 patients (mean age: 52.22 ± 11.74 year, range: 25-89), 23 (11.9%) men and 170 (88.1%) women, were included in the study. The most common sites for the face lifting surgery were the jawline (46.1%), midface (33.7%), eyebrows (12.4%), and neck (7.8%). The level of satisfaction increased from 94% in the first week after surgery to 99% in the sixth month after surgery for patients, increased from 94% to 99% for surgeon 1, and increased from 83% to 98% for surgeon 2. The results showed that the level of satisfaction of patients and surgeons increased over time. These results demonstrated that facial rejuvenation thread lift with Proma Happy Lift double needle and Silhouette Soft threads is a being cosmetically more acceptance, safe, and effective procedure associated with minor complications.


The attentional 'zoom-lens' in 8-month-old infants.
The spatial attention mechanisms of orienting and zooming cooperate to properly select visual information from the environment and plan eye movements accordingly. Despite the fact that orienting ability has been extensively studied in infancy, the zooming mechanism--namely, the ability to distribute the attentional resources to a small or large portion of the visual field--has never been tested before. The aim of the present study was to evaluate the attentional zooming abilities of 8-month-old infants. An eye-tracker device was employed to measure the saccadic latencies (SLs) at the onset of a visual target displayed at two eccentricities. The size of the more eccentric target was adjusted in order to counteract the effect of cortical magnification. Before the target display, attentional resources were automatically focused (zoom-in) or spread out (zoom-out) by using a small or large cue, respectively. Two different cue-target intervals were also employed to measure the time course of this attentional mechanism. The results showed that infants' SLs varied as a function of the cue size. Moreover, a clear time course emerged, demonstrating that infants can rapidly adjust the attentional focus size during a pre-saccadic temporal window. These findings could serve as an early marker for neurodevelopmental disorders associated with attentional zooming dysfunction such as autism and dyslexia.


Developmental and reproductive toxicology studies in IL-12p40 knockout mice.
Interleukin (IL)-12 is a cytokine that can exert regulatory effects on T and NK cells. This study was designed to identify potential developmental and reproductive hazards associated with IL-12p40 knockout in mice. In the combined fertility and teratology study, female F0 C57/BL6 wild-type control mice and female F0 C57/BL6 IL-12p40 homozgyous knockout mice were assessed for estrous cyclicity, sperm, and mating parameters. Pregnant females were euthanized on gestation day (GD) 18 and their fetuses were assessed for external, visceral, and skeletal development. In the peri and postnatal development study, the F1 wild-type control and IL-12p40 knockout mice were assessed for developmental landmarks, sexual development, passive avoidance, motor activity, and morris water maze. The IL-12p40 knockout male mice exhibited decreased testis weights when compared to the wild-type control group; however, this finding was not considered adverse, as it had no apparent functional effects on mating, fertility, and pregnancy rates or sperm motility. The IL-12p40 knockout group exhibited effects on estrous cycle length, passive avoidance, morris water maze, and motor activity when compared to the wild-type control group. However, since these findings were small in magnitude, transient and/or had no apparent effects on subsequent growth and development, they were not considered adverse. These results demonstrate that although IL-12p40 homozygous knockout in mice exhibited effects on developmental and reproductive parameters, these effects were relatively minor and were not considered adverse.


Individual-level and area-level socioeconomic inequalities in hearing impairment among Chinese adults: a population-based study.
It is unclear whether individual-level and area-level socioeconomic status (SES) is associated with hearing impairment (HI). This study determines an association of individual SES, area SES and their interaction with HI among working-aged adults. Data were obtained from the large, population-based sample of the Second China National Sample Survey on Disability, a cross-sectional study conducted in China. A total of 1 333 528 participants aged 25-59 years were included. HI was measured by pure-tone audiometry (PTA) and audiologists further ascertained for a final diagnosis. Individual SES was defined as a summed of z-scored of education level and household income per capita, and area SES was calculated as a summed of z-scored of county-level income per capita, high school rate, poverty rate and rate of upper-class occupation. Multilevel logistic regression was used. Individual and area SES were associated with HI among Chinese working-aged adults. A 1-SD increase in individual SES was associated with decreased risk of HI (OR=0.3, 95% CI: 0.3 to 0.3). Area SES was positively related to HI (OR=1.2, 95%CI: 1.2 to 1.3). The cross-level interaction on individual and area SES was significantly associated with HI, indicating that among those who lived in higher SES areas, participants with lower SES had a greater likelihood to develop HI. Significant individual and area socioeconomic inequalities were observed in HI among Chinese working-aged adults. Lower SES adults who resided in prosperous areas may face more deprivation on hearing health than those with higher SES.


Similarity network fusion to identify phenotypes of small-for-gestational-age fetuses.
Fetal growth restriction (FGR) affects 5-10% of pregnancies, is the largest contributor to fetal death, and can have long-term consequences for the child. Implementation of a standard clinical classification system is hampered by the multiphenotypic spectrum of small fetuses with substantial differences in perinatal risks. Machine learning and multiomics data can potentially revolutionize clinical decision-making in FGR by identifying new phenotypes. Herein, we describe a cluster analysis of FGR based on an unbiased machine-learning method. Our results confirm the existence of two subtypes of human FGR with distinct molecular and clinical features based on multiomic analysis. In addition, we demonstrated that clusters generated by machine learning significantly outperform single data subtype analysis and biologically support the current clinical classification in predicting adverse maternal and neonatal outcomes. Our approach can aid in the refinement of clinical classification systems for FGR supported by molecular and clinical signatures.


Comparative Identification of Differential Interactions from Trajectories of Dynamic Biological Networks.
It is often challenging to reconstruct accurately a complete dynamic biological network due to the scarcity of data collected in cost-effective experiments. This paper addresses the possibility of comparatively identifying qualitative interaction shifts between two dynamical networks from comparative time course data. An innovative approach is developed to achieve differential interaction detection by statistically comparing the trajectories, instead of numerically comparing the reconstructed interactions. The core of this approach is a statistical heterogeneity test that compares two multiple linear regression equations for the derivatives in nonlinear ordinary differential equations, statistically instead of numerically. In detecting any shift of an interaction, the uncertainty in estimated regression coefficients is taken into account by this test, while it is ignored by the reconstruction-based numerical comparison. The heterogeneity test is accomplished by assessing the gain in goodness-of-fit from using a single common interaction to using a pair of differential interactions. Compared with previous numerical comparison methods, the proposed statistical comparison always achieves higher statistical power. As sample size decreases or noise increases in a certain range, the improvement becomes substantial. The advantage is illustrated by a simulation study on the statistical power as functions of the noise level, the sample size, and the interaction complexity. This method is also capable of detecting interaction shifts in the oscillated and excitable domains of a dynamical system model describing cdc2-cyclin interactions during cell division cycle. Generally, the described approach is applicable to comparing dynamical systems of additive nonlinear ordinary differential equations.


Dietary Tryptophan and the Risk of Metabolic Syndrome: Total Effect and Mediation Effect of Sleep Duration.
Tryptophan affects energy homeostasis, glucose metabolism, blood pressure, and sleep. However, studies investigating the association between tryptophan and metabolic syndrome (MetSyn) are rare. We aimed to investigate the associations of dietary tryptophan with MetSyn incidence and potential mediation via sleep duration. Data of 7890 participants were obtained from the China Health and Nutrition Survey (1997-2011) (male: 49.9%; mean age=43.43 years;median follow-up=129.76 months; MetSyn incidence: 16.3%). A combination of individual 24-hour recall and household survey was used to assess dietary intake. In total, 6720 and 4474 participants who reported sleep duration and had blood samples taken, respectively, were incorporated into subgroup analyses. MetSyn was defined according to National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III criteria (2004), and tryptophan consumption and sleep duration were assessed by self-report in each survey. Multivariate Cox regression models were used to assess the associations between tertiles of tryptophan intake and MetSyn. Generalized linear regression models were used to evaluate the effect of tryptophan on sleep duration and plasma biomarkers. Dietary tryptophan showed a protective effect on the risk of MetSyn. The hazard ratio (95% CI) of MetSyn was 0.77 (0.65-0.90) for individuals with a high tertile of tryptophan. Sleep duration was significantly higher, and HbA1c, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (APO-B) were lower in the high tertile of tryptophan compared to the low tertile (P<0.05). In addition, mediation effects on the association between tryptophan intake and MetSyn risk were observed for sleep duration (estimated mediation percentage: 26.5%). Our study demonstrated a negative association between dietary tryptophan and MetSyn incidence, and the mediation effect of sleep duration on this association, after adjusting for numerous confounders such as nutrients and food patterns. These findings may have important public health implications for the improvement of cardiometabolic health.


Variability in the levels of exosomal miRNAs among human subjects could be explained by differential interactions of exosomes with the endothelium.
Exosomes are 30-100 nm endosome-derived membrane vesicles, that contain specific RNA transcripts including mRNAs, and microRNAs (miRNAs) and have been implicated in cell-to-cell communication. Exosomal miRNAs in blood circulation have been attracting major interest as potential diagnostic and prognostic biomarkers in a variety of diseases including stroke, cancer, and inflammatory disorders. Despite the progress made in the utilization of circulating exosomal miRNAs as biomarkers for various human diseases and conditions, there are still difficulties in functionally utilizing such methods in the clinic due to the high variability observed among subjects. Attempts to use miRNA signatures have improved but have not eliminated the problem. Additionally, standardized laboratory practices may partially reduce variability but there is still an unknown biological factor that hinders the proper use of miRNAs as biomarkers. We hypothesize that this variability might be partially attributed to a differential interaction among circulating exosomes carrying those miRNAs with endothelial surface molecules that themselves may vary among individuals due to secondary conditions, for example, inflammation status. This differential interaction could potentially add variability to the level of the examined miRNA that is not directly attributed to the primary condition under study.


Cardiac cell toxicity induced by 4-hydroperoxycyclophosphamide is modulated by glutathione.
Cardiac myocytes were exposed to 4-hydroperoxycyclophosphamide (4-HC, an activated derivative of cyclophosphamide) to assess whether early ionic events are associated with the dose limiting toxicity of this chemotherapeutic agent. Primary cultures of embryonic chick cardiac myocytes were grown to confluency and then exposed to a medium containing 4-HC. Cellular sodium, potassium, and calcium contents were measured by atomic absorption spectrophotometry and related to protein and ATP content. Pretreatment of the cultured heart cells with glutathione depleting or enhancing agents provided the basis for evaluating the involvement of glutathione in the 4-HC-induced cytotoxicity. Administration of 150 microM 4-HC to cardiac myocytes resulted in increases in cellular sodium and calcium contents and decreases in potassium, ATP, and protein contents. Pretreatment of cardiac myocytes with L-buthionine-SR-sulphoximine, a specific inhibitor of gamma-glutamylcysteine synthetase, depleted cellular glutathione to 12% of control and significantly reduced the minimum concentration of 4-HC causing cytotoxic changes. Conversely, elevation of cellular thiol content by the pretreatment of cardiac myocytes with glutathione monoethyl ester (but not glutathione) provided protection against 4-HC induced cytotoxicity. Cellular glutahione concentration can markedly influence the 4-HC induced changes in cellular ion content and ATP, which are early indicators of 4-HC induced cytotoxicity.


Bimetallic multifunctional core@shell plasmonic nanoparticles for localized surface plasmon resonance based sensing and electrocatalysis.
Smart bimetallic core@shell nanoparticles were fabricated based on gold nanoparticles (AuNPs) decorated with pH-sensitive polymer shell. Concretely, AuNPs having poly(4-vinylpyridine) (P4VP) on the surface were first fabricated through surface-initiated atom transfer radical polymerization (SI-ATRP). Then, they were mixed with selected metal precursor solutions followed by reduction using reducing agent. The metal NPs thus introduced were uniformly distributed in P4VP polymer shells. In order to explore the diversity and viable function of the resultant nanostructures, we controlled the size of AuNP, pH, selectivity of metal precursors, etc. We investigated the structural alteration during the sequential synthetic process. The bimetallic nanostructures of AuNP@P4VP nanocomposites containing another type of metal NP at the P4VP periphery exhibit a controlled sensing property in terms of the change in the refractive index of surrounding media and a typical electrocatalytic activity for methanol oxidation reaction.


Evaluation of a New Primer In Comparison With Microscopy for the Detection of Giardia lamblia Infection in Stool Samples.
Among the most important parasitic disease, causing diarrhea, Giardia lamblia is noteworthy. Nowadays detection methods for these parasites include parasitological methods such as microscopic examination. The sensitivity of these methods relies on the expertise and experience of examiners. In contrast, molecular methods such as PCR are less dependent on the expertise of the examiner. Here we developed a PCR for the detection of G. lamblia genome in stool samples in comparison with microscopy, which is the gold standard. For the evaluation of primers, 22 positive samples and 47 negative samples were used. QIAamp DNA Stool Mini Kit (QIAGEN, Germany) was used for DNA extraction from feces. Primers for PCR were designed using Primer-BLAST which uses Primer 3 to designing specific primers (NCBI/Primer-BLAST). Sensitivity of the PCR was done with 100% (95%CI: 84.56-100) for the detection of G. lamblia DNA isolated from patients stool samples which were positive for G. lamblia cysts and/or trophozoites using microscopy as gold standard. In comparison with microscopy, PCR had showed the specificity of 97.87% (95%CI: 88.71-99.95). We designed new primers for the Giardia, and PCR method for the rapid and accurate identification of Giardia parasites established. With consideration to the routine diagnosis techniques in medical parasitology and their limitations such as time consuming, laborious, less sensitivity etc. This G. lamblia PCR is a sensitive and specific application for the diagnosis of G. lamblia and provides us a reliable method in the routine intestinal parasitic infection laboratory diagnosis.