Optimisation of saponin extraction conditions with Camellia sinensis var. assamica seed and its application for a natural detergent.
Camellia sinensis var. assamica seed cake (a by-product of tea-seed oil) is an abundant resource with poor utilisation. C. sinensis var. assamica seed saponin (CSS) is one kind of non-ionic surfactant. In this study, the CSS extraction conditions were optimised by response surface methodology (RSM) and then the CSS detergent was developed. Additionally, the safety and decontamination ability of the developed detergent were evaluated. The optimised extraction conditions were including the extracting temperature of 40.04 °C, extraction time of 4.97 h, ethanol concentration of 64.11% and liquid-solid ratio of 14.57:1 mL g-1 . The formula of the CSS detergent was as follows: 20% crude CSS, 0.3% oxidised tea polyphenols (OTPs), 0.2% nisin, 0.3% sodium dehydroacetate, 0.7% sodium alginate and 0.5% sodium polyacrylate. The LD50 of the CSS detergent exceeds 14 g kg-1 in mice, indicating the detergent was non-toxic. Both of the emulsifying and the pesticide residues removal abilities of the CSS detergent were significantly stronger than the commercial detergent. A natural tea seed saponin detergent with good safety and decontamination ability was successfully developed. This can make better use of the tea seed cake, thereby creating added value in the tea seed oil industry. © 2017 Society of Chemical Industry.


Induction of islet cell surface and insulin antibodies in Balb/c mice by application of porcine insulin and Freund's adjuvant is not associated with insulitis.
To investigate whether insulin antibody (IAB) formation is associated with the appearance of islet cell cytoplasmic antibodies (ICA), islet cell surface antibodies (ICSA) and insulitis Balb/c Bln mice were immunized with porcine insulin in combination with or without Freund's adjuvant. The animals received 8 i.p. injections and were followed up to 150 days for the development of antibodies and insulitis. Mice immunized with insulin in CFA developed IAB as well as ICSA. Mice only receiving Freund's adjuvant emulsified in saline also developed ICSA. ICA were not detectable. Inflammatory infiltrates were found in the exocrine pancreatic parenchyma but not in islets. The results show that nonspecific stimulation of the immune system and the application of insulin as antigen leads to both the formation of ICSA and IAB, while insulitis was not detectable.


tRNA-like structures tag the 3' ends of genomic RNA molecules for replication: implications for the origin of protein synthesis.
Single-stranded RNA viruses often have 3'-terminal tRNA-like structures that serve as substrates for the enzymes of tRNA metabolism, including the tRNA synthases and the CCA-adding enzyme. We propose that such 3'-terminal tRNA-like structures are in fact molecular fossils of the original RNA world, where they tagged genomic RNA molecules for replication and also functioned as primitive telomeres to ensure that 3'-terminal nucleotides were not lost during replication. This picture suggests that the CCA-adding activity was originally an RNA enzyme, that modern DNA telomeres with the repetitive structure CmAn are the direct descendants of the CCA terminus of tRNA, and that the precursor of the modern enzyme RNase P evolved to convert genomic into functional RNA molecules by removing this 3'-terminal tRNA-like tag. Because early RNA replicases would have been catalytic RNA molecules that used the 3'-terminal tRNA-like tag as a template for the initiation of RNA synthesis, these tRNA-like structures could have been specifically aminoacylated with an amino acid by an aberrant activity of the replicase. We show that it is mechanistically reasonable to suppose that this aminoacylation occurred by the same sequence of reactions found in protein synthesis today. The advent of such tRNA synthases would thus have provided a pathway for the evolution of modern protein synthesis.


Neuroprotective effects of exogenous activin A on oxygen-glucose deprivation in PC12 cells.
Ischemic cerebrovascular disease is one of the most common causes of death in the World. Exogenous activin A (ActA) protects neurons against toxicity and plays a central role in regulating the brain's response to injury. In the present study, we investigated the mechanisms involved in the neuroprotective effects of ActA in a model of hypoxic-ischemic brain disease. We found that ActA could effectively increase the survival rate of PC12 cells and relieve oxygen-glucose deprivation (OGD) damage. To clarify the neuroprotective mechanisms of ActA, the effects of ActA on the ActA/Smad pathway and on the up-regulation of inducible nitric oxide synthase (NOS) and superoxide dismutase (SOD) were investigated using OGD in PC12 cells. The results showed that ActA could increase the expression of activin receptor IIA (ActRIIA), Smad3 and Smad4 and that 50 ng/mL and 100 ng/mL of ActA could reduce NO levels and increase SOD activity by 78.9% and 79.9%, respectively. These results suggested that the neuroprotective effects of ActA in ischemia could be related to the activation of the ActA/Smad signaling pathway and to its anti-oxidant activities.


Evolutionary convergence on highly-conserved 3' intron structures in intron-poor eukaryotes and insights into the ancestral eukaryotic genome.
The presence of spliceosomal introns in eukaryotes raises a range of questions about genomic evolution. Along with the fundamental mysteries of introns' initial proliferation and persistence, the evolutionary forces acting on intron sequences remain largely mysterious. Intron number varies across species from a few introns per genome to several introns per gene, and the elements of intron sequences directly implicated in splicing vary from degenerate to strict consensus motifs. We report a 50-species comparative genomic study of intron sequences across most eukaryotic groups. We find two broad and striking patterns. First, we find that some highly intron-poor lineages have undergone evolutionary convergence to strong 3' consensus intron structures. This finding holds for both branch point sequence and distance between the branch point and the 3' splice site. Interestingly, this difference appears to exist within the genomes of green alga of the genus Ostreococcus, which exhibit highly constrained intron sequences through most of the intron-poor genome, but not in one much more intron-dense genomic region. Second, we find evidence that ancestral genomes contained highly variable branch point sequences, similar to more complex modern intron-rich eukaryotic lineages. In addition, ancestral structures are likely to have included polyT tails similar to those in metazoans and plants, which we found in a variety of protist lineages. Intriguingly, intron structure evolution appears to be quite different across lineages experiencing different types of genome reduction: whereas lineages with very few introns tend towards highly regular intronic sequences, lineages with very short introns tend towards highly degenerate sequences. Together, these results attest to the complex nature of ancestral eukaryotic splicing, the qualitatively different evolutionary forces acting on intron structures across modern lineages, and the impressive evolutionary malleability of eukaryotic gene structures.


[A safely resected case of hypervascular pancreatic giant tumor after preoperative arterial embolization].
A 73-year-old woman visited our hospital for a treatment of pancreatic tumor that increased steadily in size of 6 cm in diameter in 1999 to 13 cm in 2008, while remaining in asymptomatic condition throughout this follow-up time. The tumor was big and flowed from many vessels such as portal and superior mesenteric veins and the celiac and superior mesenteric arteries. These were critical for determining tumor respectability and the risk of massive intra-operative hemorrhage was felt to be considerable. Therefore, preoperative embolization of the tumor-feeding arteries arising from the celiac axis (gastroduodenal, splenic and dorsal pancreatic arteries) was performed on the previous day of operation. Tumor resection with pancreaticoduodenectomy and partial resection of portal vein and reconstruction were performed. We got to SMA with the use of "paraduodenal mesenteric approach", we called, and we finished the operation without a blood transfusion. The final pathology confirmed the diagnosis of serous microcystic adenoma.


Drotrecogin alpha (activated) in two patients with the hantavirus cardiopulmonary syndrome.
Hantavirus cardiopulmonary syndrome (HCPS) is associated with rapid cardiopulmonary collapse from endothelial injury, resulting in massive capillary leak, shock and severe hypoxemic respiratory failure. To date, treatment remains supportive and includes mechanical ventilation, vasopressors and extracorporeal membrane oxygenation, with mortality approaching 50%. Two HCPS survivors initially given drotrecogin alpha (activated) (DAA) for presumed bacterial septic shock are described. Vasoactive medications were required for a maximum of 52 h, whereas creatinine levels and platelet counts normalized within seven to nine days. Given the similar presentations of HCPS and bacterial septic shock, empirical DAA therapy will likely be initiated before a definitive diagnosis of HCPS is made. Further observations of DAA in HCPS seem warranted.


Circulating miRNA Signature as a Potential Biomarker for the Prediction of Analgesic Efficacy of Hydromorphone.
No practical biomarkers currently exist for the prediction of the analgesic efficacy of opioids. Previously, we reported circulating miRNA signatures differentially regulated by µ-opioid receptor (MOR) agonists in healthy subjects. We hypothesized that these miRNAs could be potential pharmacodynamic biomarkers to estimate MOR stimulation, and predict the efficacy of opioids; i.e., patients with low MOR stimulation may be more vulnerable to strengthening of the MOR signal upon hydromorphone treatment. To test this hypothesis, plasma samples were obtained from 25 patients with cancer pain prior to the initiation of hydromorphone treatment and the circulating miRNA levels were evaluated, focusing on four miRNAs (i.e., hsa-miR-423-3p, hsa-let-7a-5p, hsa-miR-26a-5p, and hsa-let-7f-5p) and four miRNAs (i.e., hsa-miR-144-3p, hsa-miR-451a, hsa-miR-215, and hsa-miR-363-3p) that were most clearly up and downregulated by hydromorphone and oxycodone. The patients were classified into two classes with putative high and low MOR signal, estimated based on the plasma miRNA signature. A significant correlation was observed between the analgesic efficacy and the putative MOR signal level, and patients with low MOR signal achieved better pain control (i.e., ΔVAS < 0) through hydromorphone. These results suggested that plasma miRNA signatures could serve as clinical biomarkers for the prediction of the analgesic efficacy of hydromorphone.


RAC1 controls progressive movement and competitiveness of mammalian spermatozoa.
Mammalian spermatozoa employ calcium (Ca2+) and cyclic adenosine monophosphate (cAMP) signaling in generating flagellar beat. However, how sperm direct their movement towards the egg cells has remained elusive. Here we show that the Rho small G protein RAC1 plays an important role in controlling progressive motility, in particular average path velocity and linearity. Upon RAC1 inhibition of wild type sperm with the drug NSC23766, progressive movement is impaired. Moreover, sperm from mice homozygous for the genetically variant t-haplotype region (tw5/tw32), which are sterile, show strongly enhanced RAC1 activity in comparison to wild type (+/+) controls, and quickly become immotile in vitro. Sperm from heterozygous (t/+) males, on the other hand, display intermediate RAC1 activity, impaired progressive motility and transmission ratio distortion (TRD) in favor of t-sperm. We show that t/+-derived sperm consist of two subpopulations, highly progressive and less progressive. The majority of highly progressive sperm carry the t-haplotype, while most less progressive sperm contain the wild type (+) chromosome. Dosage-controlled RAC1 inhibition in t/+ sperm by NSC23766 rescues progressive movement of (+)-sperm in vitro, directly demonstrating that impairment of progressive motility in the latter is caused by enhanced RAC1 activity. The combined data show that RAC1 plays a pivotal role in controlling progressive motility in sperm, and that inappropriate, enhanced or reduced RAC1 activity interferes with sperm progressive movement. Differential RAC1 activity within a sperm population impairs the competitiveness of sperm cells expressing suboptimal RAC1 activity and thus their fertilization success, as demonstrated by t/+-derived sperm. In conjunction with t-haplotype triggered TRD, we propose that Rho GTPase signaling is essential for directing sperm towards the egg cells.


Modification by protons of frog skeletal muscle KATP channels: effects on ion conduction and nucleotide inhibition.
1. The molecular mechanisms underlying pH regulation of skeletal muscle ATP-sensitive K+ (KATP) channels were studied using the patch clamp technique in the inside-out configuration. Two effects of intracellular protons were studied in detail: the decrease in magnitude of single-channel currents and the increase in open probability (Po) of nucleotide-inhibited channels. 2. The pH dependence of inward unit currents under different ionic conditions was in poor agreement with either a direct block of the pore by protons or an indirect proton-induced conformational change, but was compatible with the protonation of surface charges located near the cytoplasmic entrance of the pore. This latter electrostatic mechanism was modelled using Gouy-Chapman-Stern theory, which predicted the data accurately with a surface charge density of about 0.1 negative elementary charges per square nanometre and a pK (pH value for 50% effect) value for protonation of these charges of 6.25. The same mechanism, i.e. neutralization of negative surface charges by cation binding, could also account for the previously reported reduction of inward unit currents by Mg2+. 3. Intracellular alkalization did not affect Po of the KATP channels. Acidification increased Po. In the presence of 0.1 mM ATP (no Mg2+), the channel activation vs. pH relationship could be fitted with a sigmoid curve with a Hill coefficient slightly above 2 and a pK value of 6. This latter value was dependent on the ATP concentration, decreasing from 6.3 in 30 microM ATP to 5.3 in 1 microM ATP. 4. Conversely, the channel inhibition vs. ATP concentration curve was shifted to the right when the pH was lowered. At pH 7.1, the ATP concentration causing half-maximal inhibition was about 10 microM. At pH 5.4, it was about 400 microM. The Hill coefficient values remained slightly below 2. Similar effects were observed when ADP was used as the inhibitory nucleotide. 5. These results confirm that a reciprocal competitive link exists between proton and nucleotide binding sites. Quantitatively, they are in full agreement with a steady-state model of a KATP channel possessing four identical protonation sites (microscopic pK, 6) allosterically connected to the channel open state and two identical nucleotide sites (microscopic ATP dissociation constant, approximately 30 microM) connected to the closed state.


Dynamic visual guidance with complex task improves intracortical source activities during motor imagery.
Motor imagery (MI) based brain-computer interfaces could be used clinically to trigger neurological recovery and improve motor function for patients with neural injuries. However, the factors that impact on MI performance and rehabilitative effect of MI-based brain-computer interfaces have not been characterized. According to our previous study, complex imagery tasks with dynamic visual paradigm could induce stronger MI features and obtain significantly higher average classification accuracy than nondynamic guidance. This study attempted to further investigate intracortical activities under different instructive paradigms and explore their potential effects on motor recovery. Eleven participants performed four types of different paradigms, including a nondynamic visual paradigm with simple MI task and three other dynamic visual/audiovisual paradigms with simple/complex MI tasks. A 64-channel electroencephalography was acquired and a voxel by voxel grand average of cortical source activities with statistical nonparametric mapping based on standardized low-resolution brain electromagnetic tomography were performed for comparisons among these paradigms in both alpha and beta bands. Moreover, seven regions of interest were selected to further analyze mean current source density variations for each paradigm with statistical analysis between dynamic and nondynamic paradigms. The outcomes uncovered that the dynamic visual aided paradigm with complex imagery tasks stimulated stronger cortical activities in core motor-related regions and triggered more extensive activation in the classical frontoparietal mirror regions than nondynamic paradigm. Involvement of these areas had a positive impact on the recovery of motor deficits in patients with neural injuries.


Selective inhibition of persistent sodium current by F 15845 prevents ischaemia-induced arrhythmias.
Myocardial ischaemia is associated with perturbations of electrophysiological profile of cardiac myocytes. The persistent sodium current (I(Nap)) is one of the major contributors to ischaemic arrhythmias and appears as an attractive therapeutic target. We investigated the effects of F 15845, a new anti-anginal drug on I(Nap) and in integrative models of I(Nap)-induced arrhythmias. Sodium current was investigated using patch clamp technique on wild-type and DeltaKPQ-mutated hNav1.5 channels transfected in HEK293 cells. Effects of F 15845 on action potentials (APs) were studied by the glass microelectrode technique and its anti-arrhythmic activities were investigated in ischaemia- and aconitine-induced arrhythmias in the rat. We demonstrated that F 15845 is a potent blocker of I(Nap) acting from the extracellular side of the channel. Blockade of I(Nap) was voltage dependent and characterized by an almost pure tonic block. F 15845 shortened AP from rabbit Purkinje fibres, confirming its lack of pro-arrhythmic activity, and prevented AP lengthening induced by the I(Nap) activator veratridine. F 15845 did not affect APs from rabbit atria and guinea pig papillary muscle where I(Nap) is not functional, confirming its inability to affect other cardiac ionic currents. F 15845 was effective at preventing fatal ventricular fibrillation and ventricular tachycardia during coronary ligation without modifying heart rate and blood pressure, and dose dependently increased the dose threshold of aconitine required to induce ventricular arrhythmias. F 15845, a novel anti-anginal drug targeting I(Nap), demonstrates new anti-arrhythmic properties which may be of therapeutic benefit against ischaemia-induced arrhythmias.


Genetics of dystonia.
Dystonia is characterized by muscle contractions leading to abnormal postures with involuntary twisting and repetitive movements. Inherited dystonia designated by DYT locus symbols can be separated into three broad phenotypic categories: primary torsion dystonia (PTD), where dystonia is the only clinical sign (except for tremor) (DYT1, 2, 4, 6, 7, 13, 17, and 21); dystonia plus loci, where other phenotypes in addition to dystonia, including parkinsonism or myoclonus, are present (DYT3, 5/14, 11, 12, 15, and 16); and paroxysmal forms of dystonia/dyskinesia (DYT8, 9, 10, 18, 19, and 20). Currently, 19 loci including 10 genes have been identified for inherited dystonias. In this review, the phenotypes associated with these loci and the responsible genes will be discussed.


A randomized controlled trial of the cost-effectiveness of a district co-ordinating service for terminally ill cancer patients.
The objective of this paper is to compare the cost effectiveness of a co-ordination service with standard services for terminally ill cancer patients with a prognosis of less than one year. We designed a randomized controlled trial, with patients randomized by the general practice with which they were registered. Co-ordination group patients received the assistance of two nurse coordinators whose role was to ensure that patients had access to appropriate services. The setting was in a South London health authority. Complete service use and outcome data were collected on 167 patients, 86 in the co-ordination group, and 81 in the control group. Our results, as previously reported, show that no differences in outcomes were detected between the co-ordination and control groups; the mean total costs incurred by the co-ordination group were significantly less than those of the control group. The co-ordinated group used significantly fewer inpatient days (mean 24 versus 40 inpatient days; t = 2.4, p = 0.002) and nurse home visits (mean 14.5 versus 37.5 visits; t = 0.3, p = 0.01). Mean cost per co-ordinated patient was almost half that of the control group patients 4774 pounds versus 8034 pounds, t = 2.8, p = 0.006). Although the unit cost data were relatively crude, these cost reductions were insensitive to a wide range of unit costs. These differences persisted when, in order to control for any putative differences in severity between the two groups, the analysis was restricted to patients who had died by the end of the study. The ratio of potential cost savings to the cost of co-ordination service was between 4:1 and 8:1. In conclusion, the co-ordination service for cancer patients who were terminally ill with a prognosis of less than one year was more cost effective than standard services, due to achieving the same outcomes at lower service use, particularly inpatient days in acute hospital. Assuming that the observed effects are real, improved co-ordination of palliative care offers the potential for considerable savings. Further research is needed to explore this issue.


LY294002 suppresses the malignant phenotype and sensitizes osteosarcoma cells to pirarubicin chemotherapy.
Pirarubicin is frequently used in chemotherapy against tumors. However, clinical use is severely limited by the development of progressive dose-dependent cardiomyopathy and acquired drug resistance. LY294002 is a commonly used pharmacologic inhibitor, which selectively inhibits the phosphoinositide 3-kinase-AKT nexus. The aim of this study was to investigate the combined inhibitory effect of LY294002 and pirarubicin on human osteosarcoma (OS) cells in vitro. The inhibitory effect of LY294002 plus pirarubicin on U2-OS and MG-63 OS cell proliferation, apoptosis, migration and invasion was investigated by cell proliferation, wound healing and Transwell invasion assays. The results revealed that LY294002 and pirarubicin synergistically induced apoptosis, and inhibited the growth, migration and invasion of OS cells. This indicates that LY294002 enhanced the effects of pirarubicin on OS in vitro. LY294002 combined with pirarubicin may thus be a future therapeutic strategy in OS.


A downstream kinase of the mammalian target of rapamycin, p70S6K1, regulates human double minute 2 protein phosphorylation and stability.
Human double minute 2 (HDM2) is an oncoprotein overexpressed in many human cancers. HDM2 expression is regulated at multiple levels in cells. Phosphorylation of HDM2 plays an important role in its post-translational regulation. In this study, we have shown that the phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002, and the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, have similar effects on the inhibition of HDM2 phosphorylation and protein turnover. Rapamycin inhibited p70S6K1, but not AKT activation, indicating that rapamycin affects HDM2 phosphorylation via an AKT-independent mechanism. Rapamycin also decreased HDM2 protein stability. Knockdown of p70S6K1 by a p70S6K1 siRNA resulted in the inhibition of HDM2 phosphorylation and a decrease in HDM2 protein turnover. Overexpression of p70S6K1 enhanced HDM2 phosphorylation and led to an increase in HDM2 protein turnover. Our results suggest that p70S6K1 regulates turnover of HDM2 protein for cancer development.


[Hydrolytic enzymes and spore formation in Bacillus intermedius].
The investigation of the activity of extracellular hydrolytic enzymes and sporulation in the bacterium Bacillus intermedius 3-19 showed that the activity of ribonuclease is maximal in the glucose-containing growth medium, in which sporulation is suppressed. At the sporulation stages II-IV, the synthesis of phosphatase was not regulated by the factors that influence this synthesis in the phase of growth retardation. Caseinolytic activity exhibited two peaks. The first peak was observed when thiol-dependent proteinase began accumulating in the medium. The second peak corresponded to the late stages of sporulation, i.e., the stages of spore maturation and the autolysis of sporangium. The regulatory relationship between proteinase synthesis and sporulation and the possible role of extracellular phosphatases and proteinases in the sporulation are discussed.


[Cardiac surgery in an octogenarian with idiopathic thrombocytopenic purpura: report of a case].
An 81-year-old woman was referred to our hospital for surgical treatment for mitral valve regurgitation, tricuspid valve regurgitation and atrial fibrillatory bradycardia. The platelet count on admission was 4.9 x 10(4)/microl. and the results of other studies were compatible with idiopathic thrombocytopenic purpura. Although we performed high-dose transvenous immunoglobulin infusion (400 mg/kg/day) for 5 consecutive days, the platelet count showed no remarkable change. Because of progression of heart failure, we underwent cardiac operation under thrombocytopenic condition. Intra and post-operative platelet transfusion might contribute to postoperative course uneventful without bleeding tendency. In this case, high-dose immunoglobulin therapy was not effective. However the operative course was satisfactory with adequate surgical hemostasis and platelet transfusion.


Correlation of abdominal fat ratio with hepatic CT enhancement.
The objective of the study was to evaluate the effect of abdominal fat proportion on hepatic computed tomography (CT) enhancement. CT data for 87 patients (47 men, mean age 55.09±13.27 years; 40 women, mean age 60.43±11.29 years) were analyzed by linear regression to assess the association of patient age and abdominal fat proportion with adjusted maximal hepatic enhancement (aMHE), calculated by dividing the maximal hepatic enhancement by the dose of iodine injected per kilogram of patient body weight, for each gender. The abdominal fat ratio (AFR) at the umbilical level, calculated as the volume of abdominal fat divided by the total abdominal volume, was used as a marker of abdominal fat proportion. It was found that aMHE was positively correlated with AFR for men (r=0.48, P<0.01) and women (r=0.46, P<0.01) but not with patient age (r=-0.09 and -0.14, respectively, both P>0.05). Therefore, it was concluded that determining an iodine dose on the basis of AFR might be an optimal way to maintain constant hepatic enhancement.


Brain "fog," inflammation and obesity: key aspects of neuropsychiatric disorders improved by luteolin.
Brain "fog" is a constellation of symptoms that include reduced cognition, inability to concentrate and multitask, as well as loss of short and long term memory. Brain "fog" characterizes patients with autism spectrum disorders (ASDs), celiac disease, chronic fatigue syndrome, fibromyalgia, mastocytosis, and postural tachycardia syndrome (POTS), as well as "minimal cognitive impairment," an early clinical presentation of Alzheimer's disease (AD), and other neuropsychiatric disorders. Brain "fog" may be due to inflammatory molecules, including adipocytokines and histamine released from mast cells (MCs) further stimulating microglia activation, and causing focal brain inflammation. Recent reviews have described the potential use of natural flavonoids for the treatment of neuropsychiatric and neurodegenerative diseases. The flavone luteolin has numerous useful actions that include: anti-oxidant, anti-inflammatory, microglia inhibition, neuroprotection, and memory increase. A liposomal luteolin formulation in olive fruit extract improved attention in children with ASDs and brain "fog" in mastocytosis patients. Methylated luteolin analogs with increased activity and better bioavailability could be developed into effective treatments for neuropsychiatric disorders and brain "fog."


Long-term measurement of muscle denervation and locomotor behavior in individual wild-type and ALS model mice.
The increasing number of mouse models of human degenerative and injury-related diseases that affect motor behavior raises the importance of in vivo methodologies allowing measurement of physiological and behavioral changes over an extended period of time in individual animals. A method that provides long-term measurements of muscle denervation and its behavioral consequences in individual mice for several months is presented in this article. The method is applied to mSod1(G93A) mice, which model human amyotrophic lateral sclerosis (ALS). The denervation process of gastrocnemius and soleus muscles in mSod1(G93A) mice is demonstrated for up to 3 mo. The data suggest that as muscle denervation progresses, massive behavioral compensation occurs within the spinal cord that allows animals to walk almost normally until late ages. Only around the age of 84 days is the first sign of abnormal movement during walking behavior detected as an abnormal tibialis anterior activity profile that is manifested in subtle but abnormal swing movement during walking. Additionally, this method can be used with other mouse models of human diseases, such as spinal cord injury, intracerebral hemorrhage, Parkinson's diseases, and spinal muscular atrophy.


Comparison of antitumor effects of native and recombinant human interferon-α on non-small cell lung cancer cells.
In the present work, we compared the antitumor effects of native human interferon-α (IFN-α) (nHuIFN-α) and recombinant human IFN-α (rHuIFN-α) on human lung adenocarcinoma A549 cells. The antitumor activity was determined by measuring cell viability and apoptosis, while the abundance of mRNA, measured by polymerase chain reaction (PCR), determined the potential role of p21 and survivin in antitumor activity of nHuIFN-α. The results show that nHuIFN-α significantly reduced A549 cell viability, compared to rHuIFN-α. The most potent effect of nHuIFN-α was also observed when apoptosis was measured. A549 cells treated with nHuIFN-α expressed a significantly higher amount of p21 mRNA, while the amount of survivin mRNA was significantly reduced. Considering both the anti-proliferative and anti-apoptotic effects of each IFN-α, we conclude that further elucidation of the mechanisms of the antitumor activity of nHuIFN-α will help in producing more effective and less toxic therapeutic protocols and preparations.


Mesenchymal stem cells in human meniscal regeneration: A systematic review.
Stem cell regeneration is the holy grail of meniscal tissue repair. Currently, the best treatment is to preserve the original meniscus but if it fails, a partial meniscectomy is indicated to delay the onset of osteoarthritis. The authors present a systematic review to determine the up-to-date evidence underlying the use of mesenchymal stem cells for meniscal regeneration in humans. A search was conducted using the electronic databases of MEDLINE/Pubmed, Google scholar, and the Cochrane Collaboration. Search keywords included human, meniscus, stem cells and regeneration. After screening 10 non-duplicate studies, 5 were identified based on title and abstract. 4 were included in the analysis. There were marked differences in the method of stem cell harvest techniques. 3 studies administered stem cells through percutaneous injection into the knee and 1 study used a collagen scaffold. MRI analysis, functional scores and safety were assessed and the longest follow-up period was 2 years. The Visual Analogue Score (VAS) was most commonly used to assess function and patients generally showed an improvement. There were no reported adverse events. Despite positive results from animal models, there is currently a lack of evidence in humans to conclude that stem cells can form durable neotissue similar to original human meniscus. There is a need for standardisation of protocol before further trials are considered. Initial outcomes from human studies are promising and mesenchymal stem cells may play an important role in meniscal repair in years to come.


Gorilla endoscopic sinus surgery: a life-saving collaboration between human and veterinary medicine.
Chronic rhinosinusitis is a common disease process in humans; however, in the primate population of gorillas, it has rarely been described. This case describes lifesaving sinus surgery on a critically ill gorilla performed by a human otolaryngology team in collaboration with the gorilla's veterinary medicine team. The 35-year-old western silverback gorilla was treated for 3 months with aggressive medical therapy for a worsening sinus infection. When his condition became severe, a computed tomography (CT) scan was performed showing advanced chronic rhinosinusitis with nasal polyps vs other masses and some bone erosion. As his condition deteriorated further, a tertiary otolaryngology team performed sinus surgery using the latest technology available, including image guidance, steroid-eluting sinus stents, and balloon sinus dilation. The postoperative course was complicated by subcutaneous infection and eventual fistulization. Fortunately, with culture-directed antibiotic therapy his condition gradually improved. One year later he required revision sinus surgery. At that point allergy testing was performed followed by appropriate allergy medical therapy. Now, 3 years out from his initial surgery, he continues to do well and has fathered a young female gorilla. This case represents a unique collaboration between human physicians and veterinarians. The combined medical approach was critical to heal this ailing gorilla. This case discusses many of the challenges and offers recommendations for physicians who may be involved with similar care of animals in the future. The success of the surgical and medical treatment of this gorilla's life-threatening sinus infection required many experts, careful planning, and corporate generosity. The interaction between human and animal medicine would not have been successful without the close and trusting collaborations between human and veterinary health providers. We encourage human healthcare providers to seek volunteer opportunities through their local zoos by engaging in discussions with their local veterinarians.


Ontogeny and evolution of pelvic diameters in anthropoid primates and in Australopithecus afarensis (AL 288-1).
Pelvic diameters (both anteroposterior [AP] and transverse [TR]) were investigated in a series of anthropoid primates. The ratio of diameters (AP/TR) in each of three pelvic planes (inlet, midpelvis, and outlet) was calculated. In addition to the above, the length of the iliac, pubic, and ischial axes and the angles between these axes were determined. The AP/TR ratio at the pelvic inlet is (reported in millimeters, +/- SD, unless otherwise specified) 1.81 +/- 0.27 in New World monkeys (Cebidae) and Macaca mulatta; 1.53 +/- 0.17 in hylobatids and pongids; 0.87 +/- 0.08 in Homo sapiens; and 0.58 in Australopithecus afarensis (AL 288-1). The AP/TR ratio in the midpelvis is 1.61 +/- 0.23 in nonhominid primates (Cebidae, M. mulatta, hylobatids, and pongids), 1.12 +/- 0.11 in humans, and 0.59 in AL 288-1. In monkeys (Cebidae and M. mulatta), hylobatids, pongids, H. sapiens, and AL 288-1, the ratios of the length of the pubic axis over the ischial axis were 0.84 +/- 0.06, 0.95 +/- 0.07, 1.10 +/- 0.15, and 1.46, respectively; the pubis-ilium angles were 96 +/- 11, 120 +/- 10, 131 +/- 11, and 147 degrees, respectively; and the ischium-pubis angles were 106 +/- 11, 86 +/- 8, 96 +/- 7, and 68 degrees, respectively. In none of these pelvic features was AL 288-1 "intermediate" between pongids and H. sapiens. The anatomical peculiarities of the pelvis in AL 288-1 are explained primarily as the result of early adaptation to erect posture, which resulted in the reduction of the distance between the sacroiliac joint and the hip joint. As a consequence, the sacral promontory moved toward the pubic symphysis, and this resulted in shortening of the AP diameter and widening of the TR diameter at the pelvic inlet.


Role of a family 11 carbohydrate-binding module in the function of a recombinant cellulase used to supplement a barley-based diet for broiler chickens.
1. Cellulases and xylanases display a modular architecture that comprises a catalytic module linked to one or more non-catalytic carbohydrate-binding modules (CBMs). CBMs have been classified into 52 different families, based on primary structure similarity. These non-catalytic modules mediate a prolonged and intimate contact of the enzyme with the target substrate eliciting efficient hydrolysis of the target polysaccharides. 2. A study was undertaken to investigate the importance of a family 11 CBM, displaying high affinities for barley beta-glucans, in the function of recombinant derivatives of cellulase CtLic26A-Cel5E of Clostridium thermocellum used to supplement a barley-based diet for broiler chicken. 3. The results showed that birds fed on diets containing the recombinant CtLic26A-Cel5E modular derivatives or the commercial enzyme mixture Rovabio Excel AP displayed improved performance when compared with birds fed on diets not supplemented with exogenous enzymes. 4. It is suggested that the enzyme dosage used in this study (30 U/kg of basal diet), was probably too high for the efficacy of the family 11 CBM to be noticed. It remains to be established if the targeting effect resulting from the incorporation of CBMs in plant cell wall hydrolases may be effective at lower exogenous enzyme dosages.


[The epidemiology of aging: a further stage in the demographic transition].
"Social and economic indicators depict Mexico as a country of intermediate development. It is also in intermediate stages of demographic and epidemiologic transitions. When these traits are translated into socio-demographic perspectives, all projections indicate that for the next fifty years we can expect: (i) percentage decreases in child and teen-age populations, (ii) large percentage and absolute increases in adult population, and (iii) important increases in the elderly population.... Among elders death due to infectious diseases is less common than within other sectors of [the] population. Mortality associated with chronic ailments has increased, with recent and remarkable changes during the last twenty years. This transformation is not evenly distributed. It is more accelerated in developed and urban areas as contrasted with the rural and less developed." (SUMMARY IN ENG)


Xanthine oxidase in rabbit plasma after application of a bovine milk preparation to small intestine.
The absorption of xanthine oxidase into the bloodstream was studied in rabbits given a milk/cream preparation, fortified with 130 U bovine milk xanthine oxidase or the milk/cream preparation alone (control). The preparations were injected trans-abdominally into the intestines. The rise of plasma xanthine oxidase/dehydrogenase activity was studied with a radioenzymatic assay with and without NAD+. In rabbits, which received the fortified mixture, the plasma xanthine oxidase increase in 8 h was six times more than the increase in control animals (P less than 0.001). In both groups plasma xanthine dehydrogenase activity increased 3-4 times (P less than 0.001), without a significant difference between the two groups. We estimate that only 0.003%, or about 3 micrograms, of the xanthine oxidase added, is absorbed as an active enzyme from the intestine.


Evidence for ESCRT- and clathrin-dependent microautophagy.
Microautophagy refers to a mode of autophagy in which the lysosomal or vacuolar membrane invaginates and directly engulfs target components. The molecular machinery of membrane dynamics driving microautophagy is still elusive. Using immunochemical monitoring of yeast vacuolar transmembrane proteins, Vph1 and Pho8, fused to fluorescent proteins, we obtained evidence showing an induction of microautophagy after a diauxic shift in the yeast Saccharomyces cerevisiae Components of the endosomal sorting complex required for transport machinery were found to be required for this process, and the gateway protein of the machinery, Vps27, was observed to change its localization onto the vacuolar membrane after a diauxic shift. We revealed the functional importance of Vps27's interaction with clathrin in this microautophagy that also contributed to uptake of lipid droplets into the vacuole. This study sheds light on the molecular mechanism of microautophagy, which does not require the core Atg proteins.


Machine Learning Algorithms for Prediction of Survival Curves in Breast Cancer Patients.
Today, cancer is the second leading cause of death worldwide, and the number of people diagnosed with the disease is expected to rise. Breast cancer is the most commonly diagnosed cancer in women, and it has one of the highest survival rates when treated properly. Because the effectiveness and, as a result, survival of the patient are dependent on each case, it is critical to know the modelling of their survival ahead of time. Artificial intelligence is a rapidly expanding field, and its clinical applications are following suit (having surpassed humans in many evidence-based medical tasks). From the inception of since first stable risk estimator based on statistical methods appeared in survival analysis, there have been numerous versions of it created, with machine learning being used in only a few of them. Nonlinear relationships between variables and the impact they have on the variable to be predicted are very easy to evaluate using statistical methods. However, because they are just mathematical equations, they have flaws that limit the quality of their output. The main goal of this study is to find the best machine learning algorithms for predicting the individualised survival of breast cancer patients, as well as the most appropriate treatment, and to propose new numerical variable stratifications. They will still be carried out using unsupervised machine learning methods that divide patients into groups based on their risk in each dataset. We will compare it to standard groupings to see if it has more significance. Knowing that the greatest challenge in dealing with clinical data is its quantity and quality, we have gone to great lengths to ensure their quality before replicating them. We used the Cox statistical method in conjunction with other statistical methods and tests to find the best possible dataset with which to train our model, despite its ease of multivariate analysis.


Parent and youth dopamine D4 receptor genotypes moderate multilevel contextual effects on rural African American youth's risk behavior.
The present investigation extends research on Gene × Environment interactions and youth risk behavior by linking multilevel contextual factors, such as community disadvantage and protective parenting practices, to both parental and youth dopamine D4 receptor (DRD4) genotypes. We expected community disadvantage to influence youth risk behavior via a series of indirect effects involving protective parenting and youth's planful future orientation when both parents' and youth's DRD4 status was considered. Genetic moderation processes also were tested to determine whether they conformed to a diathesis-stress or a differential susceptibility model. Hypotheses were investigated with data from 361 rural African American youth and their parents assessed 3 times when youth were ages 16 to 19. Community disadvantage interacted with parental DRD4 status to predict low levels of protective parenting. Protective parenting, in turn, interacted with youth DRD4 status to forecast increases in youth's planful future orientations, a proximal influence on changes in risk behavior. The Parental DRD4 × Community Disadvantage interaction, but not youth DRD4 × Protective Parenting, conformed to a differential susceptibility model. Indirect effect analyses revealed a significant indirect path linking community disadvantage to youth risk behavior through a series of multilevel Gene × Environment interaction processes.


Relationship between glutathione and DL alpha-lipoic acid against cadmium-induced hepatotoxicity.
Cadmium, a divalent metal toxicant, preferentially localizes in hepatocytes and causes liver injury. DL alpha-lipoic acid is a dithiol which is effective in rendering protection against cadmium-associated liver damage, by virtue of its two sulfhydryl moieties. Lipoate was administered to cadmium-exposed rats which were either prior administered with buthionine sulfoximine to deplete liver glutathione or not. During lipoate treatment, significant protection was rendered against cadmium toxicity even under glutathione-depleted experimental condition. This highlights the antioxidant property of lipoic acid and its efficacy in mitigating cadmium-associated liver assault even in the absence of glutathione synthesis.


The relationship between MHC-peptide interaction and resistance to virus in chickens.
The MHC-peptide interaction has a subtle influence on host resistance to virus. This paper aims to study the relationship between MHC-peptide interaction and MHC-related virus-resistance. By 3D homology modeling, the structure of chicken BF2 molecule BF2*0201 (PDB code: 4d0d) was studied and compared with the known structures of BF2 molecule BF2*0401 (PDB code: 4e0r) to elucidate the characteristics of BF2*0201-binding antigenic peptides. The results show that due to the amino acid difference between the two binding groove of 4e0r and 4d0d, the size of the binding groove of the two are 1130 ų and1380 ų respectively, indicating the amino acid species that 4e0r binding peptide has lower selectivity than 4d0d; and because of large side chain conformation of Arg (especially Arg111) of 4e0r replaced by small side chain Tyr111 of 4d0d, the volume of central part of the binding groove of 4d0d is obviously larger than that of 4e0r, indicating that the restrictive of binding antigenic peptides for 4d0d is narrower than that of 4e0r; and on account of the chargeability of the binding groove of the two are different, namely the binding groove chargeability of 4e0r (strong positive polarity) and 4d0d (weak negative polarity). There are generally more peptides presented by the BF2 of B2 haplotype than by that of B4 haplotype, leading to more resistance of B2 than that of B4 to virus.


Combination of bortezomib and mitotic inhibitors down-modulate Bcr-Abl and efficiently eliminates tyrosine-kinase inhibitor sensitive and resistant Bcr-Abl-positive leukemic cells.
Emergence of resistance to Tyrosine-Kinase Inhibitors (TKIs), such as imatinib, dasatinib and nilotinib, in Chronic Myelogenous Leukemia (CML) demands new therapeutic strategies. We and others have previously established bortezomib, a selective proteasome inhibitor, as an important potential treatment in CML. Here we show that the combined regimens of bortezomib with mitotic inhibitors, such as the microtubule-stabilizing agent Paclitaxel and the PLK1 inhibitor BI2536, efficiently kill TKIs-resistant and -sensitive Bcr-Abl-positive leukemic cells. Combined treatment activates caspases 8, 9 and 3, which correlate with caspase-induced PARP cleavage. These effects are associated with a marked increase in activation of the stress-related MAP kinases p38MAPK and JNK. Interestingly, combined treatment induces a marked decrease in the total and phosphorylated Bcr-Abl protein levels, and inhibits signaling pathways downstream of Bcr-Abl: downregulation of STAT3 and STAT5 phosphorylation and/or total levels and a decrease in phosphorylation of the Bcr-Abl-associated proteins CrkL and Lyn. Moreover, we found that other mitotic inhibitors (Vincristine and Docetaxel), in combination with bortezomib, also suppress the Bcr-Abl-induced pro-survival signals and result in caspase 3 activation. These results open novel possibilities for the treatment of Bcr-Abl-positive leukemias, especially in the imatinib, dasatinib and nilotinib-resistant CML cases.


Numerical solution of the transport equation describing the radon transport from subsurface soil to buildings.
A theoretical evaluation of the properties and processes affecting the radon transport from subsurface soil into buildings is presented in this work. The solution of the relevant transport equation is obtained using the explicit finite difference method (EFDM). Results are compared with analytical steady-state solution reported in the literature. Good agreement is found. It is shown that EFDM is effective and accurate for solving the equation that describes radon diffusion, advection and decay during its transport from subsurface to buildings, which is especially important when arbitrary initial and boundary conditions are required.


Phenotypic expression of natural killer cell associated membrane antigens in patients with chronic liver disease and hepatocellular carcinoma.
The function and phenotypes of peripheral blood natural killer (NK) cells from patients with chronic liver disease and hepatocellular carcinoma (HCC) were examined using a 4 hr 51Cr release NK assay and two-color flow cytometry utilizing anti-Leu-7 and anti-Leu-11 monoclonal antibodies. There was no significant difference between control and patient groups in the percent representation of a total of NK, Leu-7-11+ or Leu-7+11- cells except that the percent representation of Leu-7+11- cells was significantly increased in patients with liver cirrhosis (LC) in comparison with that of chronic active hepatitis (CAH). On the other hand, patients with LC and HCC had lower absolute numbers of a total of NK, Leu-7-11+ and Leu-7+11- cells than did controls or patients with CAH, reflecting the diminished peripheral blood lymphocyte count. Our data indicate that decreased in vitro NK activity in patients with LC and HCC observed in the present study may be due to a functional defect of NK cells.


Geometric imaging of borophene polymorphs with functionalized probes.
A common characteristic of borophene polymorphs is the presence of hollow hexagons (HHs) in an otherwise triangular lattice. The vast number of possible HH arrangements underlies the polymorphic nature of borophene, and necessitates direct HH imaging to definitively identify its atomic structure. While borophene has been imaged with scanning tunneling microscopy using conventional metal probes, the convolution of topographic and electronic features hinders unambiguous identification of the atomic lattice. Here, we overcome these limitations by employing CO-functionalized atomic force microscopy to visualize structures corresponding to boron-boron covalent bonds. Additionally, we show that CO-functionalized scanning tunneling microscopy is an equivalent and more accessible technique for HH imaging, confirming the v1/5 and v1/6 borophene models as unifying structures for all observed phases. Using this methodology, a borophene phase diagram is assembled, including a transition from rotationally commensurate to incommensurate phases at high growth temperatures, thus corroborating the chemically discrete nature of borophene.


NIRVANA-1: maintenance therapy with niraparib versus niraparib-bevacizumab in patients with advanced ovarian cancer.
Following the results of the PRIMA and PAOLA-1 trials, the most effective maintenance strategy for International Federation of Gynecology and Obstetrics stage III patients is still debated, raising the question which of those two maintenance strategies is the most effective: PARP inhibitors alone or PARP inhibitors in combination with bevacizumab. The ongoing NIRVANA-1 study will try to answer this question by assessing the efficacy and safety of niraparib + bevacizumab in comparison with niraparib alone after adjuvant chemotherapy for completely resected stage III patients. Stratification factors include tumor BRCA status, International Federation of Gynecology and Obstetrics stage (IIIA vs IIIB/IIIC) and the use of hyperthermic intraperitoneal chemotherapy during surgery - within the OVHIPEC-2 trial. The primary end point will be progression-free survival rate at 24 months. Safety, median progression-free survival and overall survival will also be studied.


Detection of pH 4.6 insoluble beta-lactoglobulin in heat-treated milk and Mozzarella cheese.
Different protein aggregates including beta-lactoglobulin (beta lg) were detected in the pH 4.6 insoluble fraction recovered from actual heat-treated milk samples by gel electrophoresis and immunoblotting. A competitive enzyme-linked immunosorbent assay (ELISA) using anti-beta lg polyclonal antibodies was developed to analyze the beta lg partition in the protein fractions obtained upon acidification of both milk and Mozzarella cheese at pH 4.6. According to ELISA determinations, nearly 90% of the pH 4.6 soluble beta lg included in raw milk was found in the pH 4.6 insoluble fraction of ultrahigh temperature (UHT)-treated milk. As concerns Mozzarella cheese analysis, ELISA results indicated that about 36% of the total beta lg milk content was transferred from pasteurized milk to Mozzarella cheese, whereas less than 0.5% was transferred from raw milk. The pH 4.6 insoluble beta lg proved to be a suitable indicator of the intensity of the heat treatment applied to milk. The ELISA-based detection of this parameter was suggested for quality control of both drinking milk and raw milk cheese.


Allosalinactinospora lopnorensis gen. nov., sp. nov., a new member of the family Nocardiopsaceae isolated from soil.
A novel actinomycete, designated strain CA15-2(T), was isolated from a soil sample collected from the rhizosphere of tamarisk in the Lop Nor region, Xinjiang, China, and was characterized by using a polyphasic taxonomic approach. Optimal growth occurred at 37 °C and pH 7.5-8.0 and with 5% (w/v) NaCl. Strain CA15-2(T) formed white to pale-yellow branched substrate mycelium without fragmentation and sparse aerial mycelium with wavelike curves. Whole-cell hydrolysates of the isolate contained meso-diaminopimelic acid as the diagnostic diamino acid of the cell wall but no diagnostic sugars. The polar lipids comprised diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, phosphatidylmethylethanolamine, phosphatidylethanolamine, one unidentified glycolipid, one unidentified phospholipid and other unidentified lipids. MK-9(H8), MK-10(H8) and MK-10(H6) were the predominant menaquinones. The major fatty acids were iso-C16:0 and C16:0. The G+C content of the genomic DNA was 69.6 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CA15-2(T) formed a distinct subclade in the family Nocardiopsaceae, with less than 95% 16S rRNA gene sequence similarity to all known members of the family Nocardiopsaceae. On the basis of the evidence from our polyphasic study, a novel genus, Allosalinactinospora gen. nov., is proposed, with the type species Allosalinactinospora lopnorensis gen. nov., sp. nov. The type strain of Allosalinactinospora lopnorensis is strain CA15-2(T) ( = DSM 45697(T) =CGMCC 4.7074(T)).


Prox1 is an early specific marker for the developing liver and pancreas in the mammalian foregut endoderm.
Although important progress has been made recently in the elucidation of the molecular mechanisms that regulate differentiation and morphogenesis of endoderm-derived tissues such as pancreas and liver, less is known about the preliminary steps of early regional specification. Recent evidence supports the proposal that the early endoderm contains a bipotential precursor cell type for pancreas and liver. We have also previously shown that the activity of the homeobox gene Prox1 controls hepatocyte migration during liver morphogenesis. Using detailed comparative analysis of whole embryos and reverse transcriptase polymerase chain reaction of dissected embryonic endoderm, we have now determined that in the early endoderm, Prox1 expression is restricted to regions giving rise to the mammalian pancreas and liver. This finding indicates that Prox1 is one of the earliest specific markers of this commonly fated region of the mammalian endoderm.


The variance of successive peaks in synaptic amplitude histograms: effects of inter-site differences in quantal size.
Variability in the measured amplitude of evoked synaptic events can arise from several factors, including: measurement noise, trial-to-trial variation in the amplitude of the response at a single release site, or variation between different release sites (inter-site variation) in the mean amplitude of the single quantal response. Classic (linear) models of variability include only the first two of these factors, although differences in the number of postsynaptic receptors or the degree of electrotonic attenuation for different release sites could cause substantial inter-site variations in quantal size. In this paper, the effect of inter-site variation on the variance of successive histogram peaks has been determined analytically and verified by computational studies. This effect is minimal at the edges of the histogram and contributes maximally to central peaks. Linear approximations to the variance of successive histogram peaks may therefore result in very poor fits to measured data if substantial inter-site variation in quantal size is involved. Our computational results indicate that for synaptic contacts with high release probabilities and substantial inter-site variation, the variance of histogram peaks will decrease with increasing quantal content.


International child health.
It is our hope that this issue of Pediatric Annals will stimulate among readers a desire to learn more about the difficult challenges faced by our colleagues who live and work in developing countries. They do so much with so little, and their dedication to their work is an inspiration to us all. Armed with such information, working as individuals and as members of political, educational, charitable, and service organizations, we can help many of the children who otherwise will be lost without our attention.


Severe bullous pemphigoid associated with pembrolizumab therapy for metastatic melanoma with complete regression.
Bullous pemphigoid (BP) is considered to be a humorally mediated autoimmune disease, but autoreactive T-cells and T-regulatory cells (Tregs) have also been implicated in this disease. Tregs and the programmed death-1 (PD-1) : programmed death ligand (PD-L) pathway are both critical in terminating immune response, and elimination of either can result in breakdown of tolerance and development of autoimmunity. We report a patient with metastatic malignant melanoma (MM), who underwent pembrolizumab (anti-PD-1) therapy following unsuccessful treatment with ipilimumab [anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4]. The patient developed BP with increasing serum titres of anti-BP180 IgG autoantibodies and increasing disease severity during pembrolizumab therapy. High doses of corticosteroids and methotrexate were needed to control the BP. Following the termination of pembrolizumab therapy, imaging showed complete regression of all metastatic sites. This result may indicate a crucial role for T-cell suppressive activity in controlling and preventing BP.


CTI-2 Inhibits Metastasis and Epithelial-Mesenchymal Transition of Breast Cancer Cells by Modulating MAPK Signaling Pathway.
Although some breast cancer patients die due to tumor metastasis rather than from the primary tumor, the molecular mechanism of metastasis remains unclear. Therefore, it is necessary to inhibit breast cancer metastasis during cancer treatment. In this case, after designing and synthesizing CTI-2, we found that CTI-2 treatment significantly reduced breast cancer cell metastasis in vivo and in vitro. Notably, with the treatment of CTI-2 in breast cancer cells, the expression level of E-cadherin increased, while the expression level of N-cadherin and vimentin decreased. In addition, after CTI-2 treatment, those outflow levels for p-ERK, p-p38, and p-JNK diminished, while no significant changes in the expression levels of ERK, JNK, or p38 were observed. Our conclusion suggested that CTI-2 inhibits the epithelial-mesenchymal transition (EMT) of breast carcinoma cells by inhibiting the activation of the mitogen-activated protein kinase (MAPK) signaling pathway, thereby inhibiting the metastasis of breast tumor cells. Therefore, we believe that CTI-2 is another candidate for breast tumor medication.


Health professionals' experiences of behavioural family therapy for adults with intellectual disabilities: a thematic analysis.
WHAT IS KNOWN ON THE SUBJECT?: Behavioural Family Therapy (BFT) has been shown to help people with some severe mental health conditions, such as schizophrenia, by reducing relapse rates and stress within families. It can be difficult to put family interventions, like BFT, into clinical practice. Families where someone has an intellectual disability can experience more stress compared to those who do not, but we know very little about using BFT with families where a member has an intellectual disability. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: We interviewed nine Community Learning Disability Nurses and Allied Health Professionals about their experiences delivering BFT to families where one member has an intellectual disability. We found that therapists' experiences of delivering BFT were broadly positive, although they found some aspects of their service frustrating. EXPLAIN THE IMPORTANCE OF THE PAPER'S FINDINGS FOR A NON-SPECIALIST AUDIENCE: The study identifies the perceived benefits of BFT as a model to work with families, where a member has an intellectual disability. The study highlights some of the challenges experienced by practitioners, notably issues with engagement and some issues specific to working with adults with an intellectual disability. The findings suggest that it needs to be clear which families would benefit most from BFT, that interventions need to be adapted for people with intellectual disabilities and that Community Learning Disability Nurses and Allied Health Professionals should have support from management to deliver these interventions. Introduction Studies have found family interventions (FIs) to be effective in reducing stress and relapse rates for a variety of mental health conditions. However, implementing FIs into clinical practice is challenging. Studies have suggested that levels of stress within some families of people with intellectual disabilities can be high. However, there is little reported about the use and implementation of FIs, such as Behavioural Family Therapy (BFT), in adult intellectual disability services. Purpose of study To explore the experiences of practitioners delivering BFT to adults with intellectual disabilities. Method A qualitative methodology was employed, using semi-structured individual interviews with BFT therapists from a health professional background (n = 9). Data were analysed thematically. Results Two overarching themes were identified: positivity and frustration. Discussion Implementation of therapy was identified as being broadly successful but with some underlying challenges, notably wider organizational issues and some issues specific to working with adults with intellectual disabilities. Implications for practice The broadly positive experiences reported provide encouragement for the delivery of FIs, such as BFT, to adults with intellectual disabilities, by professions outwith psychology. However, there is a need to provide clarity on referral processes, adapt materials accordingly for this client group and ensure that supportive management and supervision is available to therapists.


Membranous nephropathy with crescents in rheumatoid arthritis: a case report.
A 59-year-old man with long-standing rheumatoid arthritis (RA) developed renal dysfunction, proteinuria and hematuria. Neither gold nor penicillamine had been given. Light microscopy of a renal biopsy specimen revealed membranous nephropathy with crescents of various stages. The possible pathogenesis of such an unusual combination of membranous nephropathy and crescents in RA is discussed.


Two sibs with unbalanced translocations in the Waardenburg gene region.
We report two sibs with unbalanced translocations between chromosomes 2 and 11, both products of a paternal balanced reciprocal translocation involving bands 2q37.3 and 11q23.3


The medical and surgical management of chronic anal fissure.
Major advances in our understanding of the mechanisms involved in chronic anal fissure have allowed the introduction of many new medical therapies for this condition. The literature about current treatment modalities licensed for anal fissure and those novel therapies still under evaluation has been reviewed. These new treatments are examined in the context of traditional surgical management of the disease and a future treatment algorithm suggested.


Reward-based learning for virtual neurorobotics through emotional speech processing.
Reward-based learning can easily be applied to real life with a prevalence in children teaching methods. It also allows machines and software agents to automatically determine the ideal behavior from a simple reward feedback (e.g., encouragement) to maximize their performance. Advancements in affective computing, especially emotional speech processing (ESP) have allowed for more natural interaction between humans and robots. Our research focuses on integrating a novel ESP system in a relevant virtual neurorobotic (VNR) application. We created an emotional speech classifier that successfully distinguished happy and utterances. The accuracy of the system was 95.3 and 98.7% during the offline mode (using an emotional speech database) and the live mode (using live recordings), respectively. It was then integrated in a neurorobotic scenario, where a virtual neurorobot had to learn a simple exercise through reward-based learning. If the correct decision was made the robot received a spoken reward, which in turn stimulated synapses (in our simulated model) undergoing spike-timing dependent plasticity (STDP) and reinforced the corresponding neural pathways. Both our ESP and neurorobotic systems allowed our neurorobot to successfully and consistently learn the exercise. The integration of ESP in real-time computational neuroscience architecture is a first step toward the combination of human emotions and virtual neurorobotics.


Medication-related problems in CKD.
Patients with CKD are often prescribed heterogeneous medications to treat disease-associated comorbidities, to slow down progression of the disease, and to minimize morbidity and mortality rates. However, the medication regimens of this population are very complex, leading to an increased potential for medication-related problems (MRPs). As kidney function declines, the type and amount of medications a patient consumes increases, thereby putting them at a higher risk for MRPs. MRPs have been known to be associated with morbidity, mortality, and a lower quality of life. This review will summarize data on the prevalence and effect of MRPs, and strategies that can be used by clinicians to reduce and resolve MRPs.


Audiograms estimated from brainstem tone-evoked potentials in dogs from 10 days to 1.5 months of age.
The objective of this study was to build audiograms from thresholds of brainstem tone-evoked potentials in dogs and to evaluate age-related change of the audiogram in puppies. Results were obtained from 9 Beagle puppies 10-47 days of age. Vertex to mastoid brainstem auditory-evoked potentials in response to 5.1-millisecond Hanning-gated sine waves with frequencies octave-spaced from 0.5 to 32 kHz were recorded. Three dogs were examined at 10, 13, 19, 25, and 45 days. Four other dogs were examined at 16 days. Data from 7 dogs between 42 and 47 days of age were pooled to obtain audiogram reference values in 1.5-month-old puppies. The best auditory threshold lowered from above 60 dB sound pressure level (SPL) to values close to 0 dB SPL between 13 and 25 days of age and then stabilized. The audible frequency range widened, including 32 kHz in all tested dogs from the 19th day. In the 7 1.5-month-old puppies, the mean auditory threshold decreased by 11 dB per octave from 0.5 to 2 kHz. The auditory threshold was lowest and held the same value from 2 to 8 kHz. The mean auditory threshold increased by 20 dB per octave from 8 to 32 kHz. Near threshold, click-evoked potentials test only a small part of the audible frequency range in dogs. Use of tone-evoked potentials may become a powerful tool in investigating dogs with possible partial hearing loss, including during the auditory system maturation period.


Primary Cutaneous Neuroendocrine Tumor of the Vulva: A Case Report.
Primary cutaneous neuroendocrine tumors (CNET) are extremely rare. Only a few cases have been reported so far. CNET have an indolent clinical course and usually present as a single flesh-colored nodule with a predilection for the scalp and trunk in elderly patients. While primary CNET have characteristic histological and immunohistochemical features akin to other low-grade neuroendocrine tumors elsewhere in the body, diagnosing these tumors on skin biopsies can be challenging as they are particularly mistaken for other, more commonly diagnosed, entities. In the current report we present a unique case of primary CNET of the vulva. The clinical presentation will be discussed as well as the histopathologic and immunohistochemical features and most importantly the possible pitfalls in microscopic examination.


Effect of beta-glucans contained in barley- and oat-based diets and exogenous enzyme supplementation on gastrointestinal fermentation of finisher pigs and subsequent manure odor and ammonia emissions.
The objective of the current experiment was to evaluate the influence of dietary cereal sources of beta(1,3)(1,4)-d-glucan (beta-glucan) and enzyme supplementation on indices of environmental pollution from finisher pigs. An experiment with a 2 x 2 factorial arrangement of treatments was initiated to investigate the effect of dietary source of beta-glucan (barley vs. oats) and enzyme supplementation (no vs. yes) on nutrient digestibility, N utilization, intestinal fermentation, and manure odor and ammonia emissions from finisher boars (n = 4; BW = 73.9 kg; SD = 4.7). Sixteen boars were assigned to 1 of 4 dietary treatments (n = 4/treatment): 1) barley-based diet, 2) barley-based diet + exogenous enzyme, 3) oat-based diet, and 4) oat-based diet + enzyme. The enzyme supplement used contained endo-1,3(4)-beta-glucanase and endo-1,4-beta-xylanase. Experimental diets were formulated to contain similar concentrations of DE (13.5 MJ/kg) and digestible lysine (8.8 g/kg). Pigs offered oat-based diets had reduced digestibility of DM (0.795 vs. 0.849; SEM 0.007; P = 0.001), OM (0.808 vs. 0.865; SEM 0.007; P = 0.001), GE (0.806 vs. 0.845; SEM 0.006; P = 0.002), and NDF (0.233 vs. 0.423; SEM 0.033; P < 0.003) compared with those offered barley-based diets. Oat-based diets increased populations of Bifidobacterium spp. (7.26 vs. 6.38 log cfu/g of digesta; SEM 0.201; P = 0.005) and Lactobacillus spp. (6.99 vs. 6.18 log cfu/g of digesta; SEM 0.234; P = 0.022) in the proximal colon and decreased manure odor emissions [2,179.6 vs. 4,984.6 Ou(E)/m(3) (where Ou(E) refers to European odor units); SEM 653.7; P < 0.011] compared with barley-based diets. There was an interaction between cereal type and enzyme inclusion on manure ammonia emissions from 0 to 96 h (P = 0.050). Pigs offered barley-based diets containing an enzyme supplement had increased manure ammonia emissions compared with those offered unsupplemented barley-based diets. However, there was no effect of enzyme inclusion on oat-based diets. In conclusion, pigs offered oat-based diets harbored increased Bifidobacterium spp. and Lactobacillus spp. populations in the proximal colon and had decreased manure odor emissions compared with those offered barley-based diets. Enzyme inclusion had no effect on manure ammonia emissions from pigs offered oat-based diets.


ASPD: A prospective study of adequacy in Asian patients on long term, small volume, continuous ambulatory peritoneal dialysis.
The impact of small solute clearance on patient survival in continuous ambulatory peritoneal dialysis (CAPD) is not yet solidified. Previously, we demonstrated that CAPD using small volume (6 L) daily exchanges provides adequate dialysis for most Asian patients. We conducted a prospective, long-term observational study to determine the optimal dialysis adequacy that may provide better patient survival for Asian patients who receive small-volume CAPD. We recruited 294 patients. The initial CAPD regime was 3 x 2-L exchanges daily. The same regime was maintained unless there was significant loss of ultrafiltration or fluid retention despite the use of hypertonic dialysate. Median study period was 38.9 (range 5 - 76.5) months, with 81% and 27% of patients remaining in the study at 24 and 48 months respectively. The overall survival rates at 2 and 4 years were 94.0% and 74.8% respectively. Our long-term data revealed that survival rate was related to Kt/V values. Survival rates were significantly higher for patients with total Kt/V > 2.0 than for patients with Kt/V < 1.7 (p = 0.02). The former group had lower body mass index and higher residual renal function and peritoneal Kt/V than the Latter group. On analysis using Cox proportional hazards regression models, cardiovascular disease (CVD), lower urine volume, and higher body mass index were independent predictors of mortality. Patients with higher renal Kt/V had a significantly lower risk of mortality (RR = 0.018, p = 0.01) after adjusting for the effects of CVD and diabetes mellitus. Our data recommend that 1.7 be the minimal target for total Kt/V in patients on long-term CAPD. Patients with high body mass index, low residual urine volume, and significant CVD need close monitoring.


Psychometric properties of quality of life and health-related quality of life assessments in people with multiple sclerosis.
There is substantial interest in testing interventions for improving quality of life (QOL) and health-related quality of life (HRQOL) in people with multiple sclerosis (MS). Yet, there is limited research on the psychometric properties of QOL [e.g., Satisfaction with Life Scale (SWLS), Leeds MS Quality of Life Scale (LMSQOL)] and HRQOL [e.g., Short Form 12 Health Survey (SF-12) and Multiple Sclerosis Impact Scale-29 (MSIS-29)] measures in this population. Such research is important for designing and interpreting interventions. We examined the test-retest reliability, measurement error, and interpretability of QOL (i.e., SWLS and LMSQOL) and HRQOL (i.e., SF-12 and MSIS-29) measures over 6 months in people with MS. Individuals with MS (n = 274) completed the SWLS, LMSQOL, SF-12 and MSIS-29 on two occasions, 6 months apart. We estimated test-retest reliability [intraclass correlation coefficient (ICC)], measurement error [standard error of measurement (SEM) and coefficient of variation] and interpretability [smallest detectable change (SDC)]. Intraclass correlation coefficient values ranged between moderate and good (ICC range = 0.669-0.883); the MSIS-29 physical component had the best reliability, and the SF-12 mental component had the worst reliability. Measurement error, based on percent SEM, varied among measures; the physical and mental components of the SF-12 (%SEM = 4.6 and 5.3, respectively) had the best measurement error, and the MSIS-29 mental component (%SEM = 13.2) and the SWLS (%SEM = 12.7) had the worst measurement error. Interpretability, based on percent SDC, varied among measures; interpretability was best for the physical and mental components of the SF-12 (%SDC = 12.7 and 14.7, respectively) and worst for the MSIS-29 mental component (%SDC = 36.7) and the SWLS (%SDC = 35). We provide novel data for helping researchers and clinicians select and interpret QOL and HRQOL measures and scores for interventions among people with MS. Such information will better inform our understanding of intervention effectiveness.


An intelligent control scheme for precise tip-motion control in atomic force microscopy.
The paper proposes a new intelligent control method to precisely control the tip motion of the atomic force microscopy (AFM). The tip moves up and down at a high rate along the z direction during scanning, requiring the utilization of a rapid feedback controller. The standard proportional-integral (PI) feedback controller is commonly used in commercial AFMs to enable topography measurements. The controller's response performance is determined by the set of the proportional (P) parameter and the integral (I) parameter. However, the two parameters cannot be automatically altered simultaneously according to the scanning speed and the surface topography during continuors scanning, leading to an inaccurate measurement. Thus a new intelligent controller combining the fuzzy controller and the PI controller is put forward in the paper. The new controller automatically selects the most appropriate PI parameters to achieve a fast response rate on basis of the tracking errors. In the experimental setup, the new controller is realized with a digital signal process (DSP) system, implemented in a conventional AFM system. Experiments are carried out by comparing the new method with the standard PI controller. The results demonstrate that the new method is more robust and effective for the precise tip motion control, corresponding to the achievement of a highly qualified image by shortening the response time of the controller.


Microvascular changes in experimental gastric stress ulceration: the influence of allopurinol, cimetidine, and misoprostol.
The influence of stress on the structure of the gastric mucosal capillary network was investigated in an experimental model using scanning electron microscopy (SEM) to study corrosion casts of the gastric microvasculature. An index of microcirculatory patency was devised to improve the objectivity of SEM. Stress (mean score 42.4 +/- 4.7) severely disrupted the structure of the mucosal capillary network when compared with controls (mean 5.0 +/- 2.9) (P < 0.01). Disruption of the microvascular network was significantly reduced by pretreatment with allopurinol, cimetidine, and misoprostol, these groups having mean damage scores of 17.4 +/- 5.8, 21.2 +/- 7.9, and 28.6 +/- 9.3, respectively, when compared with untreated stressed controls in which the mean score was 42.4 +/- 4.7 (P < 0.02). Microvascular disruption is a significant factor in stress ulceration and the efficacy of allopurinol in minimizing the stress-induced disruption of the microvascular network provides further indirect evidence for the role of ischemia and oxygen-derived free radical generation in its etiology.


Artificial Photosynthesis with Polymeric Carbon Nitride: When Meeting Metal Nanoparticles, Single Atoms, and Molecular Complexes.
Artificial photosynthesis for solar water splitting and CO2 reduction to produce hydrogen and hydrocarbon fuels has been considered as one of the most promising ways to solve increasingly serious energy and environmental problems. As a well-documented metal-free semiconductor, polymeric carbon nitride (PCN) has been widely used and intensively investigated for photocatalytic water splitting and CO2 reduction, owing to its physicochemical stability, visible-light response, and facile synthesis. However, PCN as a photocatalyst still suffers from the fast recombination of electron-hole pairs and poor water redox reaction kinetics, greatly restricting its activity for artificial photosynthesis. Among the various modification approaches developed so far, decorating PCN with metals in different existences of nanoparticles, single atoms and molecular complexes, has been evidently very effective to overcome these limitations to improve photocatalytic performances. In this Review article, a systematic introduction to the state-of-the-art metal/PCN photocatalyst systems is given, with metals in versatility of nanoparticles, single atoms, and molecular complexes. Then, the recent processes of the metal/PCN photocatalyst systems in the applications of artificial photosynthesis, e.g., water splitting and CO2 reduction, are reviewed. Finally, the remaining challenges and opportunities for the development of high efficiency metal/PCN photocatalyst systems are presented and prospected.


Assessment of dynamic microbial community structure and rhizosphere interactions during bioaugmented phytoremediation of petroleum contaminated soil by a newly designed rhizobox system.
To understand the plant (Vigna unguiculata) and plant-growth promoting bacteria (PGPB) (Microcococcus luteus WN01) interactions in crude oil contaminated soil, experiments were conducted based on the newly designed rhizobox system. The rhizobox was divided into three main compartments namely the rhizosphere zone, the mid-zone, and the bulk soil zone, in accordance with the distance from the plant. Plants were grown in these three-chambered pots for 30 days under natural conditions. The plant root exudates were determined by analyzing for carbohydrates, amino acids, and phenolic compounds. The degradation of alkane, polycyclic aromatic hydrocarbons (PAHs), and total petroleum hydrocarbons (TPHs) were quantified by GC-FID. Soil catalase, dehydrogenase, and invertase activities were determined. The microbial community structure was assessed using denaturing gradient gel electrophoresis (DGGE). Results showed that the inoculation of M. luteus WN01 significantly enhanced cowpea root biomass and exudates, especially the phenolic compounds. Bioaugmented phytoremediation by cowpea and M. luteus promoted rhizodegradation of TPH. Cowpea stimulated microbial growth, soil dehydrogenase, and invertase activities and enhanced bacterial community diversity in oil contaminated soil. The rhizosphere zone of cowpea inoculated with M. luteus showed the highest removal efficiency, microbial activities, microbial population, and bacterial community diversity indicating the strong synergic interactions between M. luteus and cowpea.


Therapeutic drug monitoring of linezolid: a retrospective monocentric analysis.
The objective of the present retrospective observational study carried out in patients receiving a standard dosage of linezolid and undergoing routine therapeutic drug monitoring (TDM) was to assess the interindividual variability in plasma exposure, to identify the prevalence of attainment of optimal pharmacodynamics, and to define if an intensive program of TDM may be warranted in some categories of patients. Linezolid plasma concentrations (trough [C(min)] and peak [C(max)] levels) were analyzed by means of a high-performance liquid chromatography (HPLC) method, and daily drug exposure was estimated (daily area under the plasma concentration-time curve [AUC(24)]). The final database included 280 C(min) and 223 C(max) measurements performed in 92 patients who were treated with the fixed 600-mg dose every 12 h (q12h) intravenously (n = 58) or orally (n = 34). A wide variability was observed (median values [interquartile range]: 3.80 mg/liter [1.75 to 7.53 mg/liter] for C(min), 14.70 mg/liter [10.57 to 19.64] for C(max), and 196.08 mg·h/liter [144.02 to 312.10 mg·h/liter] for estimated AUC(24)). Linezolid C(min) was linearly correlated with estimated AUC(24) (r(2) = 0.85). Optimal pharmacodynamic target attainment (defined as C(min) of ≥2 mg/liter and/or AUC(24)/MIC(90) ratio of >80) was obtained in about 60 to 70% of cases, but potential overexposure (defined as C(min) of ≥10 mg/liter and/or AUC(24) of ≥400 mg·h/liter) was documented in about 12% of cases. A significantly higher proportion of cases with potential overexposure received cotreatment with omeprazole, amiodarone, or amlodipine. Our study suggests that the application of TDM might be especially worthwhile in about 30% of cases with the intent of avoiding either the risk of dose-dependent toxicity or that of treatment failure.


Matrix metalloproteinases in ureteropelvic junction obstruction.
Management of ureteropelvic junction obstruction (UPJO) remains controversial. The aim of the present study was to measure the levels of matrix metalloproteinases (MMPs) in UPJO patients who were planned to undergo surgery and thus clarify if MMPs levels could serve as potential biomarkers of surgical obstruction in UPJO. Serum samples of infants with UPJO diagnosis were compared to serum samples of healthy age-matched controls. MMP2 and MMP9 were quantified using enzyme-linked immunosorbent assay (ELISA). A total of 17 infants with UPJO diagnosis, and median age 1.5 months, were prospectively recruited. MMP9 levels were significantly decreased in the serum samples of UPJO infants compared to controls (p =0.037). Also MMP2 values were higher in UPJO infants compared to controls, but the difference was not statistically significant (p =0.206). This study found decreased concentrations of MMP9 in infants with obstructive hydronephrosis. However, the results should be tested in larger population samples and even be evaluated simultaneously with urine samples in order to delineate the ability of MMPs to serve as obstruction biomarkers. HIPPOKRATIA 2017, 21(3): 136-139.


Expression of vascular endothelial growth factor in adenocarcinomas of the uterine cervix and its relation to angiogenesis and p53 and c-erbB-2 protein expression.
The purpose of this study was to evaluate vascular endothelial growth factor (VEGF) expression in adenocarcinomas of the uterine cervix and its correlation with clinicopathologic features, angiogenesis, and expression of p53 and c-erbB-2 proteins. Thirty-seven cases of FIGO clinical stage I and II adenocarcinoma of the uterine cervix were examined by immunohistochemical studies with anti-VEGF, anti-CD34, anti-p53, and anti-c-erbB-2 antibodies. Computerized image analysis was used to evaluate microvessel density (MVD). Thirty-one tumors (83.8%) were classified as VEGF positive. Six tumors (16.2%) showed p53 protein expression while 11 tumors (29.7%) expressed the c-erbB-2 protein. MVD ranged from 13.3 to 44.8, with a median value of 25.5 (26.9 +/- 7.5). Tumors expressing VEGF had a significantly higher MVD than those that did not express VEGF (P < 0.05). VEGF expression was significantly associated with c-erbB-2 protein expression (P < 0.05). The spatial distributions of both VEGF expression and c-erbB-2 expression were similar in tumor tissues. In univariate log-rank analysis, stage (P = 0.0250), lymphovascular space invasion (P = 0.0156), and MVD (P = 0.0360) were associated with shortened survival. VEGF expression plays a role in promoting angiogenesis in cervical adenocarcinomas and c-erbB-2 is likely to be involved in the up-regulation of VEGF expression.


Cycling Stability of a VOx Nanotube Cathode in Mixture of Ethyl Acetate and Tetramethylsilane-Based Electrolytes for Rechargeable Mg-Ion Batteries.
The electrochemical cycling performance of vanadium oxide nanotubes (VOx-NTs) for Mg-ion insertion/extraction was investigated in acetonitrile (AN) and tetramethylsilane (TMS)-ethyl acetate (EA) electrolytes with Mg(ClO4)2 salt. When cycled in TMS-EA solution, the VOx-NT exhibited a higher capacity retention than when cycled in AN solution. The significant degradation of capacity in AN solution resulted from increased charge-transfer resistance caused by the reaction products of the electrolyte during cycling. Mixed TMS-EA solvent systems can increase the cell performance and stability of Mg-electrolytes owing to the higher stability of TMS toward oxidation and the strong Mg-coordination ability of EA. These results indicate that the interfacial stability of the electrolyte during the charging process plays a crucial role in determining the capacity retention of VOx-NT for Mg insertion/extraction.


Direct Oral Anticoagulants for the Treatment of Cancer-Associated Venous Thromboembolism: A Latin American Perspective.
Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in patients with cancer. On the basis of results from randomized controlled trials, direct oral anticoagulants (DOACs) are now recommended for the treatment of cancer-associated VTE. The decision to use a DOAC requires consideration of bleeding risk, particularly in patients with gastrointestinal (GI) malignancies, the cost-benefit and convenience of oral therapy, and patient preference. While efficacy with apixaban, edoxaban, and rivaroxaban versus dalteparin has been consistent in the treatment of cancer-associated VTE, heterogeneity is evident with respect to major GI bleeding, with an increased risk with edoxaban and rivaroxaban but not apixaban. Although cost and accessibility vary in different countries of Latin America, DOACs should be considered for the long-term treatment of cancer-associated VTE in all patients who are likely to benefit. Apixaban may be the preferred DOAC in patients with GI malignancies and LMWH may be preferred for patients with upper or unresected lower GI tumors. Vitamin K antagonists should only be used for anticoagulation when DOACs and low molecular weight heparin are inaccessible or unsuitable.


Protein C-terminal labeling and biotinylation using synthetic peptide and split-intein.
Site-specific protein labeling or modification can facilitate the characterization of proteins with respect to their structure, folding, and interaction with other proteins. However, current methods of site-specific protein labeling are few and with limitations, therefore new methods are needed to satisfy the increasing need and sophistications of protein labeling. A method of protein C-terminal labeling was developed using a non-canonical split-intein, through an intein-catalyzed trans-splicing reaction between a protein and a small synthetic peptide carrying the desired labeling groups. As demonstrations of this method, three different proteins were efficiently labeled at their C-termini with two different labels (fluorescein and biotin) either in solution or on a solid surface, and a transferrin receptor protein was labeled on the membrane surface of live mammalian cells. Protein biotinylation and immobilization on a streptavidin-coated surface were also achieved in a cell lysate without prior purification of the target protein. We have produced a method of site-specific labeling or modification at the C-termini of recombinant proteins. This method compares favorably with previous protein labeling methods and has several unique advantages. It is expected to have many potential applications in protein engineering and research, which include fluorescent labeling for monitoring protein folding, location, and trafficking in cells, and biotinylation for protein immobilization on streptavidin-coated surfaces including protein microchips. The types of chemical labeling may be limited only by the ability of chemical synthesis to produce the small C-intein peptide containing the desired chemical groups.


Hypersensitivity reactions associated with oxaliplatin and their clinical management.
Oxaliplatin , has become an integral part of the medical treatment of colorectal cancer and other malignancies. Increased use of the drug during the last decade, has led to increased occurrence of oxaliplatin-induced hypersensitivity reactions (HSRs), posing a significant challenge for clinicians. This article aims to review the existing literature regarding the incidence, clinical presentation, pathophysiology, risk factors and current management of oxaliplatin-induced HSRs. A systematic review of the English literature published in PubMed and Medline was undertaken. The clinical manifestations of HSRs were found to be variable and unpredictable. These reactions should be an important concern, as their potential life-threatening risks can force doctors to stop treatment and seek alternatives, which may be less effective, not as well tolerated and/or more expensive. There are a few strategies to prevent these reactions so that patients can still benefit from oxaliplatin. Such strategies include the use of premedication (steroid and antagonists of type I and II histamine receptors), prolonged infusion time and desensitization. The presented management strategies as well as novel diagnostic tools including skin/intradermal tests and specific IgE have shown promising results. However, future research and validation are warranted in bigger clinical trials.


Preliminarily comparison of nutritional composition of some fresh and processed seafood.
Processing made fish less susceptible to spoilage. Fish are rich in protein content but the protein content is reduced with processing gave a better result when long-time preservation was carried out. Aim of this study was comparison of proximate analysis of some fresh and processed seafoods. Raw materials and processed seafoods (canned mackerel tuna, frozen Sea-Bream and Pressed caviar) were obtained from different firms and analyzed. Analysis carried out according AOAC methods. Moisture, protein and fat values of tuna fish were estimated to be 51, 23.9 and 21.4%, respectively. In this study, moisture content of pressed caviar was 36%, protein content was 34.4% and fat content was 16.7%, carbohydrate and energy values were 4.9% and 316 kcal/100 g, respectively. Pressed and smoked seafoods contained lower amount of moisture but higher amounts of the other components than raw materials (p < 0.05). Canned mackerel tuna, frozen sea bream and pressed caviar also contained higher amounts of fat, carbohydrate and energy, respectively (p < 0.05) than raw material. Except canning with water, all processing technologies decreased the moisture content but increased energy values (p < 0.05) of the fish. It is concluded that processed seafoods are rich in chemical components and very nutritive. Canned tuna with salted water may be advised for low-calorie diets. Caviar pressed was one the best sea foods that was produced in Iran. Since fishes are consumed as a major protein source in food, it is very important that the protein content should not be compromised during table preparation.


Evaluation of bamboo shoot peptide preparation with angiotensin converting enzyme inhibitory and antioxidant abilities from byproducts of canned bamboo shoots.
In this paper, aqueous extract fractions from byproducts of the processing of canned bamboo shoots, including boiled water, filled liquid, and squeezed juice, were obtained by 5 kDa molecular cutoff membranes and marcoporous resin DA201-C treatment. The enriched bamboo shoot angiotensin converting enzyme (ACE) inhibitory peptide preparation fraction (called BSP for short) was extracted with ethyl acetate and n-butanol. The ethyl acetate fraction and n-butanol fraction exhibited higher antioxidant capacities than the leaving water fraction (BSML), which was attributed to the higher phenolic acid and flavonoid content of both fractions, while BSML exhibited the strongest ACE inhibitory activity. Sephadex G-15 gel filtration and semipreparative high-performance liquid chromatography were used for further purification of bamboo shoot ACE inhibitory peptide from BSML. Asp-Tyr was identified as the key active component by ultra-high-performance liquid chromatography and electrospray ionization tandem mass spectrometry. A short-term antihypertensive assay stated that both Asp-Tyr [10 mg day(-1) (kg of body weight)(-1)] and BSP [50 mg day(-1) (kg of body weight)(-1)] could significantly reduce the systolic blood pressure of spontaneously hypertensive rats (3-6 h). This study provides further examples of utilization of byproducts from the processing of canned bamboo shoots for the prevention of hypertension and attenuation of oxidative stress.


Regulation of Senescence in Carnation (Dianthus caryophyllus) by Ethylene: Mode of Action.
Carnation (Dianthus caryophyllus) flowers were exposed to 2 mul/l ethylene and examined at intervals to determine the time course of wilting, decrease in water uptake, and increase in ionic leakage in response to ethylene. A rapid decrease in water uptake was observed about 4 hours after initiating treatment with ethylene. This was followed by wilting (in-rolling of petals) about 2 hours later. Carbon dioxide inhibited the decline in water uptake and wilting and this is typical of most ethylene-induced responses. Ethylene did not affect closure of stomates. Ethylene enhanced ionic leakage, as measured by efflux of (36)Cl from the vacuole. This was judged to coincide with the decrease in water uptake. Gassing flowers with propylene initiated autocatalytic ethylene production within 2.4 hours. Since the increase in ethylene production by carnations preceded the increase in ionic leakage and the decline in water uptake by several hours, it is apparent that the change in ionic leakage does not lead to the initial increase in ethylene production as reported (Hanson and Kende 1975 Plant Physiol 55:663-669) in morning glory but may explain the autocatalytic phase of ethylene production.


[The clinico-functional status of patients with unstable stenocardia (based on Holter electrocardiographic monitoring data)].
As many as 50 patients presenting with unstable angina were examined for clinicofunctional status, using bicycle ergometry [correction of veloergometry], transesophageal electrocardiostimulation and 24-hour Holter ECG monitoring during 1-yr follow-up. The results of exercise tests at enrollment into the study suggested a dramatic decrement in the patients' exercise tolerance, as to Holter, with the painless myocardial ischemia tending to be more common among them than the painful one. A follow-up study a year later showed the course of the illness to be most variable among those cases presenting with unstable angina. A correction of their management being warranted, the latter was then tailored to the individual on the basis of findings from a comprehensive evaluation of each of them at the original admission to a hospital.