Mixed-ligand copper(II)-phenolate complexes: effect of coligand on enhanced DNA and protein binding, DNA cleavage, and anticancer activity.
The copper(II) complex [Cu(tdp)(ClO4)].0.5H2O (1), where H(tdp) is the tetradentate ligand 2-[(2-(2-hydroxyethylamino)ethylimino)methyl]phenol, and the mixed ligand complexes [Cu(tdp)(diimine)]+ (2-5), where diimine is 2,2'-bipyridine (bpy) (2), 1,10-phenanthroline (phen) (3), 3,4,7,8-tetramethyl-1,10-phenanthroline (tmp) (4), and dipyrido-[3,2-d:2',3'-f]-quinoxaline (dpq) (5), have been isolated and characterized by analytical and spectral methods. Complexes 1 and [Cu(tdp)(phen)]ClO4 (3) have been structurally characterized, and their coordination geometries around copper(II) are described as distorted octahedral. The equatorially coordinated ethanolic oxygen in 1 is displaced to an axial position upon incorporating the strongly chelating phen, as in 3. The solution structures of all the complexes have been assessed to be square-based using electronic absorption and electron paramagnetic resonance (EPR) spectroscopy. The interaction of the complexes with calf thymus DNA (CT DNA) has been explored by using absorption, emission, and circular dichroic spectral and viscometric studies, and modes of DNA binding for the complexes have been proposed. Absorption spectral (Kb = 0.071 +/- 0.005 (2), 0.90 +/- 0.03 (3), 7.0 +/- 0.2 (4), 9.0 +/- 0.1 x 10(5) M(-1) (5)), emission spectral (Kapp = 4.6 (1), 7.8 (2), 10.0 (3), 12.5 (4), 25.0 x 10(5) M(-1) (5)), and viscosity measurements reveal that 5 interacts with DNA more strongly than the other complexes through partial intercalation of the extended planar ring of the coordinated dpq with the DNA base stack. Interestingly, only complex 4 causes a B to A conformational change upon binding DNA. All the complexes hydrolytically cleave pBR322 supercoiled DNA in 10% DMF/5 mM Tris-HCl/50 mM NaCl buffer at pH 7.1 in the absence of an activating agent, and the cleavage efficiency varies in the order 5 > 3 > 2 > 4 > 1 with 5 displaying the highest Kcat value (5.47 +/- 0.10 h(-1)). The same order of cleavage is observed for the oxidative cleavage of DNA in the presence of ascorbic acid as a reducing agent. Interestingly, of all the complexes, only 5 displays efficient photonuclease activity through double-strand DNA breaks upon irradiation with 365 nm light through a mechanistic pathway involving hydroxyl radicals. The protein binding ability of 1-5 has been also monitored by using the plasma protein bovine serum albumin (BSA), and 4 exhibits a protein binding higher than that of the other complexes. Further, the anticancer activity of the complexes on human cervical epidermoid carcinoma cell line (ME180) has been examined. Interestingly, the observed IC50 values reveal that complex 4, which effects conformational change on DNA and binds to BSA more strongly, exhibits a cytotoxicity higher than the other complexes. It also exhibits approximately 100 and 6 times more potency than cisplatin and mitomycin C for 24 and 48 h incubation times, respectively, suggesting that 4 can be explored further as a potential anticancer drug. Complexes 4 and 5 mediate the arrest of S and G2/M phases in the cell cycle progression at 24 h harvesting time, which progress into apoptosis.


Extended H-Bonding through Protic Ionic Liquids Facilitates the Growth and Stability of Water Domains in Hydrophobic Environment.
Discrete water domains in hydrophobic environment find relevance in aerosols, oil refinery, the human body, etc. The interfacial microstructure plays a crucial role in the stability of such water domains. Over the decades, the amphiphile-induced electrostatic interaction is considered to be the major stabilizing factor operating at these interfaces. Here we take the representative water/AOT/oil microemulsion to show that creating a strong H-bonding network through suitable additive, such as protic ionic liquid (IL) at the interface, helps both the growth and stability of water domains in the hydrophobic phase. On the other hand, common electrolytes and aprotic ILs fail to replicate such behavior as seen by Raman, Fourier transform infrared spectroscopy, dynamic light scattering (DLS), and electron microscopy measurements. Experimental results are further supported by the all-atomic molecular dynamics (MD) simulations that showed extended H-bonding mediated by the protic IL cations that were localized at the interface. High temperature DLS and rheology studies have shown greater thermal stability and mechanical strengths of our biocompatible microemulsions, which have potential to become suitable templates for in situ synthesis of nanoparticle and various organic compounds.


Combination therapy of an inhibitor of group VIA phospholipase A2 with paclitaxel is highly effective in blocking ovarian cancer development.
We and others have shown that calcium-independent phospholipase A(2) (iPLA(2)) is involved in epithelial ovarian cancer (EOC). Hence, we propose that iPLA(2) is a potential effective and novel target for EOC. We tested this concept and found that bromoenol lactone (BEL), a selective inhibitor of iPLA(2), significantly inhibited EOC metastatic tumor growth in mouse xenograft models using human SKOV3 and HEY ovarian cancer cells. Moreover, the combination of BEL with paclitaxel (PTX), one of the most commonly used therapeutic agents in EOC, almost completely blocked tumor development in the xenograft mouse model. BEL showed no detectable cytotoxic effects in mice. Another iPLA(2) inhibitor, FKGK11, also inhibited tumor development in the xenograft mouse model, supporting that the major target of action was iPLA(2). The additional effects of BEL with PTX in vivo likely stem from their distinct cellular effects. BEL and FKGK11 reduced adhesion, migration, and invasion of EOC cells in vitro; the reduced ability to adhere, migrate, and invade seems to increase the vulnerability of tumor cells to PTX. These results provide an important basis for the development of new treatment modalities for EOC.


Cariporide (HOE642) limits S-100B release during cardiac surgery.
Cardiac surgery with cardiopulmonary bypass (CPB) results in transient cerebral swelling in most patients. Cognitive decline occurs in 24-57% of patients and 2-5% experience stroke. Serum levels of S-100B, a potential marker of increased blood-brain barrier permeability, increase during and early after surgery. The authors studied the effects of the novel Na /H exchange inhibitor cariporide (HOE642) on postoperative serum levels of S-100B and neuron-specific enolase (NSE) in 53 patients at high risk undergoing coronary artery bypass grafting. Patients were randomly assigned to one of four groups: I, placebo; II, 20 mg cariporide; III, 80 mg cariporide; IV, 120 mg cariporide). In addition, the leukocyte activation marker myeloperoxidase (MPO) and malondialdehyde (MDA), a marker for lipid peroxidation, were evaluated by enzyme-linked immunoassay. Postoperatively, five patients experienced transient ischemic attack or stroke. S-100B levels increased from 0.43 microg/l +/- 0.33 before operation to 2.27 microg/l +/- 0.69 1 hour after surgery in the placebo group. Preoperative S-100B levels in the HOE642 groups did not differ from the placebo group whereas, 1 hour after surgery, levels were significantly lower in groups II, III, and IV (1.63 microg/l +/- 0.2, 1.27 microg/l +/- 0.27, and 0.90 microg/l +/- 0.21, respectively). NSE, MPO, and MDA serum levels did not differ among groups. These findings may stimulate larger clinical studies to examine the effects of HOE642 on cerebral swelling and neurologic/cognitive outcome of cardiac surgery with CPB.


Chronic Unexpected Mild Stress Destroys Synaptic Plasticity of Neurons through a Glutamate Transporter, GLT-1, of Astrocytes in the Ischemic Stroke Rat.
Chronic unexpected mild stress (CUMS) destroys synaptic plasticity of hippocampal regenerated neurons that may be involved in the occurrence of poststroke depression. Astrocytes uptake glutamate at the synapse and provide metabolic support for neighboring neurons. Currently, we aim to investigate whether CUMS inhibits synaptic formation of regenerated neurons through a glutamate transporter, GLT-1, of astrocytes in the ischemic stroke rats. We exposed the ischemic stroke rats to ceftriaxone, during the CUMS intervention period to determine the effects of GLT-1 on glutamate circulation by immunofluorescence and mass spectrometry and its influences to synaptic plasticity by western blot and transmission electron microscopy. CUMS evidently reduced the level of astroglial GLT-1 in the hippocampus of the ischemic rats (p < 0.05), resulting in smaller amount of glutamate being transported into astrocytes surrounding synapses (p < 0.05), and then expression of synaptophysin was suppressed (p < 0.05) in hippocampal dentate gyrus. The ultrastructures of synapses in dentate gyrus were adversely influenced including decreased proportion of smile synapses, shortened thickness of postsynaptic density, reduced number of vesicles, and widened average distance of the synaptic cleft (all p < 0.05). Moreover, ceftriaxone can promote glutamate circulation and synaptic plasticity (all p < 0.05) by raising astroglial GLT-1 (p < 0.05) and then improve depressive behaviors of the CUMS-induced model rats (p < 0.05). Our study shows that CUMS destroys synaptic plasticity of regenerated neurons in the hippocampus through a glutamate transporter, GLT-1, of astrocytes in the ischemic stroke rats. This may indicate one potential pathogenesis of poststroke depression.


Long-term efficacy of primary laser trabeculoplasty.
Sixty glaucomatous eyes of 60 patients treated with laser trabeculoplasty as primary therapy were reviewed retrospectively. There were 42 eyes with capsular glaucoma and 18 with simple glaucoma. The mean prelaser intraocular pressure (IOP) was 35.2 (SD = 6.5) mmHg. Success was defined as IOP less than or equal to 22 mmHg without medication. The probability of success was 0.73 at 1 year, 0.66 at 2 years, 0.57 at 3 years, and 0.50 at 4 years. Three eyes experienced progressive visual field loss or disc damage in spite of an intraocular pressure below 22 mmHg without medication. High prelaser pressure and the severity of the visual field defects were significant predictors of treatment failure.


An Exercise Intervention to Unravel the Mechanisms Underlying Insulin Resistance in a Cohort of Black South African Women: Protocol for a Randomized Controlled Trial and Baseline Characteristics of Participants.
The pathogenesis of type 2 diabetes (T2D) in black African women is complex and differs from that in their white counterparts. However, earlier studies have been cross-sectional and provide little insight into the causal pathways. Exercise training is consistently used as a model to examine the mechanisms underlying insulin resistance and risk for T2D. The objective of the study was to examine the mechanisms underlying the changes in insulin sensitivity and secretion in response to a 12-week exercise intervention in obese black South African (SA) women. A total of 45 obese (body mass index, BMI: 30-40 kg/m2) black SA women were randomized into a control (n=22) or experimental (exercise; n=23) group. The exercise group completed 12 weeks of supervised combined aerobic and resistance training (40-60 min, 4 days/week), while the control group maintained their typical physical activity patterns, and both groups were requested not to change their dietary patterns. Before and following the 12-week intervention period, insulin sensitivity and secretion (frequently sampled intravenous glucose tolerance test) and its primary and secondary determinants were measured. Dietary intake, sleep quality and quantity, physical activity, and sedentary behaviors were measured every 4 weeks. The final sample included 20 exercise and 15 control participants. Baseline sociodemographics, cardiorespiratory fitness, anthropometry, cardiometabolic risk factors, physical activity, and diet did not differ between the groups (P>.05). The study describes a research protocol for an exercise intervention to understand the mechanisms underlying insulin sensitivity and secretion in obese black SA women and aims to identify causal pathways underlying the high prevalence of insulin resistance and risk for T2D in black SA women, targeting specific areas for therapeutic intervention. Pan African Clinical Trial Registry PACTR201711002789113; http://www.pactr.org/ATMWeb/ appmanager/atm/atmregistry?_nfpb=true&_pageLabel=portals_app_atmregistry_portal_page_13 (Archived by WebCite at http://www.webcitation.org/6xLEFqKr0).


Age-, sex-, and gonadal steroid-related changes in immunoreactive substance P in the rat anterior pituitary gland.
The interrelationship of anterior pituitary lobe (AP) immunoreactive substance P (I-SP) concentrations with age, sex, gonadal steroids, and estrous cyclicity in rats was examined. There was no difference between male and female AP I-SP levels at 0.5 month of age. At 2.0 and 5.0 months of age, a sex-linked difference in AP I-SP concentrations was evident, inasmuch as male APs contained approximately 3 and 8 times greater concentrations of I-SP, respectively, than APs from age-matched females. Long term (6 weeks) gonadectomy of adult rats resulted in an increase in I-SP concentrations in female APs and a decrease in the concentrations of the peptide in male APs compared to values in their respective sham-operated controls. Treatment of gonadectomized animals for the same length of time with gonadal steroid-filled Silastic capsule implants resulted in qualitatively identical responses in males and females; that is, estradiol benzoate decreased and 5 alpha-dihydrotestosterone propionate increased AP I-SP levels compared to the respective control values in castrates. Testosterone propionate treatment had no effect on AP I-SP levels compared with the respective gonadectomy control values. Short term (8 days) gonadectomy of adult males did not affect the AP concentration of I-SP. Likewise, gonadectomy of adult females was ineffective in altering the AP I-SP concentration compared with concentrations in females on diestrous day 1, diestrous day 2, proestrous, or estrous stages of the vaginal cycle. These data suggest that gonadal steroids are physiologically important in the regulation of I-SP concentrations in the AP. We hypothesize that I-SP is indigenous to the AP and that gonadal steroids act directly at the level of the AP to affect the synthesis and/or release of the peptide.


A case of ruptured peripheral aneurysm of the anterior inferior cerebellar artery associated with an arteriovenous malformation : a less invasive image-guided transcortical approach.
A 47-year-old man presented with a subarachnoid hemorrhage (SAH) and right cerebellar hematoma was referred for evaluation. Cerebral angiography revealed a distal anterior inferior cerebellar artery (AICA) aneurysm associated with an arteriovenous malformation (AVM). Successful obliteration and complete removal of the aneurysm and AVM were obtained using transcortical approach under the guidance of neuronavigation system. The association of a peripheral AICA aneurysm and a cerebellar AVM by the same artery is unique. The reported cases of conventional surgery for this disease complex are not common and their results are variable. Less invasive surgery using image-guided neuronavigation system would be helpful and feasible for a peripheral aneurysm combining an AVM of the posterior fossa in selective cases.


Clinicians' moral distress and family satisfaction in the intensive care unit.
This study explored the relationship between clinicians' moral distress and family satisfaction with care in five intensive care units in Italy. A total of 122 clinicians (45 physicians and 77 nurses) and 59 family members completed the Italian Moral Distress Scale-Revised and the Family Satisfaction in the ICU questionnaire, respectively. Clinicians' moral distress inversely correlated with family satisfaction related to the inclusion in the decision-making process. Specifically, physicians' moral distress inversely correlated with satisfaction regarding the respect shown toward the patient. Nurses' moral distress inversely correlated with satisfaction regarding breathlessness and agitation management, provision of emotional support, understanding of information, and inclusion in the decision-making process.


5S rRNA gene hybridizes to human chromosome 1 at two sites (1q42.11-->q42.13 and 1q43).
Hybridization of a loach (Misgurnus fossilis) oocyte 5S rRNA gene repeat with human chromosomes was carried out to refine the localization of the 5S RNA gene in the human genome. Preliminary in situ hybridization analysis showed that this repeat hybridized with human chromosome region 1q42-->q43, the same location previously reported for the human 5S rRNA gene. High-resolution banding revealed the presence of two sites of hybridization, with a main peak in chromosome region 1q42.1 and a second peak in 1q43. These results are consistent with our data on the existence in the human genome of different 5S rRNA gene clusters specified by BamHI and HindIII restriction sites in spacer DNA (Timofeeva et al., 1993) and suggest a multicluster organization of the human 5S rRNA genes.


Early diagnosis of congenital Trypanosoma cruzi infection, using shed acute phase antigen, in Ushuaia, Tierra del Fuego, Argentina.
Chagas' disease, or American trypanosomiasis, is caused by the protozoan parasite Trypanasoma cruzi. It is estimated that 15,000 new cases of congenital T. cruzi transmission occur in the Americas each year. The aim of this study was to estimate the rate of congenital T. cruzi infection in infants born to infected women living in Ushuaia, Argentina, as well to assess a serologic test using Shed Acute Phase Antigen (SAPA) for a timely diagnosis of congenital infection. The rate of congenital infection among children in the study was 4.4% (3/68). Our results show that for infants younger than 30 days of age, matched blood samples from mother and infant were capable of identifying congenital transmission of infection using an enzyme-linked immunosorbent assay with SAPA. For infants older than 3 months, congenital infection could be ruled out using the same procedure.


Pain perception, pain drug therapy and health status in patients with Parkinson's disease.
Parkinson's disease (PD) is traditionally characterized as a movement disorder; however, sensory perception problems including pain syndromes are also frequent. We performed a survey to analyze the relations between health status, pain perception and gender in 4,086 PD patients. Moreover, the participants should tick whether they took pain medications or not. The questionnaire included the EQ-5D and visual analogue scales (VAS) on pain, which asked for mean (VAS A), most (VAS B), and minimal (VAS C) intensity of pain during an interval of 4 weeks prior to the completion of the survey. PD patients were divided into three groups according to their EQ-5D total score (I: <8; II: 8-9; III: 10-15). An impairment of health status occurred in relation to the increase in pain syndromes in PD patients. There was a significant increase in VAS scores in relation to the EQ-5D group membership. Female patients reported more on pain and more frequently received a pain drug treatment than male patients. Significant associations were found between the VAS and the EQ-5D scores, and the correlation coefficients were higher in men than in women. Pain is associated with the health status of PD patients and worsens it. More female than male PD patients have to deal with handling of pain and pain drug treatment.


Congenital mesoblastic nephroma presenting with massive hematuria and hemorrhagic shock: report of one case.
Congenital mesoblastic nephroma (CMN) is a rare benign tumor that occurs during the neonatal period and early infancy. The vast majority of these tumors present as asymptomatic palpable abdominal masses. We describe an unusual presentation of a CMN in a 10-month-old male infant who presented with massive hematuria and the development of hemorrhagic shock. Abdominal ultrasound showed a heterogeneous solid complex mass measuring 4.8 x 3.5 cm arising from the upper pole of the left kidney. The patient was resuscitated using intravenous fluids and blood transfusions because persistent massive bloody urine leading to progressive shock occurred the night of the admission day. Preoperative diagnosis was possible Wilms tumor of the left kidney. The histopathological findings were consistent with the character of a cellular variant of CMN. The patient was free of recurrence and metastasis at the 2-year follow-up examination. Our case report suggests that CMN is a rare benign renal tumor during infancy and may present with unusual massive hematuria and shock.


Populus candicans and the Balm of Gilead.
Bud exudates of some poplars are compared using GC-MS. P. candicans resembles P. balsamifera. A sample of "Balm of Gilead" purchased in Oxford proved not to resemble its supposed source, P. candicans. Instead it was similar to P. nigra, from which it was presumably collected in Europe.


The role of tumor necrosis factor-α promoter genetic variation in Takayasu arteritis susceptibility and medical treatment.
Tumor necrosis factor-α (TNF-α) is a multifunctional proinflammatory cytokine that influences the pathogenesis of Takayasu arteritis (TA). There is still no evidence of the relationship between TNF-α gene promoter polymorphisms and TA. We examined whether variations in the TNF-α promoter region may lead to TA susceptibility and disease progression. Five TNF-α gene promoter polymorphisms (-238G/A, -308G/A, -857C/T, -863C/A, and -1031C/T) were analyzed in 110 Chinese Han patients with TA, with a control group of 362 unrelated healthy individuals. Genotypes of TNF-α gene promoter polymorphisms were identified by direct sequencing. TNF-α plasma concentrations were determined by ELISA. Our results indicated that the frequency of the -863A allele was significantly lower in the patients with TA than in the controls (18.2% vs 25.7%; p = 0.011), but the significance was lost after Bonferroni correction (p(c) = 0.055). The frequency of -863CA/AA genotypes was significantly lower in the patients with refractory TA than in those with the 863CC genotype (22.4% vs 44.2%; p(c) < 0.01). The frequency of the GGCCT haplotype was significantly higher in patients than in the controls, while the frequencies of GGCAT and GGCCC haplotypes were significantly lower in patients than in controls. The plasma TNF-α concentrations were significantly lower in the subjects carrying the -863A allele than in those without. Patients with active TA had a significant increase in plasma levels of TNF-α compared with remission patients and the control group. Polymorphisms of the TNF-α promoter are not associated with TA in the Chinese Han population. The A allele of the -863C/A polymorphism is associated with decreased TNF-α expression, which might affect medical treatment.


High-dimensional inference with the generalized Hopfield model: principal component analysis and corrections.
We consider the problem of inferring the interactions between a set of N binary variables from the knowledge of their frequencies and pairwise correlations. The inference framework is based on the Hopfield model, a special case of the Ising model where the interaction matrix is defined through a set of patterns in the variable space, and is of rank much smaller than N. We show that maximum likelihood inference is deeply related to principal component analysis when the amplitude of the pattern components ξ is negligible compared to √N. Using techniques from statistical mechanics, we calculate the corrections to the patterns to the first order in ξ/√N. We stress the need to generalize the Hopfield model and include both attractive and repulsive patterns in order to correctly infer networks with sparse and strong interactions. We present a simple geometrical criterion to decide how many attractive and repulsive patterns should be considered as a function of the sampling noise. We moreover discuss how many sampled configurations are required for a good inference, as a function of the system size N and of the amplitude ξ. The inference approach is illustrated on synthetic and biological data.


Molecular mechanisms linking environmental toxicants to cancer development: Significance for protective interventions with polyphenols.
Human exposure to environmental toxicants with diverse mechanisms of action is a growing concern. In addition to well-recognized carcinogens, various chemicals in environmental and occupational settings have been suggested to impact health, increasing susceptibility to cancer by inducing genetic and epigenetic changes. Accordingly, in this review, we have discussed recent insights into the pathological mechanisms of these chemicals, namely their effects on cell redox and calcium homeostasis, mitochondria and inflammatory signaling, with a focus on the possible implications for multi-stage carcinogenesis and its reversal by polyphenols. Plant-derived polyphenols, such as epigallocatechin-gallate, resveratrol, curcumin and anthocyanins reduce the incidence of cancer and can be useful nutraceuticals for alleviating the detrimental outcomes of harmful pollutants. However, development of therapies based on polyphenol administration requires further studies to validate the biological efficacy, identifying effective doses, mode of action and new delivery forms. Innovative microphysiological testing models are presented and specific proposals for future trials are given. Merging the current knowledge of multifactorial actions of specific polyphenols and chief environmental toxicants, this work aims to potentiate the delivery of phytochemical-based protective treatments to individuals at high-risk due to environmental exposure.


[Survey on quality of life of patients undergoing dialytic treatment].
The Nottingham Health Profile (NHP) was administered to 85 dialysis patients treated at Mestre Hospital, to assess their quality of life and compare any differences between haemodialysis (HD) and peritoneal dialysis (PD) patients. The two groups were similar for the main characteristics. Overall dialysis patients do not enjoy a good quality of life. Comparing baseline demographic and clinical scores, 72.9% patients have problems with energy and 69.4 with mobility, 47.1% refer pain and 54.1% sleep disorders. The main differences between HD and PD patients concern psychological reactions, where 42.9% of HD patients report "at risk/compromised" scores compared to 17.2% of PD patients. NHP showed to be an easy to administer and efficient instrument in identifying areas of concern for dialysis patients.


Improved electrodes for electrical defibrillation of rats.
Experimental induction of ventricular fibrillation in animals yields valuable information about this deadly arrhythmia. Human adult or pediatric defibrillators and their paddles can be used easily in larger animals such as dogs and pigs, but these animals are more difficult to house and handle, and available biochemical assays may be limited. In contrast, rats are easy and relatively inexpensive to house and handle, and numerous biochemical tests are available. However, in most cases, even pediatric electrodes are impractical for use in rats. Proper placement of defibrillation electrodes on the thorax requires that the electrical axis of the heart be situated between the defibrillator paddles. The most common approach to defibrillation in rats uses 2 electrodes: one is built into a board that underlies and touches the rat's back, and another is positioned manually on the anterior thorax. The aim of this study was to produce electrodes that are 1) easy to handle, 2) specifically designed for rats, 3) efficiently deliver defibrillation shocks along the electric axis of the heart, and 4) can be used for both in vivo defibrillation and on isolated heart preparations.


Pain Predictors in a Population of Temporomandibular Disorders Patients.
The aim of the present study was to assess the potential role of some biological, psychological, and social factors to predict the presence of painful temporomandibular disorders (TMDs) in a TMD-patient population. The study sample consisted of 109 consecutive adult patients (81.7% females; mean age 33.2 ± 14.7 years) who were split into two groups based on Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) diagnoses: painful TMD and non-painful TMD. The presence of pain was adopted as the depended variable to be identified by the following independent variables (i.e., predictors): age, gender, bruxism, tooth wear, chewing gum, nail biting, perceived stress level, chronic pain-related impairment (GCPS), depression (DEP), and somatization (SOM). Single-variable logistic regression analysis showed a significant relationship between TMD pain and DEP with an odds ratio of 2.9. Building up a multiple variable model did not contribute to increase the predictive value of a TMD pain model related to the presence of depression. Findings from the present study supported the existence of a relationship between pain and depression in painful TMD patients. In the future, study designs should be improved by the adoption of the best available assessment approaches for each factor.


Purification and characterization of liver microsomal cytochromes p-450: electrophoretic, spectral, catalytic, and immunochemical properties and inducibility of eight isozymes isolated from rats treated with phenobarbital or beta-naphthoflavone.
Eight different forms of cytochrome P-450 (P-450) were purified to electrophoretic homogeneity by a common procedure from liver microsomes of rats treated with phenobarbital or beta-naphthoflavone. Antibodies were prepared to seven of these forms in rabbits. The eight P-450s were distinguished by spectral properties of the ferric, ferrous, and ferrous carbonyl forms, apparent monomeric molecular weights, peptide mapping, immunological reactivity as discerned by double-diffusion immunoprecipitin analysis and crossed immunoelectrophoresis, and catalytic activities toward the substrates acetanilide, aminopyrine, aniline, benzo[a]-pyrene, d-benzphetamine, N,N-dimethylnitrosamine, 7-ethoxycoumarin, 7-ethoxyresorufin, ethylmorphine, p-nitroanisole, testosterone, and (R)- and (S)-warfarin. Crossed sodium dodecyl sulfate-polyacrylamide gel immunoelectrophoresis was used to estimate the levels of each of the eight forms of P-450 present in the liver microsomes of untreated rats and rats treated with phenobarbital, 5,6-benzoflavone, pregnenolone-16 alpha-carbonitrile, isosafrole, or the polychlorinated biphenyl mixture Aroclor 1254. In each situation, the sum of the levels of these eight P-450s was at least as high as the spectrally determined P-450 content. The results clearly demonstrate that individual forms of P-450 can be induced by different compounds and that a single compound can lower the level of one form of P-450 while inducing one or more other forms of P-450. Catalytic activities toward each of the substrates observed with microsomal preparations are compared to rates predicted on the basis of the content of each of the eight P-450s. These studies provide a basis for further studies on the regulation of individual P-450s, the physical properties of the different P-450s, and the metabolic consequences of changes in the forms of P-450 in rat liver models.


Identification of Brucella abortus genes in elk (Cervus elaphus) using in vivo-induced antigen technology (IVIAT) reveals novel markers of infection.
Elk in the Greater Yellowstone Area are a major reservoir for brucellosis, which represents an obstacle to eradication of the disease in domestic livestock. Furthermore, immune responses to Brucella abortus infection in the wild host are not well-understood. In this regard, in vivo-induced antigen technology (IVIAT) was employed to identify novel B. abortus antigens expressed during infection in elk. Sera collected from sero-positive Wyoming elk were pooled and absorbed against in vitro-grown cultures of B. abortus. Approximately 35,000 E. coli clones, expressing B. abortus DNA, were then screened by colony immunoblot, yielding ten genes with immuno-reactive products, to include seven proteins secreted beyond the inner membrane. Three products, an outer membrane protein (D15), malate dehydrogenase (Mdh), and an ion transporter (AfuA), were examined by Western blot against individual elk serum samples. Sero-reactivity was significantly more frequent for both Mdh and D15 in naturally infected animals, compared to vaccinated and uninfected elk, indicating that antibody to these two antigens is a predictor of natural infection. Cross-reactivity of all three proteins was next examined with serum samples from confirmed brucellosis-positive cattle. While variable patterns of reactivity were seen with the antigens, the sample group was equivalently reactive to AfuA and Mdh, compared to elk, suggesting that these antigens are commonly expressed during infection in both hosts. We conclude that the application of IVIAT to B. abortus may not only facilitate the identification of serologic markers for brucellosis in elk, but may provide further insight into biological processes of the pathogen in different hosts.


Macrocyclic dinuclear, helical, layered and 3-D Ag(I) complexes constructed from AgX (X = NO3(-) and ClO4(-)) and flexible bis(pyridyl) ligands with a chelating spacer: syntheses, structures and photoluminescence properties.
Reaction of AgX (X = NO3− and ClO4−) and three flexible bis(pyridyl) ligands with a chelating spacer leads to the formation of eight novel Ag(I)-bis(pyridyl) coordination complexes: {[Ag2L1(NO3)2]n·2nH2O} (1), {[AgL1]n·nClO4} (2), {[AgL2]n·nNO3} (3), {[AgL2]n·nClO4} (4), [Ag2(H2L2)2]·6ClO4·9H2O (5), {[AgL3]n·nNO3·nH2O} (6), {[AgL3]n·nClO4·nH2O} (7), and {[Ag3(L3)2(ClO4)]n·2nClO4} (8) (L1 = N,N′-bis(pyridin-2-ylmethyl)propane-1,3-diamine, L2 = N,N′-bis(pyridin-3-ylmethyl)propane-1,3-diamine, L3 = N,N′-bis(pyridin-4-ylmethyl)propane-1,3-diamine), which have been characterized by elemental analysis, IR, TG, UV-Vis DRS, PL, powder and single-crystal X-ray diffraction. Complex 1 presents a (4,4) layered motif which is furnished by the bridging of L1 molecules and nitrate anions in μ4 (κ1N1:κ1N2:κ1N3:κ1N4) and μ2 (κ1O4:κ1O6) modes. With a different μ2 (κ1N1:κ1N2:κ1N3:κ1N4) mode, L1 molecules in complex 2 join the adjacent Ag(I) cations to form a helical chain structure. Complexes 3 and 4 also show helical chain structures with the L2 molecules displaying the same μ3 (κ1N1:κ1N2:κ1N3:κ1N4) mode. The protonation of –NH– groups in the chelating spacer leads to the formation of H2L22+ cations which further results in a macrocyclic dinuclear motif in complex 5. Complexes 6 and 7 are 3-D svi-x nets with the counter-anions and lattice water molecules being encapsulated in the 1-D channels. Complex 8 exhibits a snake-shaped chain with the L3 molecules presenting μ3 (κ1N:κ1N′:κ1N″:κ1N) mode. The structural diversities of complexes 1–8 can be attributed to the coordination modes and conformations of L1–L3. The photoluminescence properties demonstrate that complexes 1, 2 and 5 exhibit ligand-based blue emission maxima from 455 to 462 nm at room temperature in the solid state.


Human vascular smooth muscle cells express a urate transporter.
An elevated serum uric acid is associated with the development of hypertension and renal disease. Renal regulation of urate excretion is largely controlled by URAT1 (SLC22A12), a member of the organic anion transporter superfamily. This study reports the specific expression of URAT1 on human aortic vascular smooth muscle cells, as assessed by reverse transcription-PCR and Western blot analysis. Expression of URAT1 was localized to the cell membrane. Evidence that the URAT1 transporter was functional was provided by the finding that uptake of 14C-urate was significantly inhibited in the presence of probenecid, an organic anion transporter inhibitor. It is proposed that URAT1 may provide a mechanism by which uric acid enters the human vascular smooth muscle cell, a finding that may be relevant to the role of uric acid in cardiovascular disease.


Brain edema in liver failure: basic physiologic principles and management.
In patients with severe liver failure, brain edema is a frequent and serious complication that may result in high intracranial pressure and brain damage. This short article focuses on basic physiologic principles that determine water flux across the blood-brain barrier. Using the Starling equation, it is evident that both the osmotic and hydrostatic pressure gradients are imbalanced across the blood-brain barrier in patients with acute liver failure. This combination will tend to favor cerebral capillary water influx to the brain. In contrast, the disequilibration of the Starling forces seems to be less pronounced in patients with cirrhosis because the regulation of cerebral blood flow is preserved and the arterial ammonia concentration is lower compared with that of patients with acute liver failure. Treatments that are known to reverse high intracranial pressure tend to decrease the osmotic pressure gradients across the blood-brain barrier. Recent studies indicate that interventions that restrict cerebral blood flow, such as hyperventilation, hypothermia, and indomethacin, are also efficient in preventing edema and high intracranial pressure, probably by decreasing the transcapillary hydrostatic pressure gradient. In our opinion, it is important to recall that rational fluid therapy, adequate ventilation, and temperature control are of direct importance to controlling cerebral capillary water flux in patients with acute liver failure. These simple interventions should be secured before more advanced experimental technologies are instituted to treat these patients.


Seroprevalence of Rift Valley fever virus in domestic ruminants of various origins in two markets of Yaoundé, Cameroon.
Rift Valley fever (RVF) is a mosquito-borne zoonosis endemic in Africa. With little known of the burden or epidemiology of RVF virus (RVFV) in Cameroon, this study aimed to determine the seroprevalence of RVFV in domestic ruminants of various origins in two markets of Yaoundé, Cameroon. The origin of animals randomly sampled at two livestock markets in Yaoundé were recorded and plasma samples collected for competitive and capture Enzyme-linked Immunosorbent Assay (ELISA) to determine the prevalence of Immunoglobulins G (IgG) and Immunoglobulins M (IgM) antibodies. Following ELISA IgM results, a real-time reverse transcription-polymerase chain reaction (qRT-PCR) was performed to detect RVFV RNA. In June-August 2019, February-March 2020, and March-April 2021, 756 plasma samples were collected from 441 cattle, 168 goats, and 147 sheep. RVFV IgG seroprevalence was 25.7% for all animals, 42.2% in cattle, 2.7% in sheep, and 2.4% in goats. However, IgM seroprevalence was low, at 0.9% in all animals, 1.1% in cattle, 1.4% in sheep, and 0% in goats. The seroprevalence rates varied according to the animal's origin with the highest rate (52.6%) in cattle from Sudan. In Cameroon, IgG and IgM rates respectively were 45.1% and 2.8% in the North, 44.8% and 0% in the Adamawa, 38.6% and 1.7% in the Far-North. All IgM positive samples were from Cameroon. In cattle, 2/5 IgM positive samples were also IgG positive, but both IgM positive samples in sheep were IgG negative. Three (42.9%) IgM positive samples were positive for viral RVFV RNA using qRT-PCR but given the high ct values, no amplicon was obtained. These findings confirm the circulation of RVFV in livestock in Cameroon with prevalence rates varying by location. Despite low IgM seroprevalence rates, RVF outbreaks can occur without being noticed. Further epidemiological studies are needed to have a broad understanding of RVFV transmission in Cameroon.


Neurobehavioral hemispheric preferences: a case of sexual dimorphism.
Ninety subjects (47 females and 43 males) with age ranging from 17 to 25 completed a neurobehavioral inventory of hemispheric preference. The inventory (Wagner & Wells, 1985) consists of 12 items, each of which has 4 statements that relate to four different functions of the two hemispheres namely: (a) Left-logical (b) Left-verbal (c) Right-manipulative/spatial and (d) Right-creative. The results indicated an overall preference for verbal-logical tasks. This preference pattern was more pronounced in males than in the female subjects. Also, the female subjects exhibited greater preference for creative tasks (activities), whereas the males showed preference for verbal tasks. These results suggests that proficiency and preference may not necessarily follow the similar pattern.


Sensory symptoms and signs and results of quantitative sensory thermal testing in patients with lacunar infarct syndromes.
Quantitative data on sensory impairment in stroke patients are limited. We measured the perception thresholds for temperature and thermal pain in patients with different lacunar syndromes, correlated the results with clinical and magnetic resonance imaging (MRI) findings, and studied the long-term prognosis of sensory dysfunction. Quantitative thermal testing was performed by means of the Marstock method in 39 patients with lacunar syndromes (pure motor, sensorimotor, or pure sensory stroke) and MRI findings compatible with occlusion of a single perforating artery. Thresholds for cold, warmth, and heat pain were obtained bilaterally from the cheek, hand, and leg. The unaffected side was used as control. Follow-up included clinical assessments and repeated quantitative thermal testing (in 17 patients) up to 1 year after stroke onset. Patients with pure sensory stroke and sensorimotor stroke (n = 22) had a significant thermal hypoesthesia on the affected side for all modalities and test locations. Patients with pure motor stroke (n = 17) exhibited thermal hypoesthesia for cold and heat pain in the hand and for cold perception in the leg. On MRI, infarcts causing pure motor and sensorimotor stroke were predominantly lenticulocapsular, while a thalamic site of infarction was found in pure sensory stroke. The prognosis of sensory impairment was favorable, except for poststroke pain syndromes in three patients. Quantitative thermal testing confirmed an involvement of spinothalamic pathways in lacunar infarcts causing pure sensory and sensorimotor stroke and revealed a subclinical sensory impairment in patients with pure motor stroke. Infarction sites were similar in patients with pure motor and sensorimotor stroke.


BeiDou Satellite Positioning Method Based on IoT and Edge Computing.
The BeiDou navigation satellite system (BDS) developed by China can provide users with high precision, as well as all-weather and real-time positioning and navigation. It can be widely used in many applications. However, new challenges emerge with the development of 5G communication system and Internet of Things (IoT) technologies. The BDS needs to be suitable for the large-scaled terminal scenario and provides higher positioning precision. In this paper, a BeiDou differential positioning method based on IoT and edge computing is proposed. The computational pressure on the data center is offloaded to the edge nodes when the massive positioning requests of IoT terminals need to be processed. To ensure the load balancing of the edge nodes, the resource allocation of the terminal positioning requests is performed with the improved genetic algorithm, thereby reducing the service delay of the entire edge network. Moreover, the optimized unscented Kalman filter based on the edge node (EUKF) algorithm is used to improve the positioning precision of IoT terminals. The results demonstrate that the proposed positioning method has better positioning performance which can provide the real-time positioning service for the large-scale IoT terminals.


Coeliac disease as a potential cause of idiopathic portal hypertension: a case report.
Idiopathic portal hypertension is a disorder that has various clinical features. It is mostly characterized by bleeding oesophageal varices, obvious splenomegaly, anaemia and, occasionally, jaundice and ascites. Here we described an interesting case of idiopathic portal hypertension caused by coeliac disease in a 38-year-old woman. By putting this patient on a gluten-free diet, liver function tests became normal and portal vein diameter returned to normal range. This report indicates that, in coeliac disease, repetitive stimulation by antigens along the portal vein-and immune responses to them-can result in the development of idiopathic portal hypertension.


Screening of Salmonella isolates from a turkey production facility for antibiotic resistance.
An ecological survey was conducted from April 1997 to June 1999 on four turkey flocks (F1 to F4). Turkey cecal contents, litter, waterers, feed, feeders, and environmental swabs were analyzed. Presence of Salmonella was determined using conventional microbiological screening techniques and confirmed by serology. Positive isolates were serotyped and screened for antibiotic resistance. From a total of 69 Salmonella isolates 25% were resistant to one or more antibiotics including gentamicin (G), spectinomycin (SP), streptomycin (S), tetracycline (T), tobramycin (TO), and trimethoprim/sulfamethoxazole. Isolates included 45 S. heidelberg, 13 S. senftenberg, 7 S. muenster, 2 S. anatum, and 2 S. worthington. Resistance to antibiotic(s) was highest among waterer isolates (55%) followed by environmental swabs (43%), feeder content samples (33%), turkey cecal contents (26%), and litter samples (5%). Frequencies of antibiotic-resistant Salmonella in F1, F2, and F4 were 27, 13, and 40%, respectively. Salmonella was undetected in F3. In F1, S. heidelberg from cecal content and waterer samples was resistant to G, SP, S, and T, whereas S. anatum from waterer samples was resistant to T and S. In F2, S. worthington from litter and feeder content samples was resistant to T, and in F4, S. muenster from environmental swabs was resistant to TO, S, SP, and G. Identifying preharvest sources and characterizing serotype and antibiotic-resistance profile can assist poultry producers and integrators in tracking movement of Salmonella on turkey farms.


[Effects of antisense bcl-2 or survivin on the growth of human neuroblastoma cell line SK-N-MC].
To study the effects of antisense bcl-2 and survivin (svv) mRNA on the growth of human neuroblastoma (NB) cell line SK-N-MC cells. The recombinant vectors PBabe puro-Asbcl-2 and PBabe puro-Assvv. were constructed by directed cloning of the EcoRI-BamHI fragments of bcl-2 cDNA or svv cDNA into the retroviral vector PBabe puro Human NB cell line SK-N-MC cells were transfected with PBabe puro-Asbcl-2, PBabe puro-Assvv, or blank vector PBabe puro as control by lipofectamine trade mark. The transfected cells were selected in the medium containing puromycine. The stably transfected cells were further studied for inhibition of protein expression of endogenous bcl-2 and SVV by immunohistochemical staining and Western blotting. The effect of antisense bcl-2 (Asbcl-2) and antisense svv (Assvv) mRNA on cell growth was determined by MTT method. The SK-N-MC cells transfected with the recombinant vectors were inoculated in nude mice to observe their carcinogenicity. Both the expression of bcl-2 and the expression of SVV significantly decreased in the antisense gene transfected cells in comparison to that in the original cells and cells transfected with blank vector. Seven days after the transfection, the MTT absorption (A(550)) was 0.374 +/- 0.001 5 in the cells transfected with Assvv, 0.289 +/- 0.000 8 in the cells transfected with Asbcl-2, both significantly lower than those in the original cells and cells transfected with blank vector (1.102 +/- 0.002 1 and 1.175 +/- 0.000 9 respectively). The induced tumors in the nude mice were smaller in the PBabe puro-Asbcl-2 transfected group and PBabe puro-Assvv transfected group than in the original and control groups. Stably expression of antisense bcl-2 and of antisense svv mRNA can effectively inhibit the expression of endogenous bcl-2 and SVV proteins. Both of them may play a role in the neoplastic formation of NB cells.


Structural priors represented by discrete cosine transform improve EIT functional imaging.
Structural prior information can improve electrical impedance tomography (EIT) reconstruction. In this contribution, we introduce a discrete cosine transformation-based (DCT-based) EIT reconstruction algorithm to demonstrate a way to incorporate the structural prior with the EIT reconstruction process. Structural prior information is obtained from other available imaging methods, e.g., thorax-CT. The DCT-based approach creates a functional EIT image of regional lung ventilation while preserving the introduced structural information. This leads to an easier interpretation in clinical settings while maintaining the advantages of EIT in terms of bedside monitoring during mechanical ventilation. Structural priors introduced in the DCT-based approach are of two categories in terms of different levels of information included: a contour prior only differentiates lung and non-lung region, while a detail prior includes information, such as atelectasis, within the lung area. To demonstrate the increased interpretability of the EIT image through structural prior in the DCT-based approach, the DCT-based reconstructions were compared with reconstructions from a widely applied one-step Gauss-Newton solver with background prior and from the advanced GREIT algorithm. The comparisons were conducted both on simulation data and retrospective patient data. In the simulation, we used two sets of forward models to simulate different lung conditions. A contour prior and a detail prior were derived from simulation ground truth. With these two structural priors, the reconstructions from the DCT-based approach were compared with the reconstructions from both the one-step Gauss-Newton solver and the GREIT. The difference between the reconstructions and the simulation ground truth is calculated by the ℓ2-norm image difference. In retrospective patient data analysis, datasets from six lung disease patients were included. For each patient, a detail prior was derived from the patient's CT, respectively. The detail prior was used for the reconstructions using the DCT-based approach, which was compared with the reconstructions from the GREIT. The reconstructions from the DCT-based approach are more comprehensive and interpretable in terms of preserving the structure specified by the priors, both in simulation and retrospective patient data analysis. In simulation analysis, the ℓ2-norm image difference of the DCT-based approach with a contour prior decreased on average by 34% from GREIT and 49% from the Gauss-Newton solver with background prior; for reconstructions of the DCT-based approach with detail prior, on average the ℓ2-norm image difference is 53% less than GREIT and 63% less than the reconstruction with background prior. In retrospective patient data analysis, the reconstructions from both the DCT-based approach and GREIT can indicate the current patient status, but the DCT-based approach yields more interpretable results. However, it is worth noting that the preserved structure in the DCT-based approach is derived from another imaging method, not from the EIT measurement. If the structural prior is outdated or wrong, the result might be misleadingly interpreted, which induces false clinical conclusions. Further research in terms of evaluating the validity of the structural prior and detecting the outdated prior is necessary.


Using Language-Specific and Bilingual Measures to Explore Lexical-Grammatical Links in Young Latino Dual-Language Learners.
This study examined the nature of the relation between language-specific vocabulary and conceptual lexical-semantic skills with grammatical abilities within and across languages in preschool Latino dual language learners (DLLs). Sixty-one typically developing, Spanish-English speaking DLLs from preschools serving low-income families participated in the study. Lexical, semantic, and grammar skills were assessed toward the end of the fall in both Spanish and English using normative and researcher-developed assessment instruments. Hierarchical linear regressions using baseline cross-sectional data were completed to determine the association of language-specific vocabulary and bilingual lexical and semantic abilities to grammatical skills measured by sentence repetition tasks in Spanish and English both within and across languages. Results from the study revealed that a considerable percentage of the variance in the grammatical ability of these Latino DLL preschoolers in both Spanish and English was explained by lexical variables in the same language (54% in English and 16% in Spanish). In the strong language (Spanish), bilingual semantic skills also played a role, explaining an additional 8% of the variance. Conceptual vocabulary was a significant predictor of English grammar in the model that excluded the language-specific vocabulary measures. These findings suggest that grammatical skills in the Latino preschoolers examined in the study are strongly related to language-specific measures of vocabulary. In contrast, no evidence supporting the relation between vocabulary and grammar skills across languages was observed. Findings from this study provide insight into the impact of bilingual lexical-semantic knowledge on the grammatical skills of dual-language preschool children developing language abilities in their 2 languages. Clinical implications are also discussed.


Functional partitioning of yeast co-expression networks after genome duplication.
Several species of yeast, including the baker's yeast Saccharomyces cerevisiae, underwent a genome duplication roughly 100 million years ago. We analyze genetic networks whose members were involved in this duplication. Many networks show detectable redundancy and strong asymmetry in their interactions. For networks of co-expressed genes, we find evidence for network partitioning whereby the paralogs appear to have formed two relatively independent subnetworks from the ancestral network. We simulate the degeneration of networks after duplication and find that a model wherein the rate of interaction loss depends on the "neighborliness" of the interacting genes produces networks with parameters similar to those seen in the real partitioned networks. We propose that the rationalization of network structure through the loss of pair-wise gene interactions after genome duplication provides a mechanism for the creation of semi-independent daughter networks through the division of ancestral functions between these daughter networks.


Bioreactivity, Guttation and Agents Influencing Surface Tension of Water Emitted by Actively Growing Indoor Mould Isolates.
The secretion of metabolites in guttation droplets by indoor moulds is not well documented. This study demonstrates the guttation of metabolites by actively growing common indoor moulds. Old and fresh biomasses of indoor isolates of Aspergillus versicolor, Chaetomium globosum, Penicillium expansum, Trichoderma atroviride, T. trixiae, Rhizopus sp. and Stachybotrys sp. were compared. Metabolic activity indicated by viability staining and guttation of liquid droplets detected in young (<3 weeks old) biomass were absent in old (>6 months old) cultures consisting of dehydrated hyphae and dormant conidia. Fresh (<3 weeks old) biomasses were toxic more than 10 times towards mammalian cell lines (PK-15 and MNA) compared to the old dormant, dry biomasses, when calculated per biomass wet weight and per conidial particle. Surfactant activity was emitted in exudates from fresh biomass of T. atroviride, Rhizopus sp. and Stachybotrys sp. Surfactant activity was also provoked by fresh conidia from T. atroviride and Stachybotrys sp. strains. Water repealing substances were emitted by cultures of P. expansum, T. atroviride and C. globosum strains. The metabolic state of the indoor fungal growth may influence emission of liquid soluble bioreactive metabolites into the indoor air.


Mobile laboratory with rapid response instruments for real-time measurements of urban and regional trace gas and particulate distributions and emission source characteristics.
Recent technological advances have allowed the development of robust, relatively compact, low power, rapid response (approximately 1 s) instruments with sufficient sensitivity and specificity to quantify many trace gases and aerosol particle components in the ambient atmosphere. Suites of such instruments can be deployed on mobile platforms to study atmospheric processes, map concentration distributions of atmospheric pollutants, and determine the composition and intensities of emission sources. A mobile laboratory containing innovative tunable infrared laser differential absorption spectroscopy (TILDAS) instruments to measure selected trace gas concentrations at sub parts-per-billion levels and an aerosol mass spectrometer (AMS) to measure size resolved distributions of the nonrefractory chemical components of fine airborne particles as well as selected commercial fast response instruments and position/velocity sensors is described. Examples of the range of measurement strategies that can be undertaken using this mobile laboratory are discussed, and samples of measurement data are presented.


Atmospheric hydrocarbon activation by the hydroxyl radical: a simple yet accurate computational protocol for calculating rate coefficients.
The overall rate coefficient at standard temperature and pressure for the hydrogen abstraction reaction by the hydroxyl radical (HO˙) from common saturated volatile organic compounds (VOCs) is derived theoretically using electronic structure calculations and transition state theory (TST). The computational approach used is based on relatively efficient methods, and hence is applicable to a large number of compounds with only a modest use of computer resources. The key methods used are density functional theory (for the calculation of barrier heights) and simple transition state theory (TST), including a simple correction for tunnelling. All thermally relevant conformers of the reactant and the abstraction TS are included in the study. For all compounds in a test set of thirty-four, the calculated rate coefficient agrees with the experimental value to within better than an order of magnitude, and to within better than a factor of three for all but six cases, so that the accuracy is of predictive utility.


Sensitive Approaches for the Assay of the Global Protein Tyrosine Phosphorylation in Complex Samples Using a Mutated SH2 Domain.
Temporal tyrosine phosphorylation (pTyr) plays a crucial role in numerous cellular functions. The characterization of the tyrosine phosphorylation states of cells is of great interest for understanding the underlying mechanisms. In this study, we developed sensitive and cost-effective methods for the assay of the global protein tyrosine phosphorylation in complex samples by using a novel engineered pTyr binding protein, Src SH2 domain triple-point mutant (Trm-SH2). Taking the advantage of the pan-specific interaction of Trm-SH2 to pTyr, a high throughput approach was developed to determine the total protein tyrosine phosphorylation level in a sample. This method allowed the detection of 0.025 ng of tyrosine phosphorylated proteins. The Trm-SH2 was further exploited to develop a method to profile the global tyrosine phosphorylation state. When this approach was applied to analyze the tyrosine phosphoproteome upon stimulation, distinct patterns were observed. This approach is readily used in many research and clinical fields for the analysis of tyrosine phosphorylated proteins in complex samples, including classifying aberrant phosphotyrosine-dependent signaling in cancer.


Assessment of the Olfactory Function in Patients With Idiopathic Intracranial Hypertension Using the Sniffin' Sticks Test: A Case-Control Study.
Despite the lack of recognition in clinical practice, there is increasing evidence that patients with idiopathic intracranial hypertension may suffer from hyposmia. The current case-control study aims to evaluate olfactory dysfunction in a large series of patients with idiopathic intracranial hypertension. All subjects, 44 idiopathic intracranial hypertension patients and 57 healthy controls, underwent olfactory function assessment using standardized "Sniffin' Sticks" test at a tertiary referral center of a university hospital. Threshold, discrimination, identification, and total threshold-discrimination-identification scores have been determined and analyzed statistically. Idiopathic intracranial hypertension patients had significantly lower threshold (6.5 [3.69] vs 8 [1.88], P < .001, 95% CI [-2.250, -0.750]) and threshold-discrimination-identification scores (29.75 [5.56] vs 32.5 [5.25], P = .003, 95% CI [-4.250, -0.750]). Twenty-five patients (57%) were diagnosed with hyposmia. Test scores of patients with active idiopathic intracranial hypertension (n = 18) were not statistically different from patients with inactive disease (n = 26), except for discrimination score (14 [2.50] vs 11 [2.25], P = .005, 95% CI [-3.000, -1.000]). Although idiopathic intracranial hypertension patients with a cerebrospinal fluid opening pressure of ≥330 mmH2 O had lower test scores, the difference was significant only for total threshold-discrimination-identification scores (28.5 [5.50] vs 30.5 [4.38], P = .044, 95% CI [0.750, 5.500]). Multiple regression analysis revealed that test scores were related to disease activity, cerebrospinal fluid opening pressure, papilledema, headache, and medication. Our clinical study revealed significant olfactory dysfunction in patients with idiopathic intracranial hypertension compared with healthy controls. Future research should employ larger samples to search for usability of olfactory testing in clinical management of patients with idiopathic intracranial hypertension.


Grape Canes from Typical Cultivars of Campania (Southern Italy) as a Source of High-Value Bioactive Compounds: Phenolic Profile, Antioxidant and Antimicrobial Activities.
The purpose of the current study was to determine the phenolic composition, antioxidant, and antimicrobial activities in grape cane extracts from typical cultivars of Southern Italy. Aqueous extracts at different pHs (1-13) were prepared from "Aglianico", "Fiano", and "Greco" grape canes. The results demonstrated that an alkaline pH (13.00) produced the best polyphenol-rich extracts, as the total phenolic content was more than double when compared to the respective extracts prepared at pH 1.00. "Greco" grape canes gave the highest quantity of phenolic compounds at each pH, ranging from 42.7 ± 0.4 to 104.3 ± 3.0 mg Gallic Acid Equivalents (GAE)/g Dry Extract (DE) from pH 1.00 to 13.00. The Radical Scavenging Activity (RSA) and the Ferric Reducing Antioxidant Power (FRAP) were measured. The highest antioxidant activity was showed by "Greco" extract at pH 7.00. Seventy-five compounds were identified in the extracts by HPLC-MS with six of them described for the first time in grape canes. Procyanidins were highly abundant in extracts at pH 7.00, whereas stilbenoids were the most represented compounds at pH 13.00. Very strong antiviral activity against herpes simplex viruses was recorded for the extracts at pH 7.00 and 13.00 that were active in the early stages of infection by acting directly against the viral particles. The overall results suggest that grape canes, currently underutilized, can be usefully valorised by providing active extracts to use as antioxidant and antiviral agents.


Menopausal hormone therapy use and risk of invasive colon cancer: the California Teachers Study.
Results from epidemiologic studies of hormone therapy use and colon cancer risk are inconsistent. This question was investigated in the California Teachers Study (1995-2006) among 56,864 perimenopausal or postmenopausal participants under 80 years of age with no prior colorectal cancer by using Cox proportional hazards regression. Incident invasive colon cancer was diagnosed among 442 participants. Baseline-recent hormone therapy users were at 36% lower risk for colon cancer versus baseline-never users (baseline-recent users: relative risk (RR) = 0.64, 95% confidence interval (CI): 0.51, 0.80). Results did not differ by formulation. Estimated risk was lower among baseline-recent hormone therapy users with increasing duration between 5 and 15 years of use (RR = 0.49, 95% CI: 0.35, 0.68), but the trend did not persist in the longest duration group, more than 15 years of use (RR = 0.69, 95% CI: 0.52, 0.92; P(trend) = 0.60). Long-term recreational physical activity, obesity, regular use of nonsteroidal antiinflammatory medications, and daily alcohol intake did not modify these effects; baseline-recent use was more strongly associated with colon cancer risk among women with a family history of colorectal cancer (P(heterogeneity) = 0.04). Baseline-recent hormone therapy use was inversely associated with invasive colon cancer risk among perimenopausal and postmenopausal women in the California Teachers Study.


Baicalein: an in vitro antigenotoxic compound from Scutellaria baicalensis.
Bioassay-guided fractionation of an H2O extract of the root of Scutellaria baicalensis has furnished an in vitro antigenotoxic flavonoid, baicalein (1) and 2',5,5',7-tetrahydroxy-6',8-dimethoxyflavone (2). Compound 1 exhibited a dose-dependent inhibition of aflatoxin B1 (AFB1) and N-methyl-N'-nitro-N-nitrosoguanidine mutagenicity in the Salmonella typhimurium bacterial mutation assay. In the chromosome aberration assay, compound 1, at a concentration of 5 microM, reduced the frequency of chromosome aberration induced by AFB1 but increased the clastogenic effect of AFB1 at a concentration of 50 microM.


Interference of Dihydrocoumarin with Hormone Transduction and Phenylpropanoid Biosynthesis Inhibits Barnyardgrass (Echinochloa crus-galli) Root Growth.
Botanical compounds with herbicidal activity exhibit safety, low toxicity, and low chances of herbicide resistance development in plants. They have widespread applications in green agricultural production and the development of organic agriculture. In the present study, dihydrocoumarin showed potential as a botanical herbicide, and its phenotypic characteristics and mechanism of action were studied in barnyardgrass [Echinochloa crus-galli (L.) P.Beauv.] seedlings. The results indicated that dihydrocoumarin inhibited the growth of barnyardgrass without causing significant inhibition of rice seedling growth at concentrations ranging between 0.5 and 1.0 g/L. Additionally, dihydrocoumarin treatment could cause oxidative stress in barnyardgrass, disrupt the cell membrane, and reduce the root cell activity, resulting in root cell death. Transcriptomic analyses revealed that dihydrocoumarin could inhibit barnyardgrass normal growth by affecting the signal transduction of plant hormones. The results showed significant differential expression of plant hormone signal transduction genes in barnyardgrass. Additionally, dihydrocoumarin interfered with the expression of numerous phenylpropanoid biosynthesis genes in barnyardgrass that affect the production of various vital metabolites. We speculate that the barnyardgrass growth was suppressed by the interaction among hormones and phenylpropanoid biosynthesis genes, indicating that dihydrocoumarin can be applied as a bioherbicide to control barnyardgrass growth in rice transplanting fields.


Mutation of conserved domain II alters the sequence specificity of DNA binding by the p53 protein.
We have mutagenized human p53 expressed in yeast and selected two mutants, 121F and 123A, which activate transcription from one, rather than the normal two, copies of the consensus p53 DNA binding sequence. Both mutants have a 6-fold increase in affinity for a single copy of the sequence GGG CATG CCC. The 121F mutant has a decrease, and the 123A mutant an increase, in the affinity for the sequence GAA CATG TTC. This genetic and biochemical evidence supports the crystallographic finding that amino acid 120 contacts guanine in the major groove at the second position in the consensus. The major p53 binding site in the p21WAF1/CIP1 promoter resembles the GAA CATG TTC form of the consensus. Compared with wild type p53, the 121F mutant has a 7-fold lower affinity for the p21WAF1/CIP1 site in vitro, and the 121F mutant is defective in p21 induction in vivo. Mutants with subtly altered sequence specificity may facilitate dissection of downstream pathways activated by p53.


Personality method validation in common marmosets (Callithrix jacchus): Getting the best of both worlds.
Animal personality, consistent interindividual differences in behavior through time, has been intensively studied across animal taxa and particularly in nonhuman primates. Two different methods have been used to study personality: questionnaires filled out by trusted raters, following the research tradition in human personality psychology, and behavioral observations or testing, based on the behavioral ecology research tradition. Systematic research of cross-method validity has, however, brought equivocal results. Here we report a systematic method comparison with strict validation criteria in common marmosets (Callithrix jacchus). We compared questionnaire data, observational behavioral data, and experimentally assessed behavioral data independently collected in two different research laboratories and across two years. Notably, we constructed a priori predictions on the degree and direction of correlations between the questionnaire-derived constructs and behaviorally derived constructs/variables. Convergent validity of the constructs/variables was present but was not found in both laboratories for any of the constructs. Discriminant validity was found to some degree for all constructs in both laboratories, with important exceptions. It seems that marmoset personality structure obtained with descriptor ratings does not consistently capture the predicted behavioral variables. Our finding that these two methods do not quite reach common ground thus urges caution in the choice of the suitable methods to study personality in nonhuman primates. We discuss the directions to which animal personality research should go so that it can get the "best of both worlds." (PsycINFO Database Record (c) 2020 APA, all rights reserved).


Quantitative investigation of ZnO nanoparticle dissolution in the presence of δ-MnO2.
The widespread use of zinc oxide nanoparticles (ZnO NPs), the second most produced nanomaterial, inevitably leads to their release into the environment. In this study, dissolution and transformation of ZnO NPs in the presence of δ-MnO2, an abundant and ubiquitous manganese (Mn) oxide mineral, was investigated via a suite of techniques covering bulk to molecular scales. Dissolution kinetics indicated that the presence of δ-MnO2 significantly affected ZnO NP dissolution rate/trend and equilibrium Zn2+ concentration, which were found to be mainly dependent on the concentration and mass ratio of ZnO NPs and δ-MnO2. Approximately 300 mg ZnO NPs per g δ-MnO2 was expected for ZnO NP uptake at pH 7.0 via ZnO NP dissolution and surface Zn2+ adsorption. X-ray diffraction (XRD), ζ potential, high-resolution transmission electron microscopy (HR-TEM), and Zn K-edge X-ray absorption spectroscopy (XAS) results revealed that when the mole content of ZnO NPs was less than the total adsorption sites of δ-MnO2 surface, ZnO NPs were completely dissolved and adsorbed on δ-MnO2 surface in the form of inner-sphere complexes. A fraction of ZnO NPs persisted when the mole ratio of ZnO to δ-MnO2 further increased. These results suggest that the transformation and fate of ZnO NPs is affected by environment-relevant minerals such as Mn oxides due to their huge capacity of fixing dissolved metal cations at the surface or interlayer structure.


Absence of pharmacokinetic interaction between intravenous peramivir and oral oseltamivir or rimantadine in humans.
Peramivir, an intravenously administered neuraminidase inhibitor, may be used concomitantly with other influenza antivirals. Two studies were conducted to assess the potential for pharmacokinetic interactions of peramivir when coadministered with oseltamivir or rimantadine. Twenty-one healthy subjects were enrolled in each randomized, open-label, crossover study, and they received 1 intravenous dose of peramivir (600 mg), 1 oral dose of oseltamivir (75 mg) or rimantadine (100 mg), or a combination of peramivir with oseltamivir or rimantadine. Assessment of the 90% confidence interval for the geometric mean ratio of peramivir and oseltamivir carboxylate or rimantadine pharmacokinetic parameters showed no effect of oseltamivir or rimantadine on the pharmacokinetics of peramivir and no effect of peramivir on the pharmacokinetics of oseltamivir carboxylate or rimantadine. The drugs were well tolerated. These results suggest no reason to expect an effect of concomitant administration of oseltamivir or rimantadine on the safety profile of peramivir in patients with influenza.


A European arena for joint innovation in healthcare: The Platform for Innovation of Procurement and Procurement of Innovation (PiPPi).
By 2000 the European Union (EU) had recognized that its innovation capacity was underperforming in comparison to similar competitors and trading partners. Although the EU has made an effort to stimulate public research and development (R&D) through policy tools like Pre-Commercial Procurement (PCP) and Public Procurement of Innovation (PPI), starting with the 2000 Lisbon strategy and continuing through the 2021 updated Guidance on Innovation Procurement, there has remained a gap in knowledge of and use of these tools, in particular within healthcare. The past decades have seen an explosion in the number and use of digital technologies across the entire spectrum of healthcare. Demand-driven R&D has lagged here, while new digital health R&D has largely been driven by the supply side in a linear fashion, which can have disappointing results. PCP and PPI could have big impacts on the development and uptake of innovative health technology. The Platform for Innovation of Procurement and Procurement of Innovation (PiPPi) project was a Horizon 2020-funded project that ran from December 2018 to May 2022 with a consortium including seven of Europe's premier research hospitals and the Catalan Agency for Health Information. To promote PCP and PPI, PiPPi established a virtual Community of Practice (CoP) that brings together all stakeholder groups to share and innovate around unmet healthcare needs. This perspective presents a brief history of PCP and PPI in Europe with a focus on digital innovation in healthcare before introducing the PiPPi project and its value proposition.


Pharmacokinetics of the anti-AIDS drug 2',3'-dideoxyinosine in the rat.
The pharmacokinetics of 2',3'-dideoxyinosine (ddlno) was examined in the male Fischer 344 rat using reversed phase HPLC with UV and radiochemical detection. Following iv doses of 12, 25, and 100 mg/kg, the parent drug was rapidly eliminated from plasma (mean residence time, 6.3 min; systemic clearance, 64 ml/min/kg). The mean terminal elimination half-life was 28 min and the volume of distribution at steady state was 0.39 liter/kg. Orally administered [3H]ddlno (100 mg/kg) was not significantly bioavailable in the rat, with only 8-11% of the dose absorbed as the parent compound over a 2 hr period. Peak plasma drug concentrations occurred 10 to 20 min following oral administration. Solution stability data suggested that ddlno was unstable at gastric pH (pH 1, t1/2 less than 30 sec). However, elevation of gastric pH with sodium bicarbonate prior to oral administration of ddlno was not effective in increasing the bioavailability of the parent drug. The drug and its metabolic products were extensively distributed into rat tissue 48 hr after iv or oral administration. Following iv infusion of [3H]ddlno to steady state conditions, the highest tissue-to-plasma ratios of radioactivity were found in the kidney (2.2), liver (1.7), and spleen (1.5). Renal clearance accounted for 99% of the eliminated dose. Liver perfusion studies showed that ddlno was not subject to significant hepatic clearance (less than 10%) and that the metabolism was not inducible with phenobarbital.


Unveiling the chemical and morphological features of Sb-SnO2 nanocrystals by the combined use of high-resolution transmission electron microscopy and ab initio surface energy calculations.
Modeling of nanocrystals supported by advanced morphological and chemical characterization is a unique tool for the development of reliable nanostructured devices, which depends on the ability to synthesize and characterize materials on the atomic scale. Among the most significant challenges in nanostructural characterization is the evaluation of crystal growth mechanisms and their dependence on the shape of nanoparticles and the distribution of doping elements. This paper presents a new strategy to characterize nanocrystals, applied here to antimony-doped tin oxide (Sb-SnO(2)) (ATO) by the combined use of experimental and simulated high-resolution transmission electron microscopy (HRTEM) images and surface energy ab initio calculations. The results show that the Wulff construction can not only describe the shape of nanocrystals as a function of surface energy distribution but also retrieve quantitative information on dopant distribution by the dimensional analysis of nanoparticle shapes. In addition, a novel three-dimensional evaluation of an oriented attachment growth mechanism is provided in the proposed methodology. This procedure is a useful approach for faceted nanocrystal shape modeling and indirect quantitative evaluation of dopant spatial distribution, which are difficult to evaluate by other techniques.


Development of a novel celecoxib-loaded nanosuspension using a wet media milling process.
To develop a novel celecoxib (CXB)-loaded drug delivery system, numerous nanosuspensions were prepared with various polymers and surfactants using a wet media milling process, and their particle sizes were subsequently determined. A 24 full factorial design was used to identify the most appropriate preparation conditions. Pharmacokinetics of the selected nanosuspension were performed in rats and compared with those of a drug powder and a commercial CXB-loaded product. Among the carriers investigated, copovidone and sodium lauryl sulphate gave the smallest particle size of the drug in the nanosuspension. In particular, the nanosuspension prepared with 5% CXB, 4% copovidone, and 0.1% sodium lauryl sulphate, under the appropriate conditions, showed a particle size of approximately 190 nm, which was physically stable for at least 8 weeks. This nanosuspension provided a significantly higher plasma concentration and AUC in rats as compared with the drug powder and the commercial product. Thus, this novel CXB-loaded nanosuspension is a promising candidate with excellent stability and enhanced oral bioavailability.


Efficiency of two sample tests via the restricted mean survival time for analyzing event time observations.
In comparing two treatments with the event time observations, the hazard ratio (HR) estimate is routinely used to quantify the treatment difference. However, this model dependent estimate may be difficult to interpret clinically especially when the proportional hazards (PH) assumption is violated. An alternative estimation procedure for treatment efficacy based on the restricted means survival time or t-year mean survival time (t-MST) has been discussed extensively in the statistical and clinical literature. On the other hand, a statistical test via the HR or its asymptotically equivalent counterpart, the logrank test, is asymptotically distribution-free. In this article, we assess the relative efficiency of the hazard ratio and t-MST tests with respect to the statistical power under various PH and non-PH models theoretically and empirically. When the PH assumption is valid, the t-MST test performs almost as well as the HR test. For non-PH models, the t-MST test can substantially outperform its HR counterpart. On the other hand, the HR test can be powerful when the true difference of two survival functions is quite large at end but not the beginning of the study. Unfortunately, for this case, the HR estimate may not have a simple clinical interpretation for the treatment effect due to the violation of the PH assumption.


Chemical constituents of Jordanian propolis.
Seventeen compounds, including a new lanostane triterpenoid, 24(Z)-1β-3β-dihydroxyeupha-7,24-dien-26-oic acid, have been isolated from the methanolic extracts of two samples of Jordanian propolis collected from two different places with different dominant flora. The structures of the isolated compounds were elucidated by spectral methods including IR, UV, MS and 1- and 2-D NMR.


Similar Postexercise Hypotension After MICT, HIIT, and SIT Exercises in Middle-Age Adults.
Acute bouts of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) transiently lower systolic blood pressure (SBP) and diastolic blood pressure (DBP) in the hours after termed postexercise hypotension (PEH); however, the effects of sprint interval training (SIT) exercise have yet to be explored in middle-age adults. Although previous work has found no effect of exercise intensity on PEH, no study has compared submaximal, near maximal, and supramaximal intensities, specifically in middle-age adults where blood pressure (BP) management strategies may be of greater importance. This study examined the effects of MICT, HIIT, and SIT exercises on PEH in the immediate (≤2 h) and 24 h after exercise specifically in middle-age adults. Fourteen participants (10 female; age, 46 ± 9 yr; SBP, 116 ± 11 mm Hg; DBP, 67 ± 6 mm Hg; one hypertensive, four prehypertensive, nine normotensive) had their BP measured before, immediately (15, 30, 60, 120 min), and over 24 h after four experimental sessions: 1) 30-min MICT exercise (65% maximal oxygen consumption), 2) 20-min HIIT exercise (10 × 1 min at 90% maximum heart rate with 1-min rest), 3) 16-min SIT exercise (8 × 15 s all-out sprints with 2-min rest), and 4) no-exercise control. Postexercise BP was compared with no-exercise control. PEH was similar for all exercise sessions for SBP ( P = 0.388, = 0.075) and DBP ( P = 0.206, = 0.108). Twenty-four-hour average SBP was similar for all sessions P = 0.453, = 0.069), and DBP was similar over 24 h except after MICT exercise compared with HIIT exercise ( P = 0.018, d = 1.04). In middle-age adults, MICT, HIIT, and SIT exercises are effective at reducing SBP; however, the effects on DBP are smaller, and neither reductions are sustained over 24 h.


The effects and mechanisms of blockage of STAT3 signaling pathway on IL-6 inducing EMT in human pancreatic cancer cells in vitro.
Aberrant Signal transducers and activators of transcription-3 (STAT3) signaling pathway is a major cause of tumor invasion and metastasis; the underlying mechanisms, however, are not well understood. Epithelial-mesenchymal transition (EMT) is an early event that occurs during invasion of cancers of an epithelial origin. It remains elusive whether STAT3signaling pathway is involved in EMT. The objective of this study was to evaluate the effect of blockage of STAT3 signaling pathway on IL-6 inducing EMT in human pancreatic cancer cells. We used SW1990 cells and induced them to undergo EMT by exposing these cells to soluble factor interleukin-6 (IL-6). The expression of Snail, E-cadherin, and Twist was detected by reverse transcription-PCR, real-time PCR, and Western blotting. Cell morphology was observed under invert phase-contrast microscope.The invasion ability was determined by cell invasion assay in vitro. Our results demonstrated that STAT3 signaling pathway was involved in pancreatic cancer cell invasion and EMT, and that EMT induced by IL-6 was associated with the activation of STAT3 signaling pathway. Inhibition of STAT3 signaling pathway by silencing of the STAT3 gene with RNAi blocked STAT3 signaling pathway activation and suppressed EMT in pancreatic cancer cells. Collectively, the STAT3 signaling pathway plays an important role in the process of EMT of pancreatic cancer by regulating Snail gene expression. Better understanding of STAT3 signaling pathways in EMT may contribute to development of novel therapeutic strategies in invasion and metastasis of pancreatic cancer.


Cassiaside C Inhibits M1 Polarization of Macrophages by Downregulating Glycolysis.
Classically activated M1 macrophages reprogram their metabolism towards enhanced glycolysis to obtain energy and produce pro-inflammatory cytokines after activation by mammalian target of rapamycin complex 1 (mTORC1) and hypoxia-inducible factor (HIF)-1α. Thus, a strategy that constrains M1 polarization of macrophages via downregulation of glycolysis is essential for treating chronic inflammatory diseases. Cassiae semen has pharmacological activity against various inflammatory diseases. However, it is unclear whether specific compounds within Cassia seeds affect M1 polarization of macrophages. Here, we investigated whether Cassiaside C napthopyrone from Cassiae semen inhibits M1 polarization by downregulating glycolysis. We found that Cassiaside C reduced expression of inducible nitric oxide synthase and cyclooxygenase-2 and the phosphorylation of nuclear factor kappa B, all of which are upregulated in lipopolysaccharide (LPS)/interferon (IFN)-γ-treated Raw264.7 cells and peritoneal macrophages. Moreover, Cassiaside C-treated macrophages showed marked suppression of LPS/IFN-γ-induced HIF-1α, pyruvate dehydrogenase kinase 1, and lactate dehydrogenase A expression, along with downregulation of the phosphoinositide 3-kinases (PI3K)/AKT/mTORC1 signaling pathway. Consequently, Cassiaside C attenuated enhanced glycolysis and lactate production, but rescued diminished oxidative phosphorylation, in M1 polarized macrophages. Thus, Cassiaside C dampens M1 polarization of macrophages by downregulating glycolysis, which could be exploited as a therapeutic strategy for chronic inflammatory conditions.


Luminescent gold nanoparticles with pH-dependent membrane adsorption.
pH regulates many cellular processes and is also an indicator of disease progression. Therefore, pH-responsive materials often serve as either tools in the fundamental understanding of cell biology or medicine for disease diagnosis and therapy. While gold nanoparticles have broad biomedical applications, very few of them exhibit pH-dependent interactions with live cells in a native biological environment due to nonspecific serum protein adsorption. Herein, we report that by coating luminescent gold nanoparticles with a natural peptide, glutathione, and the simplest stable aminothiol, cysteamine, we enabled the nanoparticles to exhibit not only high resistance to serum protein adsorption but also pH-dependent adsorption onto live cell membranes in the presence of serum proteins. Incorporating this pH-dependent membrane adsorption behavior into gold nanoparticles could potentially catalyze new biomedical applications of metal nanoparticles in the fundamental understanding of biological processes as well as disease diagnosis and therapy, where pH changes are involved.


Gastrointestinal stromal tumors of the stomach: two case reports.
Gastrointestinal stromal tumors, commonly known as GISTs, are non-epithelial gastrointestinal neoplasms seen with increasing frequency in clinical practice. These tumors were formerly classified as leiomyoblastomas or leiomyosarcomas. Recent advances in immunohistochemistry have identified gastrointestinal stromal tumors as a unique entity. Gastrointestinal stromal tumors are unique in that these neoplasms originate from the interstitial cells of Cajal, the pacemaker cells of the gastrointestinal tract. The initial events that lead to unregulated smooth muscle proliferation are unclear. Recent advances may elucidate the genetic mutations responsible. With the recent advances in cell histochemistry and gene mapping there is renewed interest in the early diagnosis and treatment of GI stromal tumors. As our understanding of GI stromal tumors improves, clinicians now must recognize GIST as a neoplasm with its own biology and treatment algorithms. The purpose of this paper is to present two cases and review recent literature to gain a better understanding of how to diagnose and treat gastrointestinal stromal tumors in clinical practice.


Bioengineering tools for the production of pharmaceuticals: current perspective and future outlook.
The bioengineering tools have significant advantages through less time-consuming and utilized as a promising stage for the production of pharmaceutical bioproducts under the single platform. This review highlighted the advantages and current improvement in the plant, animal and microbial bioengineering tools and outlines feasible approaches by biological and process's bioengineering levels for advancing the economic feasibility of pharmaceutical's production. The critical analysis results revealed that system biology and synthetic biology along with advanced bioengineering tools like transcriptome, proteome, metabolome and nano bioengineering tools have shown a promising impact on the development of pharmaceutical's bioproducts. Tools to overcome and resolve the accompanying encounters of pharmaceutical's production that include nano bioengineering tools are also discussed. As a summary and prospect, it also gives new insight into the challenges and possible breakthrough of the development of pharmaceutical's bioproducts through bioengineering tools.


Prognostic value of histopathology in Ewing's sarcoma. Long-term follow-up of distal extremity primary tumors.
The pathologic material from 56 patients diagnosed initially as Ewing's sarcoma of the distal extremity and treated on National Cancer Institute protocols between 1968 and 1984 was reviewed and correlated with clinical outcome. Histologically, the tumors were categorized, based on recent pathologic criteria, into three diagnostic groups: (1) typical Ewing's sarcoma, (2) atypical Ewing's sarcoma, and (3) other (predominantly peripheral neuroepithelioma [PN]). Thirty-two patients (57%) had typical Ewing's, 13 (23%) were atypical, and 11 (20%) were in the "other" diagnostic category (seven [13%] PN, two primitive rhabdomyosarcoma, one primitive sarcoma of bone, and one synovial cell sarcoma). No cases of metastatic neuroblastoma, osteosarcoma, or lymphoma were found. Forty-five patients had localized disease at diagnosis; 11 had metastases. Patients with typical Ewing's sarcoma were less likely to have metastatic disease at the time of diagnosis. Only two of 32 patients with typical Ewing's sarcoma had metastases compared with nine of 24 patients in the two other groups. The pattern of relapse was also different in these other groups compared with typical Ewing's patients; five patients developed lymph node metastases and two patients developed brain metastases. Although the presence of metastatic disease at diagnosis was a strong negative prognostic factor, our histologic grouping was independently prognostic of clinical outcome in patients with localized disease. Patients with typical osseous Ewing's sarcoma had an improved overall survival (P2 = 0.03) and patients with other tumors (neither typical nor atypical Ewing's sarcoma) had a poorer disease-free survival (P2 = 0.02). Since no generally accepted histopathologic prognostic criteria exist for Ewing's sarcoma, the potential value of our proposed classification should be evaluated in a larger retrospective and a prospective study.


Living with cancer-related fatigue: developing an effective management programme.
A fatigue management programme was developed for hospice day care patients. Following feedback, and using the survivorship agenda, the authors found that cancer-related fatigue was a major difficulty for many patients. Fatigue, which affects 'normal' functioning and quality of life, is often related to cancer treatments which continue even after the patient has completed active treatment. A palliative care occupational therapist and physiotherapist (the authors) created a 1-year charity-funded pilot project to develop, run and evaluate a programme for cancer patients at any stage of their illness. Patients were referred when fatigue was recognized by their clinical nurse specialists as still significantly affecting their lifestyle, even if other possible causative factors had been medically managed. Twenty-eight patients completed the 4-week courses and reported positive reductions in fatigue levels, and better functioning and ability to cope.


Disturbances in airflow dynamics and tracheal sounds during forced and quiet breathing in subjects with unilateral vocal fold paralysis.
Variable extra thoracic obstruction has been found in spirometric studies in subjects with unilateral vocal fold paralysis. The aim of the study was to further evaluate airflow dynamics in these subjects with body plethysmography and tracheal sound analysis. Ten patients with unilateral vocal fold paralysis without a history of chronic pulmonary diseases and 10 healthy control subjects were studied. Flow-volume spirometry, body plethysmography and tracheal sound analysis were performed within 1 day. The study shows that peak inspiratory flow (PIF) and specific airway conductance (SG(aw)) expressed as percentage of Finnish reference values were significantly lower and airway resistance (R(aw)) was higher among the patients than among the controls (P=0.004, P=0.026 and P=0.004, respectively). The patients had higher sound amplitude of both inspiratory and expiratory tracheal sounds than the controls [root mean square (RMS) values of the power spectra were 31.5 and 25 dB, P=0.006 in inspiration and 31.5 and 26 dB, P=0.013 in expiration, respectively]. Quartile frequencies (F25 and F50) and RMS of expiratory tracheal sounds had significant negative correlation with PIF (P=0.02, P<0.001, P=0.02, respectively) and forced inspiratory volume in 1 s (FIV(1)) (P=0.01, P<0.001, P=0.01, respectively). There was also an association between F50 and peak expiratory flow (PEF) (P=0.02). According to the present study, both quiet breathing and forced inspiration are disturbed in subjects with unilateral vocal fold paralysis. A close relationship between tracheal sounds and respiratory function tests exists.


Unilateral glomerular DNA-anti-DNA complex formation in situ.
DNA has a high affinity for collagenous structures such as glomerular basement membrane. DNA was infused into the isolated left kidney in rats to determine whether this antigen though negatively charged would bind to glomerular structures. Mainly mesangial localization with minimal capillary localization was noted. Infusion of anti-DNA antibody after glomerular DNA binding allowed for formation of DNA-anti-DNA deposits in situ.


Solid-liquid phase equilibria of the Gaussian core model fluid.
The solid-liquid phase equilibria of the Gaussian core model are determined using the GWTS [J. Ge, G.-W. Wu, B. D. Todd, and R. J. Sadus, J. Chem. Phys. 119, 11017 (2003)] algorithm, which combines equilibrium and nonequilibrium molecular dynamics simulations. This is the first reported use of the GWTS algorithm for a fluid system displaying a reentrant melting scenario. Using the GWTS algorithm, the phase envelope of the Gaussian core model can be calculated more precisely than previously possible. The results for the low-density and the high-density (reentrant melting) sides of the solid state are in good agreement with those obtained by Monte Carlo simulations in conjunction with calculations of the solid free energies. The common point on the Gaussian core envelope, where equal-density solid and liquid phases are in coexistence, could be determined with high precision.


[Congenital sternal cleft. Diagnosis and treatment].
The first known case of sternal cleft was described by Torres in 1740. Since then, many publications have appeared concerning sternal cleft, which have led to introduce a classification and some therapeutical procedures. This disease is a developmental anomaly of the sternum that usually shows vascular and cardiac malformations as well as diaphragmatic, abdominal wall, pericard and middle line organs anomalies. Two cases of sternal cleft are presented who have been treated in the neonatal period with different associated anomalies. Diagnostic procedures and therapeutical aspects are discussed.


A Strategy for the Determination of Alkaline Phosphatase Based on the Self-Triggered Degradation of Metal-Organic Frameworks by Phosphate.
Alkaline phosphatase (ALP) is widely present in the human body and is an important biomarker. Numerous ALP detection studies have been carried out, and ascorbic acid (AA) is often used as the reducing component in the sensors to monitor ALP levels since it can be produced from ascorbic acid 2-phosphate (AA2P) hydrolysis in the presence of ALP. However, it is well-known that AA is a strong reducing agent and can be easily oxidized. The disproportion between oxidized AA and reduced AA reactions results in the generation of AA free radicals with single electrons that may lead to inaccurate results in assays. To solve this problem, we synthesized a core-shell metal-organic framework sensor (PATP-Au@ZIF-8 NP) and used it as a sensitive and accurate ALP detection sensor with self-triggered control of phosphate ions (Pi) to avoid the potential inaccuracy of the method that uses AA as the reducing component. By establishing a physical shell on the surface of the gold nanoparticles (Au NPs), the sensor not only can eliminate the random assembly of metal nanoparticles caused by plasma exposure but also can generate self-triggering of Pi caused by ALP. Pi can decompose ZIF-8 through coordination with Zn2+ and thus can destroy the ZIF-8 shell structure of the prepared PAZ NPs. Au NPs are released and then become aggregated, in turn causing the SERS "hot spot" area to increase. The enhancement of the SERS signals was found to be directly associated with the level of Pi released from ALP-triggered hydrolysis. The response of the strategy was linear at ALP concentrations ranging from 0.1 to 150 mU/mL (r = 0.996) with a detection limit of 0.03 mU/mL. Lastly, the developed strategy was employed in the evaluation of ALP inhibitors, and the possibility to implement the developed SERS strategy for rapid and selective analysis of ALP in human serum was demonstrated.